Impact of Timing of Diagnosis and Breastfeeding on Postpartum Breast Cancer Outcomes

Impact of Timing of Diagnosis and Breastfeeding on Postpartum Breast Cancer Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Timing of Diagnosis and Breastfeeding on Postpartum Breast Cancer Outcomes Daniella Klebaner, Natalie Park, Kimberly Stone, Fauzia Riaz, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6523923/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jul, 2025 Read the published version in Breast Cancer Research and Treatment → Version 1 posted 8 You are reading this latest preprint version Abstract Purpose Postpartum breast cancers (PPBC) have a worse prognosis than other breast cancers, but the impact of timing postpartum (PP) and concurrent breastfeeding (BF) remains unclear. Methods We analyzed 161 PPBC patients diagnosed from 2002–2014, hypothesizing that diagnosis < 2 years PP (vs 2–5 years) and concurrent BF (vs not BF) at diagnosis would be associated with inferior outcomes. We compared 2-year PP patients (N = 60) and 2–5 year PP patients (N = 101), and subsequently, patients who were (n = 36) and were not (n = 24) BF at diagnosis among the 2-year PP group with respect to diagnostic patterns and survival. Differences were evaluated using chi-square tests. Kaplan-Meier analysis assessed overall survival (OS) and distant disease-free survival (DDFS). Results Median follow-up was 54 months. Patients in the 2-year PP group were more likely to be BF at diagnosis (60% vs 7%, p < .001), diagnosed at a higher clinical T-stage (20% vs 50% T1, p < .001) and N-stage (37% vs 61% N0, p = .01), had worse 5-year OS (79% vs 97%, p < .001), and DDFS (74% vs 93%, p = .003) compared to 2–5 year PP patients. Among 2-year PP patients, patients BF at diagnosis were more likely to be diagnosed with mastitis preceding diagnosis (31% vs 4%, p = .03), more often had their symptoms attributed to lactational change (58% vs 4%), had significantly worse 5-year DDFS (62% vs 91%, p = .032), and trended toward worse OS (74% vs 86%, p = .08) compared to those not BF. Conclusions Our findings suggest that early PPBC and BF at diagnosis are associated with poor outcomes and diagnostic delay. Figures Figure 1 Figure 2 Figure 3 Introduction Breast cancer occurring in the first five years following childbirth represents approximately 30% of breast cancer (BC) cases among women under 45 years of age, and portends poor outcomes compared to other breast cancers 1–7 . Recent efforts have been made to redefine the term “pregnancy-associated breast cancer” (PABC), which has historically referred to cancers diagnosed during pregnancy up through the first year postpartum. Postpartum breast cancer (PPBC) is a distinct biological entity from those cancers diagnosed during pregnancy, and has a worse prognosis 6 . Patients diagnosed with breast cancer in the first five years postpartum have worse outcomes compared to nulliparous patients with young-onset breast cancer, with one study demonstrating more than a 30% decrease in five-year overall survival, and double the five-year recurrence rate 7–10 . Furthermore, PPBC is associated with up to a threefold increase in metastasis and death related to BC 1 . However, the implications of timing of diagnosis during the postpartum period are unknown, though recent childbirth may be an adverse risk factor compared to birth preceding diagnosis by more than five years 11 . The increased mortality observed with PPBC may be partially biological in nature due to physiologic changes such as mammary gland involution leading to involution-induced pro-lymphangiogenic processes, which has been theorized to increase the metastatic potential of cancer cells 3,12,13 . This is a distinct biological process limited to the transition from a lactational to a non-lactational state, which is unique to the postpartum period. Additionally, the demands of the early postpartum period are often a barrier to seeking timely medical evaluation, and early cancer symptoms are often mistaken for post-partum physiologic breast changes, such as engorgement, nipple discharge, clogged milk ducts, and mastitis, resulting in diagnostic delays 14,15 . Though breastfeeding is protective against breast cancer long-term, its association with prognosis among patients with PPBC is not well understood 16 . We conducted a retrospective analysis of patients diagnosed with PPBC within 5 years after a live birth. We hypothesized that patients diagnosed earlier postpartum, and those breastfeeding at diagnosis, would have inferior outcomes compared to patients diagnosed later postpartum or not breastfeeding at diagnosis. Methods Using International Classification of Diseases Ninth and Tenth Revision (ICD-9 and ICD-10) codes, we identified 161 patients diagnosed with invasive breast cancer at Stanford Cancer Institute within the five years following a documented live birth between 2002 and 2024. We collected information on age, race/ethnicity, clinical staging at diagnosis, grade, hormone receptor status, Human Epidermal Growth Factor Receptor 2 (HER2) gene amplification, receipt of neoadjuvant chemotherapy (NAC) and surgery, pathologic staging, development of metastasis, and survival from the medical record. Patient charts were manually reviewed to identify breastfeeding status – whether they breastfed at any point during the postpartum period, whether they were breastfeeding at the time of breast cancer diagnosis, any diagnosis of mastitis in the six months preceding breast cancer diagnosis, or whether presenting symptoms of breast cancer were initially attributed to breastfeeding or lactational change by either the patient or a provider. We conducted analyses on two cohorts (Fig. 1 ). In Analysis 1, we sought to assess the effect of time postpartum on diagnostic patterns and outcomes by comparing patients diagnosed within 2 years postpartum (2-year PP, N = 60) and those diagnosed between two and five years postpartum (2–5 year PP, N = 101) among the entire cohort (N = 161). In Analysis 2, we sought to isolate the effect of breastfeeding at diagnosis on diagnostic patterns and outcomes by comparing patients who were (n = 36) and were not (n = 24) breastfeeding at diagnosis solely among the 2-year PP group (N = 60). For both analyses, demographics, clinicopathologic characteristics at diagnosis and breastfeeding details were compared between subgroups using chi-square tests for categorical variables, Fisher’s exact test in cases of small group size, and Mann-Whitney tests for continuous variables. We examined and compared response patterns and rate of pathologic complete response (pCR) among patients who received NAC. Differences in overall survival (OS) and distant disease-free survival (DDFS) between groups were assessed using Kaplan-Meier analysis and Log-Rank tests. Results Analysis 1 Between 2002 and 2024, 60 2-year PP patients and 101 2–5 year PP patients were identified (Table 1 ). The 2-year PP group was younger (median age 37.4 vs 39.6 years, p < .001) and more likely to be breastfeeding (60% vs 7%, p < .001) at the time of diagnosis, though over 90% of patients in both groups had breastfed at some point during the postpartum period. There was not a notable difference in race between groups, and a slightly lower prevalence of Hispanic ethnicity in the 2-year PP