Comparative Survival Analysis of HER2-Positive Pregnancy-Associated Breast Cancer and Non-Pregnant Cohorts: A matched control study

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Methods: Clinical and histopathological data were collected from a prospectively maintained patient database at King Hussein Cancer Center, a tertiary cancer-care center in Jordan. The study analyzed overall survival (OS), recurrence-free survival (RFS), and event-free survival (EFS) in HER2-positive PABC matched 1:1 to non-pregnant patients with HER2-positive breast cancer (non-PABC). Results : The analysis encompassed 128 patients, divided into two main groups: 64 patients diagnosed with PABC and 64 patients classified as non-PABC cases. Although there was not a statistically significant difference in OS between non-pregnant and pregnant individuals (p=0.12), it was notable that pregnant individuals experienced a significant delay in the initiation of anti-HER2 treatment (23.8± 19.3 weeks, p= 0.02). Additionally, there was a higher risk of recurrence or events in pregnant individuals, emphasizing the potential impact of pregnancy on these survival outcomes (HR=1.93, p=0.029 and HR=2.00, p=0.02, respectively). Furthermore, PABC individuals who completed the 12-months of anti-HER2 treatment were comparable to non-PABC individuals who completed the same treatment (p=0.3), while incomplete treatment significantly affected survival outcomes (HR=4.94, 95% CI: 1.41 to 17.3, p=0.012). Conclusion: Despite a notable delay in the initiation of anti-HER2 treatment in PABC patients compared to non-PABC cases, both cohorts exhibited similar prognostic outcomes in terms of overall survival when anti-HER2 treatment has been completed. This discovery emphasizes the importance of promptly initiating and completing anti-HER2 treatment in pregnant individuals to optimize prognosis. Breast cancer HER2-Positive Breast Cancer Pregnancy-Associated Breast Cancer Survival Analysis Pregnancy and Cancer Oncological Outcomes Figures Figure 1 Figure 2 Figure 3 Introduction Breast cancer remains the most common cancer and the leading cause of cancer-related mortality in Jordan [ 1 ]. Pregnancy related cancer is uncommon, with breast cancer being the most frequently diagnosed with projections of increased incidence due to increased maternal ages worldwide [ 2 , 3 ]. HER2-positive breast cancer is recognized for its aggressive nature, constituting a significant proportion of breast cancer cases and necessitates targeted therapies to improve patient outcomes [ 4 – 6 ]. PABC encompasses breast cancer diagnosed during pregnancy or in the first post-partum year, presenting a complex intersection of oncological and obstetric considerations [ 7 , 8 ]. Understanding the epidemiological nuances of both HER2-positive breast cancer and pregnancy-associated breast cancer is vital for optimizing prevention, detection, and management strategies tailored to these specific patient populations. Viuff et al showed that PABC patients exhibited decreased survival within the initial two years following diagnosis, yet no significant difference in survival was observed beyond this period [ 9 ]. Similarly, a Swedish study delved into the outcomes of 1,661 women with breast cancer, categorizing them into groups based on time since delivery, where after adjustment for confounding variables, PABC cases showed higher mortality rates in contrast to non-PABC cases, with a noticeable peak approximately two years after diagnosis [ 10 ]. Survival rates in HER2-positive breast cancer patients have significantly improved over the past few decades, primarily due to the advent of targeted therapies such as Trastuzumab (Herceptin), a cornerstone in HER2-positive breast cancer treatment, and other anti-HER2 agents [ 11 – 14 ]. However, concerns regarding its use during pregnancy and potential impact on fetal development have led to clinical hesitations and interruptions or discontinuation of therapy for pregnant patients. These interruptions or modifications in treatment pose critical questions regarding the optimal management and subsequent outcomes for this specific patient demographic [ 15 ]. Our study presents an investigation into the prognosis and treatment outcomes of HER2-positive PABC compared to non-PABC cohorts. We also aim to study the effect of delaying and interrupting anti-HER2 treatment in pregnant patients. Methods Study Population and Design: The study involved a defined population comprising individuals younger than 45 years old who were diagnosed with HER2-positive PABC and then matched with HER2-positive non-PABC of similar age, histopathology, and clinical stage. Data for this study were collected retrospectively from the cancer registry at the King Hussein Cancer Center within the timeframe of April 2006 to January 2021. None of the PABC patients received anti-HER2 therapy during pregnancy; instead, initiation of the anti-HER2 treatment was postponed until after delivery and the group was further divided into three subgroups based on the completion of anti-Her2 therapy; patients who received and completed the planned duration of therapy regimen of anti-HER2 (completion of anti-HER2), received and did not complete the regimen (partially completed) and those who did not receive any doses of the anti HER2 treatment regimen (No anti-HER2). The primary endpoint for this study was the comparative survival analysis between HER2-positive PABC and HER2-positive non-PABC. Event free survival (EFS) was defined as time from diagnosis to disease recurrence, death or the date of the last follow-up. Recurrence free survival (RFS) is the time from diagnosis of breast cancer to disease recurrence and was amended to the last follow-up date or the date of death without recurrence. Recurrence events were defined as ipsilateral breast, ipsilateral or contralateral axillary recurrence, and other tissue/organ metastasis. Overall survival was the time from diagnosis till the date of last follow up date or the date of death whether related to the disease or not. Statistical analysis: The analysis was performed using R version 4.2.1. Descriptive analysis was presented in terms of frequency and percentages. Categorical data was illustrated using cross tabulations, and associations were assessed utilizing Chi-Square or Fisher's exact test. Variables that demonstrated significance in the univariate tests were integrated into a regression model for subsequent Cox regression analysis. The significance level was set at p < 0.05. The Kaplan-Meier method was employed to estimate overall survival (OS), Recurrence-free survival (RFS), and event-free survival (EFS) for the two cohorts. Comparisons between the cohorts were conducted using the log-rank test. Results A total of 195 cases of PABC were identified from our hospital’s database. Among these cases, 64 (32.8%) patients were identified as HER2-positive PABC and 64 HER2-positive non-PABC were matched for age at diagnosis, treatment, clinical stage, and pathological response to reach an overall study population of 128. Clinical and Pathological Characteristics The mean age across the total study population was 34 years with no difference between the groups. There was no difference in tumor size (T) (p = 0.9), lymph node involvement (N) (p = 0.23), distant metastasis (M) (p = 0.23), type of breast cancer (p = 0.1), and histopathological treatment response (p = 0.908) between the two groups. Moreover, distribution of hormonal-receptor status (ER and PR) between both groups did not show statistical differences where the hormonal status in the HER2-positive PABC group revealed 81.25% positivity, and 76.56% in the non-pregnant group (p = 0.52). (Table 1) Pain was reported by 21.88% of non-pregnant and 23.44% of pregnant cases. A mass as a symptom was prevalent, noted by 84.38% of non-pregnant and 87.5% of pregnant individuals. Axillary lymph nodes were reported by 15.63% of non-pregnant and 23.44% of pregnant cases. Nipple retraction was experienced by 15.63% of non-pregnant and 12.5% of pregnant cases. There was no significant difference in symptom prevalence between the two groups (p = 0.908). (Table 1) First Treatment Type Among non-pregnant HER2-positive patients, 26.56% received surgery as their initial treatment, while 68.75% underwent neoadjuvant chemotherapy. A smaller proportion, 4.69%, received palliative chemotherapy. In comparison, among pregnant HER2-positive patients, 26.56% had surgery as the first treatment, 62.50% received neoadjuvant