Efficacy and prognostic predictors of primary systemic therapy for de novo Stage IV breast cancer. Exploratory analysis of JCOG1017 PRIM-BC.

Efficacy and prognostic predictors of primary systemic therapy for de novo Stage IV breast cancer. 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Exploratory analysis of JCOG1017 PRIM-BC. Tadahiko Shien, Makoto Ishitobi, Keita Sasaki, Kiyo Tanaka, Akihiko Shimomura, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7776614/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jan, 2026 Read the published version in Breast Cancer → Version 1 posted 5 You are reading this latest preprint version Abstract The optimal initial systemic therapy for de novo Stage IV breast cancer (BC) is critical, particularly to assess early drug efficacy. In the JCOG1017 trial, untreated de novo Stage IV BC patients received 3 months of subtype-based systemic therapy before randomization for primary tumor resection. Among 569 treated patients, the overall non-progression disease (non-PD) rate was 77.2% and the objective response rate (ORR) was 29.0%. By subtype, non-PD/ORR rates were TN (78.2%/36.4%), Luminal (75.4%/13.4%), HER2 (92.9%/81.0%), and Luminal-HER2 (66.7%/40.3%). Multivariable analysis revealed higher non-PD rates in postmenopausal patients (odds ratio (OR) 1.673, p = 0.024) and those with PgR-positive tumors (OR 2.391, p = 0.0019). Endocrine therapy was more effective for patients with PgR-positive tumors (OR 3.258, p < 0.0001) and less practical in those with visceral metastasis (OR 0.605, p = 0.0334). HPD/HPTX therapies (non-PD rate: 92.7%) were highly effective in treating visceral metastasis (OR 15.818, p = 0.0030). Patients without progression at 3 months had significantly better overall survival (HR 0.508, 95% CI [0.398, 0.648]). These findings emphasize that initial therapy must align with subtype, and endocrine monotherapy is suboptimal for ER + HER2 + BC. Effective strategies are needed for those with early progression. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction There are various guideline recommendations for the appropriate drug treatment of metastatic recurrent breast cancer (BC). The treatment of metastatic BC is based on subtypes classified by ER, PgR, and HER2 expression. Untreated de novo Stage IV patients are more likely to respond to systemic therapy than patients diagnosed with postoperative recurrent BC. Many clinical trial data reported to date for the first-line treatment of metastatic BC are mainly for patients with recurrent BC. It is unclear whether tumor response differs depending on each BC subtype or tumor location, such as primary site or distant metastasis, and whether the tumor response to primary systemic therapy (PST) affects the prognosis in patients with de novo stage IV BC. There is also limited data on predictive factors of tumor response to each treatment and prognostic factors for de novo stage IV BC. In JCOG1017, a randomized trial comparing primary tumor resection (PTR) plus systemic therapy with systemic therapy alone in de novo Stage IV BC patients, de novo Stage IV patients were treated with PST for 3 months according to BC subtypes before randomization. We already presented the results of the primary analysis . PTR could not significantly prolong the overall survival of de novo Stage IV BC patients with sensitivity to PST (median overall survival 75 months vs. 69 months, HR 0.86, 90% CI 0·69 − 1·07, one-sided p = 0·13). In this trial, we uniformly evaluated sensitivity to PST at 3 months for all subtypes and evaluated the survival. Therefore, we aimed to obtain data on the efficacy of PST and the prognosis of only de novo Stage IV BC. In addition, for tumor efficacy assessment, an increase in tumor size of 10% or more was defined as progression instead of using RECIST in this trial. We designed this JCOG1017 trial to investigate the possible benefit of PTR for de novo Stage IV BC that is sensitive to PST. This was to exclude cases of early progression within 3 months from the start of PST. It is unclear whether the definition in this trial or RECIST is more prognostic. In this exploratory analysis, we examined the efficacy and predictive factors of response to each drug in de novo Stage IV BC and whether assessing sensitivity to all drugs is appropriate. We also want to clarify the efficacy of PST for de novo Stage IV patients and develop optimal treatment strategies for de novo Stage IV BC using data from JCOG1017. Patients and Methods Study design and participants. JCOG1017 is a multicenter, open-label, randomized, controlled phase 3 trial at 44 institutions in Japan (Appendix 1) designed to confirm the superiority of PTR in addition to systemic therapy for overall survival over systemic treatment alone. This trial was conducted according to the Declaration of Helsinki, the Japanese Ethical Guidelines for Clinical Research, and the Clinical Trials Act. The Japan Clinical Oncology Group (JCOG) Protocol Review Committee and the National Cancer Center Hospital East Certified Review Board approved the study protocol. All patients provided written informed consent before enrolment. Full trial details have been published previously; the CONSORT diagram is shown in Fig. 1 ii . The eligible patients were aged 20–80 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (PS 2 caused by the symptoms of bone metastasis is also eligible), histologically proven invasive BC, and without bilateral BC or extension to the contralateral breast. The patients with at least one measurable metastatic lesion other than the breast tumor and axillary lymph nodes, and without brain metastasis, were included. The second registration and randomization were performed for patients without progression after PST. This exploratory analysis was conducted on patients enrolled in the first registration and who underwent PST. Procedures All enrolled patients for the first registration received PST. The PST regimen was decided according to the ER and HER2 status and the disease situation (Appendix 2). ER-positive patients, regardless of HER2 status, with no life-threatening diseases received endocrine therapy, which was oral tamoxifen 20 mg/body daily plus subcutaneous goserelin 3·6 mg/body (day 1) every 4 weeks for premenopausal patients and oral letrozole 2·5 mg/body daily for 4 weeks for post-menopausal patients. CDK4/6 inhibitors were not used because they were preapproved during this trial. Patients with ER-negative and/or life-threatening diseases received the following chemotherapy; for HER2-positive patients, intravenous paclitaxel 80 mg/m 2 (days 1, 8, 15) plus weekly trastuzumab 2 mg/kg (days 1, 8, 15, 22) every 4 weeks (before reported the results of CLEOPATRA study) (HPTX)or intravenous docetaxel 75 mg/m 2 (day1) plus trastuzumab 6mg/kg (day1), pertuzumab 420mg/body (day1) every 3 weeks (after 2020 when reported the results of CLEOPATRA study )(HPD), and for HER2-negative patients intravenous paclitaxel 80 mg/m 2 (days 1, 8, 15) every 4 weeks. Pembrolizumab was not used to treat triple-negative BC because it was not approved at the time of this trial. After each regimen, tumor assessment was conducted after three cycles, while the docetaxel, trastuzumab, and pertuzumab regimens underwent evaluation after four cycles. In the PTR plus systemic therapy arm, the patients underwent the complete resection of the primary breast tumor within 42 days after the second registration. Adjuvant radiotherapy after partial or total mastectomy was not allowed. After surgery, the same systemic therapy was continued as soon as possible. In the systemic therapy alone arm, the patients continued the same systemic therapy after the second registration. Outcomes The non-PD (Progressive Disease) rate and the response rate were examined. In the non-PD rate, PD was defined as meeting any of the following criteria after 3 months of systemic therapy: i) the diameter of the primary tumor lesion increased 10% or more compared to the most minor recorded diameter, ii) the sum of the diameters of distant metastases increased 10% or more compared to the smallest recorded sum of the diameters, iii) unequivocal progression of existing non-target lesions, iv) appearance of new malignant lesions. The response rate was defined as a proportion of patients with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 . We considered patients with CR or PR as responders, and patients with stable disease or progression disease, defined by RECIST ver 1.1, non-responders. The overall survival of responders vs. non-responders and the PD vs. non-PD group was also evaluated. Overall survival was defined as the number of days from the date of randomization to the date of death from any cause. Statistical analysis The non-PD and response rates were reported as percentages and 95% confidence intervals (CIs) calculated by the Clopper-Pearson method. To examine the predictive factors for the non-PD rate and the response rate for all the first registered patients and each drug, univariable and multivariable logistic regression models were performed with the following clinical factors as covariates: menopausal status (pre/post), cT (cT1/ cT3/ cT3/ cT4), cN (cN0/ cN1/ cN2/ cN3), visceral mets (yes/no), histology (IDC/special types), ER (negative/positive; univariable only), PgR (negative/positive; univariable only), HER2 (negative/positive) and subtype (ER (-) and HER2 (-)/ ER (+) and HER2 (-)/ ER (-) and HER2 (+)/ ER (+) and HER2 (+)). OS was estimated with the Kaplan-Meier method. The univariable analyses were performed with the Cox proportional hazard model to calculate the hazard ratio between the responders and non-responders, as well as PD and non-PD. All statistical analyses were conducted using SAS software (version 9.4). Results Of 570 de novo Stage IV patients enrolled in the JCOG1017, 569 patients who received PST were examined in this exploratory analysis. 372 patients with ER+/non-life-threatening metastases received endocrine therapy (tamoxifen + LH-RH agonist or letrozole), 109 patients with ER-/HER2 + or ER+/HER2+/ life-threatening metastases received HPD or HPTX and 88 patients with ER-/HER2- tumors received PTX. The details of the clinical and pathological features are in Table 1. Median age was 57, and 198 (34.8%) patients were premenopausal. Table 2 shows the tumor response of PST for 3 months. The non-PD rate for all patients was 77.2% (439/569, 95%CI: 73.5–80.5%), and the predictive factors of non-PD were post-menopausal (odds ratio [OR] 1.673, 95%CI: 1.070–2.617, p = 0.024), PgR positive (OR 2.391, 95%CI: 1.380–4.140, p = 0.0019), and subtypes in multivariable analysis (Table 2 − 1). Non-PD rate of endocrine therapy was 72.9% (271/372, 95%CI 68.0-77.3%), and that of tamoxifen + LH-RH agonist and letrozole were 68.5% (89/130, 95% CI: 59.7–76.3%) and 75.2% (182/242, 95% CI: 69.3–80.5%), respectively. The predictive factors of non-PD of endocrine therapy were visceral metastasis status (positive: OR 0.605, 95%CI 0.381–0.961, p = 0.033; reference group: negative), PgR status (positive: OR 3.258, 95%CI 1.886–5.628, p < 0.0001; reference group: negative) and HER2 status (positive: OR 0.365, 95%CI 0.195–0.684, p = 0.0016; reference group: negative). (Table 2 – 2 ) The non-PD rate of PTX was 76.1% (67/88, 95%CI 65.9–84.6%). There was no significant predictive factor of non-PD. (Table 2 –3) The non-PD rate for HPD/HPTX was 92.7% (101/109, 95%CI 86.1–96.8%), and that of HPD and HPTX was 92.6% (75/81, 95%CI 84.6–97.2%) and 92.9% (26/28, 95%CI 76.5–99.1%). The predictive factor of non-PD for HPD/HPTX was visceral metastases (OR 15.818, 95%CI: 2.547–24.942, p = 0.0030). (Table 2 –4) According to the RECIST ver. 1.1, the response rate of 3 months systemic therapy for all patients was 29.0% (165/569, 95%CI 25.3–32.9%), and that of endocrine therapy, PTX and HPD/HPTX were 11.6% (43/372, 95%CI 8.5–15.3%), 36.4% (32/88, 95% CI 26.4–47.3%) and 82.6% (90/109, 95%CI 74.1–89.2%). (Table 5) The CR in the primary site was only the HPD/HPTX regimen (18/109, 16.5%). The CR in metastatic lesions was 0.5% (2/372), 11.9% (13/109), and 1.1% (1/88) by endocrine, HPD/HPTX, and PTX, respectively. ( Overall survival was better in patients with non-PD than PD (MST 6.1 years vs. 3.5 years, HR 0.508[95%CI: 0.398–0.648], two-sided log-rank p < 0.0001) (Fig. 2 ). OS between non-PD and PD was significantly different, regardless of drug. (Endocrine therapy; HR 0.532 [95%CI: 0.399–0.711], two-sided log-rank p < 0.0001, HPD/HPTX; HR 0.306 [95%CI:0.119–0.783], two-sided log-rank p = 0.0088, PTX; HR 0.555 [95%CI:0.322–0.956], two-sided log-rank p = 0.0315). As per the RECIST