Schedin, Pepper

Abstract Background: Breast cancers in recently postpartum women may have worse outcomes, but studies examining tumor molecular features by pregnancy recency have shown conflicting results. Methods: This analysis used Carolina Breast Cancer Study data to examine clinical and molecular tumor features among women less than 50 years of age who were recently (≤10 years prior) or remotely (>10 years prior) postpartum, or nulliparous. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were estimated using multivariable models. Results: Recently postpartum women (N = 618) were more frequently lymph node–positive [POR (95% CI): 1.66 (1.26–2.19)], estrogen receptor (ER)-negative [1.37 (1.02–1.83)], and IHC-based triple negative [1.57 (1.00–2.47)] compared with nulliparous (N = 360) women. Some differences were identified between recent versus remotely postpartum; smaller tumor size [0.67 (0.52–0.86)], p53 wildtype [0.53 (0.36–0.77)], and non–basal-like phenotype [0.53 (0.33–0.84)] were more common among recently postpartum. Recently postpartum (vs. nulliparous) had significant enrichment for adaptive immunity, T cells, B cells, CD8 T cells, activated CD8 T cells/natural killer (NK) cells, and T follicular helper (Tfh) cells and higher overall immune cell scores. These differences were attenuated in remotely (compared with recently) postpartum women. Conclusions: These results suggest a dominant effect of parity (vs. nulliparity) and a lesser effect of pregnancy recency on tumor molecular features, although tumor immune microenvironments were altered in association with pregnancy recency. Impact: Our study is unique in examining tumor immune microenvironment and RNA-based markers according to time since last childbirth. Future studies should examine the interplay between tumor features, postdiagnostic treatment, and outcomes among recently postpartum women. See related commentary by McDonald et al., p. 518

Abstract Background. The increase in breast cancer risk during pregnancy and postpartum is well known; however, the molecular phenotype of breast cancers occurring shortly after pregnancy has not been well studied. Given this, we investigated whether nulliparity and the time interval since pregnancy among parous women affects the breast cancer phenotype in young women. Materials and Methods. We examined molecular phenotype in relation to time since pregnancy in a prospective cohort of 707 young women (aged ≤40 years) with breast cancer. Parity was ascertained from study questionnaires. Using tumor histologic grade on central review and biomarker expression, cancers were categorized as luminal A- or B-like, HER2 enriched, and triple negative. Results. Overall, 32% were luminal A-like, 41% were luminal B-like, 9% were HER2 enriched, and 18% were triple negative. Although, numerically, patients diagnosed >5 years after pregnancy had more luminal A-like subtypes than women with shorter intervals since pregnancy, there was no evidence of a relationship between these intervals and molecular subtypes once family history of breast cancer and age at diagnosis were considered. Conclusion. Distribution of breast cancer molecular phenotype did not differ significantly among young women by parity or time interval since parturition when important predictors of tumor phenotype such as age and family history were considered. Implications for Practice: Distribution of breast cancer molecular phenotype did not differ among parous young women by time interval since pregnancy. The implication of these findings for clinical practice suggests that pregnancy-associated breast cancers may be seen up to 5 years beyond parturition.