chemotherapy, and a slightly larger percentage, 10.94%, received palliative chemotherapy. The p-value of 0.2 suggests no statistically significant difference in the choice of initial treatment between the non-pregnant and pregnant HER2-positive groups. (Table 1) Anti-HER2 (Herceptin) Therapy Concerning the duration of Herceptin therapy, a significant distinction is observed. Among non-pregnant patients, 71.88% completed the recommended 12-month Herceptin regimen, 9.38% received Herceptin for less than a year, and 18.75% did not undertake the therapy. In contrast, pregnant patients exhibited a different pattern, with 45.3% completing the full 12-month regimen, 18.8% receiving Herceptin for a shorter duration, and 35.9% not initiating Herceptin. This disparity is statistically significant, underscored by a p-value of 0.01, indicating the influence of pregnancy on the duration of Herceptin therapy. Additionally, the data addressed the timing of Herceptin initiation from diagnosis, measured in weeks. The mean time to initiate Herceptin was 16.9 weeks for non-pregnant individuals and 23.8 weeks for pregnant patients. The median time to commence Herceptin varied considerably, ranging from 0.57 to 35.05 weeks for non-pregnant individuals and from 3.28 to 125.66 weeks for pregnant individuals. This difference in the timing of Herceptin initiation holds statistical significance, corroborated by a p-value of 0.02. (Table 1) Table (1): Comparison of clinical characteristics, histological, immunohistochemical characteristics, and Treatments received in HER2-positive PABC and HER2 non-PABC groups. Variable Total Non-Pregnant HER2 Positive Pregnant HER2 Positive p Value N (%) 128 64(50%) 64(50%) Age(years) Mean (Std.) 34.06 (4.190) 34.19 (3.995) 33.97 (4.398) 0.72 Median (Min-Max) 34 (25–25) 34(25–45) 33(26–45) Clinical T T0/Tis 7 5.47% 3 4.69% 4 6.25% 0.9 T1 11 8.59% 6 9.38% 5 7.81% T2 49 38.28% 24 37.50% 25 39.06% T3 41 32.03% 20 31.25% 21 32.81% T4 20 15.63% 11 17.19% 9 14.06% Clinical N N0 39 30.47% 19 29.69% 20 31.25% 0.23 N1 58 45.31% 30 46.88% 28 43.75% N2 20 15.63% 7 10.94% 13 20.31% N3 11 8.59% 8 12.50% 3 4.69% Clinical M M0 108 84.38% 56 87.50% 52 81.25% 0.24 M1 20 15.63% 8 12.50% 12 18.75% Pathological Response Complete 26 20.31% 17 26.56% 9 14.06% 0.31 Partial 31 24.22% 15 23.44% 16 25.00% No Response 49 38.28% 21 32.81% 28 43.75% Progression 5 3.91% 2 3.13% 3 4.69% NA 17 13.28% 9 14.06% 8 12.50% Histopathology IDC 121 94.53% 58 90.63% 63 98.44% 0.1 ILC 4 3.13% 4 6.25% 0 0.00% IMC 3 2.34% 2 3.13% 1 1.56% Symptoms Pain 29 22.66% 14 21.88% 15 23.44% 0.908 Mass 110 85.94% 54 84.38% 56 87.50% Axillary LNs 25 19.53% 10 15.63% 15 23.44% Nipple Retraction 18 14.06% 10 15.63% 8 12.50% Other 28 21.88% 13 20.31% 15 23.44% First Treatment Type Surgery 34 26.56% 17 26.56% 17 26.56% 0.22 Neoadjuvant CTX 84 65.63% 44 68.75% 40 62.50% Palliative CTX 10 7.81% 3 4.69% 7 10.94% Hormonal Status Positive 101 78.91% 49 76.56% 52 81.25% 0.52 Negative 27 21.09% 15 23.44% 12 18.75% Anti-HER 2 (Herceptin) Completed planned therapy duration 75 58.59% 46 71.88% 29 45.31% 0.007 Did not complete planned therapy duration 18 14.06% 6 9.38% 12 18.75% Didn’t take 35 27.34% 12 18.75% 23 35.94% Time to initiate Herceptin (week) Mean(± Std.) 20 (± 14.1) 16.9 (± 6.5) 23.8 (± 19.3) 0.02 Median(Min-Max) 18.2 (0.57-125.66) 16.81 (0.57–35.05) 19.52 (3.28-125.66) Survival analysis: The median follow-up duration for the study was 38.84 months (0.95 to 183.3 months). Among the 128 individuals, 32 events were recorded. The median survival was estimated at 122 months. The 10-year survival rate was 54% (95% CI 41% -72%) whereas for the 5-year survival, the rate was 76% (95% CI 67% − 85%). Overall survival There was no statistically significant difference in overall survival between non-pregnant and pregnant individuals. (Fig. 1 a). The 5-year survival rate for HER2-positive non-PABC was 83% (95% CI: 72–95%), indicating a favorable survival outcome during this period. In contrast, the 5-year survival rate for HER2-positive PABC was slightly lower at 68% (95% CI: 55–83%), suggesting a comparatively lower survival rate for this group within the same period. (p = 0.051) (Table 2) HER2-positive non-PABC showed a 10-year survival rate of 49% (95% CI: 25–97%), suggesting that nearly half of the patients survived up to that point. On the other hand, HER2-positive PABC demonstrated a slightly higher 10-year survival rate of 53% (95% CI: 39–72%), indicating a somewhat improved long-term survival compared to the 5-year mark. (p = 0.2) (Table 2). Overall, while HER2-positive PABC initially showed a lower 5-year survival rate compared to HER2-positive non-PABC, the 10-year survival rates are relatively comparable, exhibit potential improvements in survival for HER2-positive PABC over a longer period. Recurrence free survival The Kaplan-meier RFS curve illustrated higher likelihood of recurrences in the HER2-positive PABC group (HR 1.93 (1.07–3.49) (p = 0.029)). (Fig. 1 b). At the 5-year mark, RFS rates were 69% (95% CI: 57–83%) for non-PABC patients and 52% (95% CI: 40–68%) for PABC patients (p = 0.03). This trend persisted at the 10-year mark, with RFS rates of 46% (95% CI: 20–100%) for non-PABC and 40% (95% CI: 25–64%) for PABC (p-value: 0.03). These findings underscore that, in terms of RFS rates, non-PABC patients exhibited a relatively better outcome than those with a history of pregnancy-associated diagnosis. (Table-2) Event free survival The same was also reflected in the EFS Kaplan-meier curve, where pregnant individuals showed a higher chance of events compared to non-pregnant participants (HR 2.00 (1.11–3.60) (p = 0.02). (Fig. 1 c). The event-free survival (EFS) rates at the 5-year mark revealed significant differences, with rates of 69% (95% CI: 57–83%) for non-PABC and 51% (95% CI: 39–67%) for PABC (p = 0.02). Similarly, at the 10-year mark, the differences persisted, displaying EFS rates of 46% (95% CI: 20–100%) for non-PABC and 39% (95% CI: 24–100%) for PABC (p-value: 0.018). These results emphasize that, in terms of event-free survival rates, non-PABC patients demonstrated a comparatively better outcome than those with a history of pregnancy-associated diagnosis. (Table-2). Table (2): OS, RFS and DFS (5 and 10-year survival) rate in HER2-positive PABC and non-PABC HER2-positive non-PABC HER2-positive PABC P value OS 5-year rate (95% CI) 83% (72%, 95%) 68% (55%, 83%) 0.051 10-year rate (95% CI) 49% (25%, 97%) 53% (39%, 72%) 0.2 RFS 5-year rate (95% CI) 69% (57–83%) 52% (40–68%) 0.03 10-year rate (95% CI) 46% (20–100%) 40% (25–64%) 0.03 EFS 5-year rate (95% CI) 69% (57–83%) 51% (39–67%) 0.02 10-year rate (95% CI) 46% (20–100%) 39% (24–100%) 0.018 Subgroup Survival analysis – completion of Anti-HER2 treatment This sub-analysis focused on the completeness of the 12-month anti-HER2 (Herceptin) treatment. There was no significant difference between pregnant individuals who completed the 12-month anti-HER2 treatment and non-pregnant individuals who completed the 12-month anti-HER2 treatment, (HR = 1.89, 95%CI 0.57–6.28, p = 0.3). However, pregnant individuals who did not complete the 12-month anti-HER2 treatment exhibited a worse prognosis compared to the non-pregnant group (HR = 4.94, 95% CI 1.41–17.3, p = 0.012). (Fig. 2 a). Furthermore, considering the entire cohort, a notable distinction in survival curves was observed. Completing the 12-month anti-HER2 treatment resulted in a superior survival curve compared to patient who did not complete the regimen ((HR 4.67 95% CI: 1.93 to 11.3 p = < 0.001). A similar trend was observed for patients who did not initiate any anti-HER2 treatment in terms of prognosis, although it did not reach a significant statistical level ((HR 2.00 (95% CI: 0.86 to 4.66 p = 0.11)) (Fig. 2 b). These findings underscore the importance of completing the full 12-month anti-HER2 treatment regimen in improving outcomes for HER2-positive breast cancer patients in the studied cohort. Subgroup Survival analysis – Pregnancy trimester There was no difference in OS when analyzing across pregnancy trimesters (first, second and third) and time after pregnancy, 5-years survival rates were 100%, 50%, 73%, & 55%, respectively. (p = 0.05) (Fig. 3 ) Multivariate Analysis In the Cox regression model assessing the relationship between specific factors and overall survival, we incorporated significant factors identified in the univariate analysis, namely time to initiate anti-HER2 treatment, and completeness of anti-HER2 treatment. This multivariate