group (5 vs 14%, p = .14). Patients in the 2-year PP group were diagnosed at a higher clinical T-stage, with fewer having T1 tumors at diagnosis (20% vs 50%), and more having T3-4 tumors (36% vs 17%) compared to 2–5 year PP patients (p < .001). Patients who were 2-year PP were less likely to be node-negative (37% vs 61%), and had a higher clinical N-stage (29% vs 11% cN2-3) compared to the 2–5 year PP group (p = .01). There was a trend toward increased metastasis (12% vs 3%, p = .06), but no difference in Grade 3 disease (65% vs 55%, p = .21) at diagnosis for 2-year PP compared to 2–5 year PP patients. Estrogen and progesterone receptor positivity and triple negative disease did not differ significantly between groups, but HER2 + disease was more common among 2-year PP in comparison to 2–5 year PP patients (36% vs 17%, p = .012). Symptoms of breast cancer were attributed to breastfeeding or lactational change in 37% of < 2-year PP patients and 9% of 2–5 year PP patients (p < .001). Among the 72 patients who received NAC, there was not a significant difference in the proportion of patients who had pCR between < 2 year and 2–5 year PP patients (40% for 2-year PP vs 30% for 2–5 year PP, p = 0.54; Table 2 ). Median follow-up was 54 months. The 2-year PP group had significantly worse OS (5-year OS 79% [95% CI 67–93] vs 97% [95% CI 93–100], p < .001) and DDFS (5-year DDFS 74% [95% CI 60–90] vs 93% [95% CI 87–99], p = .003) compared to 2–5 year PP patients (Fig. 2 A-B). Analysis 2 Among 2-year PP patients, breastfeeding patients and non-breastfeeding patients were of similar race, ethnicity, and age (Table 1 ). There was no difference in clinical T stage at diagnosis by breastfeeding status, but breastfeeding at diagnosis showed a trend toward a lower likelihood of node-negative disease and higher clinical N-stage (71% vs 50% cN0, 37% vs 17% cN2-3, p = .17) and metastasis at diagnosis (17% vs 4%, p = .29). There was a similar prevalence of Grade 3 disease between breastfeeding and non-breastfeeding patients (67% vs 63%, p = 0.25). Estrogen and progesterone positivity were similar between groups, but HER2 positivity was numerically more common in breastfeeding patients, though this was not statistically significant (44% vs 22%, p = .13). Breastfeeding patients were significantly more likely to have a diagnosis of mastitis in the six months preceding cancer diagnosis (31% vs 4%, p = .03) and to have their breast cancer symptoms initially attributed to breastfeeding or lactational change (58% vs 4%, p < .001). There was no difference in months postpartum at diagnosis between breastfeeding and non-breastfeeding patients (median 11.8 months vs 13.5 months, p = .7). There was no difference in pCR rate between breastfeeding and non-breastfeeding patients (37% vs 46%, p = 0.94) among the 31 < 2-year PP patients treated with NAC (Table 2 ). There was a trend toward worse OS (5-year OS 74% [95% CI 59–93] vs 86% [95% CI 70–100], p = .08), and significantly worse DDFS (5-year DDFS 62% [95% CI 45–86] vs 91% [95% CI 75–100], p = .032) for those breastfeeding vs not breastfeeding at diagnosis (Fig. 2 C-D). Patients in the 2-year PP group who were not breastfeeding appeared to have similar OS and DDFS to patients in the 2–5 year PP group. None of the 7 patients in the 2–5 year PP group who were breastfeeding at diagnosis developed distant disease or metastasis during follow-up (Fig. 3 A-B). Of these 7 patients, 6 had ER+/PR+/HER2- disease, and one had ER-/PR-/HER2 + disease. Table 1 Clinicopathologic characteristics and lactation-related factors by years postpartum and concurrent breastfeeding status at the time of PPBC diagnosis Years postpartum at diagnosis (Analysis 1) Breastfeeding status at diagnosis among 2-year PP patients (Analysis 2) < 2 years 2 to 5 years p 1 Yes No p 1 n 60 101 36 24 Breastfeeding at diagnosis, n (%) 36 (60) 7 (6.9) < 0.001 Age at diagnosis, median [IQR 2 ] 37.4 [34.6, 40] 39.6 [36.7, 42] < 0.001 37.6 [34.4, 40] 36.5 [34.7, 39.9] 0.78 Race, n (%) 0.701 0.99 White 28 (47) 46 (46) 17 (47) 11 (46) Black/African American 0 (0) 2 (2) 0 (0) 0 (0) Asian 20 (33) 35 (35) 12 (33) 8 (33) Other 12 (20) 17 (17) 7 (19) 5 (21) Hispanic ethnicity, n (%) 3 (5.3) 14 (14) 0.14 2 (5.7) 1 (4.5) 1.0 cTstage, n (%) < 0.001 0.51 T0 3 ( 5.1) 1 ( 1.0) 2 ( 5.7) 1 (4.5) T1 12 (20) 49 (50) 6 ( 17) 6 (25) T2 23 (39) 32 (32) 13 ( 37) 10 (42) T3 17 (29) 17 (17) 10 ( 29) 7 (29) T4 4 ( 6.8) 0 (0.0) 4 ( 11) 0 ( 0.0) cNstage (%) 0.01 0.17 N0 22 (37) 61 (60) 10 ( 29) 12 (50) N1 20 (34) 28 (28) 12 ( 34) 8 (33) N2 9 (15) 5 (5.0) 8 ( 23) 1 ( 4.2) N3 8 (14) 6 (6.0) 5 ( 14) 3 (13) Metastasis at diagnosis (%) 7 (12) 3 (3.0) 0.061 6 ( 17) 1 ( 4.2) 0.29 Grade (%) 0.21 0.25 1 3 ( 5.0) 13 (13) 3 ( 8.3) 0 ( 0.0) 2 18 (30) 33 (33) 9 ( 25) 9 (38) 3 39 (65) 55 (55) 24 ( 67) 15 (63) ER + 3 40 (68) 81 (80) 0.12 23 ( 64) 17 (74) 0.6 PR + 4 33 (56) 72 (71) 0.072 20 ( 56) 13 (57) 1.0 HER2 + 5 21 (36) 17 (17) 0.012 16 ( 44) 5 (22) 0.13 TNBC 6 10 (17) 14 (14) 0.77 6 ( 17) 4 (17) 1.0 Received neoadjuvant chemotherapy 31 (55) 41 (41) 0.13 20 ( 59) 11 (50) 0.71 Breastfed at any time postpartum 56 (93) 99 (99) 0.13 36 (100) 20 (83) 0.045 Symptoms attributed to lactational change or breastfeeding 22 (37) 9 ( 8.9) < 0.001 21 ( 58) 1 ( 4.2) < 0.001 Diagnosis of mastitis in 6 months preceding PPBC diagnosis 12 (20) 2 ( 2.0) < 0.001 11 ( 31) 1 ( 4.2) 0.03 Estimated using chi-square test for categorical variables and Kruskal-Wallis test for continuous variables Interquartile range Estrogen receptor Progesterone receptor Human Epidermal Growth Factor Receptor 2 Triple-Negative Breast Cancer Table 2 Pathologic staging at surgery among patients treated with neoadjuvant chemotherapy by years postpartum and concurrent breastfeeding status at the time of PPBC diagnosis Years Postpartum at diagnosis (Analysis 1) Breastfeeding status at diagnosis among 2-year PP patients (Analysis 2) < 2 years 2 to 5 years p 2 Yes No p 2 n 30 40 19 11 Overall pCR 1 (ypT0N0) 12 (40) 12 (30) 0.54 7 (37) 5 (46) 0.94 Response by nodal status cN+ 25 28 17 8 ypT + N+ 9 (36) 14 (50) 6 (35) 3 (38) ypT0N+ 2 (8) 1 (3.6) 1 (5.9) 1 (13) ypT + N0 7 (28) 4 (14) 5 (29) 2 (25) pCR (ypT0N0) 7 (28) 9 (32) 5 (29) 2 (25) cN0 5 12 2 3 ypT + N+ 0 (0) 2 (17) 0 (0) 0 (0) ypT0N+ 0 (0) 0 (0) 0 (0) 0 (0) ypT + N0 0 (0) 7 (58) 0 (0) 0 (0) pCR (ypT0N0) 5 (100) 3 (25) 2 (100) 3 (100) 1. Pathologic complete response 2. Estimated using chi-square test Discussion To our knowledge, this is the first report that evaluates the role of timing of PPBC diagnosis with breastfeeding status. We found that PPBC diagnosed in the first two years postpartum is associated with worse survival compared to cancers diagnosed 2–5 year PP. Moreover, patients who were breastfeeding at diagnosis in our study trended towards a worse prognosis compared to those who were not breastfeeding in the first two years postpartum. Notably, we found that there was no difference in overall pCR rates among patients who received NAC, or prevalence of high-grade disease at diagnosis, based on timing of PP diagnosis or breastfeeding status. Importantly, given the findings of later stage at diagnosis for patients diagnosed earlier postpartum and those breastfeeding at diagnosis, this suggests that the disparity in survival is likely driven by delayed diagnosis rather than an inherently inferior