Identifying factors predicting the response to neoadjuvant chemotherapy in breast carcinoma

Identifying factors predicting the response to neoadjuvant chemotherapy in breast carcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Identifying factors predicting the response to neoadjuvant chemotherapy in breast carcinoma Wiem Ben Makhlouf, Ons Boudawara, Wala Ben Kridis, Olfa Boudawara, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6397234/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Neoadjuvant chemotherapy (NAC) improves outcomes of patients with non-metastatic breast carcinomas (BC). This statement is particularly true once a complete pathological response (pCR) to chemotherapy is achieved. We aimed through this study to identify the potential predictors of pCR in BC and to investigate its prognostic impact on both overall survival (OS) and progression-free survival (PFS). A total of 97 patients with non-metastatic breast carcinoma was enrolled in our study. Only 11 patients among them reached pCR (11.3%). Oestrogen and progesterone receptors negative BC as well as HER2 overexpressed molecular subtype exhibited higher pCR rates (p=0.005, p=0.01 and p<0.001 respectively). Furthermore, the use of sequential NAC regimen and of neoadjuvant trastuzumab were significantly predictive of pCR (p=0.03 and 0.02 respectively). Mean OS and PFS were 84 months and 56 months, respectively. On univariate analysis, patients who had achieved pCR showed longer OS and PFS, although the association was statistically significant only for PFS (p = 0.03). Thus, pathologist’s role seems to be crucial in predicting long-term outcomes through assessing the quality of pathological response to NAC. Further researches should focus on optimizing treatment regimens to increase pCR rates and improve outcomes. Breast cancer Neoadjuvant chemotherapy Pathological complete response Survival molecular subtype Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Breast cancer is the world's leading cancer in women, in terms of both incidence and mortality ( 1 ). Chemotherapy (CT) plays a crucial role in the management of breast carcinomas (BC), evolving from mainly adjuvant use after surgery to more frequent neoadjuvant applications before breast surgery. This shift has expanded the landscape of neoadjuvant chemotherapy (NAC) applications to include large unresectable tumors, increasing consequently the patient’s opportunity to undergo a breast conserving surgery rather than a radical mastectomy. Moreover, NAC allows to assess tumor responsiveness to chemotherapeutic drugs used preoperatively, improving then postoperative therapy planning( 2 – 4 ). However, survival benefits expected from NAC are mostly to be reached once a complete pathological response (pCR) to chemotherapy is achieved( 3 , 5 ). We aimed through this study to to identify clinico-pathological features and treatment patterns predictive of a pCR in BC treated by NAC followed by surgery. Furthermore, we explored the impact of pCR on patients’ outcomes in terms of overall survival (OS) and progression-free survival (PFS). MATERIALS & METHODS We conducted a single-institution retrospective study, performing a database search at Habib Bourguiba University Hospital between 2013 and 2023. Through this screening, we identified 134 patients with breast cancer (BC) who were consecutively treated with neoadjuvant chemotherapy (NAC) followed by surgery. We included in this study female patients with histologically proven BC and available molecular subtype data, determined from a preoperative biopsy. Patients with metastatic BC were excluded from the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Our study was approved by the local Habib Bourguiba Hospital committee (01/22). Informed consent to participate in this study was obtained directly from participants. The data were collected from the medical records of these patients and the corresponding pathology reports of the breast biopsy specimens and surgical specimens. The clinicopathological data were extracted from these records, ensuring that the molecular subtypes were determined based on the preoperative biopsy results. A total of 97 female patients were enrolled in our analysis. Clinico-pathological and treatment characteristics as well as survival outcomes were retrieved from review of medical records of all patients. Estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER-2) and Ki67 index were determined by immunohistochemistry (IHC). ER and PR were deemed positive when at least 1% of tumor cells showed positive nuclear staining. Tumors were considered Her-2 positive when Her-2 score assessed by IHC alone reached 3+. Otherwise, for BC having an equivocal HER2 score i.e. 2+, further fluorescence in situ hybridization (FISH) analysis was performed to confirm Her-2 gene amplification, thus affirming HER-2 status positivity. The cutoff value of high Ki-67 index was fixed to 20%. The neoadjuvant treatment protocol consisted of sequential chemotherapy (3 to 4 cycles of anthracyclines followed by 3 to 4 cycles of taxanes) or continuous chemotherapy (based on anthracyclines), with or without HER-2 targeted therapy for HER-2-positive patients. We have adopted the Residual Cancer Burden (RCB) score to assess pathological response. Accordingly, a pCR is defined as a total absence of invasive tumor cells in both breast and lymph nodes, with or without a residual in situ carcinoma component in the breast (ypT0 or Tis/N0). Statistical analyses were performed using SPSS Version 17 for Windows. The descriptive study was carried out by calculating proportions for categorical variables. For continuous variables, we used means, standard deviations, medians, and extreme values. Categorical variables were compared using the Chi-square test in independent samples or the Fischer's exact test, after checking the conditions of application of each test. OS and PFS were calculated using the Kaplan-Meier method. A univariate study using the log-rank test was performed to determine the impact of pathological response on patients’ outcomes. P-values of < 0.05 were deemed statistically significant. RESULTS DESCRIPTIVE STUDY: The mean age at BC diagnosis was 48 ± 10.7 years. At that time, 37 patients (38.1%) were already postmenopausal. Clinical evaluation followed by breast imaging concluded to a mean tumor size of 59 ± 28 mm, with suspicious axillary and/or supraclavicular lymph nodes in 71.1% of cases. According to the 2017 cTNM classification, 46.4% of tumors were assigned a cT4 stage, with 32% exhibiting inflammatory signs (cT4d stage). Nodal involvement was clinically assessed as cN1 in 49.5% of cases. The macroscopic aspects of the tumor bed are illustrated in Fig. 1 . Histological findings revealed that invasive BC were mainly of no special subtype, accounting for 92.7% of cases. Most tumors (60 cases, 61.9%) were assigned an intermediate histologic grade (grade 2). The mean