Representativeness of Study Participants

Representative multiplex immunofluorescence image with nuclei (blue), CD8 (aqua), PDL1 (green), FOXP3 (yellow), PD1 (orange), CD3 (red), and cytokeratin (white) stains depicted.

RISE UP (Revolutionizing Investigations to StEp Up Prevention) for breast cancer brought together leading cancer specialists, women’s health providers, basic and population scientists, regulators, politicians, industry leaders, patient advocates, and more from around the world to discuss and chart a radical rethinking of breast cancer prevention and risk reduction through a lens of hormonal management across a woman’s life course. The presentations at RISE UP were organized to outline a path forward by leveraging what we know about breast cancer biology, early detection, treatment, and endocrine therapy toward a better and sustainable approach for breast cancer prevention. Important conference considerations were to expand our thinking about prevention by broadly considering how the hormonal environment during different life phases or common benign conditions could be better managed to minimize breast cancer risk. This set the stage for transitioning to advances in risk prediction, promising risk-reducing agents, and biomarker-driven trials to test them. Biomarker-based trials discussed focused on 1) lower or intermittent doses of standard prevention agents, 2) drugs already approved for other health purposes, and 3) maximizing benefits from lifestyle interventions alone or in combination. Throughout RISE UP, there was a strong focus on promoting health equity, including comprehensive reproductive health access, equitable representation in clinical trials, and strategies to educate women, providers, and advocates about disparities in care and how to successfully reduce them. The meeting concluded with a competition for innovative approaches to breast cancer prevention that could be integrated into hormonal and women’s health interventions. RISE UP was an innovative conference that provided a forum for cross-cutting topics in women’s health that do not currently exist. The insights shared at RISE UP will be paradigm shifting in breast cancer prevention and women’s health space in the years to come.

PURPOSE:The role of tumor-infiltrating lymphocytes (TIL) remains unclear in hormone receptor (HR)-positive/HER2-negative breast cancer, particularly in young patients, whose immune microenvironment could be altered by age-related host and tumor differences. EXPERIMENTAL DESIGN:Patients with stage I to III HR-positive/HER2-negative tumors were identified from a prospective cohort study of patients with breast cancer diagnosed at age ≤40 years. Multiplexed immunofluorescence and semiautomated quantitative software measured cytotoxic T, non-CD8 T, T regulatory, exhausted T, and PDL1+ cells in stroma and tumor. Univariate analyses assessed differences in clinicopathologic characteristics by high versus low immune infiltration, divided based on median. TIL subtypes were evaluated as a continuous variable per 10% increase in Cox regression analyses for invasive breast cancer-free survival, distant disease-free survival (DDFS), and overall survival, adjusted for clinicopathologic parameters. RESULTS:Among 390 patients, high immune infiltration was associated with increasing age, Black race, grade 3 tumors, and metaplastic or micropapillary histologic subtypes. Over a median follow-up of 8 years, higher stromal and intratumoral non-CD8 T-cell infiltration, T regulatory-cell infiltration, and PDL1 expression were associated with improved invasive breast cancer-free survival. Higher intratumoral non-CD8 T-cell infiltration, T regulatory-cell infiltration, and PDL1 expression were associated with improved DDFS; higher stromal PDL1 expression was also associated with improved DDFS. Higher intratumoral cytotoxic T-cell infiltration and PDL1 expression were associated with improved overall survival. CONCLUSIONS:Characterization of immune subpopulations could help refine the prognostic value of TILs in young patients with HR-positive breast cancer, who may benefit from risk stratification for treatment individualization. See related commentary by Salgado and Kok, p. 2133.

Pearson’s correlation coefficients between tumor-infiltrating lymphocyte subtypes within stroma, with p-values in parentheses.

Representative multiplex immunofluorescence images with nuclei (blue), CD8 (aqua), FOXP3 (yellow), CD3 (red), and cytokeratin (white) stains depicted.

Multivariate survival analysis by moderate or marked versus absent or mild stromal lymphocytic infiltration, with adjustment for tumor grade, stage, and chemotherapy receipt.

Tumor-infiltrating lymphocytes assessment workflow.

Multiplex immunofluorescence staining conditions.

Pearson’s correlation coefficients between tumor-infiltrating lymphocyte subtypes within tumor, with p-values in parentheses.