analysis provided crucial insights into the role of these factors concerning survival outcomes. First, the timing of initiating anti-HER2 treatment, whether before or after 18 weeks from diagnosis (sample Median), did not exhibit a statistically significant impact on survival (HR = 1.15, 95% CI: [0.40, 3.32], p = 0.8). However, the completeness of anti-HER2 treatment emerged as a significant factor. Patients who partially completed anti-HER2 treatment showed worse outcomes (HR = 3.78, 95% CI: [1.48, 9.64], p = 0.005) compared to those who completed the treatment. These findings emphasize the importance of completing the anti-HER2 treatment for optimal outcomes irrespective of delay in initiating therapy for different patient groups within the HER2 positive cohort. (Table 3) Table (3): Cox_regression model Characteristic HR 1 95% CI 1 p-value Time of anti-HER2 initiation Less than 18weeks — — More than 18weeks 1.15 0.40, 3.32 0.8 Completeness of Anti-HER2 Completed anti-HER2 treatment — — Partially completed anti-HER2 3.78 1.48, 9.64 0.005 HER2 positive groups Non-pregnant — — pregnant 1.06 0.37, 3.00 > 0.9 1 HR = Hazard Ratio, CI = Confidence Interval Discussion Our study conducted a comprehensive comparative prognosis analysis, focusing on the distinct clinical outcomes of HER2-positive Pregnancy-Associated Breast Cancer (PABC) compared to HER2-positive non-PABC. This investigation, involving 128 patients (64 with PABC and 64 non-PABC), aimed to elucidate the influence of pregnancy on the prognosis of HER2-positive breast cancer, an area that remains underexplored. The analysis revealed that patients with HER2-positive PABC exhibited worse recurrence and event free survivals than their non-pregnant counterparts, although this was not reflected on overall survival, which was similar. Analysis from the French CALG (Cancer Associe a La Grossesse) network done by Boudy et al. also expressed similar findings of negative effects on recurrence free survival but not overall survival [ 16 ]. A novel aspect of our study is the examination of the timing of anti-HER2 therapy initiation on overall survival. We observed a significant delay in initiating Herceptin treatment among pregnant patients (23.8 weeks) compared to non-pregnant patients (16.9 weeks). Despite this delay, there was no significant difference in overall survival between the two groups. This suggests that the timing of Herceptin initiation, while delayed in pregnant patients, does not adversely impact overall survival outcomes​​​​ if the regimen was completed. Further analysis highlights the importance of completing the anti-HER2 treatment. Patients who partially completed their treatment showed significantly worse outcomes (HR = 3.78, 95% CI: 1.48–9.64, p = 0.005) compared to those who completed the treatment. This emphasizes the critical need for ensuring treatment adherence in pregnant patients to achieve optimal outcomes​​. Our findings, in line with Sardesai et al.'s study [ 17 ], emphasize the criticality of completing the anti-HER2 treatment without interruption for HER2-positive individuals. The study encompassed data from The Ohio State University collected between January 2005 and December 2015, defining treatment interruption as any delay of or exceeding 2 weeks during Trastuzumab therapy, encompassing permanent discontinuation of the therapy before the intended duration has completed. Notably, 11% of patients had permanent discontinuation of planned Trastuzumab therapy. Those with treatment interruption or discontinuation exhibited significantly worse overall survival outcomes (HR: 4.8, p < 0.001). It is worth noting that delaying anti-HER2 therapy might have an effect on breast cancer prognosis in pregnant women as our cohort expressed decreased event and recurrence free survival, similar to the cohort from the French CALG, as several studies showed increased rates of pathological complete response when received neoadjuvant anti-HER2 therapy [ 5 , 18 ]. Our study results in relation to the effect of the pregnancy term on prognosis also fall in line with the results published by Larouzee et al., which showed that pregnancy itself is prognostic indicator irrelevant of the term of pregnancy [ 19 ]. We acknowledge the limitations of our study, including the relatively modest sample size. A larger-scale investigation is warranted to validate and reinforce these findings and to discern any potential variations in survival outcomes with a more substantial dataset. Secondly, the relatively small sample size, particularly in subgroups, may have restricted the statistical power to detect subtle yet significant differences. Additionally, the study's focus on a specific geographic location may limit the generalizability of our findings to a broader, more diverse population. Conclusion In this study, we conducted an analysis of various factors pertinent to HER2-positive Pregnancy-Associated Breast Cancer (PABC) prognosis, aiming to identify potential determinants of overall survival. While pregnancy did not appear to affect overall survival, a notable outcome from our findings highlights the critical role of completing the anti-HER2 treatment regimen, where incomplete adherence was linked to a detrimental impact on overall survival. This insight is true for pregnant individuals and emphasizes the necessity for tailored treatment strategies for this specific cohort, highlighting the importance of completing anti-HER2 treatment. Interestingly, despite a notable delay in the initiation of anti-HER2 treatment in PABC compared to non-PABC cases, both cohorts exhibited similar prognostic outcomes in terms of overall survival. Further research and collaborative efforts are essential to validate and build upon these findings, advancing the field and optimizing treatment strategies for HER2-positive Pregnancy-Associated Breast Cancer. Abbreviations Abbreviations Description CI Confidence Interval EFS Event Free Survival ER Estrogen Receptor HER2 Human Epidermal Growth Factor Receptor 2 HR Hazards Ratio OS Overall Survival PABC Pregnancy-Associated Breast Cancer PR Progesterone Receptor RFS Recurrence Free Survival Declarations Competing Interests Financial interests: The authors declare they have no financial interests related to this work. Non-financial interests: The authors have no relevant non-financial interests to disclose. Ethics Approval This retrospective chart review study was performed in accordance with the principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of King Hussein Cancer Center (Approval Date: 1/6/2016, No: 16 khcc 28). Consent to Participate Due to the retrospective nature of the study, informed consent from individual participants was not required. All patient data was anonymized to ensure confidentiality. Consent to Publish As this study involves retrospective data and does not include individual data or images that could identify participants, consent for publication was not required. Funding The authors declare that no funds, grants, or other supports were received during the preparation of this manuscript. Author Contribution All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr. Mahmoud Al-Masri, Dr. Basim Aljalabneh, Dr. Rama AlMasri, Dr. Osama Alayyan, Dr. Mohammad Almasri, and Yasmin Safi. The first draft of the manuscript was written by Yasmin Safi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgement We would like to express our sincere appreciation to everyone who helped us to successfully complete this research project. We would like to express our profound thanks to the Institutional Examination Board (IRB) of the King Hussein Cancer Center for their meticulous review and perceptive remarks, which ensured the study's ethical conduct and safeguarded the participants' safety. Data Availability The datasets analyzed during the current study are available upon reasonable request from the corresponding author. Due to privacy concerns associated with patient data, the datasets are not publicly available. References Ministry of Health Non-Communicable Diseases Directorate (2019) Jordan Cancer RegistryCancer Incidence in Jordan Parazzini F, Franchi M, Tavani A et al (2017) Frequency of Pregnancy Related Cancer: A Population Based Linkage Study in Lombardy, Italy. 