mitotic rate was 9.6 mitoses/mm² [0–46 mitoses/mm 2 ]. Hormone receptor positivity was identified in 73.2% of cases, while HER-2 status was considered positive in 50.5% of cases. Ki-67 index, assessed in 69 out of 97 BC, was high in 85.5% of cases. In terms of molecular subtype, IHC study combined when applicable to Her-2 FISH analysis showed that almost half of cases (46.4%) were of luminal B subtype. The remaining cases were subdivided as follow: luminal (due to unavailable Ki-67 immunostaining) in 17.5%, HER2-overexpressed in 14.4%, triple-negative in 13.4%, and luminal A in 8.2%. On a therapeutic scale, the majority of our patients (81.4%) underwent sequential NAC. Anti-Her-2 targeted therapy, based in all cases on trastuzumab, was administered for 39 patients (79.6% of Her-2 positive BC). Clinico-radiological assessment after NAC concluded to a complete tumor mass disappearance in 3.1% of patients. Thirty-seven patients among those having had suspicious lymph nodes at diagnosis (53.6%), had no longer detectable lymph nodes neither clinically nor radiologically. Inflammatory signs resolved in 35.5% of inflammatory cancers. Histological evaluation of breast surgical specimens after NAC evidenced a pCR in 11 cases (11.34%) (Fig. 2 b and c, Fig. 3 b), whereas residual invasive carcinoma was noticed in 86 cases (88,7%), either in breast (Fig. 2 a) or in lymph nodes (Fig. 3 a). Patients’ characteristics are summarized in Table I. ANALATYCAL STUDY: pCR rates were significantly higher in ER and PR negative tumors (p = 0.005 and p = 0.01, respectively) as well as HER-2 overexpressed molecular subtype (p < 0.001). Moreover, the use of sequential NAC regimen and of neoadjuvant trastuzumab were significantly associated to better pCR rates (p = 0.03 and 0.02 respectively). Yet, we did not find any additional associations between histological response to NAC and the other clinico-pathological and treatment features (Table II). In our series, mean OS and PFS were 84 months and 56 months, respectively [95% IC]. On univariate analysis, patients who had achieved pCR showed longer OS and PFS, but relationship was statistically significant for only PFS (p = 0.03) (Fig. 4 ). DISCUSSION Pathologic response to NAC in breast cancer is deemed as an early indicator of patients’ outcomes as it provides an opportunity to assess tumor responsiveness to chemotherapeutic drugs used preoperatively. Thus, achieving pCR reflects a totally responsive tumor and is the aim of all clinicians. However, only 10–30% of patients may attain pCR( 6 ) (11.3% in our series). In this study, negative hormone receptors status, HER2-overexpressed molecular subtype, sequential NAC regimen and the use of neoadjuvant trastuzumab were pCR predictors in BC. The data of the literature are consistent with our findings. In fact, for most hormone receptors positive BC, pCR rates are low, and chemotherapy does not seem to be too helpful( 7 , 8 ). Thus, it is believed that hormone receptors negative BC respond well to NAC, irrespective of whether they are HER2 positive. Indeed, HER2-overexpressed and triple-negative BC have the highest pCR values (60–80%); while luminal-A subtype tumors are the least likely to achieve pCR( 9 – 13 ). Interestingly, the HER2-overexpressed subtype, in particular, is the one who responds the best to NAC with pCR rates reaching up 89% in some studies( 7 ). Some authors thought that HER-2 positivity itself is associated with better pathological response to NAC( 14 – 16 ). However, the majority of studies have approved that this association is conditioned by the incorporation of anti-HER-2 treatment in the NAC protocol, allowing a 3-fold increase of pCR rates( 17 , 18 ). This improvement is even more significant and associated with higher survival rates in the case of double anti-HER-2 blockade combining trastuzumab and pertuzumab( 19 , 20 ). Meanwhile, when focusing solely on studies using neoadjuvant chemotherapy (NAC) without anti-Her-2 targeted therapy, HER-2 overexpressed BC seem to behave similarly to their triple negative counterparts( 17 , 21 ). In terms of chemotherapy protocols, the sequential use of anthracyclines and taxanes has been associated with a better pathologic response in comparison with older continuous regimens. This finding was confirmed by prior studies, demonstrating that pCR rates were twice higher when using a sequential NAC regimen( 22 , 23 ). The remaining investigated factors including clinic-pathological features and treatment patterns showed no statistical association with pathologic response to chemotherapy. These data were partially consistent with those of prior studies. In fact, according to the literature, some of these features were significantly predicting of a good response to NAC namely– younger age( 24 ), postmenopausal status( 9 ), small tumor size( 9 , 14 , 25 ), the absence of lymph node metastasis( 14 , 15 ), histologic subtype of no special subtype( 26 , 27 ), high histologic grade( 25 , 28 ), increased mitotic rate( 28 ) and Ki67 index( 16 , 28 , 29 ). Focusing on patients’ outcomes, our analysis revealed that patients who achieved pCR after NAC have shown better PFS and OS in comparison with those who failed to attain pCR. Our findings agree with the international literature considering pCR as a well-known surrogate endpoint for long-term outcomes. Several clinical trials support the concept that pCR is implicated in survival benefits through improving PFS and OS rates( 30 – 33 ). Additionally, the pattern of response to NAC was also important. Actually, the CTNeoBC study showed that pathological complete response in the breast and axillae was associated with increased PFS and OS rates compared to pathological complete response in the breast exclusively( 34 ). This association was much more pronounced in high grade BC as well as in triple-negative and HER-2 overexpressed molecular subtypes( 34 ). CONCLUSION Assessment of the quality of pathologic response to NAC concluded to a pCR in 11.3% of our BC patients. Non luminal BC, particularly those of HER-2 overexpressed molecular subtype, demonstrated the highest pCR rates. Moreover, sequential NAC regimen was much more associated to a better pathologic response in comparison with continuous regimens. In HER-2 positive BC, the addition of neoadjuvant trastuzumab improved pCR rates as well. Finally, as shown in prior studies, achieving pCR had a significant impact on BC patients’ outcomes, allowing longer longer PFS and OS. Abbreviations Neoadjuvant chemotherapy (NAC) Breast carcinomas (BC). Pathological complete response (pCR) Overall survival (OS) Progression-free survival (PFS) Estrogen receptors (ER), Progesterone receptors (PR) Hormone receptors (HR) Human epidermal growth factor receptor (HER-2) Immunohistochemistry (IHC) Declarations Data Availability Statement The datasets generated during and/or analyzed during the current study are not publicly available due to participant confidentiality, but are available from the corresponding author upon reasonable request. Conflicts of Interest: There is no conflit of interest Sources of Funding: We do not have a funding source Clinical trial number: not applicable. Ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional local Habib Bourguiba Hospital committee (01/22) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. 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Tables Table I: Patients’ characteristics Patients’ characteristics N (%) Age (years) 45 32 (33%) 65 (67%) Menopausal status Yes No 35 (36,8%) 60 (63,1%) Clinical tumor size (mm) 5 65 (67) cT stage T1 T2 T3 T4 2 (2%) 20 (20,6%) 29 (29,8%) 46 (47,4%) cN stage N0 N1 N2 N3 26 (26,8%) 48 (49,4) 13 (13,4%) 10 (10,3%) Clinical stage Stage I Stage II Stage III 13 (13,4%) 22 (22,6%) 62 (63,9%) Histological subtype No special subtype Lobular carcinoma Micropapillary carcinoma Apocrine carcinoma 90 (92,7%) 4 (4,1%) 2 (2,1%) 1 (1%) Histologic grade Grade II Grade III 60 (61,8%) 37 (38,1%) Mitotic index on biopsy a 20 mitoses 79 (87,7%) 11 (12,2%) ER status Positive Negative 70 (72,1%) 27 (27,8%) PR status Positive Negative 58 (59,7%) 39 (40,2%) Her-2 status Positive Negative 49 (50,5%) 48 (49,4%) Ki67 index b 20% 10 (14,4%) 59 (85,5%) Molecular subtype Luminal A Luminal B Luminal Her-2 overexpressed Triple negative 8 (8,2%) 45 (46,4%) 17 (17,5%) 14 (14,4%) 13 (13,4%) NAC regimen Sequential Continuous 79 (81,4%) 18 (18,5%) Neoadjuvant trastuzumab c Yes No 27 (55,1%) 22 (44,8%) Pathologic response pCR no pCR 11 (11,3%) 86 (88,7%) a. The mitotic index on biopsy was calculated in 90 cases b. Ki67 index was assessed in 69 cases c. The addition of neoadjuvant trastuzumab was evaluated for HER-2 positive BC (n=49) CT: Chemotherapy; NAC: Neoadjuvant chemotherapy; pCR: Pathological complete response; HER-2: Human Epidermal Growth Factor Receptor 2; ER: Estrogen receptor; PR: Progesterone receptor Table II: Pathological response to chemotherapy according to epidemiological, clinico-pathological and therapeutic features of breast carcinomas Variable Total of cases (N=97) pCR (N=11) no pCR (N=86) p Age (years) 45 32 (33%) 65 (67%) 2 (2%) 9 (9,2%) 30 (30,9%) 56 (57,7%) 0,158 Menopausal status Yes No 35 (36,8%) 60 (63,1%) 6 (6,3%) 5 (5,2%) 29 (30,5%) 55 (57,9%) 0,196 Clinical tumor size (mm) 5 65 (67) 5 (5,1%) 60 (61,8%) cT stage T1 T2 T3 T4 2 (2%) 0 (0%) 2 (2%) 20 (20,6%) 29 (29,8%) 3 (3,1%) 2 (2%) 17 (17,5%) 27 (27,8%) 0,747 46 (47,4%) 6 (6,1%) 40 (41,2%) cN stage N0 N1 N2 N3 26 (26,8%) 2 (2%) 24 (24,7%) 48 (49,4) 13 (13,4%) 9 (9,2%) 0 (0%) 39 (40,2%) 13 (13,4%) 0,116 10 (10,3%) 0 (0%) 10 (10,3%) Clinical stage Stage I Stage II Stage III 13 (13,4%) 22 (22,6%) 62 (63,9%) 3 (3,1%) 2 (2%) 6 (6,1%) 10 (10,3%) 20 (20,6%) 56 (57,7%) 0,355 Histological subtype No special subtype Lobular carcinoma Other subtypes 90 (92,7%) 11 (11,3%) 80 (82,4%) 4 (4,1%) 3 (3%) 0 (0%) 0 (0%) 4 (4,1%) 3 (3%) 0,931 Histologic grade Grade II Grade III 60 (61,8%) 37 (38,1%) 6 (6,1%) 5 (5,1%) 54 (55,6%) 32 (32,9%) 0,596 Mitotic index on biopsy a 20 mitoses 79 (87,7%) 11 (12,2%) 8 (8,8%) 1 (1,1%) 71 (78,8%) 10 (11,1%) 0,915 ER status Positive Negative 70 (72,1%) 27 (27,8%) 4 (4,1%) 7 (7,2%) 66 (68%) 20 (20,6%) 0,005 PR status Positive Negative 58 (59,7%) 39 (40,2%) 3 (3,1%) 8 (8,2%) 55 (56,7%) 31 (31,9%) 0,019 Her-2 status Positive Negative 49 (50,5%) 48 (49,4%) 8 (8,2%) 3 (3,1%) 41 (42,2%) 45 (46,3%) 0,118 Ki67 index b 20% 10 (14,4%) 59 (85,5%) 0 (0%) 9 (13%) 10 (14,4%) 50 (72,4%) 0,185 Molecular subtype Luminal Her-2 overexpressed Triple negative 70 (72,1%) 14 (14,4%) 13 (13,4%) 4 (4,1%) 6 (6,1%) 1 (1%) 66 (68%) 8 (8,2%) 12 (12,3%) <0,001 NAC regimen Sequential Continuous 79 (81,4%) 18 (18,5%) 11 (11,3%) 0 (0%) 68 (70,1%) 18 (18,5%) 0,039 Neoadjuvant trastuzumab c Yes No 27 (55,1%) 22 (44,8%) 6 (12,2%) 2 (4%) 21 (42,8%) 20 (40,8%) 0,02 a. The mitotic index on biopsy was calculated in 90 cases b. Ki67 index was assessed in 69 cases c. The addition of neoadjuvant trastuzumab was evaluated for HER-2 positive BC (n=49) CT: Chemotherapy; NAC: Neoadjuvant chemotherapy; pCR: Pathological complete response; HER-2: Human Epidermal Growth Factor Receptor 2; ER: Estrogen receptor; PR: Progesterone receptor Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6397234","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":456456483,"identity":"fb478615-47b1-4eca-b66b-e6ca80312807","order_by":0,"name":"Wiem Ben Makhlouf","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIie2PMUsDMRTHcxQyVbLJKw79BEKkEASLfpUEId1EcLlJOp2TdLX4EVwODkLHQLBd7ugacbmpTkJdpFtNbiu9O3UTzA8C70/ej/ceQoHAX6TjXjT2FcaoRIgQX/Prnyocod7UB06/mbSjpNqHFoUuOs9pNBteHd/NZcljA4Plk1iXFPXJoa5XDJY2yuUNy+WC8twAs+8ZuMVOpo+8VmGmy2yUGKH0KAGRmFtmi9QrnL42KeTTKVuhlm+VAoOHItu0K13sFC2UlfNKoeRetU65MJhZkV86ZSWB5yMAe6BOOYXGW3oTs7Ifs3O3mGSwjs+ATIrsZRMP++SoXqnY/YIqQnP7PkT/pjsQCAT+AV9W3mhy4DReRgAAAABJRU5ErkJggg==","orcid":"","institution":"Hopital Universitaire Habib Bourguiba","correspondingAuthor":true,"prefix":"","firstName":"Wiem","middleName":"Ben","lastName":"Makhlouf","suffix":""},{"id":456456484,"identity":"91849fbd-84d1-42b3-8abd-dbcafa8ba8bf","order_by":1,"name":"Ons Boudawara","email":"","orcid":"","institution":"Hopital Universitaire Habib Bourguiba","correspondingAuthor":false,"prefix":"","firstName":"Ons","middleName":"","lastName":"Boudawara","suffix":""},{"id":456456485,"identity":"a425193f-a8ad-42cd-b9e6-22b3ff45d618","order_by":2,"name":"Wala Ben Kridis","email":"","orcid":"","institution":"Hopital Universitaire Habib Bourguiba","correspondingAuthor":false,"prefix":"","firstName":"Wala","middleName":"Ben","lastName":"Kridis","suffix":""},{"id":456456487,"identity":"c4de5174-138f-4fb0-a910-100e27069dde","order_by":3,"name":"Olfa Boudawara","email":"","orcid":"","institution":"Hopital Universitaire Habib Bourguiba","correspondingAuthor":false,"prefix":"","firstName":"Olfa","middleName":"","lastName":"Boudawara","suffix":""},{"id":456456488,"identity":"00dc07ac-12c2-47d3-b8b8-03b9f907ebca","order_by":4,"name":"Afef Khanfir","email":"","orcid":"","institution":"Hopital Universitaire Habib Bourguiba","correspondingAuthor":false,"prefix":"","firstName":"Afef","middleName":"","lastName":"Khanfir","suffix":""},{"id":456456489,"identity":"a8d6f223-fe7f-4653-9550-07158f606b22","order_by":5,"name":"Tahya Sellami Boudawara","email":"","orcid":"","institution":"Hopital Universitaire Habib Bourguiba","correspondingAuthor":false,"prefix":"","firstName":"Tahya","middleName":"Sellami","lastName":"Boudawara","suffix":""}],"badges":[],"createdAt":"2025-04-07 20:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6397234/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6397234/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82901451,"identity":"025082b8-3f83-4d1f-ab7b-99488ef8eec7","added_by":"auto","created_at":"2025-05-16 13:32:13","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1270946,"visible":true,"origin":"","legend":"\u003cp\u003eMacroscopic