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PLoS One. 2018 Nov 7;13(11):e0205034. doi: 10.1371/journal.pone.0205034. eCollection 2018.

Menopausal Hormone Therapy use and breast cancer risk by receptor subtypes: Results from the New South Wales Cancer Lifestyle and EvaluAtion of Risk (CLEAR) study.

Author information

Cancer Research Division, Cancer Council NSW, Woolloomooloo, Sydney, New South Wales, Australia.
Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.
Sax Institute, Sydney, New South Wales, Australia.
School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia.
Prince of Wales Clinical School, UNSW, Sydney, Australia.


Breast cancer risk is increased with current Menopausal Hormone Therapy (MHT) use, with higher risks reported for ER+ (Estrogen Receptor positive), and ER+/PR+ (Estrogen and Progesterone Receptor positive) breast cancers than those of ER- and ER-/PR- status, respectively. There is limited evidence to suggest MHT use is associated with the specific subtype characterised as ER+/PR+/HER2- (Estrogen and Progesterone Receptor positive and Human Epidermal growth factor Receptor2 negative) status. This study aims to investigate the MHT-breast cancer relationship for breast cancer tumor receptor subtypes defined by ER expression alone, by ER and PR expression only and by joint expression of ER, PR, and HER2. Analyses compared 399 cancer registry-verified breast cancer cases with receptor status information and 324 cancer-free controls. We used multinomial logistic regression to estimate adjusted odds ratios (aORs) and 95% Confidence Intervals (CI) for current and past versus never MHT use, for subgroups defined by tumor receptor expression. Current, but not past, use of MHT was associated with an elevated risk of ER+ breast cancer (aOR = 2.04, 95%CI: 1.28-3.24) and ER+/PR+ breast cancer (aOR = 2.29, 1.41-3.72). Current MHT use was also associated with an elevated risk of the ER+/PR+/HER2- subtype (aOR = 2.30, 1.42-3.73). None of the other subtypes based on ER, ER/PR or ER/PR/HER2 expression were significantly associated with current MHT use in this analysis. Current, but not past, use of MHT increases the risk of breast cancer, with consistently higher risks reported for ER+ and ER+/PR+ subtypes and mounting evidence regarding the specific ER+/PR+/HER2- subtype. Our findings contribute to quantification of the effects of MHT, and support efforts to articulate the receptor-mediated mechanisms by which MHT increases the risk of breast cancer.

Conflict of interest statement

The authors have declared that no competing interests exist. KC is co-principal investigator of an investigator-initiated trial of cytology and primary HPV screening in Australia (Compass; ACTRN12613001207707 and NCT02328872), which is conducted and funded by the Victorian Cytology Service (VCS), a government-funded health promotion charity. VCS has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Ventana USA. KC is also an investigator for Compass in New Zealand (Compass NZ; ACTRN12614000714684), which is conducted and funded by Diagnostic Medlab (DML), now Auckland District Health Board. DML received an equipment and funding contribution for the Compass trial from Roche Molecular Systems. However neither KC nor her institution on her behalf (Cancer Council NSW) receive direct or indirect funding from industry for Compass Australia or NZ or any other project. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

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