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Cochrane database Syst Rev 2014:CD006242. https://doi.org/10.1002/14651858.CD006242.pub2 Larouzee E, Allegre L, Boudy AS et al (2021) Predicting the likelihood of recurrence of pregnancy-associated breast cancer: Nomogram based on analysis of the French cancer network: Cancer Associé à La Grossesse. J Gynecol Obstet Hum Reprod 50. https://doi.org/10.1016/j.jogoh.2020.101766 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-4873580","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":347845606,"identity":"2acc073c-8340-4d82-b175-74067d4fa783","order_by":0,"name":"Mahmoud Al-Masri","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYFAC5gYQycPPwwOi2YjRwgjRItlDqhYGgzM8RDpLt/1g64Yff+7JGJ85e/DDDwY+OYJazM4ktt3sbSvmMTvblyzZw8BmTFjLgcS2G7wNCTxm53nMmIF+SWwgqOX8w7abf/4k8Bj3E63lRmLbbR62BB4D3h6itTxsuy3blsAjceaMsWSPATF+OZ987OabPwn2/D05hh9+VBwjHGJowOAYqToYGGpI1zIKRsEoGAXDHgAAycw6YiT9rzsAAAAASUVORK5CYII=","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Al-Masri","suffix":""},{"id":347845607,"identity":"a704a9ed-1272-4989-9a7f-bb1bdd67703e","order_by":1,"name":"Basim Aljalabneh","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Basim","middleName":"","lastName":"Aljalabneh","suffix":""},{"id":347845608,"identity":"ae0482de-81f8-4350-8401-72a19d1ccb86","order_by":2,"name":"Rama AlMasri","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Rama","middleName":"","lastName":"AlMasri","suffix":""},{"id":347845609,"identity":"3391a160-0f36-4be9-b4b3-815860f30013","order_by":3,"name":"Osama Alayyan","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"","lastName":"Alayyan","suffix":""},{"id":347845610,"identity":"24cd7436-c5fd-456f-9f84-bb21d0d4acd6","order_by":4,"name":"Mohammad Almasri","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Almasri","suffix":""},{"id":347845611,"identity":"c45d58b3-73e0-4f1c-bafe-bfbd6ce1876c","order_by":5,"name":"Yasmin Safi","email":"","orcid":"","institution":"King Hussein Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Yasmin","middleName":"","lastName":"Safi","suffix":""}],"badges":[],"createdAt":"2024-08-07 09:32:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4873580/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4873580/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64711681,"identity":"8439df10-b0a2-44af-81b7-7d705cc4486f","added_by":"auto","created_at":"2024-09-18 01:59:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":104402,"visible":true,"origin":"","legend":"\u003cp\u003ea: Overall survival curve and HR for HER2=positive PABC vs. HER2-positive non-PABC. b: Recurrence-free survival curve and HR for HER2=positive PABC vs. HER2-positive non-PABC. c: Event-free survival curve and HR for HER2=positive PABC vs. HER2-positive non-PABC.Top of Form\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4873580/v1/3b2536ef0ff8a1d0b5f66307.jpg"},{"id":64712864,"identity":"53ee15cc-7cb7-458d-a8c1-18ee0a09f53b","added_by":"auto","created_at":"2024-09-18 02:07:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58289,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ea sub-analysis overall survival for anti-Herceptin treatment completeness groups. (a): PABC sub-group, (b): All cohort.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4873580/v1/6b7b846691d4db521b4789e9.jpg"},{"id":64711679,"identity":"101cf7d3-a126-4fb4-8a1e-e5850733e94d","added_by":"auto","created_at":"2024-09-18 01:59:53","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":54282,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eA sub-analysis overall survival for pregnant sub-groups based on trimester.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4873580/v1/08c773a3afe8221a067c2dc6.jpg"},{"id":64930889,"identity":"4e5980d0-ba9b-4667-8db9-5dc46f4ad582","added_by":"auto","created_at":"2024-09-20 13:55:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":934404,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4873580/v1/a7db8a9e-6e61-4868-91ac-c1d19a81b9e7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eComparative Survival Analysis of HER2-Positive Pregnancy-Associated Breast Cancer and Non-Pregnant Cohorts: A matched control study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer remains the most common cancer and the leading cause of cancer-related mortality in Jordan [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Pregnancy related cancer is uncommon, with breast cancer being the most frequently diagnosed with projections of increased incidence due to increased maternal ages worldwide [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHER2-positive breast cancer is recognized for its aggressive nature, constituting a significant proportion of breast cancer cases and necessitates targeted therapies to improve patient outcomes [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. PABC encompasses breast cancer diagnosed during pregnancy or in the first post-partum year, presenting a complex intersection of oncological and obstetric considerations [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Understanding the epidemiological nuances of both HER2-positive breast cancer and pregnancy-associated breast cancer is vital for optimizing prevention, detection, and management strategies tailored to these specific patient populations.\u003c/p\u003e \u003cp\u003eViuff et al showed that PABC patients exhibited decreased survival within the initial two years following diagnosis, yet no significant difference in survival was observed beyond this period [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Similarly, a Swedish study delved into the outcomes of 1,661 women with breast cancer, categorizing them into groups based on time since delivery, where after adjustment for confounding variables, PABC cases showed higher mortality rates in contrast to non-PABC cases, with a noticeable peak approximately two years after diagnosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSurvival rates in HER2-positive breast cancer patients have significantly improved over the past few decades, primarily due to the advent of targeted therapies such as Trastuzumab (Herceptin), a cornerstone in HER2-positive breast cancer treatment, and other anti-HER2 agents [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, concerns regarding its use during pregnancy and potential impact on fetal development have led to clinical hesitations and interruptions or discontinuation of therapy for pregnant patients. These interruptions or modifications in treatment pose critical questions regarding the optimal management and subsequent outcomes for this specific patient demographic [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study presents an investigation into the prognosis and treatment outcomes of HER2-positive PABC compared to non-PABC cohorts. We also aim to study the effect of delaying and interrupting anti-HER2 treatment in pregnant patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population and Design:\u003c/h2\u003e \u003cp\u003eThe study involved a defined population comprising individuals younger than 45 years old who were diagnosed with HER2-positive PABC and then matched with HER2-positive non-PABC of similar age, histopathology, and clinical stage. Data for this study were collected retrospectively from the cancer registry at the King Hussein Cancer Center within the timeframe of April 2006 to January 2021.\u003c/p\u003e \u003cp\u003eNone of the PABC patients received anti-HER2 therapy during pregnancy; instead, initiation of the anti-HER2 treatment was postponed until after delivery and the group was further divided into three subgroups based on the completion of anti-Her2 therapy; patients who received and completed the planned duration of therapy regimen of anti-HER2 (completion of anti-HER2), received and did not complete the regimen (partially completed) and those who did not receive any doses of the anti HER2 treatment regimen (No anti-HER2).\u003c/p\u003e \u003cp\u003eThe primary endpoint for this study was the comparative survival analysis between HER2-positive PABC and HER2-positive non-PABC. Event free survival (EFS) was defined as time from diagnosis to disease recurrence, death or the date of the last follow-up. Recurrence free survival (RFS) is the time from diagnosis of breast cancer to disease recurrence and was amended to the last follow-up date or the date of death without recurrence. Recurrence events were defined as ipsilateral breast, ipsilateral or contralateral axillary recurrence, and other tissue/organ metastasis. Overall survival was the time from diagnosis till the date of last follow up date or the date of death whether related to the disease or not.