appearance of the tumour bed :\u003c/p\u003e\n\u003cp\u003e(a): Whitish, indurated tumor bed, clearly visible macroscopically (blue dotted circle)\u003c/p\u003e\n\u003cp\u003e(b): No visible tumor bed on gross examination\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6397234/v1/077f9dbe070a29e1aae4bf68.jpeg"},{"id":82900752,"identity":"09e5747c-7f5f-41a4-9214-d98d99e1af9d","added_by":"auto","created_at":"2025-05-16 13:24:13","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":910401,"visible":true,"origin":"","legend":"\u003cp\u003ePatterns of pathological response in breast carcinomas (HE x50)\u003c/p\u003e\n\u003cp\u003e(a): residual invasive carcinoma (black arrows)\u003c/p\u003e\n\u003cp\u003e(b / c): complete pathologic response: presence of therapeutic effect without residual carcinoma: stromal hyalinisation (yellow star) and hemosiderin deposits (red circle)\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6397234/v1/0b4cc523d97ac5b4c94fd533.jpeg"},{"id":82902417,"identity":"242b74e3-dab6-4614-9cc2-2db1034f932d","added_by":"auto","created_at":"2025-05-16 13:40:13","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1362410,"visible":true,"origin":"","legend":"\u003cp\u003ePatterns of pathological response in lymph nodes (HEx50)\u003c/p\u003e\n\u003cp\u003e(a): metastatic lymph node with therapeutic effect\u003c/p\u003e\n\u003cp\u003e(b): sterilized lymph node with therapeutic effect (fibrous changes) (red star)\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6397234/v1/ab1ea0a6941b41c4dadb0eea.jpeg"},{"id":82900754,"identity":"02457cd0-dff5-43b4-8785-6d2c3776fa2b","added_by":"auto","created_at":"2025-05-16 13:24:13","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":238919,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival curve according to pathological response\u003c/p\u003e\n\u003cp\u003e(a): Overall survival (OS)\u003c/p\u003e\n\u003cp\u003e(b): Progression-free survival (PFS)\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6397234/v1/31529b7c290e86177a4cfed3.jpeg"},{"id":84953385,"identity":"7f6ae644-ea1c-40dd-8826-43de183e1122","added_by":"auto","created_at":"2025-06-19 07:39:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4686653,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6397234/v1/dcee43e0-01b2-459d-85e0-da7a2e3a3ff1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Identifying factors predicting the response to neoadjuvant chemotherapy in breast carcinoma","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBreast cancer is the world's leading cancer in women, in terms of both incidence and mortality (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Chemotherapy (CT) plays a crucial role in the management of breast carcinomas (BC), evolving from mainly adjuvant use after surgery to more frequent neoadjuvant applications before breast surgery. This shift has expanded the landscape of neoadjuvant chemotherapy (NAC) applications to include large unresectable tumors, increasing consequently the patient\u0026rsquo;s opportunity to undergo a breast conserving surgery rather than a radical mastectomy. Moreover, NAC allows to assess tumor responsiveness to chemotherapeutic drugs used preoperatively, improving then postoperative therapy planning(\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, survival benefits expected from NAC are mostly to be reached once a complete pathological response (pCR) to chemotherapy is achieved(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e We aimed through this study to to identify clinico-pathological features and treatment patterns predictive of a pCR in BC treated by NAC followed by surgery. Furthermore, we explored the impact of pCR on patients\u0026rsquo; outcomes in terms of overall survival (OS) and progression-free survival (PFS).\u003c/p\u003e"},{"header":"MATERIALS \u0026 METHODS","content":"\u003cp\u003eWe conducted a single-institution retrospective study, performing a database search at Habib Bourguiba University Hospital between 2013 and 2023. Through this screening, we identified 134 patients with breast cancer (BC) who were consecutively treated with neoadjuvant chemotherapy (NAC) followed by surgery. We included in this study female patients with histologically proven BC and available molecular subtype data, determined from a preoperative biopsy. Patients with metastatic BC were excluded from the study.\u003c/p\u003e \u003cp\u003e All procedures performed in studies involving human participants were in accordance with the ethical standards of 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Our study was approved by the local Habib Bourguiba Hospital committee (01/22). Informed consent to participate in this study was obtained directly from participants.\u003c/p\u003e \u003cp\u003eThe data were collected from the medical records of these patients and the corresponding pathology reports of the breast biopsy specimens and surgical specimens. The clinicopathological data were extracted from these records, ensuring that the molecular subtypes were determined based on the preoperative biopsy results. A total of 97 female patients were enrolled in our analysis.\u003c/p\u003e \u003cp\u003eClinico-pathological and treatment characteristics as well as survival outcomes were retrieved from review of medical records of all patients. Estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER-2) and Ki67 index were determined by immunohistochemistry (IHC). ER and PR were deemed positive when at least 1% of tumor cells showed positive nuclear staining. Tumors were considered Her-2 positive when Her-2 score assessed by IHC alone reached 3+. Otherwise, for BC having an equivocal HER2 score i.e. 2+, further fluorescence in situ hybridization (FISH) analysis was performed to confirm Her-2 gene amplification, thus affirming HER-2 status positivity. The cutoff value of high Ki-67 index was fixed to 20%.\u003c/p\u003e \u003cp\u003eThe neoadjuvant treatment protocol consisted of sequential chemotherapy (3 to 4 cycles of anthracyclines followed by 3 to 4 cycles of taxanes) or continuous chemotherapy (based on anthracyclines), with or without HER-2 targeted therapy for HER-2-positive patients.\u003c/p\u003e \u003cp\u003eWe have adopted the Residual Cancer Burden (RCB) score to assess pathological response. Accordingly, a pCR is defined as a total absence of invasive tumor cells in both breast and lymph nodes, with or without a residual in situ carcinoma component in the breast (ypT0 or Tis/N0).