criteria, OS between responders (CR + PR) and non-responders was not significant (HR 0.788[95%CI:0.617–1.005], two-sided log-rank p = 0.0538). However, there was an important difference between PD and others (CR, PR, and SD) (HR 0.508[95%CI: 0.398–0.648]). Discussion In this analysis, response predictive factors to PST for non-PD were post-menopausal, PgR positive, and subtype. An ER-/HER2 + tumor was more likely to respond than an ER-/HER2—tumor, while an ER+/HER2—tumor was less likely to respond. The response and predictors of response to PST differed by subtype. PgR, HER2 expression, and the status of visceral metastasis may have affected the efficacy. The response rate for first-line treatment with LH-RH agonist and tamoxifen for MBC, including both recurrent and de novo Stage IV BC, is reported to be 38–48%, and the median progression-free survival is 8.7 months. The response rate for first-line treatment with letrozole was 32%, and the median progression-free survival was reported to be 9.4 months. PgR is a target gene of ER, and PgR expression is considered a prognostic predictor of ER-positive BC as an indicator of activation of the ER pathway. More recently, it has also been shown to regulate tumor progression directly, and activation of PgR inhibits breast cancer cell proliferation and is associated with a favorable prognosis. HER2 is a target for molecular targeted drugs. In this trial, endocrine therapy alone was used as first-line treatment in ER-positive HER2-positive BC without life-threatening metastasis. However, this study showed that endocrine therapy was less effective in these subjects. Conversely, patients treated with anti-HER2 drugs showed very high efficacy at 3 months. Therefore, endocrine therapy is not recommended as primary therapy in ER-positive HER2-positive patients. The efficacy of HPD therapy as the primary treatment for HER2-positive metastatic BC was reported in the CLEOPATRA trial. The median PFS was 12.4 months, and the response rate was 80.2%, which is consistent with the results of this study, which reported that HPD is highly effective in ER-positive as well as ER-negative metastatic BC. The efficacy of Taxane (paclitaxel and docetaxel) in HER2-negative metastatic BC is reported to be around a 34% response rate. However, no clinically useful predictors of response to Taxane have been reported. In summary, the results of the present study on the efficacy and predictors of initial drug therapy for de novo Stage IV BC were consistent with those reported previously for recurrent BC as a whole. Therefore, the optimal drug therapy for de novo Stage IV BC should be selected based on the biology and metastatic status of BC, even more so than for recurrent BC. In ER-positive MBC, patients deriving no clinical benefit from first-line endocrine therapy (± CDK4/6 inhibitors) have significantly worse OS than responders. For example, an extensive analysis found median OS ~ 62 months in patients with a first-line objective response versus ~ 41 months in non-responders (p < 0.001) . Primary endocrine resistance is thus a strong negative prognostic factor for survival in this subtype. Similarly, lack of response in HER2 + disease treated first-line with trastuzumab-based regimens (e.g., trastuzumab ± pertuzumab plus chemotherapy) portends inferior survival. Patients achieving an objective response to initial anti-HER2 therapy enjoy markedly longer OS; one study reported median OS 10.2 years in those with complete response vs < 6.3 years in patients with only stable disease . In contrast, those who fail to respond to anti-HER2 therapy face substantially shorter survival. TNBC has the poorest prognosis – median OS is only about 12–18 months with standard first-line chemotherapy . Non-responders to initial therapy (chemotherapy or PARP inhibitors in BRCA-mutant TNBC) have especially short survival, whereas patients who respond can achieve longer OS outcomes . In the JCOG1017 trial, we used a method to determine the efficacy of PST, where PD was assessed if there was even a slight increase in tumor size, instead of using RECIST. We wanted to exclude patients who do not respond to PST and progress early. The study examined the effect of PST from 3 months after the start of treatment using two methods. The results showed that both methods equally identified patients with poor prognosis. However, it is challenging to determine PD early after the start of treatment because the RECIST method cannot accurately determine PD in the case of small metastatic lesions, and SD is determined when the disease worsens by 20% or less. From these points of view, we believe that our method (even a slight increase is judged as progression) is an easy and reasonable method to judge patients with a poor prognosis at an early stage after the start of treatment. And we believe this method will be helpful in strategies such as the JCOG1017 trial, in which treatment efficacy is determined early, patients are differentiated according to this efficacy, and subsequent treatment is modified accordingly. We are currently using the same method to evaluate whether local therapy, including metastases, prolongs prognosis in patients with oligometastasis who are sensitive to PST (JCOG2110 trial, jRCTs 031230439, NCT06135714). There were some limitations in this study. Although new effective drugs have recently been developed to improve prognosis, these drugs were not used in the present study. CDK4/6 inhibitors, standard drugs for ER-positive BC, were also not used. Immune checkpoint inhibitors are used for TN BC, and PARP inhibitors for BRCA mutation-positive BC, but not in this study. Their efficacy or predictive factors are not clear from the results of the present study. On the other hand, in the present study, efficacy was uniformly determined at 3 months for all drugs. This was done to assess the efficacy of the drugs at an early stage and to determine the indication for primary resection. However, it is expected that the maximum efficacy of each drug will not necessarily be three months. The present study cannot examine medium- and long-term drug effects. In addition, primary site excision may affect subsequent drug efficacy and prognosis. Conclusion The choice of initial systemic therapy for de novo Stage IV BC is essential to be appropriate for the subtype. Endocrine mono-therapy was not recommended for patients with ER + HER + BC. The prognosis of patients with PD response after 3 months from the start of treatment is poor, and effective systemic therapy needs to be developed for these patients. Declarations Acknowledgments Corresponding Author: Tadahiko Shien MD, PhD, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. （ [email protected] ） Author Contributions: TS had full access to all of the study's data and is responsible for its integrity and accuracy. Concept and design: TS, MI, KT, TT, YS, AS, YK, OM, HY, TI, KT, KG, YN, FH, TF, KS, HF, HI designed the concept and helped write the manuscript. TS, HF, GO, SS, HF, and HI performed the statistical analysis and acquired, analyzed, or interpreted the data. TS obtained the foundation. Ethics approval and consent to participate All methods were performed by the relevant guidelines and regulations. This study was approved by the Ethics Committee of National Cancer Center Hospital East Certified Review Board, and the approval reference number is CRB3180009. Informed consent was obtained from all participants involved in the study. Conflict of Interest Disclosures: Dr. Shien reported grants from the Ministry of Health, Labour and Welfare of Japan and from the Japan Agency for Medical Research and Development (AMED) during the conduct of the study, as well as personal fees from Pfizer, Chugai, Lilly, Daiichi Sankyo, MSD, Eizai, AstraZeneca, Taiho, Nihonkayaku, Gilead. Dr. Hara reported the personal fees from Pfizer, Ili Lilly, Daiichi Sankyo, Kyowa Kirin, Chugai, MSD. Dr. Ogawa reported the grants from Japan Agency for Medical Research and Development and Ministry of Health, Labour and Welfare, Japan. Dr. Fukuda reported the grants from National Cancer Center and AstraZeneca, Ono Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Takeda Pharmaceutical Company Limited and the personal fees from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., CMIC Co., Ltd. Dr. Iwata reported the grants from Pfizer and Chugai, Daiichi Sankyo, AstraZeneca and personal fees from Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Taiho, Kyowa Kirin. No other disclosures were reported. Funding/support This study received partial support from the National Cancer Research and Development Fund (23-A-19, 26-A-4, 29-A-3, 2020-J-3, 2023-J-03), Health and Labour Sciences Research Grant for Clinical Cancer Research (H26-applied-general-03) from the Ministry of Health, Labour and Welfare of Japan and AMED under Grant Number JP22ck0106593, JP19ck0106307, JP16ck106046. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication. Meeting Presentation: The results of this study were presented in part at the San Antonio Breast Cancer Symposium, Dec. 2023, San Antonio, Texas. Data sharing Individual participant data that underline the results reported in this article will not be shared because the follow-up of the patients is continued until May 2028. After the publication using data as of May, 2029, individual participant data that underlie the results after deidentification will be shared if investigators whose proposed use of the data has been approved by the investigators from Breast Cancer Study Group of JCOG identified for this purpose. Proposals should be directed to [email protected] . The date will be available for achieving aims in the approved proposal. Additional Contributions: We thank all the patients and their families, all the study site coordinators and investigators, and the data managers at the JCOG Data Center. Institutions that participated in this study: NHO Hokkaido Cancer Center, Iwate Medical University, Tohoku University Hospital, Faculty of Medicine, University of Tsukuba, Tochigi Cancer Center, Jichi Medical University, Gunma Prefectural Cancer Center, Saitama Cancer Center, National Cancer Center Hospital East, Chiba Cancer Center, National Cancer Center Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, National Hospital Organization Tokyo Medical Center, Showa University School of Medicine, Cancer Institute Hospital, Toranomon Hospital, St. Luke’s International Hospital, Tokai University School of Medicine, St. Marianna University, Kanagawa Cancer Center, Kitasato University School of Medicine, Yokohama Rosai Hospital, Niigata Cancer Center Hospital, Shizuoka General Hospital, Shizuoka Cancer Center, Aichi Cancer Center Hospital, Nagoya City University Hospital, Nagoya Medical Center, Kinki University School of Medicine, Osaka International Cancer Institute, Osaka National Hospital, Okayama University Hospital, Kure Medical Center Chugoku Cancer Center, NHO Fukuyama Medical Center, Hiroshima University Hospital, Hiroshima City Hospital, Hiroshima City Asa Hospital, NHO Shikoku Cancer Center, National Kyushu Cancer Center, Kitakyushu Municipal Medical Center, Nagasaki Medical Center, Kumamoto University Medical School, Social medical corporation Hakuaikai Sagara Hospital. Members of the JCOG Breast Cancer Study Group who contributed to this manuscript: Tadahiko Shien1, Makoto Ishitobi2, Kiyo Tanaka4, Akihiko Shimomura5, Takahiro Tsukioki1, Yasuaki Sagara6, Yuri Kimura7, Kori Terata8, Takayuki Ishiba9, Hiroyuki Yasojima9, Makiko Fuchigami-Ono11, Kyoko Goda12, Yoichi Naito13, Tomomi Fujisawa14, Fumikata Hara15, Hiroji Iwata16. References Shien T, Nakamura K, Shibata T, Kinoshita T, Aogi K, Fujisawa T, et al. A randomized controlled trial comparing primary tumour resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (PRIM-BC): Japan Clinical Oncology Group Study JCOG1017. Jpn J Clin Oncol. 42(10):970-3, 2012. Shien T, Hara F, Aogi K, Yanagida Y, Tsuneizumi M, Yamamoto N, et al. Primary tumor resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): A Randomized Clinical Trial. British J Cancer. 2025. Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, et al. 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Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001 ; 19 : 2596 –606. Carroll JS, Hickey TE, Tarulli GA, Williams M, Tilley WD. Deciphering the divergent roles of progestogens in breast cancer. Nat Rev Cancer. 2017 Jan;17(1):54-64. Farcas AM, Nagarajan S, Cosulich S, Carroll JS. Genome-Wide Estrogen Receptor Activity in Breast Cancer. Endocrinology. 2021 Feb 1;162(2):bqaa224. Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, et al. Phase ? trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer:an intergroup trial(E1193). 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Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period. Breast Care (Basel). 2022 Jun;17(3):264-271. Ishiba T, Nishibuchi I, Hara F, Shikama N, Shien T, Iwata H. Metastasis-directed therapy for oligometastases in breast cancer. Jpn J Clin Oncol. 53(10):893-898, 2023. Tables Table 1: Patient characteristics Tam+LH-RH or LET HPD or HPTX PTX Total n=372 n=109 n=88 n=569 Age Median (min-max) 58 (23-79) 55 (31-79) 57 (25-80) 57 (23-80) Menopausal status premenopausal 130 (34.9) 35 (32.1) 33 (37.5) 198 (34.8) postmenopausal 242 (65.1) 74 (67.9) 55 (62.5) 371 (65.2) cT cT1 26 (7.0) 4 (3.7) 5 (5.7) 35 (6.2) cT2 165 (44.4) 50 (45.9) 36 (40.9) 251 (44.1) cT3 42 (11.3) 19 (17.4) 8 (9.1) 69 (12.1) cT4 139 (37.4) 36 (33.0) 39 (44.3) 214 (37.6) cN cN0 47 (12.6) 7 (6.4) 8 (9.1) 62 (10.9) cN1 169 (45.4) 47 (43.1) 27 (30.7) 243 (42.7) cN2 55 (14.8) 15 (13.8) 16 (18.2) 86 (15.1) cN3 101 (27.2) 40 (36.7) 37 (42.0) 178 (31.3) Visceral metastasis No 185 (49.7) 31 (28.4) 27 (30.7) 243 (42.7) Yes 187 (50.3) 78 (71.6) 61 (69.3) 326 (57.3) Histology Invasive ductal carcinoma 334 (89.8) 104 (95.4) 80 (90.9) 518 (91.0) Special types 38 (10.2) 5 (4.6) 8 (9.1) 51 (9.0) ER Negative 0 (0.0) 84 (77.1) 55 (62.5) 139 (24.4) Positive 372 (100.0) 25 (22.9) 33 (37.5) 430 (75.6) PgR Negative 68 (18.3) 93 (85.3) 59 (67.0) 220 (38.7) Positive 304 (81.7) 16 (14.7) 29 (33.0) 349 (61.3) HER2 Negative 325 (87.4) 0 (0.0) 88 (100.0) 413 (72.6) Positive 47 (12.6) 109 (100.0) 0 (0.0) 156 (27.4) Subtypes ER (-) HER2 (-) 0 (0.0) 0 (0.0) 55 (62.5) 55 (9.7) ER (+) HER2 (-) 325 (87.4) 0 (0.0) 33 (37.5) 358 (62.9) ER (-) HER2 (+) 0 (0.0) 84 (77.1) 0 (0.0) 84 (14.8) ER (+) HER2 (+) 47 (12.6) 25 (22.9) 0 (0.0) 72 (12.7) Table 2: Univariable and Multivariable analysis of predictors to PST. Table 2-1 All patients Univariable analysis Multivariable analysis Factor Non-PD/N Non-PD Rate (95% CI) Odds ratio (95% CI) P-value Odds ratio (95% CI) P-value Menopausal status premenopausal 146/198 73.7% (67.0%-79.7%) 1 1 postmenopausal 293/371 79.0% (74.5%-83.0%) 1.340 (0.896-2.004) 0.1544 1.673 (1.070-2.617) 0.0240 cT cT1 25/35 71.4% (53.7%-85.4%) 1 1 cT2 199/251 79.3% (73.7%-84.1%) 1.565 (0.710-3.448) 0.2666 1.429 (0.630-3.239) 0.3932 cT3 53/69 76.8% (65.1%-86.1%) 1.335 (0.534-3.339) 0.5366 1.502 (0.577-3.909) 0.4043 cT4 162/214 75.7% (69.4%-81.3%) 1.275 (0.577-2.816) 0.5487 1.182 (0.511-2.732) 0.6956 cN cN0 53/62 85.5% (74.2%-93.1%) 1 1 cN1 190/243 78.2% (72.5%-83.2%) 0.633 (0.296-1.351) 0.2369 0.562 (0.258-1.226) 0.1476 cN2 62/86 72.1% (61.4%-81.2%) 0.453 (0.196-1.049) 0.0646 0.452 (0.188-1.083) 0.0748 cN3 134/178 75.3% (68.3%-81.4%) 0.537 (0.248-1.164) 0.1154 0.454 (0.204-1.010) 0.0529 Visceral metastasis No 188/243 77.4% (71.6%-82.5%) 1 1 Yes 251/326 77.0% (72.0%-81.5%) 0.981 (0.660-1.456) 0.9231 0.926 (0.608-1.411) 0.7210 Histology Invasive ductal carcinoma 402/518 77.6% (73.8%-81.1%) 1 1 Special types 37/51 72.5% (58.3%-84.1%) 0.749 (0.393-1.429) 0.3801 0.768 (0.391-1.511) 0.4452 ER* Negative 121/139 87.1% (80.3%-92.1%) 1 Positive 318/430 74.0% (69.5%-78.0%) 0.431 (0.252-0.737) 0.0021 PgR Negative 168/220 76.4% (70.2%-81.8%) 1 1 Positive 271/349 77.7% (72.9%-81.9%) 1.078 (0.723-1.607) 0.7139 2.391 (1.380-4.140) 0.0019 HER2* Negative 313/413 75.8% (71.4%-79.8%) 1 Positive 126/156 80.8% (73.7%-86.6%) 1.330 (0.843-2.098) 0.2207 Subtype ER (-) & HER2 (-) 43/55 78.2% (65.0%-88.2%) 1 1 ER (+) & HER2 (-) 270/358 75.4% (70.6%-79.8%) 0.878 (0.446-1.731) 0.7078 0.434 (0.193-0.978) 0.0439 ER (-) & HER2 (+) 78/84 92.9% (85.1%-97.3%) 3.468 (1.245-9.663) 0.0174 3.374 (1.210-9.407) 0.0201 ER (+) & HER2 (+) 48/72 66.7% (54.6%-77.3%) 0.569 (0.255-1.268) 0.1676 0.345 (0.146-0.816) 0.0153 Overall 439/569 77.2% (73.5%-80.5%) Table 2-2 Patients received Endocrine therapy Univariable analysis Factor Non-PD/N Non-PD Rate (95% CI) Odds ratio (95% CI) P-value cT cT1 18/26 69.2% (48.2%-85.7%) 1 cT2 124/165 75.2% (67.8%-81.5%) 1.378 (0.561-3.389) 0.4844 cT3 29/42 69.0% (52.9%-82.4%) 1.004 (0.350-2.879) 0.9940 cT4 100/139 71.9% (63.7%-79.2%) 1.169 (0.472-2.894) 0.7356 cN cN0 39/47 83.0% (69.2%-92.4%) 1 cN1 124/169 73.4% (66.0%-79.9%) 0.589 (0.259-1.340) 0.2070 cN2 38/55 69.1% (55.2%-80.9%) 0.473 (0.185-1.214) 0.1195 cN3 70/101 69.3% (59.3%-78.1%) 0.482 (0.204-1.138) 0.0958 Visceral metastasis No 144/185 77.8% (71.2%-83.6%) 1 Yes 127/187 67.9% (60.7%-74.5%) 0.605 (0.381-0.961) 0.0334 Histology Invasive ductal carcinoma 244/334 73.1% (68.0%-77.7%) 1 Special types 27/38 71.1% (54.1%-84.6%) 0.885 (0.423-1.852) 0.7461 PgR Negative 35/68 51.5% (39.0%-63.8%) 1 Positive 236/304 77.6% (72.5%-82.2%) 3.258 (1.886-5.628) <0.0001 HER2 Negative 246/325 75.7% (70.7%-80.3%) 1 Positive 25/47 53.2% (38.1%-67.9%) 0.365 (0.195-0.684) 0.0016 Overall 271/372 72.9% (68.0%-77.3%) Table 2-3 patients received weekly PTX Univariable analysis Factor Non-PD/N Non-PD Rate (95% CI) Odds ratio (95% CI) P-value Menopausal status premenopausal 24/33 72.7% (54.5%-86.7%) 1 postmenopausal 43/55 78.2% (65.0%-88.2%) 1.349 (0.501-3.633) 0.5532 cT cT1 3/5 60.0% (14.7%-94.7%) 1 cT2 29/36 80.6% (64.0%-91.8%) 2.811 (0.398-19.850) 0.3001 cT3 6/8 75.0% (34.9%-96.8%) 1.858 (0.176-19.614) 0.6064 cT4 29/39 74.4% (57.9%-87.0%) 2.008 (0.296-13.635) 0.4757 cN cN0 7/8 87.5% (47.3%-99.7%) 1 cN1 20/27 74.1% (53.7%-88.9%) 0.547 (0.071-4.226) 0.5628 cN2 13/16 81.3% (54.4%-96.0%) 0.772 (0.084-7.099) 0.8188 cN3 27/37 73.0% (55.9%-86.2%) 0.524 (0.071-3.848) 0.5252 Visceral metastasis No 20/27 74.1% (53.7%-88.9%) 1 Yes 47/61 77.0% (64.5%-86.8%) 1.198 (0.425-3.383) 0.7324 Histology Invasive ductal carcinoma 62/80 77.5% (66.8%-86.1%) 1 Special types 5/8 62.5% (24.5%-91.5%) 0.465 (0.102-2.115) 0.3221 ER Negative 43/55 78.2% (65.0%-88.2%) 1 Positive 24/33 72.7% (54.5%-86.7%) 0.741 (0.275-1.995) 0.5532 PgR Negative 46/59 78.0% (65.3%-87.7%) 1 Positive 21/29 72.4% (52.8%-87.3%) 0.734 (0.267-2.022) 0.5501 Overall 67/88 76.1% (65.9% - 84.6%) Table2-4 Patients received HPD/HPTX therapy Univariable analysis Factor Non-PD/N Non-PD Rate (95% CI) Odds ratio (95% CI) P-value Menopausal status premenopausal 33/35 94.3% (80.8%-99.3%) 1 postmenopausal 68/74 91.9% (83.2%-97.0%) 0.786 (0.170-3.648) 0.7588 cT cT1 4/4 100.0% (39.8%-100.0%) 1 cT2 46/50 92.0% (80.8%-97.8%) 1.147 (0.038-34.742) 0.9370 cT3 18/19 94.7% (74.0%-99.9%) 1.370 (0.034-54.651) 0.8672 cT4 33/36 91.7% (77.5%-98.2%) 1.063 (0.034-33.574) 0.9724 cN cN0 7/7 100.0% (59.0%-100.0%) 1 cN1 46/47 97.9% (88.7%-99.9%) 2.067 (0.064-66.654) 0.6821 cN2 11/15 73.3% (44.9%-92.2%) 0.170 (0.007-4.442) 0.2875 cN3 37/40 92.5% (79.6%-98.4%) 0.714 (0.028-18.516) 0.8394 Visceral metastasis No 24/31 77.4% (58.9%-90.4%) 1 Yes 77/78 98.7% (93.1%-100.0%) 15.818 (2.547-98.228) 0.0030 Histology Invasive ductal carcinoma 96/104 92.3% (85.4%-96.6%) 1 Special types 5/5 100.0% (47.8%-100.0%) 0.969 (0.038-24.942) 0.9847 ER Negative 78/84 92.9% (85.1%-97.3%) 1 Positive 23/25 92.0% (74.0%-99.0%) 0.778 (0.165-3.682) 0.7520 PgR Negative 87/93 93.5% (86.5%-97.6%) 1 Positive 14/16 87.5% (61.7%-98.4%) 0.431 (0.087-2.131) 0.3019 Overall 101/109 92.7% (86.1%-96.8%) Supplementary Files AppendixJCOG1017S2.docx Cite Share Download PDF Status: Published Journal Publication published 31 Jan, 2026 Read the published version in Breast Cancer → Version 1 posted Editorial decision: Major Revision 25 Oct, 2025 Reviewers agreed at journal 09 Oct, 2025 Reviewers invited by journal 05 Oct, 2025 Editor assigned by journal 04 Oct, 2025 First submitted to journal 03 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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1","display":"","copyAsset":false,"role":"figure","size":50680,"visible":true,"origin":"","legend":"\u003cp\u003eConsort diagram\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/315a9b05fcc77441bec7a7f3.png"},{"id":93730310,"identity":"404dfc48-a734-4819-a2a0-b66f619fe6aa","added_by":"auto","created_at":"2025-10-17 02:20:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":46096,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-1: Overall survival for Responder vs. non-Responder (all patients)\u003c/p\u003e","description":"","filename":"2.1.png","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/26ee8fbe3c136041a1962dc4.png"},{"id":93730304,"identity":"a706624b-d1a6-427d-8012-9ce36012bd2b","added_by":"auto","created_at":"2025-10-17 02:20:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":40089,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-2: Overall survival for PD vs. non-PD (all patients)\u003c/p\u003e","description":"","filename":"2.2.png","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/e4a0369b1e7a2378b8027c0e.png"},{"id":93730305,"identity":"6e2e744d-0843-4889-951c-a181fa4c7071","added_by":"auto","created_at":"2025-10-17 02:20:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":39361,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-3: Overall survival for PD vs. non-PD (endocrine therapy)\u003c/p\u003e","description":"","filename":"2.3.png","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/699a2f73a26d32c2f36d4a8c.png"},{"id":93732112,"identity":"563850f2-c30d-4c11-8e1a-e9dcebe54e2f","added_by":"auto","created_at":"2025-10-17 02:28:10","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":33219,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-4: Overall survival for PD vs. non-PD (HPD/HPTX)\u003c/p\u003e","description":"","filename":"2.4.png","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/de0387aa9dd682e778a27541.png"},{"id":93730316,"identity":"ab7e5e84-38c5-4ef0-b6ed-8b0e770df8b7","added_by":"auto","created_at":"2025-10-17 02:20:10","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":32592,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-5: Overall survival for PD vs. non-PD (PTX)\u003c/p\u003e","description":"","filename":"2.5.png","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/67634b15f9a7b0661d9e3fca.png"},{"id":101691606,"identity":"e49c480a-28fb-4f52-a63d-0abe682ff8a5","added_by":"auto","created_at":"2026-02-02 16:14:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1241408,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/6e174dbf-7aa3-44cb-9baf-195d55719bec.pdf"},{"id":93730317,"identity":"e49e90d4-61a8-47a8-9fed-3fd206f440eb","added_by":"auto","created_at":"2025-10-17 02:20:10","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":94799,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixJCOG1017S2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7776614/v1/08082953eb9c0b495f7b69fc.docx"}],"financialInterests":"","formattedTitle":"Efficacy and prognostic predictors of primary systemic therapy for de novo Stage IV breast cancer. Exploratory analysis of JCOG1017 PRIM-BC.","fulltext":[{"header":"Introduction","content":"\u003cp\u003e There are various guideline recommendations for the appropriate drug treatment of metastatic recurrent breast cancer (BC). The treatment of metastatic BC is based on subtypes classified by ER, PgR, and HER2 expression. Untreated de novo Stage IV patients are more likely to respond to systemic therapy than patients diagnosed with postoperative recurrent BC. Many clinical trial data reported to date for the first-line treatment of metastatic BC are mainly for patients with recurrent BC. It is unclear whether tumor response differs depending on each BC subtype or tumor location, such as primary site or distant metastasis, and whether the tumor response to primary systemic therapy (PST) affects the prognosis in patients with de novo stage IV BC. There is also limited data on predictive factors of tumor response to each treatment and prognostic factors for de novo stage IV BC.\u003c/p\u003e\u003cp\u003eIn JCOG1017, a randomized trial comparing primary tumor resection (PTR) plus systemic therapy with systemic therapy alone in de novo Stage IV BC patients, de novo Stage IV patients were treated with PST for 3 months according to BC subtypes before randomization.\u003ca class=\"FNLink\" href=\"#Fn1\" id=\"#FNLinkFn1\"\u003e\u003c/a\u003e We already presented the results of the primary analysis\u003ca class=\"FNLink\" href=\"#Fn2\" id=\"#FNLinkFn2\"\u003e\u003c/a\u003e. PTR could not significantly prolong the overall survival of de novo Stage IV BC patients with sensitivity to PST (median overall survival 75 months vs. 69 months, HR 0.86, 90% CI 0\u0026middot;69\u0026thinsp;\u0026minus;\u0026thinsp;1\u0026middot;07, one-sided p\u0026thinsp;=\u0026thinsp;0\u0026middot;13). In this trial, we uniformly evaluated sensitivity to PST at 3 months for all subtypes and evaluated the survival. Therefore, we aimed to obtain data on the efficacy of PST and the prognosis of only de novo Stage IV BC.