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Persistent vasomotor symptoms and breast cancer in the Women's Health Initiative

Chlebowski, Rowan T., MD, PhD1; Mortimer, Joanne E., MD1; Crandall, Carolyn J., MD2; Pan, Kathy, MD3; Manson, JoAnn E., MD, Dr.PH4; Nelson, Rebecca, PhD1; Johnson, Karen C., MD5; Vitolin, Mara Z., Dr.PH6; Lane, Dorothy, MD, MPH7; Wactawski-Wende, Jean, PhD8; Kwan, Karen, MD9; Stefanick, Marcia L., PhD10

doi: 10.1097/GME.0000000000001283
Original Articles

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.

1City of Hope National Medical Center, Duarte, CA

2David Geffen School of Medicine at UCLA, Los Angeles, CA

3Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA

4Brigham and Women's Hospital, Harvard Medical School, Boston, MA

5University of Tennessee Health Science Center, Memphis, TN

6Wake Forest Baptist Medical Center, Winston Salem, NC

7Stony Brook University School of Medicine, Stony Brook, NY

8University of Buffalo, Buffalo, NY

9Southern California Permanente Medical Group, Los Angeles, CA

10Stanford Prevention Research Center, Stanford, CA.

Address correspondence to: Rowan T. Chlebowski, MD, PhD, City of Hope National Medical Center, Duarte, CA 91010. E-mail:

Received 8 April, 2018

Revised 31 August, 2018

Accepted 31 August, 2018

Funding/Support: The WHI program is reported by the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.

Financial disclosure/conflicts of interest: R.T.C. has received honoraria from Novartis and AstraZeneca and consulting fees from Novartis, AstraZeneca, Pfizer, and Genentech. J.E.M. has received honoraria from Novartis and consulting fees from Puma Biotechnology, Pfizer, and Novartis. Remaining authors report no conflicts of interest.

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Online date: December 28, 2018

© 2019 by The North American Menopause Society.