Over a decade ago, collaborating academic cancer centers formed the Oncology Research Information Exchange Network® (ORIEN) to develop a patient-driven, federated infrastructure for oncology research. Aster Insights is the network’s operational, commercial, and research partner. Together ORIEN and Aster Insights have built a unique multimodal dataset on the active engagement and consent of patients who opted into the Total Cancer Care® (TCC) protocol to contribute their data and biospecimens for research. Over 400,000 cancer patients have been enrolled in TCC, >32,500 of which have an in silico “Avatar” generated to represent their individual patient experience and molecular profile to support a broad range of network and industry research use cases. We provide an overview of ORIEN’s evolution, demonstrate the power of our data resources through a landmark analysis of >37,000 tumors across all cancer types collected for the Avatar program, and provide a vision for ORIEN to fuel collaborative research.

Background: Activating mutations in the gene of phosphotydylinisotol-3 kinase catalytic subunit alpha (PIK3CA) are present in up to 40% of breast cancers overexpressing human epidermal growth factor receptor 2 (HER2). These mutations are linked to resistance to HER2-targeted agents and poorer patient outcomes. Based on preclinical efficacy, we are conducting a study to evaluate the combination of HER2-inhibitor tucatinib and PI3Kα-inhibitor alpelisib in patients with HER2-positive (HER2+) PIK3CA-mutated metastatic breast cancer (MBC) (NCT05230810). Methods: This phase IB study aims to determine the maximal tolerated doses of tucatinib and alpelisib using the Time-to-Event Bayesian Optimal Interval Design, with dose limiting toxicity (DLT) window of 28 days. Safety is evaluated by CTCAE v.5.0 with standard definition for DLTs. Eligible participants include post-menopausal women or pre-menopausal women undergoing ovarian suppression, diagnosed with HER2+ PIK3CA-mutated MBC, and previously treated with at least two HER2-targeted agents. Patients are allowed 1 prior line of HER2 tyrosine kinase inhibitor for MBC, including prior tucatinib. Treatment consists of twice-daily tucatinib and daily alpelisib at prespecified dose level (DL) with concurrent fulvestrant for hormone receptor-positive cases. Results: As of July 1st, 2024, 8 patients have been treated. The median age was 53 years (range: 45-66), with a median of 2 prior lines of therapy for MBC (range: 1-4). Prior HER2-targeted therapies included trastuzumab and pertuzumab (8 patients), T-DM1 (5 patients), tucatinib (4 patients), T-DXd (4 patients), and margetuximab (1 patient). Six patients had visceral metastases and 4 had CNS metastases. No DLTs were observed in 4 patients treated at DL1 (tucatinib 300 mg BID, alpelisib 250 mg daily), with one additional patient in the DLT window at the time of data cut-off. At DL2 (tucatinib 300 mg BID, alpelisib 300 mg daily), all 3 patients experienced DLT. Two patients had grade 3 (G3) diarrhea despite maximal anti-diarrheal regimen that resolved with treatment hold and dose reduction. One patient developed G3 rash with mucositis, eosinophilia and G4 elevated creatinine and came off study, all symptoms resolved without sequelae with hydration and steroid treatment. Other notable adverse events, primarily G1-2, included hyperglycemia (6 patients), decreased appetite (5 patients), weight loss (5 patients), fatigue (5 patients) and elevated liver enzymes (4 patients). These side effects were managed with supportive medications, nutritionist consultations and avoidance of hepatotoxic agents. No new safety signals were observed from the study drugs. One heavily pretreated patient developed progressive CNS metastases after 6 months on study and died on hospice within 30 days of follow up. At the time of data cutoff, 5 patients were evaluable for tumor response: 2 had stable disease, and 3 had partial response (PR). All patients who experienced PR had PIK3CA H1047R mutation. All PRs occurred after 2 cycles of therapy and included significant reduction of breast tumors, liver and lung metastases and resolution of cancer lymphangitic spread in the lungs. Four out of 8 patients remained on the regimen for more than 6 months. The longest treatment duration is 15 months and ongoing. Conclusions: The combination of tucatinib and alpelisib is tolerable at DL1 and shows remarkable antitumor activity with partial responses in 3 out of 5 evaluable patients (60% overall response rate), including responses in patients treated with prior tucatinib and T-DXd. Enrollment continues at DL1. Updated safety and efficacy findings will be presented at SABCS 2024 conference. Citation Format: Elena Shagisultanova, Chelsea D. Gawryletz, Colleen Dougherty-Gray, Leah Adams, Amelia Hardeman, Michelle Loch, Marina Sharifi, Peter Kabos, Virginia Borges. Safety and Preliminary Efficacy of Tucatinib and Alpelisib in Patients with HER2-positive PIK3CA-Mutated Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-03-10.