\u003c/p\u003e\u003cp\u003eIn addition, for tumor efficacy assessment, an increase in tumor size of 10% or more was defined as progression instead of using RECIST in this trial. We designed this JCOG1017 trial to investigate the possible benefit of PTR for de novo Stage IV BC that is sensitive to PST. This was to exclude cases of early progression within 3 months from the start of PST. It is unclear whether the definition in this trial or RECIST is more prognostic.\u003c/p\u003e\u003cp\u003eIn this exploratory analysis, we examined the efficacy and predictive factors of response to each drug in de novo Stage IV BC and whether assessing sensitivity to all drugs is appropriate. We also want to clarify the efficacy of PST for de novo Stage IV patients and develop optimal treatment strategies for de novo Stage IV BC using data from JCOG1017.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eStudy design and participants.\u003c/p\u003e\u003cp\u003eJCOG1017 is a multicenter, open-label, randomized, controlled phase 3 trial at 44 institutions in Japan (Appendix 1) designed to confirm the superiority of PTR in addition to systemic therapy for overall survival over systemic treatment alone. This trial was conducted according to the Declaration of Helsinki, the Japanese Ethical Guidelines for Clinical Research, and the Clinical Trials Act. The Japan Clinical Oncology Group (JCOG) Protocol Review Committee and the National Cancer Center Hospital East Certified Review Board approved the study protocol. All patients provided written informed consent before enrolment. Full trial details have been published previously; the CONSORT diagram is shown in Fig.\u0026nbsp;1\u003csup\u003eii\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe eligible patients were aged 20\u0026ndash;80 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (PS 2 caused by the symptoms of bone metastasis is also eligible), histologically proven invasive BC, and without bilateral BC or extension to the contralateral breast. The patients with at least one measurable metastatic lesion other than the breast tumor and axillary lymph nodes, and without brain metastasis, were included. The second registration and randomization were performed for patients without progression after PST. This exploratory analysis was conducted on patients enrolled in the first registration and who underwent PST.\u003c/p\u003e\u003cp\u003eProcedures\u003c/p\u003e\u003cp\u003eAll enrolled patients for the first registration received PST. The PST regimen was decided according to the ER and HER2 status and the disease situation (Appendix 2). ER-positive patients, regardless of HER2 status, with no life-threatening diseases received endocrine therapy, which was oral tamoxifen 20 mg/body daily plus subcutaneous goserelin 3\u0026middot;6 mg/body (day 1) every 4 weeks for premenopausal patients and oral letrozole 2\u0026middot;5 mg/body daily for 4 weeks for post-menopausal patients. CDK4/6 inhibitors were not used because they were preapproved during this trial. Patients with ER-negative and/or life-threatening diseases received the following chemotherapy; for HER2-positive patients, intravenous paclitaxel 80 mg/m\u003csup\u003e2\u003c/sup\u003e (days 1, 8, 15) plus weekly trastuzumab 2 mg/kg (days 1, 8, 15, 22) every 4 weeks (before reported the results of CLEOPATRA study) (HPTX)or intravenous docetaxel 75 mg/m\u003csup\u003e2\u003c/sup\u003e (day1) plus trastuzumab 6mg/kg (day1), pertuzumab 420mg/body (day1) every 3 weeks (after 2020 when reported the results of CLEOPATRA study\u003ca class=\"FNLink\" href=\"#Fn3\" id=\"#FNLinkFn3\"\u003e\u003c/a\u003e)(HPD), and for HER2-negative patients intravenous paclitaxel 80 mg/m\u003csup\u003e2\u003c/sup\u003e (days 1, 8, 15) every 4 weeks. Pembrolizumab was not used to treat triple-negative BC because it was not approved at the time of this trial. After each regimen, tumor assessment was conducted after three cycles, while the docetaxel, trastuzumab, and pertuzumab regimens underwent evaluation after four cycles. In the PTR plus systemic therapy arm, the patients underwent the complete resection of the primary breast tumor within 42 days after the second registration. Adjuvant radiotherapy after partial or total mastectomy was not allowed. After surgery, the same systemic therapy was continued as soon as possible. In the systemic therapy alone arm, the patients continued the same systemic therapy after the second registration.\u003c/p\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003cp\u003eThe non-PD (Progressive Disease) rate and the response rate were examined.\u003c/p\u003e\u003cp\u003eIn the non-PD rate, PD was defined as meeting any of the following criteria after 3 months of systemic therapy: i) the diameter of the primary tumor lesion increased 10% or more compared to the most minor recorded diameter, ii) the sum of the diameters of distant metastases increased 10% or more compared to the smallest recorded sum of the diameters, iii) unequivocal progression of existing non-target lesions, iv) appearance of new malignant lesions.\u003c/p\u003e\u003cp\u003eThe response rate was defined as a proportion of patients with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1\u003ca class=\"FNLink\" href=\"#Fn4\" id=\"#FNLinkFn4\"\u003e\u003c/a\u003e. We considered patients with CR or PR as responders, and patients with stable disease or progression disease, defined by RECIST ver 1.1, non-responders.\u003c/p\u003e\u003cp\u003eThe overall survival of responders vs. non-responders and the PD vs. non-PD group was also evaluated. Overall survival was defined as the number of days from the date of randomization to the date of death from any cause.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe non-PD and response rates were reported as percentages and 95% confidence intervals (CIs) calculated by the Clopper-Pearson method. To examine the predictive factors for the non-PD rate and the response rate for all the first registered patients and each drug, univariable and multivariable logistic regression models were performed with the following clinical factors as covariates: menopausal status (pre/post), cT (cT1/ cT3/ cT3/ cT4), cN (cN0/ cN1/ cN2/ cN3), visceral mets (yes/no), histology (IDC/special types), ER (negative/positive; univariable only), PgR (negative/positive; univariable only), HER2 (negative/positive) and subtype (ER (-) and HER2 (-)/ ER (+) and HER2 (-)/ ER (-) and HER2 (+)/ ER (+) and HER2 (+)). OS was estimated with the Kaplan-Meier method. The univariable analyses were performed with the Cox proportional hazard model to calculate the hazard ratio between the responders and non-responders, as well as PD and non-PD. All statistical analyses were conducted using SAS software (version 9.4).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOf 570 de novo Stage IV patients enrolled in the JCOG1017, 569 patients who received PST were examined in this exploratory analysis. 372 patients with ER+/non-life-threatening metastases received endocrine therapy (tamoxifen\u0026thinsp;+\u0026thinsp;LH-RH agonist or letrozole), 109 patients with ER-/HER2\u0026thinsp;+\u0026thinsp;or ER+/HER2+/ life-threatening metastases received HPD or HPTX and 88 patients with ER-/HER2- tumors received PTX. The details of the clinical and pathological features are in Table\u0026nbsp;1. Median age was 57, and 198 (34.8%) patients were premenopausal.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e shows the tumor response of PST for 3 months. The non-PD rate for all patients was 77.2% (439/569, 95%CI: 73.5\u0026ndash;80.5%), and the predictive factors of non-PD were post-menopausal (odds ratio [OR] 1.673, 95%CI: 1.070\u0026ndash;2.617, p\u0026thinsp;=\u0026thinsp;0.024), PgR positive (OR 2.391, 95%CI: 1.380\u0026ndash;4.140, p\u0026thinsp;=\u0026thinsp;0.0019), and subtypes in multivariable analysis (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026thinsp;\u0026minus;\u0026thinsp;1).\u003c/p\u003e\n\u003cp\u003eNon-PD rate of endocrine therapy was 72.9% (271/372, 95%CI 68.0-77.3%), and that of tamoxifen\u0026thinsp;+\u0026thinsp;LH-RH agonist and letrozole were 68.5% (89/130, 95% CI: 59.7\u0026ndash;76.3%) and 75.2% (182/242, 95% CI: 69.3\u0026ndash;80.5%), respectively. The predictive factors of non-PD of endocrine therapy were visceral metastasis status (positive: OR 0.605, 95%CI 0.381\u0026ndash;0.961, p\u0026thinsp;=\u0026thinsp;0.033; reference group: negative), PgR status (positive: OR 3.258, 95%CI 1.886\u0026ndash;5.628, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; reference group: negative) and HER2 status (positive: OR 0.365, 95%CI 0.195\u0026ndash;0.684, p\u0026thinsp;=\u0026thinsp;0.0016; reference group: negative). (Table\u0026nbsp;\u0026lt;link rid=\u0026quot;tb4\u0026quot;\u0026gt;\u003cspan class=\"InternalRef\"\u003e2\u0026lt;/link\u0026gt;\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eThe non-PD rate of PTX was 76.1% (67/88, 95%CI 65.9\u0026ndash;84.6%). There was no significant predictive factor of non-PD. (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;3)\u003c/p\u003e\n\u003cp\u003eThe non-PD rate for HPD/HPTX was 92.7% (101/109, 95%CI 86.1\u0026ndash;96.8%), and that of HPD and HPTX was 92.6% (75/81, 95%CI 84.6\u0026ndash;97.2%) and 92.9% (26/28, 95%CI 76.5\u0026ndash;99.1%). The predictive factor of non-PD for HPD/HPTX was visceral metastases (OR 15.818, 95%CI: 2.547\u0026ndash;24.942, p\u0026thinsp;=\u0026thinsp;0.0030). (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;4) According to the RECIST ver. 1.1, the response rate of 3 months systemic therapy for all patients was 29.0% (165/569, 95%CI 25.3\u0026ndash;32.9%), and that of endocrine therapy, PTX and HPD/HPTX were 11.6% (43/372, 95%CI 8.5\u0026ndash;15.3%), 36.4% (32/88, 95% CI 26.4\u0026ndash;47.3%) and 82.6% (90/109, 95%CI 74.1\u0026ndash;89.2%). (Table\u0026nbsp;5) The CR in the primary site was only the HPD/HPTX regimen (18/109, 16.5%). The CR in metastatic lesions was 0.5% (2/372), 11.9% (13/109), and 1.1% (1/88) by endocrine, HPD/HPTX, and PTX, respectively. (\u003c/p\u003e\n\u003cp\u003eOverall survival was better in patients with non-PD than PD (MST 6.1 years vs. 3.5 years, HR 0.508[95%CI: 0.398\u0026ndash;0.648], two-sided log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). OS between non-PD and PD was significantly different, regardless of drug. (Endocrine therapy; HR 0.532 [95%CI: 0.399\u0026ndash;0.711], two-sided log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, HPD/HPTX; HR 0.306 [95%CI:0.119\u0026ndash;0.783], two-sided log-rank p\u0026thinsp;=\u0026thinsp;0.0088, PTX; HR 0.555 [95%CI:0.322\u0026ndash;0.956], two-sided log-rank p\u0026thinsp;=\u0026thinsp;0.0315). As per the RECIST criteria, OS between responders (CR\u0026thinsp;+\u0026thinsp;PR) and non-responders was not significant (HR 0.788[95%CI:0.617\u0026ndash;1.005], two-sided log-rank p\u0026thinsp;=\u0026thinsp;0.0538). However, there was an important difference between PD and others (CR, PR, and SD) (HR 0.508[95%CI: 0.398\u0026ndash;0.648]).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this analysis, response predictive factors to PST for non-PD were post-menopausal, PgR positive, and subtype. An ER-/HER2\u0026thinsp;+\u0026thinsp;tumor was more likely to respond than an ER-/HER2\u0026mdash;tumor, while an ER+/HER2\u0026mdash;tumor was less likely to respond. The response and predictors of response to PST differed by subtype.\u003c/p\u003e\u003cp\u003ePgR, HER2 expression, and the status of visceral metastasis may have affected the efficacy.\u003c/p\u003e\u003cp\u003eThe response rate for first-line treatment with LH-RH agonist and tamoxifen for MBC, including both recurrent and de novo Stage IV BC, is reported to be 38\u0026ndash;48%, and the median progression-free survival is 8.7 months.\u003ca class=\"FNLink\" href=\"#Fn5\" id=\"#FNLinkFn5\"\u003e\u003c/a\u003e The response rate for first-line treatment with letrozole was 32%, and the median progression-free survival was reported to be 9.4 months.\u003ca class=\"FNLink\" href=\"#Fn6\" id=\"#FNLinkFn6\"\u003e\u003c/a\u003e PgR is a target gene of ER, and PgR expression is considered a prognostic predictor of ER-positive BC as an indicator of activation of the ER pathway.\u003ca class=\"FNLink\" href=\"#Fn7\" id=\"#FNLinkFn7\"\u003e\u003c/a\u003e More recently, it has also been shown to regulate tumor progression directly, and activation of PgR inhibits breast cancer cell proliferation and is associated with a favorable prognosis.