Background: Prior observational studies have identified an elevated breast cancer risk associated with current MHT use for ER+ (Estrogen Receptor positive), and for ER+ / PR+ (Estrogen and Progesterone Receptor positive) breast cancers than for ER- and ER-/PR- subtypes respectively. We have previously reported, from a large case-control study for all cancer types (the NSW CLEAR study) that current MHT use was associated with a doubling of the odds of breast cancer. Here, we describe further analyses investigating the MHT-breast cancer association for the breast cancer tumor receptor subtypes defined by ER expression, by ER and PR expression and by the joint expression of ER, PR, and HER-2 (Human Epidermal growth factor Receptor-2).

Methods: Analyses were carried out for a subset of registry-verified CLEAR breast cancer cases with hormone receptor status data (n=410) and CLEAR (cancer-free) controls recruited over the same period (n=324). We used a multinomial logistic regression model to estimate Odds Ratios (ORs) adjusted for other breast cancer risk factors and 95% Confidence Intervals (CI) for current and past MHT use in subgroups defined by tumor receptor subtypes. Never users comprised the reference group.

Findings: In a multinomial model, current MHT use was associated with an elevated risk of ER+ breast cancer (aOR= 2.04, 95%CI: 1.28 -3.24). When breast cancers were categorised by ER and PR status, current use was associated with an elevated risk of developing ER+PR+ breast cancer (aOR= 2.29, 1.41-3.72). Current MHT use was associated with the surrogate luminal A breast cancer characterized by ER+/PR+/HER2- phenotype (aOR= 2.30, 1.42-3.73). None of the other subtypes of breast cancer (ER+/PR+/HER2+, ER-/PR-/HER2+, and ER-/PR-/HER2-) were significantly associated with current MHT use. A significant difference in the odds of developing breast cancer for current MHT users was detected between the surrogate luminal A and luminal B (ER+/PR+/HER2+) subtypes only (aOR= 0.28, 0.09-0.88, p=0.029). None of the other groups were significantly differently associated with MHT use, although this may be due to lack of power. Past MHT use was not associated with an increased risk of breast cancer for any breast cancer subtype.

Conclusion: The findings from this contemporary Australian study are consistent with findings from other studies that current, but not past, use of MHT is associated with increased risk of breast cancer, with higher risks reported for ER+, ER+ and PR+ and ER+/PR+/HER2- (surrogate luminal A) subtypes. Our findings are consistent with the hypothesis that breast cancers induced by MHT may occur through receptor-mediated mechanisms.

Citation Format: Usha G. Salagame, Emily Banks, Dianne O’Connell, Sam Egger, Karen Canfell. Menopausal hormone therapy (MHT) use and breast cancer risk by receptor subtypes: results from the New South Wales Cancer Lifestyle and EvAluation of Risk (CLEAR) study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2285. doi:10.1158/1538-7445.AM2017-2285