\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using SPSS Version 17 for Windows. The descriptive study was carried out by calculating proportions for categorical variables. For continuous variables, we used means, standard deviations, medians, and extreme values. Categorical variables were compared using the Chi-square test in independent samples or the Fischer's exact test, after checking the conditions of application of each test. OS and PFS were calculated using the Kaplan-Meier method. A univariate study using the log-rank test was performed to determine the impact of pathological response on patients\u0026rsquo; outcomes. P-values of \u0026lt;\u0026thinsp;0.05 were deemed statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDESCRIPTIVE STUDY:\u003c/h2\u003e \u003cp\u003eThe mean age at BC diagnosis was 48\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7 years. At that time, 37 patients (38.1%) were already postmenopausal. Clinical evaluation followed by breast imaging concluded to a mean tumor size of 59\u0026thinsp;\u0026plusmn;\u0026thinsp;28 mm, with suspicious axillary and/or supraclavicular lymph nodes in 71.1% of cases. According to the 2017 cTNM classification, 46.4% of tumors were assigned a cT4 stage, with 32% exhibiting inflammatory signs (cT4d stage). Nodal involvement was clinically assessed as cN1 in 49.5% of cases. The macroscopic aspects of the tumor bed are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistological findings revealed that invasive BC were mainly of no special subtype, accounting for 92.7% of cases. Most tumors (60 cases, 61.9%) were assigned an intermediate histologic grade (grade 2). The mean mitotic rate was 9.6 mitoses/mm\u0026sup2; [0\u0026ndash;46 mitoses/mm\u003csup\u003e2\u003c/sup\u003e]. Hormone receptor positivity was identified in 73.2% of cases, while HER-2 status was considered positive in 50.5% of cases. Ki-67 index, assessed in 69 out of 97 BC, was high in 85.5% of cases.\u003c/p\u003e \u003cp\u003eIn terms of molecular subtype, IHC study combined when applicable to Her-2 FISH analysis showed that almost half of cases (46.4%) were of luminal B subtype. The remaining cases were subdivided as follow: luminal (due to unavailable Ki-67 immunostaining) in 17.5%, HER2-overexpressed in 14.4%, triple-negative in 13.4%, and luminal A in 8.2%.\u003c/p\u003e \u003cp\u003eOn a therapeutic scale, the majority of our patients (81.4%) underwent sequential NAC. Anti-Her-2 targeted therapy, based in all cases on trastuzumab, was administered for 39 patients (79.6% of Her-2 positive BC).\u003c/p\u003e \u003cp\u003eClinico-radiological assessment after NAC concluded to a complete tumor mass disappearance in 3.1% of patients. Thirty-seven patients among those having had suspicious lymph nodes at diagnosis (53.6%), had no longer detectable lymph nodes neither clinically nor radiologically. Inflammatory signs resolved in 35.5% of inflammatory cancers.\u003c/p\u003e \u003cp\u003eHistological evaluation of breast surgical specimens after NAC evidenced a pCR in 11 cases (11.34%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb and c, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), whereas residual invasive carcinoma was noticed in 86 cases (88,7%), either in breast (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea) or in lymph nodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients\u0026rsquo; characteristics are summarized in Table I.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eANALATYCAL STUDY:\u003c/h3\u003e\n\u003cp\u003epCR rates were significantly higher in ER and PR negative tumors (p\u0026thinsp;=\u0026thinsp;0.005 and p\u0026thinsp;=\u0026thinsp;0.01, respectively) as well as HER-2 overexpressed molecular subtype (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Moreover, the use of sequential NAC regimen and of neoadjuvant trastuzumab were significantly associated to better pCR rates (p\u0026thinsp;=\u0026thinsp;0.03 and 0.02 respectively). Yet, we did not find any additional associations between histological response to NAC and the other clinico-pathological and treatment features (Table II).\u003c/p\u003e \u003cp\u003eIn our series, mean OS and PFS were 84 months and 56 months, respectively [95% IC]. On univariate analysis, patients who had achieved pCR showed longer OS and PFS, but relationship was statistically significant for only PFS (p\u0026thinsp;=\u0026thinsp;0.03) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003ePathologic response to NAC in breast cancer is deemed as an early indicator of patients\u0026rsquo; outcomes as it provides an opportunity to assess tumor responsiveness to chemotherapeutic drugs used preoperatively. Thus, achieving pCR reflects a totally responsive tumor and is the aim of all clinicians. However, only 10\u0026ndash;30% of patients may attain pCR(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) (11.3% in our series).\u003c/p\u003e \u003cp\u003eIn this study, negative hormone receptors status, HER2-overexpressed molecular subtype, sequential NAC regimen and the use of neoadjuvant trastuzumab were pCR predictors in BC. The data of the literature are consistent with our findings. In fact, for most hormone receptors positive BC, pCR rates are low, and chemotherapy does not seem to be too helpful(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Thus, it is believed that hormone receptors negative BC respond well to NAC, irrespective of whether they are HER2 positive. Indeed, HER2-overexpressed and triple-negative BC have the highest pCR values (60\u0026ndash;80%); while luminal-A subtype tumors are the least likely to achieve pCR(\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Interestingly, the HER2-overexpressed subtype, in particular, is the one who responds the best to NAC with pCR rates reaching up 89% in some studies(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Some authors thought that HER-2 positivity itself is associated with better pathological response to NAC(\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, the majority of studies have approved that this association is conditioned by the incorporation of anti-HER-2 treatment in the NAC protocol, allowing a 3-fold increase of pCR rates(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). This improvement is even more significant and associated with higher survival rates in the case of double anti-HER-2 blockade combining trastuzumab and pertuzumab(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Meanwhile, when focusing solely on studies using neoadjuvant chemotherapy (NAC) without anti-Her-2 targeted therapy, HER-2 overexpressed BC seem to behave similarly to their triple negative counterparts(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In terms of chemotherapy protocols, the sequential use of anthracyclines and taxanes has been associated with a better pathologic response in comparison with older continuous regimens. This finding was confirmed by prior studies, demonstrating that pCR rates were twice higher when using a sequential NAC regimen(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe remaining investigated factors including clinic-pathological features and treatment patterns showed no statistical association with pathologic response to chemotherapy. These data were partially consistent with those of prior studies. In