\u003ca class=\"FNLink\" href=\"#Fn8\" id=\"#FNLinkFn8\"\u003e\u003c/a\u003e HER2 is a target for molecular targeted drugs. In this trial, endocrine therapy alone was used as first-line treatment in ER-positive HER2-positive BC without life-threatening metastasis. However, this study showed that endocrine therapy was less effective in these subjects. Conversely, patients treated with anti-HER2 drugs showed very high efficacy at 3 months. Therefore, endocrine therapy is not recommended as primary therapy in ER-positive HER2-positive patients. The efficacy of HPD therapy as the primary treatment for HER2-positive metastatic BC was reported in the CLEOPATRA trial.\u003ca class=\"FNLink\" href=\"#Fn9\" id=\"#FNLinkFn9\"\u003e\u003c/a\u003e The median PFS was 12.4 months, and the response rate was 80.2%, which is consistent with the results of this study, which reported that HPD is highly effective in ER-positive as well as ER-negative metastatic BC. The efficacy of Taxane (paclitaxel and docetaxel) in HER2-negative metastatic BC is reported to be around a 34% response rate.\u003ca class=\"FNLink\" href=\"#Fn10\" id=\"#FNLinkFn10\"\u003e\u003c/a\u003e However, no clinically useful predictors of response to Taxane have been reported. In summary, the results of the present study on the efficacy and predictors of initial drug therapy for de novo Stage IV BC were consistent with those reported previously for recurrent BC as a whole. Therefore, the optimal drug therapy for de novo Stage IV BC should be selected based on the biology and metastatic status of BC, even more so than for recurrent BC. In ER-positive MBC, patients deriving no clinical benefit from first-line endocrine therapy (\u0026plusmn;\u0026thinsp;CDK4/6 inhibitors) have significantly worse OS than responders. For example, an extensive analysis found median OS\u0026thinsp;~\u0026thinsp;62 months in patients with a first-line objective response versus ~\u0026thinsp;41 months in non-responders (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003ca class=\"FNLink\" href=\"#Fn11\" id=\"#FNLinkFn11\"\u003e\u003c/a\u003e. Primary endocrine resistance is thus a strong negative prognostic factor for survival in this subtype. Similarly, lack of response in HER2\u0026thinsp;+\u0026thinsp;disease treated first-line with trastuzumab-based regimens (e.g., trastuzumab\u0026thinsp;\u0026plusmn;\u0026thinsp;pertuzumab plus chemotherapy) portends inferior survival. Patients achieving an objective response to initial anti-HER2 therapy enjoy markedly longer OS; one study reported median OS 10.2 years in those with complete response vs\u0026thinsp;\u0026lt;\u0026thinsp;6.3 years in patients with only stable disease\u003ca class=\"FNLink\" href=\"#Fn12\" id=\"#FNLinkFn12\"\u003e\u003c/a\u003e. In contrast, those who fail to respond to anti-HER2 therapy face substantially shorter survival. TNBC has the poorest prognosis \u0026ndash; median OS is only about 12\u0026ndash;18 months with standard first-line chemotherapy\u003ca class=\"FNLink\" href=\"#Fn13\" id=\"#FNLinkFn13\"\u003e\u003c/a\u003e. Non-responders to initial therapy (chemotherapy or PARP inhibitors in BRCA-mutant TNBC) have especially short survival, whereas patients who respond can achieve longer OS outcomes\u003ca class=\"FNLink\" href=\"#Fn14\" id=\"#FNLinkFn14\"\u003e\u003c/a\u003e.\u003c/p\u003e\u003cp\u003eIn the JCOG1017 trial, we used a method to determine the efficacy of PST, where PD was assessed if there was even a slight increase in tumor size, instead of using RECIST. We wanted to exclude patients who do not respond to PST and progress early.\u003c/p\u003e\u003cp\u003eThe study examined the effect of PST from 3 months after the start of treatment using two methods. The results showed that both methods equally identified patients with poor prognosis. However, it is challenging to determine PD early after the start of treatment because the RECIST method cannot accurately determine PD in the case of small metastatic lesions, and SD is determined when the disease worsens by 20% or less. From these points of view, we believe that our method (even a slight increase is judged as progression) is an easy and reasonable method to judge patients with a poor prognosis at an early stage after the start of treatment. And we believe this method will be helpful in strategies such as the JCOG1017 trial, in which treatment efficacy is determined early, patients are differentiated according to this efficacy, and subsequent treatment is modified accordingly. We are currently using the same method to evaluate whether local therapy, including metastases, prolongs prognosis in patients with oligometastasis who are sensitive to PST (JCOG2110 trial, jRCTs 031230439, NCT06135714). \u003ca class=\"FNLink\" href=\"#Fn15\" id=\"#FNLinkFn15\"\u003e\u003c/a\u003e There were some limitations in this study. Although new effective drugs have recently been developed to improve prognosis, these drugs were not used in the present study. CDK4/6 inhibitors, standard drugs for ER-positive BC, were also not used. Immune checkpoint inhibitors are used for TN BC, and PARP inhibitors for BRCA mutation-positive BC, but not in this study. Their efficacy or predictive factors are not clear from the results of the present study. On the other hand, in the present study, efficacy was uniformly determined at 3 months for all drugs. This was done to assess the efficacy of the drugs at an early stage and to determine the indication for primary resection. However, it is expected that the maximum efficacy of each drug will not necessarily be three months. The present study cannot examine medium- and long-term drug effects. In addition, primary site excision may affect subsequent drug efficacy and prognosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe choice of initial systemic therapy for de novo Stage IV BC is essential to be appropriate for the subtype. Endocrine mono-therapy was not recommended for patients with ER\u0026thinsp;+\u0026thinsp;HER\u0026thinsp;+\u0026thinsp;BC. The prognosis of patients with PD response after 3 months from the start of treatment is poor, and effective systemic therapy needs to be developed for these patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding Author:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTadahiko Shien MD, PhD, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. （[email protected]）\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e TS had full access to all of the study\u0026apos;s data and is responsible for its integrity and accuracy.\u003c/p\u003e\n\u003cp\u003eConcept and design: TS, MI, KT, TT, YS, AS, YK, OM, HY, TI, KT, KG, YN, FH, TF, KS, HF, HI designed the concept and helped write the manuscript.\u003c/p\u003e\n\u003cp\u003eTS, HF, GO, SS, HF, and HI performed the statistical analysis and acquired, analyzed, or interpreted the data.\u003c/p\u003e\n\u003cp\u003eTS obtained the foundation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods were performed by the relevant guidelines and regulations. This study was approved by the Ethics Committee of National Cancer Center Hospital East Certified Review Board, and the approval reference number is CRB3180009. Informed consent was obtained from all participants involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures:\u003c/strong\u003e Dr. Shien reported grants from the Ministry of Health, Labour and Welfare of Japan and from the Japan Agency for Medical Research and Development (AMED) during the conduct of the study, as well as personal fees from Pfizer, Chugai, Lilly, Daiichi Sankyo, MSD, Eizai, AstraZeneca, Taiho, Nihonkayaku, Gilead. Dr. Hara reported the personal fees from Pfizer, Ili Lilly, Daiichi Sankyo, Kyowa Kirin, Chugai, MSD. Dr. Ogawa reported the grants from Japan Agency for Medical Research and Development and Ministry of Health, Labour and Welfare, Japan. Dr. Fukuda reported the grants from National Cancer Center and AstraZeneca, Ono Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd, Takeda Pharmaceutical Company Limited and the personal fees from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., CMIC Co., Ltd. Dr. Iwata reported the grants from Pfizer and Chugai, Daiichi Sankyo, AstraZeneca and personal fees from Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Taiho, Kyowa Kirin. No other disclosures were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received partial support from the National Cancer Research and Development Fund (23-A-19, 26-A-4, 29-A-3, 2020-J-3, 2023-J-03), Health and Labour Sciences Research Grant for Clinical Cancer Research (H26-applied-general-03) from the Ministry of Health, Labour and Welfare of Japan and AMED under Grant Number JP22ck0106593, JP19ck0106307, JP16ck106046.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of the Funder/Sponsor:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The funders had no role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeeting Presentation:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of this study were presented in part at the San Antonio Breast Cancer Symposium, Dec. 2023, San Antonio, Texas.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIndividual participant data that underline the results reported in this article will not be shared because the follow-up of the patients is continued until May 2028. After the publication using data as of May, 2029, individual participant data that underlie the results after deidentification will be shared if investigators whose proposed use of the data has been approved by the investigators from Breast Cancer Study Group of JCOG identified for this purpose. Proposals should be directed to [email protected]. The date will be available for achieving aims in the approved proposal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the patients and their families, all the study site coordinators and investigators, and the data managers at the JCOG Data Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutions that participated in this study:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNHO Hokkaido Cancer Center, Iwate Medical University, Tohoku University Hospital, Faculty of Medicine, University of Tsukuba, Tochigi Cancer Center, Jichi Medical University, Gunma Prefectural Cancer Center, Saitama Cancer Center, National Cancer Center Hospital East, Chiba Cancer Center, National Cancer Center Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, National Hospital Organization Tokyo Medical Center, Showa University School of Medicine, Cancer Institute Hospital, Toranomon Hospital, St. Luke\u0026rsquo;s International Hospital, Tokai University School of Medicine, St. Marianna University, Kanagawa Cancer Center, Kitasato University School of Medicine, Yokohama Rosai Hospital, Niigata Cancer Center Hospital, Shizuoka General Hospital, Shizuoka Cancer Center, Aichi Cancer Center Hospital, Nagoya City University Hospital, Nagoya Medical Center, Kinki University School of Medicine, Osaka International Cancer Institute, Osaka National Hospital, Okayama University Hospital, Kure Medical Center Chugoku Cancer Center, NHO Fukuyama Medical Center, Hiroshima University Hospital, Hiroshima City Hospital, Hiroshima City Asa Hospital, NHO Shikoku Cancer Center, National Kyushu Cancer Center, Kitakyushu Municipal Medical Center, Nagasaki Medical Center, Kumamoto University Medical School, Social medical corporation Hakuaikai Sagara Hospital.\u003c/p\u003e\n\u003cp\u003eMembers of the JCOG Breast Cancer Study Group who contributed to this manuscript: Tadahiko Shien1, Makoto Ishitobi2, Kiyo Tanaka4, Akihiko Shimomura5, Takahiro Tsukioki1, Yasuaki Sagara6, Yuri Kimura7, Kori Terata8, Takayuki Ishiba9, Hiroyuki Yasojima9, Makiko Fuchigami-Ono11, Kyoko Goda12, Yoichi Naito13, Tomomi Fujisawa14, Fumikata Hara15, Hiroji Iwata16.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShien T, Nakamura K, Shibata T, Kinoshita T, Aogi K, Fujisawa T, et al. A randomized controlled trial comparing primary tumour resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (PRIM-BC): Japan Clinical Oncology Group Study JCOG1017. Jpn J Clin Oncol. 42(10):970-3, 2012.\u003c/li\u003e\n\u003cli\u003eShien T, Hara F, Aogi K, Yanagida Y, Tsuneizumi M, Yamamoto N, et al. Primary tumor resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): A Randomized Clinical Trial. British J Cancer. 2025.\u003c/li\u003e\n\u003cli\u003eSwain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, et al. CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530.