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eThe analysis was performed using R version 4.2.1. Descriptive analysis was presented in terms of frequency and percentages. Categorical data was illustrated using cross tabulations, and associations were assessed utilizing Chi-Square or Fisher's exact test. Variables that demonstrated significance in the univariate tests were integrated into a regression model for subsequent Cox regression analysis. The significance level was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The Kaplan-Meier method was employed to estimate overall survival (OS), Recurrence-free survival (RFS), and event-free survival (EFS) for the two cohorts. Comparisons between the cohorts were conducted using the log-rank test.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 195 cases of PABC were identified from our hospital\u0026rsquo;s database. Among these cases, 64 (32.8%) patients were identified as HER2-positive PABC and 64 HER2-positive non-PABC were matched for age at diagnosis, treatment, clinical stage, and pathological response to reach an overall study population of 128.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Pathological Characteristics\u003c/h2\u003e \u003cp\u003eThe mean age across the total study population was 34 years with no difference between the groups. There was no difference in tumor size (T) (p\u0026thinsp;=\u0026thinsp;0.9), lymph node involvement (N) (p\u0026thinsp;=\u0026thinsp;0.23), distant metastasis (M) (p\u0026thinsp;=\u0026thinsp;0.23), type of breast cancer (p\u0026thinsp;=\u0026thinsp;0.1), and histopathological treatment response (p\u0026thinsp;=\u0026thinsp;0.908) between the two groups.\u003c/p\u003e \u003cp\u003eMoreover, distribution of hormonal-receptor status (ER and PR) between both groups did not show statistical differences where the hormonal status in the HER2-positive PABC group revealed 81.25% positivity, and 76.56% in the non-pregnant group (p\u0026thinsp;=\u0026thinsp;0.52). (Table\u0026nbsp;1)\u003c/p\u003e \u003cp\u003ePain was reported by 21.88% of non-pregnant and 23.44% of pregnant cases. A mass as a symptom was prevalent, noted by 84.38% of non-pregnant and 87.5% of pregnant individuals. Axillary lymph nodes were reported by 15.63% of non-pregnant and 23.44% of pregnant cases. Nipple retraction was experienced by 15.63% of non-pregnant and 12.5% of pregnant cases. There was no significant difference in symptom prevalence between the two groups (p\u0026thinsp;=\u0026thinsp;0.908). (Table\u0026nbsp;1)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eFirst Treatment Type\u003c/h2\u003e \u003cp\u003eAmong non-pregnant HER2-positive patients, 26.56% received surgery as their initial treatment, while 68.75% underwent neoadjuvant chemotherapy. A smaller proportion, 4.69%, received palliative chemotherapy. In comparison, among pregnant HER2-positive patients, 26.56% had surgery as the first treatment, 62.50% received neoadjuvant chemotherapy, and a slightly larger percentage, 10.94%, received palliative chemotherapy. The p-value of 0.2 suggests no statistically significant difference in the choice of initial treatment between the non-pregnant and pregnant HER2-positive groups. (Table\u0026nbsp;1)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAnti-HER2 (Herceptin) Therapy\u003c/h2\u003e \u003cp\u003eConcerning the duration of Herceptin therapy, a significant distinction is observed. Among non-pregnant patients, 71.88% completed the recommended 12-month Herceptin regimen, 9.38% received Herceptin for less than a year, and 18.75% did not undertake the therapy. In contrast, pregnant patients exhibited a different pattern, with 45.3% completing the full 12-month regimen, 18.8% receiving Herceptin for a shorter duration, and 35.9% not initiating Herceptin. This disparity is statistically significant, underscored by a p-value of 0.01, indicating the influence of pregnancy on the duration of Herceptin therapy.\u003c/p\u003e \u003cp\u003eAdditionally, the data addressed the timing of Herceptin initiation from diagnosis, measured in weeks. The mean time to initiate Herceptin was 16.9 weeks for non-pregnant individuals and 23.8 weeks for pregnant patients. The median time to commence Herceptin varied considerably, ranging from 0.57 to 35.05 weeks for non-pregnant individuals and from 3.28 to 125.66 weeks for pregnant individuals. This difference in the timing of Herceptin initiation holds statistical significance, corroborated by a p-value of 0.02. (Table\u0026nbsp;1)\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;(1): Comparison of clinical characteristics, histological, immunohistochemical characteristics, and Treatments received in HER2-positive PABC and HER2 non-PABC groups.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNon-Pregnant HER2 Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003ePregnant HER2 Positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e64(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e64(50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (Std.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e34.06 (4.190)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e34.19 (3.995)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e33.97 (4.398)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian (Min-Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e34 (25\u0026ndash;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e34(25\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e33(26\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eClinical T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT0/Tis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.47%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.69%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.59%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.81%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.28%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e39.06%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.03%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e32.81%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17.19%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.06%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eClinical N\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.47%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29.69%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e31.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45.31%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46.88%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e43.75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.94%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20.31%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.59%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.69%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eClinical M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e87.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e81.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003ePathological Response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.31%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.56%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.06%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePartial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.22%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.44%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25.00%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.28%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e43.75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProgression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.91%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.13%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.69%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.28%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.06%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.50%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eHistopathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIDC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94.53%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e98.44%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eILC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.13%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIMC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.34%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.13%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.56%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.66%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.88%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.44%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.908\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85.94%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e87.50%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAxillary LNs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.53%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.44%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNipple Retraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.06%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.50%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.88%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.31%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.44%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFirst Treatment Type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.56%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.56%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e26.56%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeoadjuvant CTX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68.75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.50%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePalliative CTX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.69%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.94%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHormonal Status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.91%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.56%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e81.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.09%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.44%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAnti-HER 2 (Herceptin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompleted planned therapy duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.59%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e71.88%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e45.31%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDid not complete planned therapy duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.06%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDidn\u0026rsquo;t take\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.34%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e35.94%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTime to initiate Herceptin\u003c/p\u003e \u003cp\u003e(week)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean(\u0026plusmn;\u0026thinsp;Std.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e20 (\u0026plusmn;\u0026thinsp;14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e16.9 (\u0026plusmn;\u0026thinsp;6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e23.8 (\u0026plusmn;\u0026thinsp;19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian(Min-Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e18.2\u003c/p\u003e \u003cp\u003e(0.57-125.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e16.81\u003c/p\u003e \u003cp\u003e(0.57\u0026ndash;35.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e19.52\u003c/p\u003e \u003cp\u003e(3.28-125.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eSurvival analysis:\u003c/h2\u003e \u003cp\u003eThe median follow-up duration for the study was 38.84 months (0.95 to 183.3 months). Among the 128 individuals, 32 events were recorded. The median survival was estimated at 122 months. The 10-year survival rate was 54% (95% CI 41% -72%) whereas for the 5-year survival, the rate was 76% (95% CI 67% \u0026minus;\u0026thinsp;85%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eOverall survival\u003c/h2\u003e \u003cp\u003eThere was no statistically significant difference in overall survival between non-pregnant and pregnant individuals. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003eThe 5-year survival rate for HER2-positive non-PABC was 83% (95% CI: 72\u0026ndash;95%), indicating a favorable survival outcome during this period. In contrast, the 5-year survival rate for HER2-positive PABC was slightly lower at 68% (95% CI: 55\u0026ndash;83%), suggesting a comparatively lower survival rate for this group within the same period. (p\u0026thinsp;=\u0026thinsp;0.051) (Table\u0026nbsp;2)\u003c/p\u003e \u003cp\u003eHER2-positive non-PABC showed a 10-year survival rate of 49% (95% CI: 25\u0026ndash;97%), suggesting that nearly half of the patients survived up to that point. On the other hand, HER2-positive PABC demonstrated a slightly higher 10-year survival rate of 53% (95% CI: 39\u0026ndash;72%), indicating a somewhat improved long-term survival compared to the 5-year mark. (p\u0026thinsp;=\u0026thinsp;0.2) (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eOverall, while HER2-positive PABC initially showed a lower 5-year survival rate compared to HER2-positive non-PABC, the 10-year survival rates are relatively comparable, exhibit potential improvements in survival for HER2-positive PABC over a longer period.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRecurrence free survival\u003c/h2\u003e \u003cp\u003eThe Kaplan-meier RFS curve illustrated higher likelihood of recurrences in the HER2-positive PABC group (HR 1.93 (1.07\u0026ndash;3.49) (p\u0026thinsp;=\u0026thinsp;0.029)). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003eAt the 5-year mark, RFS rates were 69% (95% CI: 57\u0026ndash;83%) for non-PABC patients and 52% (95% CI: 40\u0026ndash;68%) for PABC patients (p\u0026thinsp;=\u0026thinsp;0.03). This trend persisted at the 10-year mark, with RFS rates of 46% (95% CI: 20\u0026ndash;100%) for non-PABC and 40% (95% CI: 25\u0026ndash;64%) for PABC (p-value: 0.03). These findings underscore that, in terms of RFS rates, non-PABC patients exhibited a relatively better outcome than those with a history of pregnancy-associated diagnosis. (Table-2)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEvent free survival\u003c/h2\u003e \u003cp\u003eThe same was also reflected in the EFS Kaplan-meier curve, where pregnant individuals showed a higher chance of events compared to non-pregnant participants (HR 2.00 (1.11\u0026ndash;3.60) (p\u0026thinsp;=\u0026thinsp;0.02). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003eThe event-free survival (EFS) rates at the 5-year mark revealed significant differences, with rates of 69% (95% CI: 57\u0026ndash;83%) for non-PABC and 51% (95% CI: 39\u0026ndash;67%) for PABC (p\u0026thinsp;=\u0026thinsp;0.02). Similarly, at the 10-year mark, the differences persisted, displaying EFS rates of 46% (95% CI: 20\u0026ndash;100%) for non-PABC and 39% (95% CI: 24\u0026ndash;100%) for PABC (p-value: 0.018). These results emphasize that, in terms of event-free survival rates, non-PABC patients demonstrated a comparatively better outcome than those with a history of pregnancy-associated diagnosis. (Table-2).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(2): OS, RFS and DFS (5 and 10-year survival) rate in HER2-positive PABC and non-PABC\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHER2-positive non-PABC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHER2-positive PABC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-year rate\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83%\u003c/p\u003e \u003cp\u003e(72%, 95%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68%\u003c/p\u003e \u003cp\u003e(55%, 83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10-year rate (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49%\u003c/p\u003e \u003cp\u003e(25%, 97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53%\u003c/p\u003e \u003cp\u003e(39%, 72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-year rate\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69%\u003c/p\u003e \u003cp\u003e(57\u0026ndash;83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52%\u003c/p\u003e \u003cp\u003e(40\u0026ndash;68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10-year rate (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46%\u003c/p\u003e \u003cp\u003e(20\u0026ndash;100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003cp\u003e(25\u0026ndash;64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-year rate\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69%\u003c/p\u003e \u003cp\u003e(57\u0026ndash;83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51%\u003c/p\u003e \u003cp\u003e(39\u0026ndash;67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10-year rate (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46%\u003c/p\u003e \u003cp\u003e(20\u0026ndash;100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39%\u003c/p\u003e \u003cp\u003e(24\u0026ndash;100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup Survival analysis \u0026ndash; completion of Anti-HER2 treatment\u003c/h2\u003e \u003cp\u003e This sub-analysis focused on the completeness of the 12-month anti-HER2 (Herceptin) treatment. There was no significant difference between pregnant individuals who completed the 12-month anti-HER2 treatment and non-pregnant individuals who completed the 12-month anti-HER2 treatment, (HR\u0026thinsp;=\u0026thinsp;1.89, 95%CI 0.57\u0026ndash;6.28, p\u0026thinsp;=\u0026thinsp;0.3).