Background: The majority of ER+ breast cancers (BC) express androgen receptors (AR). In a randomized phase II trial for women with ER+/HER2- primary BC T2 or greater, neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) was given for 4 months prior to surgery. A total of 59 patients were evaluable: 33 on Combo and 26 on Fulv. The addition of AR blockade to Fulv reduced residual tumor at time of surgery as measured by modified preoperative endocrine predictive index (PEPI) score. Fresh tumor biopsies were required at study entry (baseline), after 4 weeks on therapy (W5), and at surgery. The Combo arm achieved PEPI=0 more frequently (24%: 8/33) than Fulv (8%: 2/26). Interestingly, the odds of response were 4.6-fold (95% CI: 0.9-22) higher for patients with invasive lobular cancer (IDC) versus invasive ductal (IDC). Results: When examining all tumors, gene expression analyses showed significantly decreased estrogen response and cell division gene sets in tumors in both arms; however, only Combo treated tumors exhibited significant enrichment of immune activation genes sets, including interferon gamma, complement, inflammation, antigen processing, and B and T cell activation. AR protein was significantly reduced by time of surgery in the Combo arm only (P<0.05) as measured by immunohistochemistry. AR was also significantly lower at time of surgery in the PEPI=0 as compared to PEPI >0 (P<0.05) and in the Ki67 responders versus non-responders (p<0.02). Because of the 4.6-fold higher odds of PEPI=0 response in ILCs versus IDC, we examined phosphoproteins that changed with treatment in these two histologic groups by reverse phase phosphoprotein assay (RPPA) from frozen tumor sections. Both AR and phosphoS650 AR showed significantly more decrease from BL to W5 in ILC versus IDC. Cyclin D1, S6RP, HIF-1 alpha, ATP citrate lyase, were significantly lower in ILC than IDC, while CHK1 and ALK were higher. As would be expected with the higher odds of response in ILC, cell cycle proteins decreased significantly more with treatment in this histologic subtype, as did growth/survival and metabolism proteins. Polaris Multiplex immunofluorescence, used to study the tumor immune microenvironment (TIME), revealed that the number of tertiary lymphoid structures (TLS) per area surrounding resected tumor at time of surgery was higher in the Combo arm and was significantly higher near tumors that achieved PEPI=0 (P<0.03). Additionally, the average number of TLS/mm2 was higher in the ILC versus IDC (P < 0.059). T regulatory cells were reduced in the Combo arm (p<0.0002) and in Ki67 responsive tumors (p<0.004); however, T regs were not significantly different in ILC versus IDC. Tumor-associated macrophages decreased by time of surgery only in the Combo arm (p<0.0001), only in tumors that achieved PEPI=0 (p<0.0005) and trended towards decreased numbers in ILC vs IDC. Conclusions: AR inhibition in combination with a SERD activates the immune system in ER+ BC, particularly in ILC. Citation Format: Jennifer Richer, Anthony D. Elias, Alyse W. Staley, Monica Fornier, Gregory A. Vidal, Vida Alami, Sharon Sams, Nicole S. Spoelstra, Andrew Goodspeed, Peter Kabos, Jennifer R. Diamond, Elena Shagisultanova, Rosa I Gallagher, Julia Wulfkuhle, Emanuel Petricoin, Kathryn Zolman, Tessa McSpadden, Christian Rickert, Kimberly R. Jordon, Jill E. Slansky, Virginia F. Borges, Dexiang Gao. Differential odds of response in ILC versus IDC correlate with changes in the TIME in a phase II trial of pre-operative fulvestrant with or without enzalutamide [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS18-07.