\u003c/li\u003e\n\u003cli\u003eE A Eisenhauer, P Therasse, J Bogaerts, L H Schwartz, D Sargent, R Ford, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009 Jan;45(2):228-47.\u003c/li\u003e\n\u003cli\u003eKlijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R; Combined Hormone Agents Trialists\u0026apos; Group and the European Organization for Research and Treatment of Cancer. Combined\u003c/li\u003e\n\u003cli\u003etamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol. 2001 Jan 15;19(2):343-53.\u003c/li\u003e\n\u003cli\u003eMouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001 ; 19 : 2596 \u0026ndash;606.\u003c/li\u003e\n\u003cli\u003eCarroll JS, Hickey TE, Tarulli GA, Williams M, Tilley WD. Deciphering the divergent roles of progestogens in breast cancer. Nat Rev Cancer. 2017 Jan;17(1):54-64.\u003c/li\u003e\n\u003cli\u003eFarcas AM, Nagarajan S, Cosulich S, Carroll JS. Genome-Wide Estrogen Receptor Activity in Breast Cancer. Endocrinology. 2021 Feb 1;162(2):bqaa224.\u003c/li\u003e\n\u003cli\u003eBaselga J, Cort\u0026eacute;s J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19.\u003c/li\u003e\n\u003cli\u003eSledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, et al. Phase ? trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer:an intergroup trial(E1193). J Clin Oncol. 2003;21(4):588-92.\u003c/li\u003e\n\u003cli\u003eMatikas A, Kotsakis A, Perraki M, Hatzidaki D, Kalbakis K, Kontopodis E, et al. Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period. Breast Care (Basel). 2022 Jun;17(3):264-271.\u003c/li\u003e\n\u003cli\u003eCucciniello L, Blondeaux E, Bighin C, Gasparro S, Russo S, Dri A, et al. Clinico-pathological predictors of radiologic complete response to first-line anti-HER2 therapy in metastatic breast cancer. NPJ Breast Cancer. 2024 Dec 18;10(1):105.\u003c/li\u003e\n\u003cli\u003eSakach E, O\u0026apos;Regan R, Meisel J, Li X. Molecular Classification of Triple Negative Breast Cancer and the Emergence of Targeted Therapies. Clin Breast Cancer. 2021 Dec;21(6):509-520.\u003c/li\u003e\n\u003cli\u003eMatikas A, Kotsakis A, Perraki M, Hatzidaki D, Kalbakis K, Kontopodis E, et al. Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period. Breast Care (Basel). 2022 Jun;17(3):264-271.\u003c/li\u003e\n\u003cli\u003eIshiba T, Nishibuchi I, Hara F, Shikama N, Shien T, Iwata H. Metastasis-directed therapy for oligometastases in breast cancer. Jpn J Clin Oncol. 53(10):893-898, 2023.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Patient characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"869\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003eTam+LH-RH or LET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003eHPD or HPTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003ePTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003en=372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003en=109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003en=88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003en=569\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003e\u0026nbsp;Age Median (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e58 (23-79) \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e55 (31-79)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e57 (25-80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e57 (23-80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eMenopausal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003epremenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e130 (34.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e35 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e33 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e198 (34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003epostmenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e242 (65.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e74 (67.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e55 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e371 (65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e26 (7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e4 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e5 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e35 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e165 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e50 (45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e36 (40.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e251 (44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e42 (11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e19 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e69 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e139 (37.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e36 (33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e39 (44.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e214 (37.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e47 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e7 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e62 (10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e169 (45.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e47 (43.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e27 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e243 (42.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e55 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e15 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e16 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e86 (15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ecN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e101 (27.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e40 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e37 (42.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e178 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eVisceral metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e185 (49.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e31 (28.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e27 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e243 (42.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e187 (50.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e78 (71.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e61 (69.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e326 (57.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e334 (89.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e104 (95.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e80 (90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e518 (91.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eSpecial types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e38 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e5 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e51 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e84 (77.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e55 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e139 (24.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e372 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e25 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e33 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e430 (75.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ePgR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e68 (18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e93 (85.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e59 (67.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e220 (38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e304 (81.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e16 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e29 (33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e349 (61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e325 (87.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e88 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e413 (72.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e47 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e109 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e156 (27.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eSubtypes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eER (-) HER2 (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e55 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e55 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eER (+) HER2 (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e325 (87.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e33 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e358 (62.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eER (-) HER2 (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e84 (77.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e84 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 21.2888%;\"\u003e\n \u003cp\u003eER (+) HER2 (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e47 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e25 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.6778%;\"\u003e\n \u003cp\u003e72 (12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2: Univariable and Multivariable analysis of predictors to PST.\u003c/p\u003e\n\u003cp\u003eTable 2-1 All patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"952\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 230px;\"\u003e\n \u003cp\u003eUnivariable analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 241px;\"\u003e\n \u003cp\u003eMultivariable analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003eNon-PD/N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eNon-PD Rate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eMenopausal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003epremenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e146/198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e73.7%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(67.0%-79.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003epostmenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e293/371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e79.0%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(74.5%-83.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.340\u003c/p\u003e\n \u003cp\u003e(0.896-2.004)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.1544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1.673\u003c/p\u003e\n \u003cp\u003e(1.070-2.617)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0240\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e25/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e71.4%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(53.7%-85.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e199/251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e79.3%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(73.7%-84.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.565\u003c/p\u003e\n \u003cp\u003e(0.710-3.448)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.2666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1.429\u003c/p\u003e\n \u003cp\u003e(0.630-3.239)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.3932\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e53/69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e76.8%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(65.1%-86.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.335\u003c/p\u003e\n \u003cp\u003e(0.534-3.339)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1.502\u003c/p\u003e\n \u003cp\u003e(0.577-3.909)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.4043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e162/214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.7%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(69.4%-81.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.275\u003c/p\u003e\n \u003cp\u003e(0.577-2.816)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1.182\u003c/p\u003e\n \u003cp\u003e(0.511-2.732)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.6956\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e53/62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e85.5%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(74.2%-93.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e190/243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e78.2%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(72.5%-83.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003cp\u003e(0.296-1.351)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.2369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.562\u003c/p\u003e\n \u003cp\u003e(0.258-1.226)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.1476\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e62/86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e72.1%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(61.4%-81.