\u003c/p\u003e \u003cp\u003eHowever, pregnant individuals who did not complete the 12-month anti-HER2 treatment exhibited a worse prognosis compared to the non-pregnant group (HR\u0026thinsp;=\u0026thinsp;4.94, 95% CI 1.41\u0026ndash;17.3, p\u0026thinsp;=\u0026thinsp;0.012). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003eFurthermore, considering the entire cohort, a notable distinction in survival curves was observed. Completing the 12-month anti-HER2 treatment resulted in a superior survival curve compared to patient who did not complete the regimen ((HR 4.67 95% CI: 1.93 to 11.3 p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A similar trend was observed for patients who did not initiate any anti-HER2 treatment in terms of prognosis, although it did not reach a significant statistical level ((HR 2.00 (95% CI: 0.86 to 4.66 p\u0026thinsp;=\u0026thinsp;0.11)) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). These findings underscore the importance of completing the full 12-month anti-HER2 treatment regimen in improving outcomes for HER2-positive breast cancer patients in the studied cohort.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup Survival analysis \u0026ndash; Pregnancy trimester\u003c/h2\u003e \u003cp\u003eThere was no difference in OS when analyzing across pregnancy trimesters (first, second and third) and time after pregnancy, 5-years survival rates were 100%, 50%, 73%, \u0026amp; 55%, respectively. (p\u0026thinsp;=\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eMultivariate Analysis\u003c/h2\u003e \u003cp\u003eIn the Cox regression model assessing the relationship between specific factors and overall survival, we incorporated significant factors identified in the univariate analysis, namely time to initiate anti-HER2 treatment, and completeness of anti-HER2 treatment. This multivariate analysis provided crucial insights into the role of these factors concerning survival outcomes. First, the timing of initiating anti-HER2 treatment, whether before or after 18 weeks from diagnosis (sample Median), did not exhibit a statistically significant impact on survival (HR\u0026thinsp;=\u0026thinsp;1.15, 95% CI: [0.40, 3.32], p\u0026thinsp;=\u0026thinsp;0.8). However, the completeness of anti-HER2 treatment emerged as a significant factor. Patients who partially completed anti-HER2 treatment showed worse outcomes (HR\u0026thinsp;=\u0026thinsp;3.78, 95% CI: [1.48, 9.64], p\u0026thinsp;=\u0026thinsp;0.005) compared to those who completed the treatment. These findings emphasize the importance of completing the anti-HER2 treatment for optimal outcomes irrespective of delay in initiating therapy for different patient groups within the HER2 positive cohort. (Table\u0026nbsp;3)\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;(3): Cox_regression model\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime of anti-HER2 initiation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than 18weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 18weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.40, 3.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCompleteness of Anti-HER2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompleted anti-HER2 treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartially completed anti-HER2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.48, 9.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHER2 positive groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-pregnant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epregnant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.37, 3.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e1\u003c/sup\u003e\u0026nbsp;HR\u0026thinsp;=\u0026thinsp;Hazard Ratio, CI\u0026thinsp;=\u0026thinsp;Confidence Interval\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study conducted a comprehensive comparative prognosis analysis, focusing on the distinct clinical outcomes of HER2-positive Pregnancy-Associated Breast Cancer (PABC) compared to HER2-positive non-PABC. This investigation, involving 128 patients (64 with PABC and 64 non-PABC), aimed to elucidate the influence of pregnancy on the prognosis of HER2-positive breast cancer, an area that remains underexplored. The analysis revealed that patients with HER2-positive PABC exhibited worse recurrence and event free survivals than their non-pregnant counterparts, although this was not reflected on overall survival, which was similar. Analysis from the French CALG (Cancer Associe a La Grossesse) network done by Boudy et al. also expressed similar findings of negative effects on recurrence free survival but not overall survival [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA novel aspect of our study is the examination of the timing of anti-HER2 therapy initiation on overall survival. We observed a significant delay in initiating Herceptin treatment among pregnant patients (23.8 weeks) compared to non-pregnant patients (16.9 weeks). Despite this delay, there was no significant difference in overall survival between the two groups. This suggests that the timing of Herceptin initiation, while delayed in pregnant patients, does not adversely impact overall survival outcomes​​​​ if the regimen was completed.\u003c/p\u003e \u003cp\u003eFurther analysis highlights the importance of completing the anti-HER2 treatment. Patients who partially completed their treatment showed significantly worse outcomes (HR\u0026thinsp;=\u0026thinsp;3.78, 95% CI: 1.48\u0026ndash;9.64, p\u0026thinsp;=\u0026thinsp;0.005) compared to those who completed the treatment. This emphasizes the critical need for ensuring treatment adherence in pregnant patients to achieve optimal outcomes​​. Our findings, in line with Sardesai et al.'s study [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], emphasize the criticality of completing the anti-HER2 treatment without interruption for HER2-positive individuals. The study encompassed data from The Ohio State University collected between January 2005 and December 2015, defining treatment interruption as any delay of or exceeding 2 weeks during Trastuzumab therapy, encompassing permanent discontinuation of the therapy before the intended duration has completed. Notably, 11% of patients had permanent discontinuation of planned Trastuzumab therapy. Those with treatment interruption or discontinuation exhibited significantly worse overall survival outcomes (HR: 4.8, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIt is worth noting that delaying anti-HER2 therapy might have an effect on breast cancer prognosis in pregnant women as our cohort expressed decreased event and recurrence free survival, similar to the cohort from the French CALG, as several studies showed increased rates of pathological complete response when received neoadjuvant anti-HER2 therapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study results in relation to the effect of the pregnancy term on prognosis also fall in line with the results published by Larouzee et al., which showed that pregnancy itself is prognostic indicator irrelevant of the term of pregnancy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe acknowledge the limitations of our study, including the relatively modest sample size. A larger-scale investigation is warranted to validate and reinforce these findings and to discern any potential variations in survival outcomes with a more substantial dataset. Secondly, the relatively small sample size, particularly in subgroups, may have restricted the statistical power to detect subtle yet significant differences. Additionally, the study's focus on a specific geographic location may limit the generalizability of our findings to a broader, more diverse population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, we conducted an analysis of various factors pertinent to HER2-positive Pregnancy-Associated Breast Cancer (PABC) prognosis, aiming to identify potential determinants of overall survival. While pregnancy did not appear to affect overall survival, a notable outcome from our findings highlights the critical role of completing the anti-HER2 treatment regimen, where incomplete adherence was linked to a detrimental impact on overall survival. This insight is true for pregnant individuals and emphasizes the necessity for tailored treatment strategies for this specific cohort, highlighting the importance of completing anti-HER2 treatment. Interestingly, despite a notable delay in the initiation of anti-HER2 treatment in PABC compared to non-PABC cases, both cohorts exhibited similar prognostic outcomes in terms of overall survival. Further research and collaborative efforts are essential to validate and build upon these findings, advancing the field and optimizing treatment strategies for HER2-positive Pregnancy-Associated Breast Cancer.