response to treatment. Previous case series have reported delayed breast cancer diagnosis due to changes associated with breastfeeding or lactation. In our study, nearly 60% of breastfeeding patients experienced a delayed diagnosis, compared to only 4% of non-breastfeeding patients 14,15,17,18 . The unique challenges of the early postpartum years, which may lead to delays in seeking medical care, coupled with the frequent misattribution of breast cancer symptoms to lactation, create a particularly vulnerable period for missed diagnoses. One study found that among pregnant women, symptoms were often interpreted as pregnancy-related by both patients and healthcare providers 19 . In addition, breast cancers in pre-menopausal patients are often self-palpated rather than detected on screening, and a woman finding her own mass has been associated with inappropriate reassurance that a malignant lump was benign 20 . Furthermore, breast cancer screening is often delayed for eligible lactating patients to cessation of breastfeeding due to concern for inaccurate results, despite national guidelines and the aggressiveness of cancers diagnosed during this period 21–23 . It is unclear whether concurrent breastfeeding has biological implications for breast cancer; a recent large pooled analysis found that parous women had a higher risk of TNBC right after their last birth, and a history of breastfeeding was associated with a lower risk of TNBC, as has been shown in other studies 24–26 . Interestingly, our study found that among patients diagnosed with PPBC, HER2 + disease was more common among patients diagnosed earlier compared to later postpartum, and among breastfeeding compared to non-breastfeeding patients, but the etiology behind this is unknown. The theory behind increased metastatic potential during the postpartum period is mammary gland involution, which can mimic a wound healing state and contribute to a tumorigenic microenvironment 13,27 . One experiment comparing nulliparous to immediate post-weaning mice found increased tumor number, burden, and higher Ki-67 index in the post-weaning group 13 . While this explains the general observation of poor outcomes in PPBC, as well as the comparatively poorer survival in patients diagnosed in the first two years postpartum in our study as this often coincides with the weaning period, it does not explain the worse outcomes seen in breastfeeding patients, who would be expected to harbor a less tumorigenic microenvironment. As the “weaning” period is gradual, there is likely some degree of mammary gland involution even early postpartum when milk supply first regulates, and later when breastmilk no longer is the sole source of nutrition for infants. However, altogether, the longer survival observed among non-breastfeeding patients, as well as earlier stage at presentation suggests that a disparity in prompt diagnosis may be driving the different outcomes rather than an inherent biological mechanism. Limitations of our study include a relatively small, single-institution cohort, which limits both the statistical power of our analyses and the generalizability of our findings to broader populations. Still, our findings underscore the association between diagnostic timing and concurrent breastfeeding status on PPBC outcomes, suggesting that awareness of symptoms and risks among patients and healthcare providers may enhance early detection and ultimately improve overall survival. Further, large-scale, multi-institutional studies are warranted to validate these findings and inform evidence-based guidelines for postpartum patients. Declarations Funding: None Competing Interests: KS has received research funding from Lumicell. The remaining authors have no additional disclosures. Data availability: The datasets generated during the current study are not publicly available due to patient confidentiality, but are available from the corresponding author on reasonable request. Author Contributions: DK: Conceptualization, Methodology, Formal Analysis, Investigation, Data Curation, Writing – Original Draft, Writing – Review and Editing, Visualization. NP: Investigation, Data Curation, Writing – Original Draft, Writing – Review and Editing, Project administration. KS: Resources, Writing – Review and Editing. FR: Resources, Writing – Review and Editing. SC: Writing – Review and Editing. MT: Resources. CM: Resources, Writing – Review and Editing, Supervision. KH: Resources, Writing – Review and Editing, Supervision Ethics approval: This was an observational studied and approved by our Institutional Review Board, Protocol 35536. References Callihan EB, Gao D, Jindal S, et al. Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer. Breast Cancer Res Treat . 2013;138(2):549–559. doi:10.1007/s10549-013-2437-x Shao C, Yu Z, Xiao J, et al. 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Cite Share Download PDF Status: Published Journal Publication published 30 Jul, 2025 Read the published version in Breast Cancer Research and Treatment → Version 1 posted Editorial decision: Revision requested 04 Jun, 2025 Reviews received at journal 26 May, 2025 Reviewers agreed at journal 12 May, 2025 Reviewers agreed at journal 08 May, 2025 Reviewers invited by journal 07 May, 2025 Editor assigned by journal 26 Apr, 2025 Submission checks completed at journal 26 Apr, 2025 First submitted to journal 24 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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-6523923","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":455602388,"identity":"ead8c8ba-d9af-4d56-88d4-c81ffc3d7e1c","order_by":0,"name":"Daniella Klebaner","email":"","orcid":"","institution":"Stanford Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Daniella","middleName":"","lastName":"Klebaner","suffix":""},{"id":455602389,"identity":"f3a92c72-d680-4330-bd7e-891f94e6a80f","order_by":1,"name":"Natalie Park","email":"","orcid":"","institution":"Stanford Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Natalie","middleName":"","lastName":"Park","suffix":""},{"id":455602390,"identity":"76a30cc3-13d5-4234-ba3a-68d0f5f5d64f","order_by":2,"name":"Kimberly Stone","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kimberly","middleName":"","lastName":"Stone","suffix":""},{"id":455602391,"identity":"81507bef-37dc-4b77-9706-3b1732d8f2b3","order_by":3,"name":"Fauzia Riaz","email":"","orcid":"","institution":"Stanford Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Fauzia","middleName":"","lastName":"Riaz","suffix":""},{"id":455602392,"identity":"5a98c951-e1c5-4882-98cf-6dd0db37fa02","order_by":4,"name":"Susan Crowe","email":"","orcid":"","institution":"Stanford University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Crowe","suffix":""},{"id":455602393,"identity":"a128c54e-c4fc-43df-94b3-5c528944c54c","order_by":5,"name":"Melinda Telli","email":"","orcid":"","institution":"Stanford Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Melinda","middleName":"","lastName":"Telli","suffix":""},{"id":455602394,"identity":"f87921f2-94f6-48cd-b131-c8e5b455ee46","order_by":6,"name":"Carol Marquez","email":"","orcid":"","institution":"Stanford Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Carol","middleName":"","lastName":"Marquez","suffix":""},{"id":455602395,"identity":"ce4222a0-eaa2-4e19-9300-0f28500f52c9","order_by":7,"name":"Kathleen