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.453\u003c/p\u003e\n \u003cp\u003e(0.196-1.049)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0646\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.452\u003c/p\u003e\n \u003cp\u003e(0.188-1.083)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0748\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e134/178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.3%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(68.3%-81.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003cp\u003e(0.248-1.164)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.1154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.454\u003c/p\u003e\n \u003cp\u003e(0.204-1.010)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0529\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eVisceral metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e188/243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.4%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(71.6%-82.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e251/326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.0%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(72.0%-81.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.981\u003c/p\u003e\n \u003cp\u003e(0.660-1.456)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.9231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.926\u003c/p\u003e\n \u003cp\u003e(0.608-1.411)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.7210\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e402/518\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.6%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(73.8%-81.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSpecial types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e37/51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e72.5%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(58.3%-84.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.749\u003c/p\u003e\n \u003cp\u003e(0.393-1.429)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.3801\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003cp\u003e(0.391-1.511)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.4452\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eER*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e121/139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e87.1%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(80.3%-92.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e318/430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e74.0%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(69.5%-78.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003cp\u003e(0.252-0.737)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ePgR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e168/220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e76.4%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(70.2%-81.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e271/349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.7%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(72.9%-81.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.078\u003c/p\u003e\n \u003cp\u003e(0.723-1.607)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2.391\u003c/p\u003e\n \u003cp\u003e(1.380-4.140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eHER2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e313/413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.8%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(71.4%-79.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e126/156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e80.8%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(73.7%-86.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.330\u003c/p\u003e\n \u003cp\u003e(0.843-2.098)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.2207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eSubtype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eER (-) \u0026amp; HER2 (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e43/55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e78.2%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(65.0%-88.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eER (+) \u0026amp; HER2 (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e270/358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.4%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(70.6%-79.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.878\u003c/p\u003e\n \u003cp\u003e(0.446-1.731)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7078\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.434\u003c/p\u003e\n \u003cp\u003e(0.193-0.978)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0439\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eER (-) \u0026amp; HER2 (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e78/84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.9%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(85.1%-97.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e3.468\u003c/p\u003e\n \u003cp\u003e(1.245-9.663)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e3.374\u003c/p\u003e\n \u003cp\u003e(1.210-9.407)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eER (+) \u0026amp; HER2 (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e48/72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e66.7%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(54.6%-77.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.569\u003c/p\u003e\n \u003cp\u003e(0.255-1.268)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.1676\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e0.345\u003c/p\u003e\n \u003cp\u003e(0.146-0.816)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e0.0153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 255px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e439/569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.2%\u003c/p\u003e\n \u003cp\u003e(73.5%-80.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ch2\u003eTable 2-2 Patients received Endocrine therapy\u003c/h2\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"711\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 230px;\"\u003e\n \u003cp\u003eUnivariable analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003eNon-PD/N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eNon-PD Rate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e18/26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e69.2%\u003c/p\u003e\n \u003cp\u003e(48.2%-85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e124/165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.2%\u003c/p\u003e\n \u003cp\u003e(67.8%-81.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.378\u003c/p\u003e\n \u003cp\u003e(0.561-3.389)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.4844\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e29/42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e69.0%\u003c/p\u003e\n \u003cp\u003e(52.9%-82.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.004\u003c/p\u003e\n \u003cp\u003e(0.350-2.879)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.9940\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e100/139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e71.9%\u003c/p\u003e\n \u003cp\u003e(63.7%-79.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.169\u003c/p\u003e\n \u003cp\u003e(0.472-2.894)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7356\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e39/47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e83.0%\u003c/p\u003e\n \u003cp\u003e(69.2%-92.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e124/169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e73.4%\u003c/p\u003e\n \u003cp\u003e(66.0%-79.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.589\u003c/p\u003e\n \u003cp\u003e(0.259-1.340)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.2070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e38/55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e69.1%\u003c/p\u003e\n \u003cp\u003e(55.2%-80.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.473\u003c/p\u003e\n \u003cp\u003e(0.185-1.214)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.1195\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e70/101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e69.3%\u003c/p\u003e\n \u003cp\u003e(59.3%-78.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.482\u003c/p\u003e\n \u003cp\u003e(0.204-1.138)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0958\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eVisceral metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e144/185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.8%\u003c/p\u003e\n \u003cp\u003e(71.2%-83.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e127/187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e67.9%\u003c/p\u003e\n \u003cp\u003e(60.7%-74.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.605\u003c/p\u003e\n \u003cp\u003e(0.381-0.961)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0334\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e244/334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e73.1%\u003c/p\u003e\n \u003cp\u003e(68.0%-77.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSpecial types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e27/38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e71.1%\u003c/p\u003e\n \u003cp\u003e(54.1%-84.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.885\u003c/p\u003e\n \u003cp\u003e(0.423-1.852)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7461\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ePgR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e35/68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e51.5%\u003c/p\u003e\n \u003cp\u003e(39.0%-63.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e236/304\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.6%\u003c/p\u003e\n \u003cp\u003e(72.5%-82.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e3.258\u003c/p\u003e\n \u003cp\u003e(1.886-5.628)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e246/325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.7%\u003c/p\u003e\n \u003cp\u003e(70.7%-80.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e25/47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e53.2%\u003c/p\u003e\n \u003cp\u003e(38.1%-67.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003cp\u003e(0.195-0.684)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 255px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e271/372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e72.9%\u003c/p\u003e\n \u003cp\u003e(68.0%-77.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eTable 2-3 patients received weekly PTX\u003c/h2\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"711\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 230px;\"\u003e\n \u003cp\u003eUnivariable analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003eNon-PD/N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eNon-PD Rate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eMenopausal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003epremenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e24/33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e72.7%\u003c/p\u003e\n \u003cp\u003e(54.5%-86.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003epostmenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e43/55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e78.2%\u003c/p\u003e\n \u003cp\u003e(65.0%-88.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.349\u003c/p\u003e\n \u003cp\u003e(0.501-3.633)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e3/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e60.0%\u003c/p\u003e\n \u003cp\u003e(14.7%-94.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e29/36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e80.6%\u003c/p\u003e\n \u003cp\u003e(64.0%-91.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2.811\u003c/p\u003e\n \u003cp\u003e(0.398-19.850)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.3001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e6/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e75.0%\u003c/p\u003e\n \u003cp\u003e(34.9%-96.