Menopausal hormone therapy and mortality in breast cancer survivors

In women with breast cancer, a history of taking menopausal hormone therapy (MHT) before diagnosis was associated with a 23% to 43% reduction in risk of all-cause mortality and mortality from breast cancer and cardiovascular disease (CVD), according to results from the Long Island Breast Cancer Study Project (LIBCSP).¹

Furthermore, the study in the International Journal of Cancer found a 17% risk reduction in the age-matched comparison group from the same source population: women without breast cancer but who also had a history of MHT use.

“MHT increases the risk of developing breast cancer through the mechanisms of promoting breast cell proliferation and division.

These mechanisms are also believed to influence prognosis for breast cancer,” said first author Tengteng Wang, PhD, a research fellow in epidemiology at Harvard University and Brigham and Women’s Hospital in Boston.

“However, most observational epidemiologic studies conducted among women with breast cancer have reported that prediagnosis MHT is associated with a reduced risk of mortality. Such conflicting results inspired me to further clarify the association between MHT and mortality outcomes, especially among breast cancer survivors.”

The investigators interviewed 1,508 women from LIBSCP who had been newly diagnosed with first primary breast cancer between 1996 and 1997, along with 1,556 age-matched women without breast cancer from LIBSCP. Both groups were asked about MHT usage.

The National Death Index (NDI) provided vital status after a median follow-up of 16 years, during which time there were 915 overall deaths in the two groups combined.

Women with breast cancer who had taken MHT prior to diagnosis were 23% less likely to die overall, 31% less likely to die from breast cancer specifically, and 43% less likely to die from CVD compared with MHT never users.

Differences in breast cancer-specific mortality according to hormone receptor (HR) status were also observed: 56% less risk for negative tumors and 4% less risk for positive tumors in ever vs. never users.

“I was surprised that except for breast cancer mortality, prediagnosis MHT was associated with a strong risk reduction of CVD-specific mortality, because previous studies that investigated the association between prediagnosis MHT and mortality among women with breast cancer did not report CVD mortality as a major outcome,” Dr. Wang told Contemporary OB/GYN.

“I also found unexpected a more pronounced mortality reduction for breast cancer with hormone receptor-negative tumors than for positive tumors, because prior studies mostly report similar associations of MHT-breast cancer mortality by hormone receptor status.”

The study underscores that for patients with breast cancer who used MHT before diagnosis, MHT may be part of the cause of the breast cancer, but that these patients need not worry that such exposure history may increase their likelihood of dying from breast cancer.

“This is an important message that directly helps clinicians in counseling women about MHT,” Dr. Wang said.

Although usage of MHT has declined dramatically in recent years, “most older American women currently diagnosed with breast cancer have used MHT at some point in their lifetime,” Dr. Wang said.

Besides women needing to understand the broad health risks and benefits of taking MHT, “the therapy should be given according to Food and Drug Administration (FDA) recommendations, which is at the lowest effective dose and for the shortest duration that is consistent with treatment goals and risks for individual,” Dr. Wang said.

To further clarify the effect of MHT on breast cancer mortality, Dr. Wang advocates future studies that examine the link between MHT and mortality by tumor molecular subtypes, as well as other tumor characteristics of aggressiveness.

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Dr. Wang reports no relevant financial disclosures.

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Reference

1. Wang T, Bradshaw PT, Moorman PG, et al. Menopausal hormone therapy use and long-term all-cause and cause-specific mortality in the Long Island Breast Cancer Study Project. Int J Cancer. Published online June 25, 2020. doi:10.1002/ijc.33174