fact, according to the literature, some of these features were significantly predicting of a good response to NAC namely\u0026ndash; younger age(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), postmenopausal status(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), small tumor size(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), the absence of lymph node metastasis(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), histologic subtype of no special subtype(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), high histologic grade(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), increased mitotic rate(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) and Ki67 index(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFocusing on patients\u0026rsquo; outcomes, our analysis revealed that patients who achieved pCR after NAC have shown better PFS and OS in comparison with those who failed to attain pCR. Our findings agree with the international literature considering pCR as a well-known surrogate endpoint for long-term outcomes. Several clinical trials support the concept that pCR is implicated in survival benefits through improving PFS and OS rates(\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Additionally, the pattern of response to NAC was also important. Actually, the CTNeoBC study showed that pathological complete response in the breast and axillae was associated with increased PFS and OS rates compared to pathological complete response in the breast exclusively(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). This association was much more pronounced in high grade BC as well as in triple-negative and HER-2 overexpressed molecular subtypes(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAssessment of the quality of pathologic response to NAC concluded to a pCR in 11.3% of our BC patients. Non luminal BC, particularly those of HER-2 overexpressed molecular subtype, demonstrated the highest pCR rates. Moreover, sequential NAC regimen was much more associated to a better pathologic response in comparison with continuous regimens. In HER-2 positive BC, the addition of neoadjuvant trastuzumab improved pCR rates as well. Finally, as shown in prior studies, achieving pCR had a significant impact on BC patients\u0026rsquo; outcomes, allowing longer longer PFS and OS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul\u003e\n \u003cli\u003eNeoadjuvant chemotherapy (NAC)\u003c/li\u003e\n \u003cli\u003eBreast carcinomas (BC).\u003c/li\u003e\n \u003cli\u003ePathological complete response (pCR)\u003c/li\u003e\n \u003cli\u003eOverall survival (OS)\u003c/li\u003e\n \u003cli\u003eProgression-free survival (PFS)\u003c/li\u003e\n \u003cli\u003eEstrogen receptors (ER),\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eProgesterone receptors (PR)\u003c/li\u003e\n \u003cli\u003eHormone receptors (HR)\u003c/li\u003e\n \u003cli\u003eHuman epidermal growth factor receptor (HER-2)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eImmunohistochemistry (IHC)\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are not publicly available due to participant confidentiality, but are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003eThere is no conflit of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSources of Funding:\u0026nbsp;\u003c/strong\u003eWe do not have a funding source\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional local Habib Bourguiba Hospital committee (01/22)\u0026nbsp;and\u0026nbsp;with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate declaration:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained directly from patient(s).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCancer du sein [Internet]. 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Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies. J Clin Oncol 1 d\u0026eacute;c. 2014;32(34):3883\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 12 juill. 2014;384(9938):164\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable I:\u003c/strong\u003e Patients\u0026rsquo; characteristics \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"558\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients\u0026rsquo; characteristics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN (%)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;45\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026gt;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e32 (33%)\u003c/p\u003e\n \u003cp\u003e65 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMenopausal status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e35 (36,8%)\u003c/p\u003e\n \u003cp\u003e60 (63,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical tumor size (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026lt; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e2-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e28 (28,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026gt; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e65 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecT stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e20 (20,6%)\u003c/p\u003e\n \u003cp\u003e29 (29,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e46 (47,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecN stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e26 (26,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e48 (49,4)\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e10 (10,3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eStage I\u003c/p\u003e\n \u003cp\u003eStage II\u003c/p\u003e\n \u003cp\u003eStage III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003cp\u003e22 (22,6%)\u003c/p\u003e\n \u003cp\u003e62 (63,9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistological subtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo special subtype\u003c/p\u003e\n \u003cp\u003eLobular carcinoma\u003c/p\u003e\n \u003cp\u003eMicropapillary carcinoma\u003c/p\u003e\n \u003cp\u003eApocrine carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e90 (92,7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003cp\u003e2 (2,1%)\u003c/p\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistologic grade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGrade II\u003c/p\u003e\n \u003cp\u003eGrade III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e60 (61,8%)\u003c/p\u003e\n \u003cp\u003e37 (38,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMitotic index on biopsy\u0026nbsp;\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 20 mitoses\u003c/p\u003e\n \u003cp\u003e\u0026gt; 20 mitoses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e79 (87,7%)\u003c/p\u003e\n \u003cp\u003e11 (12,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eER status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e70 (72,1%)\u003c/p\u003e\n \u003cp\u003e27 (27,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e58 (59,7%)\u003c/p\u003e\n \u003cp\u003e39 (40,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHer-2 status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e49 (50,5%)\u003c/p\u003e\n \u003cp\u003e48 (49,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKi67 index\u0026nbsp;\u003c/strong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 20%\u003c/p\u003e\n \u003cp\u003e\u0026gt; 20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e10 (14,4%)\u003c/p\u003e\n \u003cp\u003e59 (85,5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMolecular subtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLuminal A\u003c/p\u003e\n \u003cp\u003eLuminal B\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eLuminal\u003c/p\u003e\n \u003cp\u003eHer-2\u0026nbsp;overexpressed\u003c/p\u003e\n \u003cp\u003eTriple negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e8 (8,2%)\u003c/p\u003e\n \u003cp\u003e45 (46,4%)\u003c/p\u003e\n \u003cp\u003e17 (17,5%)\u003c/p\u003e\n \u003cp\u003e14 (14,4%)\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNAC regimen\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSequential\u003c/p\u003e\n \u003cp\u003eContinuous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e79 (81,4%)\u003c/p\u003e\n \u003cp\u003e18 (18,5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeoadjuvant trastuzumab\u0026nbsp;\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e27 (55,1%)\u003c/p\u003e\n \u003cp\u003e22 (44,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathologic response\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003epCR\u003c/p\u003e\n \u003cp\u003eno pCR\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e11 (11,3%)\u003c/p\u003e\n \u003cp\u003e86 (88,7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ea. The mitotic index on biopsy was calculated in 90 cases\u003c/p\u003e\n\u003cp\u003eb. Ki67 index was assessed in 69 cases\u003c/p\u003e\n\u003cp\u003ec. The addition of neoadjuvant trastuzumab was evaluated for HER-2 positive BC (n=49)\u003c/p\u003e\n\u003cp\u003eCT: Chemotherapy; NAC: Neoadjuvant chemotherapy; pCR: Pathological complete response; HER-2: Human Epidermal Growth Factor Receptor 2; ER: Estrogen receptor; PR: Progesterone receptor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable II:\u003c/strong\u003e Pathological response to chemotherapy according to epidemiological, clinico-pathological and therapeutic features of breast carcinomas\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eVariable\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eTotal of cases\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e(N=97)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003epCR\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e(N=11)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eno pCR\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e(N=86)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;45\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026gt;45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e32 (33%)\u003c/p\u003e\n \u003cp\u003e65 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003cp\u003e9 (9,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (30,9%)\u003c/p\u003e\n \u003cp\u003e56 (57,7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0,158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMenopausal status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e35 (36,8%)\u003c/p\u003e\n \u003cp\u003e60 (63,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e6 (6,3%)\u003c/p\u003e\n \u003cp\u003e5 (5,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e29 (30,5%)\u003c/p\u003e\n \u003cp\u003e55 (57,9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0,196\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical tumor size (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u0026lt; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e2-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e28 (28,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e6 (6,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e22 (22,6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0,12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u0026gt; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e65 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e5 (5,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e60 (61,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecT stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e20 (20,6%)\u003c/p\u003e\n \u003cp\u003e29 (29,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e3 (3,1%)\u003c/p\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e17 (17,5%)\u003c/p\u003e\n \u003cp\u003e27 (27,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0,747\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e46 (47,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e6 (6,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e40 (41,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecN stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e26 (26,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e24 (24,7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e48 (49,4)\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e9 (9,2%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e39 (40,2%)\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0,116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e10 (10,3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e10 (10,3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eStage I\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eStage II\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eStage III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003cp\u003e22 (22,6%)\u003c/p\u003e\n \u003cp\u003e62 (63,9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3,1%)\u003c/p\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003cp\u003e6 (6,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e10 (10,3%)\u003c/p\u003e\n \u003cp\u003e20 (20,6%)\u003c/p\u003e\n \u003cp\u003e56 (57,7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0,355\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistological subtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo special subtype\u003c/p\u003e\n \u003cp\u003eLobular carcinoma\u003c/p\u003e\n \u003cp\u003eOther subtypes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e90 (92,7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e11 (11,3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e80 (82,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003cp\u003e3 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003cp\u003e3 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0,931\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistologic grade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGrade II\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGrade III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e60 (61,8%)\u003c/p\u003e\n \u003cp\u003e37 (38,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e6 (6,1%)\u003c/p\u003e\n \u003cp\u003e5 (5,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e54 (55,6%)\u003c/p\u003e\n \u003cp\u003e32 (32,9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0,596\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMitotic index on biopsy\u0026nbsp;\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 20 mitoses\u003c/p\u003e\n \u003cp\u003e\u0026gt; 20 mitoses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e79 (87,7%)\u003c/p\u003e\n \u003cp\u003e11 (12,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e8 (8,8%)\u003c/p\u003e\n \u003cp\u003e1 (1,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e71 (78,8%)\u003c/p\u003e\n \u003cp\u003e10 (11,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0,915\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eER status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePositive\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e70 (72,1%)\u003c/p\u003e\n \u003cp\u003e27 (27,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003cp\u003e7 (7,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e66 (68%)\u003c/p\u003e\n \u003cp\u003e20 (20,6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e58 (59,7%)\u003c/p\u003e\n \u003cp\u003e39 (40,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e3 (3,1%)\u003c/p\u003e\n \u003cp\u003e8 (8,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e55 (56,7%)\u003c/p\u003e\n \u003cp\u003e31 (31,9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHer-2 status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e49 (50,5%)\u003c/p\u003e\n \u003cp\u003e48 (49,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e8 (8,2%)\u003c/p\u003e\n \u003cp\u003e3 (3,1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e41 (42,2%)\u003c/p\u003e\n \u003cp\u003e45 (46,3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0,118\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKi67 index\u0026nbsp;\u003c/strong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt; 20%\u003c/p\u003e\n \u003cp\u003e\u0026gt; 20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e10 (14,4%)\u003c/p\u003e\n \u003cp\u003e59 (85,5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e9 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e10 (14,4%)\u003c/p\u003e\n \u003cp\u003e50 (72,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0,185\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMolecular subtype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLuminal\u003c/p\u003e\n \u003cp\u003eHer-2\u0026nbsp;overexpressed\u003c/p\u003e\n \u003cp\u003eTriple negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e70 (72,1%)\u003c/p\u003e\n \u003cp\u003e14 (14,4%)\u003c/p\u003e\n \u003cp\u003e13 (13,4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e4 (4,1%)\u003c/p\u003e\n \u003cp\u003e6 (6,1%)\u003c/p\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e66 (68%)\u003c/p\u003e\n \u003cp\u003e8 (8,2%)\u003c/p\u003e\n \u003cp\u003e12 (12,3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNAC regimen\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSequential\u003c/p\u003e\n \u003cp\u003eContinuous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e79 (81,4%)\u003c/p\u003e\n \u003cp\u003e18 (18,5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e11 (11,3%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e68 (70,1%)\u003c/p\u003e\n \u003cp\u003e18 (18,5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,039\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeoadjuvant trastuzumab\u0026nbsp;\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eYes \u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e27 (55,1%)\u003c/p\u003e\n \u003cp\u003e22 (44,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e6 (12,2%)\u003c/p\u003e\n \u003cp\u003e2 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e21 (42,8%)\u003c/p\u003e\n \u003cp\u003e20 (40,8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0,02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea. The mitotic index on biopsy was calculated in 90 cases\u003c/p\u003e\n\u003cp\u003eb. Ki67 index was assessed in 69 cases\u003c/p\u003e\n\u003cp\u003ec. The addition of neoadjuvant trastuzumab was evaluated for HER-2 positive BC (n=49)\u003c/p\u003e\n\u003cp\u003eCT: Chemotherapy; NAC: Neoadjuvant chemotherapy; pCR: Pathological complete response; HER-2: Human Epidermal Growth Factor Receptor 2; ER: Estrogen receptor; PR: Progesterone receptor\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, Neoadjuvant chemotherapy, Pathological complete response, Survival, molecular subtype","lastPublishedDoi":"10.21203/rs.3.rs-6397234/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6397234/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNeoadjuvant chemotherapy (NAC) improves outcomes of patients with non-metastatic breast carcinomas (BC). This statement is particularly true once a complete pathological response (pCR) to chemotherapy is achieved. We aimed through this study to identify the potential predictors of pCR in BC and to investigate its prognostic impact on both overall survival (OS) and progression-free survival (PFS).\u003c/p\u003e\n\u003cp\u003eA total of 97 patients with non-metastatic breast carcinoma was enrolled in our study. Only 11 patients among them reached pCR (11.3%). Oestrogen and progesterone receptors negative BC as well as HER2 overexpressed molecular subtype exhibited higher pCR rates (p=0.005, p=0.01 and p\u0026amp;lt;0.001 respectively). Furthermore, the use of sequential NAC regimen and of neoadjuvant trastuzumab were significantly predictive of pCR (p=0.03 and 0.02 respectively). Mean OS and PFS were 84 months and 56 months, respectively. On univariate analysis, patients who had achieved pCR showed longer OS and PFS, although the association was statistically significant only for PFS (p = 0.03). Thus, pathologist’s role seems to be crucial in predicting long-term outcomes through assessing the quality of pathological response to NAC. Further researches should focus on optimizing treatment regimens to increase pCR rates and improve outcomes.\u003c/p\u003e","manuscriptTitle":"Identifying factors predicting the response to neoadjuvant chemotherapy in breast carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 13:24:09","doi":"10.21203/rs.3.rs-6397234/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6d805de8-1e80-4072-a00e-80881a9cc7f5","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-19T07:38:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-16 13:24:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6397234","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6397234","identity":"rs-6397234","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}