Horst","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYBACCSBmZqgAMRkfMDCwAekDBLUwA+EZkFZmAxK0MLaRokWy/fzBx4Xz6ur4ZzczPq4oY5Dju5GAX4s0TzKz8cxthyUk7hxmNjxzjsFYkpAWOYZkNmnebQckGG7kH5NsbGNI3EBQC/9j9t+8c+ok5G8ks4G01BPUIi2RzMbM28AsYQDVkmBASIvkjMfG0jzHDktuvJHMbNhwTsJw5pkH+LVInE98+Jmnpo5f7kYy48OGMht5vuMEbMEwgjTlo2AUjIJRMAqwAwAp2z+BtqPljQAAAABJRU5ErkJggg==","orcid":"","institution":"Stanford Cancer Institute","correspondingAuthor":true,"prefix":"","firstName":"Kathleen","middleName":"","lastName":"Horst","suffix":""}],"badges":[],"createdAt":"2025-04-24 23:08:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6523923/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6523923/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10549-025-07796-2","type":"published","date":"2025-07-30T16:12:55+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82758722,"identity":"7db96872-cd0f-41a7-9ce4-ea94097773ac","added_by":"auto","created_at":"2025-05-15 02:23:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":7242,"visible":true,"origin":"","legend":"\u003cp\u003eStudy cohorts used for Analysis 1 and 2. Analysis 1 compared patients who were diagnosed within two years postpartum (2-year PP) and two to five years postpartum (2-5 year PP). Analysis 2 compared patients who were and were not breastfeeding at diagnosis among 2-year PP patients.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6523923/v1/3d08b29e3b9e5e5cb07665b3.png"},{"id":82758689,"identity":"840e220d-b9c9-40b6-9215-1770fba7ed84","added_by":"auto","created_at":"2025-05-15 02:23:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":22938,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves depicting A) Overall survival by years postpartum at diagnosis (Analysis 1), B) Distant disease-free survival by years postpartum at diagnosis (Analysis 1), C) Limited to 2-year PP patients: overall survival by breastfeeding status at diagnosis (Yes/No) (Analysis 2), D) Limited to 2-year PP patients: distant disease-free survival by breastfeeding status at diagnosis (Yes/No) (Analysis 2)\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6523923/v1/cb8fcfc3481a7f1d1e498d00.png"},{"id":82758701,"identity":"75240234-9db0-486f-9f7e-e26f0629d2f5","added_by":"auto","created_at":"2025-05-15 02:23:22","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":264969,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves depicting A) Overall survival and b) Distant disease-free survival by years postpartum and breastfeeding status at diagnosis (Yes/No)\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6523923/v1/9d1c1947369c7bcef60378b0.jpeg"},{"id":88268149,"identity":"d0a2441b-898b-4462-9d43-7f0ff9664bf6","added_by":"auto","created_at":"2025-08-04 16:49:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1014774,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6523923/v1/4ddc2bdb-d287-4f30-9db1-40ac734a308f.pdf"}],"financialInterests":"Competing interest reported. KS has received research funding from Lumicell. The remaining authors have no additional disclosures.","formattedTitle":"Impact of Timing of Diagnosis and Breastfeeding on Postpartum Breast Cancer Outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer occurring in the first five years following childbirth represents approximately 30% of breast cancer (BC) cases among women under 45 years of age, and portends poor outcomes compared to other breast cancers\u003csup\u003e1\u0026ndash;7\u003c/sup\u003e. Recent efforts have been made to redefine the term \u0026ldquo;pregnancy-associated breast cancer\u0026rdquo; (PABC), which has historically referred to cancers diagnosed during pregnancy up through the first year postpartum. Postpartum breast cancer (PPBC) is a distinct biological entity from those cancers diagnosed during pregnancy, and has a worse prognosis\u003csup\u003e6\u003c/sup\u003e. Patients diagnosed with breast cancer in the first five years postpartum have worse outcomes compared to nulliparous patients with young-onset breast cancer, with one study demonstrating more than a 30% decrease in five-year overall survival, and double the five-year recurrence rate\u003csup\u003e7\u0026ndash;10\u003c/sup\u003e. Furthermore, PPBC is associated with up to a threefold increase in metastasis and death related to BC\u003csup\u003e1\u003c/sup\u003e. However, the implications of timing of diagnosis during the postpartum period are unknown, though recent childbirth may be an adverse risk factor compared to birth preceding diagnosis by more than five years\u003csup\u003e11\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe increased mortality observed with PPBC may be partially biological in nature due to physiologic changes such as mammary gland involution leading to involution-induced pro-lymphangiogenic processes, which has been theorized to increase the metastatic potential of cancer cells\u003csup\u003e3,12,13\u003c/sup\u003e. This is a distinct biological process limited to the transition from a lactational to a non-lactational state, which is unique to the postpartum period. Additionally, the demands of the early postpartum period are often a barrier to seeking timely medical evaluation, and early cancer symptoms are often mistaken for post-partum physiologic breast changes, such as engorgement, nipple discharge, clogged milk ducts, and mastitis, resulting in diagnostic delays\u003csup\u003e14,15\u003c/sup\u003e. Though breastfeeding is protective against breast cancer long-term, its association with prognosis among patients with PPBC is not well understood\u003csup\u003e16\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWe conducted a retrospective analysis of patients diagnosed with PPBC within 5 years after a live birth. We hypothesized that patients diagnosed earlier postpartum, and those breastfeeding at diagnosis, would have inferior outcomes compared to patients diagnosed later postpartum or not breastfeeding at diagnosis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eUsing International Classification of Diseases Ninth and Tenth Revision (ICD-9 and ICD-10) codes, we identified 161 patients diagnosed with invasive breast cancer at Stanford Cancer Institute within the five years following a documented live birth between 2002 and 2024. We collected information on age, race/ethnicity, clinical staging at diagnosis, grade, hormone receptor status, Human Epidermal Growth Factor Receptor 2 (HER2) gene amplification, receipt of neoadjuvant chemotherapy (NAC) and surgery, pathologic staging, development of metastasis, and survival from the medical record. Patient charts were manually reviewed to identify breastfeeding status \u0026ndash; whether they breastfed at any point during the postpartum period, whether they were breastfeeding at the time of breast cancer diagnosis, any diagnosis of mastitis in the six months preceding breast cancer diagnosis, or whether presenting symptoms of breast cancer were initially attributed to breastfeeding or lactational change by either the patient or a provider.\u003c/p\u003e \u003cp\u003eWe conducted analyses on two cohorts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In Analysis 1, we sought to assess the effect of time postpartum on diagnostic patterns and outcomes by comparing patients diagnosed within 2 years postpartum (2-year PP, N\u0026thinsp;=\u0026thinsp;60) and those diagnosed between two and five years postpartum (2\u0026ndash;5 year PP, N\u0026thinsp;=\u0026thinsp;101) among the entire cohort (N\u0026thinsp;=\u0026thinsp;161).