OBJECTIVES:Many patients with breast cancer (BC) experience reproductive concerns that contribute to psychosocial distress. Although many patients experience elevated levels of distress, few pursue psychosocial support (PSS) to manage their distress. We characterized the associations between BC patients' PSS utilization and demoralization, hopelessness, anxiety, depression, health-related quality of life (HRQOL), and previous experiences with psychosocial providers. METHODS:One hundred and four BC patients with reproductive concerns were recruited. Bivariate correlations assessed the relationships between measures of psychosocial distress and health care utilization. Independent logistic regressions were run to evaluate the unique associations between predictors of interest and PSS utilization. RESULTS:Most participants (57.7%) reported utilizing PSS during treatment. Higher levels of demoralization (OR = 1.109, p = 0.004) and HRQOL (OR = 0.964, p = 0.010) were significantly associated with increased odds of PSS utilization. Prior satisfaction with mental healthcare practitioners was also significantly associated with psychosocial utilization (OR = 0.561, p = 0.018). Anxiety, depression, and hopelessness were not significantly associated with PSS utilization. CONCLUSIONS:These data underscore the role of demoralization, HRQOL, and prior mental health care experiences in BC patient's PSS utilization. Many distress screening tools assess patients for the presence of depression and anxiety, but do not assess for demoralization. Thus, incorporating demoralization into screening tools may better identify and engage BC patients with reproductive concerns in PSS services.

Purpose: The POSITIVE trial showed that premenopausal women with breast cancer (BC) can safely pause adjuvant endocrine treatment (ET) to attempt conception. 74 % of patients conceived spontaneously or through assisted reproductive technology (ART); Investigating hormonal factors that predict fertility was a key secondary endpoint. Methods: Hormonal factors were assessed in non-pregnant women at months 3, 6, and 12 after ET interruption. The frequency of low ovarian reserve, defined as anti-Mullerian hormone (AMH) < 0.5 ng/mL at month 3, and of premature ovarian insufficiency (POI), defined as follicle stimulating hormone (FSH) > 25 IU/L at month 12, were primary measures. Secondary analyses to predict pregnancy included AMH, FSH, thyroid stimulating hormone (TSH), prolactin and ovulatory status (defined as progesterone >3 ng/mL at month 6), considering covariates such as age, treatment, and ART use. Results: Of 518 women enrolled in POSITIVE, 438 were eligible for low ovarian reserve analysis. Low ovarian reserve was observed in 209 women (47.7 %), more frequently among older women and those with prior chemotherapy, but not in relation to ET type or duration. Overall, low ovarian reserve was associated with reduced odds of pregnancy (OR:0.52; 95 % CI:0.31–0.87). Of 142 patients evaluated for POI, 16.7 % of those who received prior chemotherapy experienced POI. FSH at month 3 was associated with POI, but only modestly with spontaneous pregnancy (OR:0.96; 95 %CI: 0.93–1.00); other factors were not predictive of pregnancy. Conclusion: Hormonal factors are associated with pregnancy in BC patients pausing adjuvant ET to conceive, and their assessment may help to optimize fertility counseling. Trial registration: ClinicalTrials.gov number NCT02308085.