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.858\u003c/p\u003e\n \u003cp\u003e(0.176-19.614)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.6064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e29/39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e74.4%\u003c/p\u003e\n \u003cp\u003e(57.9%-87.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2.008\u003c/p\u003e\n \u003cp\u003e(0.296-13.635)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.4757\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e7/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e87.5%\u003c/p\u003e\n \u003cp\u003e(47.3%-99.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e20/27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e74.1%\u003c/p\u003e\n \u003cp\u003e(53.7%-88.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.547\u003c/p\u003e\n \u003cp\u003e(0.071-4.226)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5628\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e13/16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e81.3%\u003c/p\u003e\n \u003cp\u003e(54.4%-96.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.772\u003c/p\u003e\n \u003cp\u003e(0.084-7.099)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.8188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e27/37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e73.0%\u003c/p\u003e\n \u003cp\u003e(55.9%-86.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.524\u003c/p\u003e\n \u003cp\u003e(0.071-3.848)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eVisceral metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e20/27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e74.1%\u003c/p\u003e\n \u003cp\u003e(53.7%-88.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e47/61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.0%\u003c/p\u003e\n \u003cp\u003e(64.5%-86.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.198\u003c/p\u003e\n \u003cp\u003e(0.425-3.383)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7324\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e62/80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.5%\u003c/p\u003e\n \u003cp\u003e(66.8%-86.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSpecial types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e5/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e62.5%\u003c/p\u003e\n \u003cp\u003e(24.5%-91.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.465\u003c/p\u003e\n \u003cp\u003e(0.102-2.115)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.3221\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e43/55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e78.2%\u003c/p\u003e\n \u003cp\u003e(65.0%-88.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e24/33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e72.7%\u003c/p\u003e\n \u003cp\u003e(54.5%-86.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.741\u003c/p\u003e\n \u003cp\u003e(0.275-1.995)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ePgR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e46/59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e78.0%\u003c/p\u003e\n \u003cp\u003e(65.3%-87.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e21/29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e72.4%\u003c/p\u003e\n \u003cp\u003e(52.8%-87.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.734\u003c/p\u003e\n \u003cp\u003e(0.267-2.022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.5501\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 255px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e67/88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e76.1%\u003c/p\u003e\n \u003cp\u003e(65.9% - 84.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ch2\u003eTable2-4 Patients received HPD/HPTX therapy\u003c/h2\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"711\" class=\"fr-table-selection-hover\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 230px;\"\u003e\n \u003cp\u003eUnivariable analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eFactor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003eNon-PD/N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003eNon-PD Rate\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eMenopausal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003epremenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e33/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e94.3%\u003c/p\u003e\n \u003cp\u003e(80.8%-99.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003epostmenopausal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e68/74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e91.9%\u003c/p\u003e\n \u003cp\u003e(83.2%-97.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.786\u003c/p\u003e\n \u003cp\u003e(0.170-3.648)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7588\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e4/4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e100.0%\u003c/p\u003e\n \u003cp\u003e(39.8%-100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e46/50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.0%\u003c/p\u003e\n \u003cp\u003e(80.8%-97.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.147\u003c/p\u003e\n \u003cp\u003e(0.038-34.742)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.9370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e18/19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e94.7%\u003c/p\u003e\n \u003cp\u003e(74.0%-99.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.370\u003c/p\u003e\n \u003cp\u003e(0.034-54.651)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.8672\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e33/36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e91.7%\u003c/p\u003e\n \u003cp\u003e(77.5%-98.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1.063\u003c/p\u003e\n \u003cp\u003e(0.034-33.574)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.9724\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ecN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e7/7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e100.0%\u003c/p\u003e\n \u003cp\u003e(59.0%-100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e46/47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e97.9%\u003c/p\u003e\n \u003cp\u003e(88.7%-99.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2.067\u003c/p\u003e\n \u003cp\u003e(0.064-66.654)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.6821\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e11/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e73.3%\u003c/p\u003e\n \u003cp\u003e(44.9%-92.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.170\u003c/p\u003e\n \u003cp\u003e(0.007-4.442)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.2875\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ecN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e37/40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.5%\u003c/p\u003e\n \u003cp\u003e(79.6%-98.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.714\u003c/p\u003e\n \u003cp\u003e(0.028-18.516)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.8394\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eVisceral metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e24/31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e77.4%\u003c/p\u003e\n \u003cp\u003e(58.9%-90.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e77/78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e98.7%\u003c/p\u003e\n \u003cp\u003e(93.1%-100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e15.818\u003c/p\u003e\n \u003cp\u003e(2.547-98.228)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.0030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e96/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.3%\u003c/p\u003e\n \u003cp\u003e(85.4%-96.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSpecial types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e5/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e100.0%\u003c/p\u003e\n \u003cp\u003e(47.8%-100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.969\u003c/p\u003e\n \u003cp\u003e(0.038-24.942)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.9847\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e78/84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.9%\u003c/p\u003e\n \u003cp\u003e(85.1%-97.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e23/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.0%\u003c/p\u003e\n \u003cp\u003e(74.0%-99.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.778\u003c/p\u003e\n \u003cp\u003e(0.165-3.682)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.7520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003ePgR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e87/93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e93.5%\u003c/p\u003e\n \u003cp\u003e(86.5%-97.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 157px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e14/16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e87.5%\u003c/p\u003e\n \u003cp\u003e(61.7%-98.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003cp\u003e(0.087-2.131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.3019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 255px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e101/109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e92.7%\u003c/p\u003e\n \u003cp\u003e(86.1%-96.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7776614/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7776614/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe optimal initial systemic therapy for de novo Stage IV breast cancer (BC) is critical, particularly to assess early drug efficacy. In the JCOG1017 trial, untreated de novo Stage IV BC patients received 3 months of subtype-based systemic therapy before randomization for primary tumor resection. Among 569 treated patients, the overall non-progression disease (non-PD) rate was 77.2% and the objective response rate (ORR) was 29.0%. By subtype, non-PD/ORR rates were TN (78.2%/36.4%), Luminal (75.4%/13.4%), HER2 (92.9%/81.0%), and Luminal-HER2 (66.7%/40.3%). Multivariable analysis revealed higher non-PD rates in postmenopausal patients (odds ratio (OR) 1.673, p\u0026thinsp;=\u0026thinsp;0.024) and those with PgR-positive tumors (OR 2.391, p\u0026thinsp;=\u0026thinsp;0.0019). Endocrine therapy was more effective for patients with PgR-positive tumors (OR 3.258, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and less practical in those with visceral metastasis (OR 0.605, p\u0026thinsp;=\u0026thinsp;0.0334). HPD/HPTX therapies (non-PD rate: 92.7%) were highly effective in treating visceral metastasis (OR 15.818, p\u0026thinsp;=\u0026thinsp;0.0030). Patients without progression at 3 months had significantly better overall survival (HR 0.508, 95% CI [0.398, 0.648]). These findings emphasize that initial therapy must align with subtype, and endocrine monotherapy is suboptimal for ER\u0026thinsp;+\u0026thinsp;HER2\u0026thinsp;+\u0026thinsp;BC. Effective strategies are needed for those with early progression.\u003c/p\u003e","manuscriptTitle":"Efficacy and prognostic predictors of primary systemic therapy for de novo Stage IV breast cancer. Exploratory analysis of JCOG1017 PRIM-BC.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 02:20:05","doi":"10.21203/rs.3.rs-7776614/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2025-10-26T01:28:08+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-10-09T23:30:53+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-05T14:22:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-04T08:20:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer","date":"2025-10-04T03:27:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"41870fde-8aa1-4229-be42-cde814271d32","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:10:20+00:00","versionOfRecord":{"articleIdentity":"rs-7776614","link":"https://doi.org/10.1007/s12282-025-01821-4","journal":{"identity":"breast-cancer","isVorOnly":false,"title":"Breast Cancer"},"publishedOn":"2026-01-31 15:58:23","publishedOnDateReadable":"January 31st, 2026"},"versionCreatedAt":"2025-10-17 02:20:05","video":"","vorDoi":"10.1007/s12282-025-01821-4","vorDoiUrl":"https://doi.org/10.1007/s12282-025-01821-4","workflowStages":[]},"version":"v1","identity":"rs-7776614","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7776614","identity":"rs-7776614","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}