\u003c/p\u003e \u003cp\u003eIn Analysis 2, we sought to isolate the effect of breastfeeding at diagnosis on diagnostic patterns and outcomes by comparing patients who were (n\u0026thinsp;=\u0026thinsp;36) and were not (n\u0026thinsp;=\u0026thinsp;24) breastfeeding at diagnosis solely among the 2-year PP group (N\u0026thinsp;=\u0026thinsp;60).\u003c/p\u003e \u003cp\u003eFor both analyses, demographics, clinicopathologic characteristics at diagnosis and breastfeeding details were compared between subgroups using chi-square tests for categorical variables, Fisher\u0026rsquo;s exact test in cases of small group size, and Mann-Whitney tests for continuous variables. We examined and compared response patterns and rate of pathologic complete response (pCR) among patients who received NAC. Differences in overall survival (OS) and distant disease-free survival (DDFS) between groups were assessed using Kaplan-Meier analysis and Log-Rank tests.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis 1\u003c/h2\u003e \u003cp\u003eBetween 2002 and 2024, 60 2-year PP patients and 101 2\u0026ndash;5 year PP patients were identified (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The 2-year PP group was younger (median age 37.4 vs 39.6 years, p\u0026thinsp;\u0026lt;\u0026thinsp;.001) and more likely to be breastfeeding (60% vs 7%, p\u0026thinsp;\u0026lt;\u0026thinsp;.001) at the time of diagnosis, though over 90% of patients in both groups had breastfed at some point during the postpartum period. There was not a notable difference in race between groups, and a slightly lower prevalence of Hispanic ethnicity in the 2-year PP group (5 vs 14%, p\u0026thinsp;=\u0026thinsp;.14). Patients in the 2-year PP group were diagnosed at a higher clinical T-stage, with fewer having T1 tumors at diagnosis (20% vs 50%), and more having T3-4 tumors (36% vs 17%) compared to 2\u0026ndash;5 year PP patients (p\u0026thinsp;\u0026lt;\u0026thinsp;.001). Patients who were 2-year PP were less likely to be node-negative (37% vs 61%), and had a higher clinical N-stage (29% vs 11% cN2-3) compared to the 2\u0026ndash;5 year PP group (p\u0026thinsp;=\u0026thinsp;.01). There was a trend toward increased metastasis (12% vs 3%, p\u0026thinsp;=\u0026thinsp;.06), but no difference in Grade 3 disease (65% vs 55%, p\u0026thinsp;=\u0026thinsp;.21) at diagnosis for 2-year PP compared to 2\u0026ndash;5 year PP patients. Estrogen and progesterone receptor positivity and triple negative disease did not differ significantly between groups, but HER2\u0026thinsp;+\u0026thinsp;disease was more common among 2-year PP in comparison to 2\u0026ndash;5 year PP patients (36% vs 17%, p\u0026thinsp;=\u0026thinsp;.012). Symptoms of breast cancer were attributed to breastfeeding or lactational change in 37% of \u0026lt;\u0026thinsp;2-year PP patients and 9% of 2\u0026ndash;5 year PP patients (p\u0026thinsp;\u0026lt;\u0026thinsp;.001). Among the 72 patients who received NAC, there was not a significant difference in the proportion of patients who had pCR between \u0026lt;\u0026thinsp;2 year and 2\u0026ndash;5 year PP patients (40% for 2-year PP vs 30% for 2\u0026ndash;5 year PP, p\u0026thinsp;=\u0026thinsp;0.54; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMedian follow-up was 54 months. The 2-year PP group had significantly worse OS (5-year OS 79% [95% CI 67\u0026ndash;93] vs 97% [95% CI 93\u0026ndash;100], p\u0026thinsp;\u0026lt;\u0026thinsp;.001) and DDFS (5-year DDFS 74% [95% CI 60\u0026ndash;90] vs 93% [95% CI 87\u0026ndash;99], p\u0026thinsp;=\u0026thinsp;.003) compared to 2\u0026ndash;5 year PP patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-B).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnalysis 2\u003c/h3\u003e\n\u003cp\u003eAmong 2-year PP patients, breastfeeding patients and non-breastfeeding patients were of similar race, ethnicity, and age (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There was no difference in clinical T stage at diagnosis by breastfeeding status, but breastfeeding at diagnosis showed a trend toward a lower likelihood of node-negative disease and higher clinical N-stage (71% vs 50% cN0, 37% vs 17% cN2-3, p\u0026thinsp;=\u0026thinsp;.17) and metastasis at diagnosis (17% vs 4%, p\u0026thinsp;=\u0026thinsp;.29). There was a similar prevalence of Grade 3 disease between breastfeeding and non-breastfeeding patients (67% vs 63%, p\u0026thinsp;=\u0026thinsp;0.25). Estrogen and progesterone positivity were similar between groups, but HER2 positivity was numerically more common in breastfeeding patients, though this was not statistically significant (44% vs 22%, p\u0026thinsp;=\u0026thinsp;.13). Breastfeeding patients were significantly more likely to have a diagnosis of mastitis in the six months preceding cancer diagnosis (31% vs 4%, p\u0026thinsp;=\u0026thinsp;.03) and to have their breast cancer symptoms initially attributed to breastfeeding or lactational change (58% vs 4%, p\u0026thinsp;\u0026lt;\u0026thinsp;.001). There was no difference in months postpartum at diagnosis between breastfeeding and non-breastfeeding patients (median 11.8 months vs 13.5 months, p\u0026thinsp;=\u0026thinsp;.7). There was no difference in pCR rate between breastfeeding and non-breastfeeding patients (37% vs 46%, p\u0026thinsp;=\u0026thinsp;0.94) among the 31\u0026thinsp;\u0026lt;\u0026thinsp;2-year PP patients treated with NAC (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere was a trend toward worse OS (5-year OS 74% [95% CI 59\u0026ndash;93] vs 86% [95% CI 70\u0026ndash;100], p\u0026thinsp;=\u0026thinsp;.08), and significantly worse DDFS (5-year DDFS 62% [95% CI 45\u0026ndash;86] vs 91% [95% CI 75\u0026ndash;100], p\u0026thinsp;=\u0026thinsp;.032) for those breastfeeding vs not breastfeeding at diagnosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC-D).\u003c/p\u003e \u003cp\u003ePatients in the 2-year PP group who were not breastfeeding appeared to have similar OS and DDFS to patients in the 2\u0026ndash;5 year PP group. None of the 7 patients in the 2\u0026ndash;5 year PP group who were breastfeeding at diagnosis developed distant disease or metastasis during follow-up (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA-B). Of these 7 patients, 6 had ER+/PR+/HER2- disease, and one had ER-/PR-/HER2\u0026thinsp;+\u0026thinsp;disease.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathologic characteristics and lactation-related factors by years postpartum and concurrent breastfeeding status at the time of PPBC diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYears postpartum at diagnosis\u003c/p\u003e \u003cp\u003e(Analysis 1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eBreastfeeding status at diagnosis among 2-year PP patients\u003c/p\u003e \u003cp\u003e(Analysis 2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 to 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreastfeeding at diagnosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at diagnosis, median [IQR\u003csup\u003e2\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.4 [34.6, 40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.6 [36.7, 42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.6 [34.4, 40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36.5 [34.7, 39.