Persistent Vasomotor Symptoms and Breast Cancer in the Women's Health Initiative

Rowan T. Chlebowski, MD, PhD; Joanne E. Mortimer, MD; Carolyn J. Crandall, MD; Kathy Pan, MD; JoAnn E. Manson, MD, Dr.PH; Rebecca Nelson, PhD; Karen C. Johnson, MD; Mara Z. Vitolin, Dr.PH; Dorothy Lane, MD, MPH; Jean Wactawski-Wende, PhD; Karen Kwan, MD; Marcia L. Stefanick, PhD


Menopause. 2019;26(6):578-587. 

In This Article

Abstract and Introduction


Objective: Vasomotor symptoms (VMS) including hot flashes and night sweats are common during the menopausal transition and may persist. Although VMS pathophysiology is complex, estrogen's efficiency as VMS therapy suggests hormonal environment change may influence this process. As studies of VMS and breast cancer are inconsistent, we examined associations between persistent VMS and breast cancer incidence and mortality.

Methods: The analytic sample included 25,499 postmenopausal women aged 50 to 79 in the Women's Health Initiative (WHI) without current/former menopausal hormone therapy use with information on VMS status (never vs persistent). Breast cancers were verified by medical record review. Cause of death attribution was enhanced by serial National Death Index queries. Associations between VMS status and breast cancer incidence and mortality was determined using time dependent Cox regression analyses adjusted for breast cancer risk factors.

Results: Through 17.9 years (median) follow-up, 1,399 incident breast cancers were seen. Women with persistent VMS (VMS median duration 10+ years) (n = 9,715), compared to women with never VMS (n = 15,784), had a higher breast cancer incidence (hazard ratio [HR] 1.13 95% confidence interval [CI] 1.02–1.27). While breast cancer-specific mortality was higher in women with persistent VMS (HR 1.33 95% CI 0.88–2.02), the difference was not statistically significant. Persistent VMS status had no influence on breast cancer overall survival (HR 1.02 95% CI 0.81–1.29).

Conclusion: Women with persistent VMS are more likely to be diagnosed with breast cancer than women who never experienced VMS, but not more likely to die from breast cancer.


Vasomotor symptoms (VMS) including hot flashes and/or night sweats are common in women during the menopause transition and may persist. The etiology of VMS is complex, involving overactivity of the sympathetic nervous system. The symptoms follow small elevations in core body temperature related, at least in part, to ovarian senescence and the resulting estrogen decline.[1,2] However, as plasma estrogen levels between women with and without VMS do not consistently differ,[3] other factors must be involved. Nonetheless, exogenous hormone therapy is the most effective VMS intervention,[4] suggesting hormonal environment change may play a role in this process.[1] As endogenous sex hormones levels are related to postmenopausal breast cancer risk,[5] there has been interest in examining associations between VMS status and breast cancer incidence and outcome.

At the present time, studies examining the association between VMS frequency and persistence with breast cancer incidence have been limited and provide conflicting results. VMS were associated with lower breast cancer risk in 2 case-control studies comparing findings in ever VMS to never VMS groups[6,7] and in 1 cohort study,[8] the latter including only 108 incident breast cancer cases. In contrast, a larger cohort study with 348 incident breast cancer cases found no association between VMS and breast cancer incidence.[9]

As the nature of the association between the VMS and breast cancer risk has not been settled, with long term, persistent VMS receiving limited attention and associations with breast cancer mortality not reported, we examined associations between persistent VMS and breast cancer incidence and breast cancer mortality in postmenopausal women participating in the Women's Health Initiative (WHI) clinical trials and observational study. In addition, we examined associations among breast cancer incidence and outcome with breast cancer risk factors more generally to facilitate comparisons with findings related to persistent VMS.