Abstract A080: Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study
Authors: Lynn Brittny C Davis , Cora Renata , Pfeiffer Ruth M , Bethea Traci N , Zirpoli Gary , Palmer Julie R , Gierach Gretchen L 
Published: September 2020

Background: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm2, TDLU span (μm), and number of acini/TDLU, and that these metrics may be elevated in the background normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. However, it is unknown if this relationship exists in black women, who have the highest incidence of TN breast cancer as well as the highest overall breast cancer mortality rate. We sought to determine the relationships of quantitative measures of TDLU involution with breast cancer molecular subtype among participants in the Black Women’s Health Study. Methods: We digitized hematoxylin and eosin stained normal adjacent tissues from TN (estrogen receptor negative (ER), progesterone receptor negative, and human epidermal growth factor 2 (HER2) negative; n=67) and luminal A (ER positive and HER2 negative; n=162) breast cancer cases from the Black Women’s Health Study. We used logistic regression to evaluate associations between TDLU metrics and breast cancer subtype (TN vs. luminal A), with adjustment for age and body mass index. We performed ordinal logistic regression to evaluate relationships between population and clinical characteristics and TDLU metrics. Results: Among the 229 breast cancer cases, mean age at diagnosis was 53.7 years; 68.7% of TN and 54.3% of luminal A cases were under 55 years of age. Most women had a body mass index (BMI) &gt;30kg/m2, were parous, did not smoke, and did not have a family history of breast cancer. The odds of TN breast cancer were elevated for the second and third tertiles of TDLU count relative to the first tertile, with odds ratios (95% confidence interval) of 2.89 (1.11, 4.86) and 1.92 (0.93, 4.08), respectively. Similarly, the odds of TN breast cancer increased with increasing tertiles of median TDLU span, with odds ratios of 2.25 (1.06, 4.91) and 2.38 (1.14, 5.15) for the second and third tertiles, respectively, compared to the first tertile. These associations persisted even after adjustment for age and BMI. No association was observed with median acini count/TDLU and TN breast cancer. We also observed significant associations of some breast cancer risk factors with measures of TDLU involution. Higher TDLU count was associated with younger age, more physical activity, lower BMI, current use of oral contraceptives or menopausal hormones, and premenopausal status. Conclusion: The associations of TDLU metrics with breast cancer subtype observed in this population of black women are consistent with previous studies of white and Asian women, with reduced TDLU involution in TN breast cancers compared with luminal A. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype.

Citation Format: Brittny C Davis Lynn, Renata Cora, Ruth M Pfeiffer, Traci N Bethea, Gary Zirpoli, Julie R Palmer, Gretchen L Gierach. Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A080.