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace, n (%)\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 \u003cp\u003e0.701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack/African American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic ethnicity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecTstage, n (%)\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 \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 ( 5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 ( 1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 ( 5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 ( 17)\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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 ( 37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 ( 29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 ( 6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 ( 11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 ( 0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecNstage (%)\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 \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 ( 29)\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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 ( 34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 ( 23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 ( 4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 ( 14)\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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetastasis at diagnosis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 ( 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 ( 4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade (%)\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 \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 ( 5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 ( 8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 ( 0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 ( 25)\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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 ( 67)\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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER\u0026thinsp;+\u0026thinsp;\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 ( 64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17 (74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u0026thinsp;+\u0026thinsp;\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 ( 56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHER2\u0026thinsp;+\u0026thinsp;\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 ( 44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNBC\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 ( 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceived neoadjuvant chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 ( 59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreastfed at any time postpartum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99 (99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptoms attributed to lactational change or breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 ( 8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 ( 58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 ( 4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis of mastitis in 6 months preceding PPBC diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 ( 2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 ( 31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 ( 4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.03\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 \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eEstimated using chi-square test for categorical variables and Kruskal-Wallis test for continuous variables\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eInterquartile range\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eEstrogen receptor\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eProgesterone receptor\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHuman Epidermal Growth Factor Receptor 2\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTriple-Negative Breast Cancer\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePathologic staging at surgery among patients treated with neoadjuvant chemotherapy by years postpartum and concurrent breastfeeding status at the time of PPBC diagnosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eYears Postpartum at diagnosis\u003c/p\u003e \u003cp\u003e(Analysis 1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eBreastfeeding status at diagnosis among 2-year PP patients\u003c/p\u003e \u003cp\u003e(Analysis 2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 to 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall pCR\u003csup\u003e1\u003c/sup\u003e (ypT0N0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse by nodal status\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 \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eypT\u0026thinsp;+\u0026thinsp;N+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eypT0N+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eypT\u0026thinsp;+\u0026thinsp;N0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epCR (ypT0N0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eypT\u0026thinsp;+\u0026thinsp;N+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eypT0N+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eypT\u0026thinsp;+\u0026thinsp;N0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epCR (ypT0N0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e1. Pathologic complete response\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e2. Estimated using chi-square test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first report that evaluates the role of timing of PPBC diagnosis with breastfeeding status. We found that PPBC diagnosed in the first two years postpartum is associated with worse survival compared to cancers diagnosed 2\u0026ndash;5 year PP. Moreover, patients who were breastfeeding at diagnosis in our study trended towards a worse prognosis compared to those who were not breastfeeding in the first two years postpartum. Notably, we found that there was no difference in overall pCR rates among patients who received NAC, or prevalence of high-grade disease at diagnosis, based on timing of PP diagnosis or breastfeeding status. Importantly, given the findings of later stage at diagnosis for patients diagnosed earlier postpartum and those breastfeeding at diagnosis, this suggests that the disparity in survival is likely driven by delayed diagnosis rather than an inherently inferior response to treatment.