Background: Increased TILs are associated with higher pathologic complete response (pCR) rates after NACT for breast cancer, but scant data exist in patients ≤ 40 years old, in whom age-related differences in host and tumor immune microenvironment may exist. We assessed the extent and composition of immune infiltration in breast tumors of young women undergoing NACT and correlated with clinicopathologic features and treatment response. Methods: Patients with stage I-III breast cancer who had NACT and available pre-treatment tumor tissue were identified from a prospective cohort study of women with breast cancer diagnosed at age ≤ 40 years. Multiplexed immunofluorescence was used to quantify cytotoxic T (CD8+), T helper (CD3+CD8-), T regulatory (Treg, FOXP3+CD3+), exhausted T (PD1+CD8+), and PDL1+ cells in stroma and tumor as a percentage value of positive cells. Univariate analyses tested associations of TIL levels (high vs. low, divided based on median) with clinicopathologic variables and compared TIL levels (continuous) between pCR and non-pCR cases. Logistic regression tested associations between TIL subtypes (continuous, per 10% increase) and pCR. Results: Among 194 patients, median age was 36 years (range 22-40 years), 14% were positive for BRCA1/2 mutations, and most had grade 3 (71%), > 2 cm (87%), node-positive (79%) tumors. Forty-one percent of tumors were hormone receptor (HR)-positive/HER2-negative, 33% HER2-positive/HR-positive or -negative, and 27% triple-negative. Sixty-one patients (31%) experienced pCR after NACT. Patients with recent pregnancies (≤ 5 years prior, n=80) had higher stromal infiltration of T helper (P=.020) and cytotoxic T (P=.002) cells as well as higher intratumoral infiltration of cytotoxic T (P=.001), Treg (P=.018) and exhausted T (P=.049) cells compared to those who were nulliparous (n=52), pregnant at diagnosis (n=7) or pregnant > 5 years prior (n=24). BRCA1 mutations (n=19) were associated with high levels of exhausted T cells in stroma (P=.021) and tumor (P=.048). Grade 3 tumors (n=137) had higher levels of T helper cells in stroma (P=.030) and tumor (P=.010). Triple-negative (n=52) and HER2-positive (n=63) tumors had higher stromal Treg infiltration (P=.046). Triple-negative and stage III tumors (n=66) were associated with high levels of PDL1+ cells in stroma (P=.033) and tumor (P=.005), respectively. No differences in TILs were seen according to age, race, ethnicity or histological subtype. Patients with pCR had greater stromal Treg (P=.0189), intratumoral T helper (P=.0043) and intratumoral PDL1+ cell infiltration (P=.0372). Increased stromal Tregs was predictive of pCR, controlling for breast cancer stage, grade and subtype (OR 1.63, 95% CI 1.12-2.28, P=.011). Increased levels of all intratumoral TIL subtypes was predictive of pCR, with odds ratios ranging from 1.14 (95% CI 1.02-1.29, P=.026) for PDL1+ cells to 2.02 (95% CI 1.31-3.12, P=.002) for Tregs for each 10% increment, controlling for breast cancer stage, grade and subtype. Conclusions: The distribution of TIL subtypes in young patients’ breast tumors pre-treatment varied according to recency of pregnancy, BRCA1/2 mutation status and tumor characteristics. High levels of most TIL subtypes was associated with improved response to NACT, independent of breast cancer subtype. The relationship between TILs and pCR in young women appears similar to that in older women, suggesting that tumors of younger and older patients may not be fundamentally different when analyzed according to clinically relevant biologic features. Characterization of immune subpopulations could help refine the predictive value of TILs in young patients with breast cancer, who may benefit from individualized escalated and de-escalated treatment strategies. Citation Format: Megan Tesch, Yaileen D. Guzmán-Arocho, Laura C. Collins, Yujing J. Heng, Shoshana M. Rosenberg, Kathryn J. Ruddy, Rulla Tamimi, Lidia Schapira, Jeffrey Peppercorn, Virginia Borges, Steven E. Come, Craig Snow, Eric P. Winer, Elizabeth A. Mittendorf, Ann H. Partridge. Tumor-infiltrating lymphocytes (TILs) and response to neoadjuvant chemotherapy in young patients with breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS1-04.

PURPOSE:We investigated breastfeeding patterns, behaviors, and association with breast cancer (BC) outcomes in women with early hormone receptor-positive (HR+) BC who had a live birth in the POSITIVE trial. PATIENTS AND METHODS:POSITIVE is a prospective trial that demonstrated no increased short-term risk of BC events in women with early HR+ BC who interrupted endocrine therapy (ET) to attempt pregnancy. We describe the frequency, duration, and laterality of breastfeeding and estimate the cumulative incidence of BC events by breastfeeding status. RESULTS:At a median follow-up of 41 months, 317 patients had at least one live birth and 313 were eligible for this analysis. A total of 196 of 313 (62.6%) patients breastfed. A total of 130 of the 167 women (77.8%) who had breast-conserving surgery breastfed, and 90 of 130 (69.2%) breastfed from the unaffected breast only. Sixty-six of the 146 women (45.2%) who underwent unilateral mastectomy breastfed. The frequency of breastfeeding was higher in women older than 35 years (67.6% v 55.7%) and in those without previous children (66.4% v 48.5%). Over half (103 of 196, 52.6%) of women breastfed their first live birth for >4 months (median 4.4 months; 95% CI, 4.0 to 5.3). The cumulative incidence of a BC event at 24 months from first on-study live birth was 3.6% and 3.1% in the breastfeeding and nonbreastfeeding groups, respectively (0.5% difference; 95% CI, -4.3% to 5.2%). CONCLUSION:In POSITIVE, two thirds of women who gave birth after BC diagnosis breastfed, mostly for 4 months or more. In early follow-up, we did not observe differences in BC-related events in women who breastfed compared with those who did not. These results are key for women who wish to pursue pregnancy and breastfeeding after BC.

