Analysis of healthy breast tissue from Komen Tissue Bank shows distinct histology, decreased proliferation, and lower periductal collagen deposition in women with prolonged history of breastfeeding.

Abstract

1538 Background: Epidemiological studies have shown that prolonged breastfeeding is associated with a reduced risk of developing triple negative/basal-like breast cancer (TN/BLBC). We have modeled abrupt involution (AI) following short breastfeeding and gradual involution (GI) of the mammary gland that occurs over time upon prolonged breastfeeding in wild-type FVB/N mice and discovered prominent histological and molecular changes in the AI glands over time. Further, we demonstrated that breast tissue from healthy women who breastfed <6 months showed enrichment in stem-cell and cell renewal pathways. Here, we corroborate those studies using normal human breast tissue obtained from Susan G. Komen for the Cure Tissue Bank (KTB). Methods: FFPE breast tissue sections obtained from KTB (Protocol #2017CO184). Donors were parous women, aged 18 to 45, without history of breast cancer and for whom breastfeeding history was available. H&E sections and TDLU, the primary anatomical source of most breast cancers, of women who breastfed for ≥6 months (GI, n=49) vs. those who breastfed for ≤3 months (AI, n=20) were evaluated by a blinded pathologist. Masson Trichrome stain was used to measure collagen deposition. Ki67 immunohistochemistry was utilized to determine proliferation. Statistical significance was measured using Fisher’s exact t-test and two-sample t-test with a p-value of <0.05. Results: H&E analysis revealed that breast tissue obtained from women in the AI cohort exhibited histological features of inflammation (p-value= 0.025). Using Ki67 IHC (AI, n=15; GI, n=32) and Masson Trichome stain (AI, n=3; GI, n=4), sections in the AI cohort showed 2-fold increase in proliferation of lobular epithelium (p-value= 0.048) and 1.4-fold increase in periductal collagen deposition (p-value= 0.027) when compared to GI cohort. Age, race, and BMI were not statistically different between AI and GI cohorts. Conclusions: Breast tissue from parous women who breastfed ≤3 months is histologically different than tissue of women with ≥6 months history of breastfeeding. We are currently staining more breast tissue samples obtained from KTB. Experiments are underway to assess the long-term effect of breastfeeding on breast epithelial cell hierarchy and biomarkers of inflammation. Understanding this mechanistic link will help in developing prevention strategies, particularly for African-American women who have lower prevalence of breastfeeding and higher incidence of TN/BLBC.