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"456\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eAbbreviations\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eDescription\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eEFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eEvent Free Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eEstrogen Receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eHuman Epidermal Growth Factor Receptor 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eHazards Ratio\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eOverall Survival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003ePABC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003ePregnancy-Associated Breast Cancer\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eProgesterone Receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 36.2768%;\"\u003e\n \u003cp\u003eRFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"58.55263157894737%\" valign=\"top\" style=\"width: 63.7232%;\"\u003e\n \u003cp\u003eRecurrence Free Survival\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eFinancial interests: The authors declare they have no financial interests related to this work. Non-financial interests: The authors have no relevant non-financial interests to disclose.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthics Approval\u003c/h2\u003e \u003cp\u003e This retrospective chart review study was performed in accordance with the principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of King Hussein Cancer Center (Approval Date: 1/6/2016, No: 16 khcc 28).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to Participate\u003c/strong\u003e \u003cp\u003e Due to the retrospective nature of the study, informed consent from individual participants was not required. All patient data was anonymized to ensure confidentiality.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to Publish\u003c/strong\u003e \u003cp\u003eAs this study involves retrospective data and does not include individual data or images that could identify participants, consent for publication was not required.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that no funds, grants, or other supports were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr. Mahmoud Al-Masri, Dr. Basim Aljalabneh, Dr. Rama AlMasri, Dr. Osama Alayyan, Dr. Mohammad Almasri, and Yasmin Safi. The first draft of the manuscript was written by Yasmin Safi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eWe would like to express our sincere appreciation to everyone who helped us to successfully complete this research project. We would like to express our profound thanks to the Institutional Examination Board (IRB) of the King Hussein Cancer Center for their meticulous review and perceptive remarks, which ensured the study's ethical conduct and safeguarded the participants' safety.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e \u003cp\u003eThe datasets analyzed during the current study are available upon reasonable request from the corresponding author. Due to privacy concerns associated with patient data, the datasets are not publicly available.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMinistry of Health Non-Communicable Diseases Directorate (2019) Jordan Cancer RegistryCancer Incidence in Jordan\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParazzini F, Franchi M, Tavani A et al (2017) Frequency of Pregnancy Related Cancer: A Population Based Linkage Study in Lombardy, Italy. 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Cochrane database Syst Rev 2014:CD006242. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/14651858.CD006242.pub2\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD006242.pub2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarouzee E, Allegre L, Boudy AS et al (2021) Predicting the likelihood of recurrence of pregnancy-associated breast cancer: Nomogram based on analysis of the French cancer network: Cancer Associ\u0026eacute; \u0026agrave; La Grossesse. J Gynecol Obstet Hum Reprod 50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jogoh.2020.101766\u003c/span\u003e\u003cspan address=\"10.1016/j.jogoh.2020.101766\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\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, HER2-Positive Breast Cancer, Pregnancy-Associated Breast Cancer, Survival Analysis, Pregnancy and Cancer, Oncological Outcomes","lastPublishedDoi":"10.21203/rs.3.rs-4873580/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4873580/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: This retrospective matched cohort single-center study focused on comparing prognosis between HER2-positive PABC and non-pregnant individuals with HER2-positive breast cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eClinical and histopathological data were collected from a prospectively maintained patient database at King Hussein Cancer Center, a tertiary cancer-care center in Jordan. The study analyzed overall survival (OS), recurrence-free survival (RFS), and event-free survival (EFS) in HER2-positive PABC matched 1:1 to non-pregnant patients with HER2-positive breast cancer (non-PABC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The analysis encompassed 128 patients, divided into two main groups: 64 patients diagnosed with PABC and 64 patients classified as non-PABC cases. Although there was not a statistically significant difference in OS between non-pregnant and pregnant individuals (p=0.12), it was notable that pregnant individuals experienced a significant delay in the initiation of anti-HER2 treatment (23.8± 19.3 weeks, p= 0.02). Additionally, there was a higher risk of recurrence or events in pregnant individuals, emphasizing the potential impact of pregnancy on these survival outcomes (HR=1.93, p=0.029 and HR=2.00, p=0.02, respectively). Furthermore, PABC individuals who completed the 12-months of anti-HER2 treatment were comparable to non-PABC individuals who completed the same treatment (p=0.3), while incomplete treatment significantly affected survival outcomes (HR=4.94, 95% CI: 1.41 to 17.3, p=0.012).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Despite a notable delay in the initiation of anti-HER2 treatment in PABC patients compared to non-PABC cases, both cohorts exhibited similar prognostic outcomes in terms of overall survival when anti-HER2 treatment has been completed. This discovery emphasizes the importance of promptly initiating and completing anti-HER2 treatment in pregnant individuals to optimize prognosis.\u003c/p\u003e","manuscriptTitle":"Comparative Survival Analysis of HER2-Positive Pregnancy-Associated Breast Cancer and Non-Pregnant Cohorts: A matched control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-18 01:59:49","doi":"10.21203/rs.3.rs-4873580/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":"d83ee474-1713-4c51-aea5-48d449ab8793","owner":[],"postedDate":"September 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-23T09:52:51+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-18 01:59:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4873580","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4873580","identity":"rs-4873580","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}