e12562 Background: Previous research has suggested that breast cancer (BC) diagnosed during pregnancy or the postpartum period exhibits more aggressive clinical features, possibly due to pregnancy-related hormonal changes, immune modulation, and alterations in the mammary microenvironment compared to nulligravid or women many years out from pregnancy. Emerging data have demonstrated potential worse outcomes for patients (pts) diagnosed in post-partum. This study evaluated the influence of timing of diagnosis in relation to pregnancy history and recency of childbirth on long-term outcomes in a modern cohort of young pts with early-stage BC. Methods: Pts with stage I–III BC age < 40y in the prospective Young Women’s Breast Cancer Study (YWBCS) were categorized at diagnosis as Nulligravid (no prior pregnancy), Nulliparous (prior pregnancy without live birth), Currently Pregnant, or Parous (subdivided by time since last childbirth: within 5 years [≤ 5y PP], and 5–10 years postpartum [5–10y PP]). Baseline characteristics and outcomes were compared across BC subtypes (estrogen receptor+/HER2- [ER+/HER2-], HER2+, and triple-negative BC [TNBC]). Prognostic analyses for distant recurrence-free survival (DRFS) used Cox models. Results: 859 pts were included, 257 (30%) nulligravid, 50 (6%) nulliparous, 37 (4%) pregnant, and 515 (60%) parous (348 [68%] were ≤5y PP, and 167 [32%] were 5–10y PP). Median follow-up was 133 (6–209) months. Median age at diagnosis was lower in nulligravid pts (33 vs. 35–38 years); T1 tumors were most common in pts >5y PP (62%), and N0 status was highest in nulligravid pts (64%) (all p < 0.0001). Pregnant pts had higher rates of TNBC (27%), and T3 tumors (14%), N1 status, N1 (41%), and Grade 3 (81%) tumors compared to other groups (all p < 0.0001). Overall, only tumor size (T2-T4 vs T1, HR 2.03; 95% CI 1.37–3.03) and nodal status (N1 vs N0, HR 2.22; 1.48–3.34; N2/3 vs N0, HR 3.23; 1.96-5.33) were independently associated with worse DRFS; pregnancy history was not: nulligravid + nulliparous pts had no significant differences in DRFS compared to Pregnant (HR 1.46; 0.75–2.86), Parous <5y PP (HR 0.86; 0.58–1.26), and Parous 5–10y PP (HR 0.89; 0.54–1.48). Subgroup analyses by BC subtype (Table) and sensitivity analyses (excluding currently pregnant pts or separating nulligravid and nulliparous pts) demonstrated no significant associations between pregnancy history and DRFS. Conclusions: In this cohort study of very young patients with early breast cancer with contemporary treatment including management of breast cancer during pregnancy, pregnancy history and recency of pregnancy were not independent predictors of long-term disease outcomes. DRFS results by subgroup. Pregnancy Group N (%) HR (95% CI) ER+/HER2- Nulligravid + Nulliparous 173 (38.1) Ref Pregnant 16 (3.5) 0.93 (0.32–2.70) Parous ≤5y PP 177 (39.0) 0.77 (0.45–1.29) Parous 5–10y PP 88 (19.4) 0.78 (0.39–1.53) HER2+ Nulligravid + Nulliparous 77 (30.8) Ref Pregnant 11 (4.4) 3.27 (0.80–13.38) Parous ≤5y PP 113 (45.2) 1.50 (0.60–3.75) Parous 5–10y PP 49 (19.6) 1.45 (0.45–4.66) TNBC Nulligravid + Nulliparous 56 (36.8) Ref Pregnant 10 (6.6) 1.92 (0.61–6.09) Parous ≤5y PP 57 (37.5) 0.68 (0.28–1.63) Parous 5–10y PP 29 (19.1) 1.16 (0.43–3.14)