\u003c/p\u003e \u003cp\u003ePrevious case series have reported delayed breast cancer diagnosis due to changes associated with breastfeeding or lactation. In our study, nearly 60% of breastfeeding patients experienced a delayed diagnosis, compared to only 4% of non-breastfeeding patients\u003csup\u003e14,15,17,18\u003c/sup\u003e. The unique challenges of the early postpartum years, which may lead to delays in seeking medical care, coupled with the frequent misattribution of breast cancer symptoms to lactation, create a particularly vulnerable period for missed diagnoses. One study found that among pregnant women, symptoms were often interpreted as pregnancy-related by both patients and healthcare providers\u003csup\u003e19\u003c/sup\u003e. In addition, breast cancers in pre-menopausal patients are often self-palpated rather than detected on screening, and a woman finding her own mass has been associated with inappropriate reassurance that a malignant lump was benign\u003csup\u003e20\u003c/sup\u003e. Furthermore, breast cancer screening is often delayed for eligible lactating patients to cessation of breastfeeding due to concern for inaccurate results, despite national guidelines and the aggressiveness of cancers diagnosed during this period\u003csup\u003e21\u0026ndash;23\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is unclear whether concurrent breastfeeding has biological implications for breast cancer; a recent large pooled analysis found that parous women had a higher risk of TNBC right after their last birth, and a history of breastfeeding was associated with a lower risk of TNBC, as has been shown in other studies\u003csup\u003e24\u0026ndash;26\u003c/sup\u003e. Interestingly, our study found that among patients diagnosed with PPBC, HER2\u0026thinsp;+\u0026thinsp;disease was more common among patients diagnosed earlier compared to later postpartum, and among breastfeeding compared to non-breastfeeding patients, but the etiology behind this is unknown. The theory behind increased metastatic potential during the postpartum period is mammary gland involution, which can mimic a wound healing state and contribute to a tumorigenic microenvironment\u003csup\u003e13,27\u003c/sup\u003e. One experiment comparing nulliparous to immediate post-weaning mice found increased tumor number, burden, and higher Ki-67 index in the post-weaning group\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile this explains the general observation of poor outcomes in PPBC, as well as the comparatively poorer survival in patients diagnosed in the first two years postpartum in our study as this often coincides with the weaning period, it does not explain the worse outcomes seen in breastfeeding patients, who would be expected to harbor a less tumorigenic microenvironment. As the \u0026ldquo;weaning\u0026rdquo; period is gradual, there is likely some degree of mammary gland involution even early postpartum when milk supply first regulates, and later when breastmilk no longer is the sole source of nutrition for infants. However, altogether, the longer survival observed among non-breastfeeding patients, as well as earlier stage at presentation suggests that a disparity in prompt diagnosis may be driving the different outcomes rather than an inherent biological mechanism.\u003c/p\u003e \u003cp\u003eLimitations of our study include a relatively small, single-institution cohort, which limits both the statistical power of our analyses and the generalizability of our findings to broader populations. Still, our findings underscore the association between diagnostic timing and concurrent breastfeeding status on PPBC outcomes, suggesting that awareness of symptoms and risks among patients and healthcare providers may enhance early detection and ultimately improve overall survival. Further, large-scale, multi-institutional studies are warranted to validate these findings and inform evidence-based guidelines for postpartum patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: None\u003c/p\u003e\n\u003cp\u003eCompeting Interests: KS has received research funding from Lumicell. The remaining authors have no additional disclosures.\u003c/p\u003e\n\u003cp\u003eData availability: The datasets generated during the current study are not publicly available due to patient confidentiality, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: DK: Conceptualization, Methodology, Formal Analysis, Investigation, Data Curation, Writing \u0026ndash; Original Draft, Writing \u0026ndash; Review and Editing, Visualization. NP: Investigation, Data Curation, Writing \u0026ndash; Original Draft, Writing \u0026ndash; Review and Editing, Project administration. KS: Resources, Writing \u0026ndash; Review and Editing. FR: Resources, Writing \u0026ndash; Review and Editing. SC: Writing \u0026ndash; Review and Editing. MT: Resources. CM: Resources, Writing \u0026ndash; Review and Editing, Supervision. KH: Resources, Writing \u0026ndash; Review and Editing, Supervision\u003c/p\u003e\n\u003cp\u003eEthics approval: This was an observational studied and approved by our Institutional Review Board, Protocol 35536.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCallihan EB, Gao D, Jindal S, et al. Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer. \u003cem\u003eBreast Cancer Res Treat\u003c/em\u003e. 2013;138(2):549\u0026ndash;559. doi:10.1007/s10549-013-2437-x\u003c/li\u003e\n\u003cli\u003eShao C, Yu Z, Xiao J, et al. Prognosis of pregnancy-associated breast cancer: a meta-analysis. \u003cem\u003eBMC Cancer\u003c/em\u003e. 2020;20(1):746. doi:10.1186/s12885-020-07248-8\u003c/li\u003e\n\u003cli\u003eLyons TR, Schedin PJ, Borges VF. Pregnancy and Breast Cancer: when They Collide. \u003cem\u003eJ Mammary Gland Biol Neoplasia\u003c/em\u003e. 2009;14(2):87\u0026ndash;98. doi:10.1007/s10911-009-9119-7\u003c/li\u003e\n\u003cli\u003eLefr\u0026egrave;re H, Floris G, Schmidt MK, et al. Breast cancer diagnosed in the post-weaning period is indicative for a poor outcome. \u003cem\u003eEur J Cancer\u003c/em\u003e. 2021;155:13\u0026ndash;24. doi:10.1016/j.ejca.2021.06.009\u003c/li\u003e\n\u003cli\u003eNichols HB, Schoemaker MJ, Cai J, et al. Breast Cancer Risk After Recent Childbirth:A Pooled Analysis of 15 Prospective Studies. \u003cem\u003eAnn Intern Med\u003c/em\u003e. 2019;170(1):22\u0026ndash;30. doi:10.7326/M18-1323\u003c/li\u003e\n\u003cli\u003eAmant F, Lefr\u0026egrave;re H, Borges VF, et al. The definition of pregnancy-associated breast cancer is outdated and should no longer be used. \u003cem\u003eLancet Oncol\u003c/em\u003e. 2021;22(6):753\u0026ndash;754. doi:10.1016/S1470-2045(21)00183-2\u003c/li\u003e\n\u003cli\u003eShagisultanova E, Gao D, Callihan E, et al. Overall survival is the lowest among young women with postpartum breast cancer. \u003cem\u003eEur J Cancer Oxf Engl 1990\u003c/em\u003e. 2022;168:119\u0026ndash;127. doi:10.1016/j.ejca.2022.03.014\u003c/li\u003e\n\u003cli\u003eZhang Z, Bassale S, Jindal S, et al. Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah. \u003cem\u003eJAMA Netw Open\u003c/em\u003e. 2022;5(10):e2236763. doi:10.1001/jamanetworkopen.2022.36763\u003c/li\u003e\n\u003cli\u003eStensheim H, M\u0026oslash;ller B, van Dijk T, Foss\u0026aring; SD. 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Deciphering pro-lymphangiogenic programs during mammary involution and postpartum breast cancer. \u003cem\u003eFront Oncol\u003c/em\u003e. 2016;6. doi:10.3389/fonc.2016.00227\u003c/li\u003e\n\u003cli\u003eLyons TR, O\u0026rsquo;Brien J, Borges VF, et al. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. \u003cem\u003eNat Med\u003c/em\u003e. 2011;17(9):1109\u0026ndash;1115. doi:10.1038/nm.2416\u003c/li\u003e\n\u003cli\u003eWijesinghe K, Jayarajah U, Gamage H, De Silva S, De Silva A. Breast cancer in lactating mothers: A case series of delayed diagnosis. \u003cem\u003eInt J Surg Case Rep\u003c/em\u003e. 2023;102:107856. doi:10.1016/j.ijscr.2022.107856\u003c/li\u003e\n\u003cli\u003ePoorvu PD, Zheng Y, Sella T, et al. Diagnostic and treatment delays in young women with breast cancer. \u003cem\u003eJ Clin Oncol\u003c/em\u003e. 2019;37(15_suppl):6575\u0026ndash;6575. doi:10.1200/JCO.2019.37.15_suppl.6575\u003c/li\u003e\n\u003cli\u003eCollaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. \u003cem\u003eLancet Lond Engl\u003c/em\u003e. 2002;360(9328):187\u0026ndash;195. doi:10.1016/S0140-6736(02)09454-0\u003c/li\u003e\n\u003cli\u003eBanda JF, Donthireddy K. Abstract PO1-20-11: Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation \u0026ldquo;Case Report.\u0026rdquo; \u003cem\u003eCancer Res\u003c/em\u003e. 2024;84(9_Supplement):PO1-20-11. doi:10.1158/1538-7445.SABCS23-PO1-20-11\u003c/li\u003e\n\u003cli\u003eSeth A, Slama EM. Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum. \u003cem\u003eAm Surg\u003c/em\u003e. 2024;90(7):1925\u0026ndash;1927. doi:10.1177/00031348241241736\u003c/li\u003e\n\u003cli\u003eMarcu A, Ream E, Poole K, et al. Symptom appraisal and help- seeking before a cancer diagnosis during pregnancy: a qualitative study. \u003cem\u003eBr J Gen Pract\u003c/em\u003e. Published online January 17, 2025. doi:10.3399/BJGP.2024.0208\u003c/li\u003e\n\u003cli\u003eGoodson WH III, Moore DH II. Causes of Physician Delay in the Diagnosis of Breast Cancer. \u003cem\u003eArch Intern Med\u003c/em\u003e. 2002;162(12):1343\u0026ndash;1348. doi:10.1001/archinte.162.12.1343\u003c/li\u003e\n\u003cli\u003ediFlorio-Alexander RM, Slanetz PJ, Moy L, et al. ACR Appropriateness Criteria\u0026reg; Breast Imaging of Pregnant and Lactating Women. \u003cem\u003eAm Coll Radiol\u003c/em\u003e. 2018;15(11, Supplement):S263-S275. doi:10.1016/j.jacr.2018.09.013\u003c/li\u003e\n\u003cli\u003ePeterson MS, Gegios AR, Elezaby MA, et al. Breast Imaging and Intervention during Pregnancy and Lactation. \u003cem\u003eRadioGraphics\u003c/em\u003e. 2023;43(10):e230014. doi:10.1148/rg.230014\u003c/li\u003e\n\u003cli\u003eKieturakis AJ, Wahab RA, Vijapura C, Mahoney MC. Current Recommendations for Breast Imaging of the Pregnant and Lactating Patient. \u003cem\u003eAm J Roentgenol\u003c/em\u003e. 2021;216(6):1462\u0026ndash;1475. doi:10.2214/AJR.20.23905\u003c/li\u003e\n\u003cli\u003eJung AY, Ahearn TU, Behrens S, et al. Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies. \u003cem\u003eJ Natl Cancer Inst\u003c/em\u003e. 2022;114(12):1706\u0026ndash;1719. doi:10.1093/jnci/djac117\u003c/li\u003e\n\u003cli\u003eIslami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status\u0026mdash;a systematic review and meta-analysis. \u003cem\u003eAnn Oncol\u003c/em\u003e. 2015;26(12):2398\u0026ndash;2407. doi:10.1093/annonc/mdv379\u003c/li\u003e\n\u003cli\u003eFortner RT, Sisti J, Chai B, et al. Parity, breastfeeding, and breast cancer risk by hormone receptor status and molecular phenotype: results from the Nurses\u0026rsquo; Health Studies. \u003cem\u003eBreast Cancer Res\u003c/em\u003e. 2019;21(1):40. doi:10.1186/s13058-019-1119-y\u003c/li\u003e\n\u003cli\u003eMcDaniel SM, Rumer KK, Biroc SL, et al. Remodeling of the Mammary Microenvironment after Lactation Promotes Breast Tumor Cell Metastasis. \u003cem\u003eAm J Pathol\u003c/em\u003e. 2006;168(2):608\u0026ndash;620. doi:10.2353/ajpath.2006.050677\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6523923/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6523923/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003ePostpartum breast cancers (PPBC) have a worse prognosis than other breast cancers, but the impact of timing postpartum (PP) and concurrent breastfeeding (BF) remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe analyzed 161 PPBC patients diagnosed from 2002\u0026ndash;2014, hypothesizing that diagnosis\u0026thinsp;\u0026lt;\u0026thinsp;2 years PP (vs 2\u0026ndash;5 years) and concurrent BF (vs not BF) at diagnosis would be associated with inferior outcomes. We compared 2-year PP patients (N\u0026thinsp;=\u0026thinsp;60) and 2\u0026ndash;5 year PP patients (N\u0026thinsp;=\u0026thinsp;101), and subsequently, patients who were (n\u0026thinsp;=\u0026thinsp;36) and were not (n\u0026thinsp;=\u0026thinsp;24) BF at diagnosis among the 2-year PP group with respect to diagnostic patterns and survival. Differences were evaluated using chi-square tests. Kaplan-Meier analysis assessed overall survival (OS) and distant disease-free survival (DDFS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMedian follow-up was 54 months. Patients in the 2-year PP group were more likely to be BF at diagnosis (60% vs 7%, p\u0026thinsp;\u0026lt;\u0026thinsp;.001), diagnosed at a higher clinical T-stage (20% vs 50% T1, p\u0026thinsp;\u0026lt;\u0026thinsp;.001) and N-stage (37% vs 61% N0, p\u0026thinsp;=\u0026thinsp;.01), had worse 5-year OS (79% vs 97%, p\u0026thinsp;\u0026lt;\u0026thinsp;.001), and DDFS (74% vs 93%, p\u0026thinsp;=\u0026thinsp;.003) compared to 2\u0026ndash;5 year PP patients. Among 2-year PP patients, patients BF at diagnosis were more likely to be diagnosed with mastitis preceding diagnosis (31% vs 4%, p\u0026thinsp;=\u0026thinsp;.03), more often had their symptoms attributed to lactational change (58% vs 4%), had significantly worse 5-year DDFS (62% vs 91%, p\u0026thinsp;=\u0026thinsp;.032), and trended toward worse OS (74% vs 86%, p\u0026thinsp;=\u0026thinsp;.08) compared to those not BF.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings suggest that early PPBC and BF at diagnosis are associated with poor outcomes and diagnostic delay.\u003c/p\u003e","manuscriptTitle":"Impact of Timing of Diagnosis and Breastfeeding on Postpartum Breast Cancer Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 02:23:09","doi":"10.21203/rs.3.rs-6523923/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-04T18:15:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-26T16:43:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215774213804610512924005771227344739393","date":"2025-05-12T22:49:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299334523343379894040603138936829797645","date":"2025-05-08T11:41:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-07T22:37:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-26T08:17:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-26T08:14:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer Research and Treatment","date":"2025-04-24T22:53:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"aa96c61d-288a-419a-b93b-f5e5224f5074","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T16:39:35+00:00","versionOfRecord":{"articleIdentity":"rs-6523923","link":"https://doi.org/10.1007/s10549-025-07796-2","journal":{"identity":"breast-cancer-research-and-treatment","isVorOnly":false,"title":"Breast Cancer Research and Treatment"},"publishedOn":"2025-07-30 16:12:55","publishedOnDateReadable":"July 30th, 2025"},"versionCreatedAt":"2025-05-15 02:23:09","video":"","vorDoi":"10.1007/s10549-025-07796-2","vorDoiUrl":"https://doi.org/10.1007/s10549-025-07796-2","workflowStages":[]},"version":"v1","identity":"rs-6523923","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6523923","identity":"rs-6523923","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}