Abstract B99: Hot flashes, hormone therapy, and breast cancer risk: The Women's Health Initiative Clinical Trials
Authors: Farhat Ghada N. , LaCroix Andrea , Grady Deborah , Chlebowski Rowan , Vitolins Mara , Manson JoAnn , Yasmeen Shagufta , Messina Catherine , LeBlanc Erin , Cummings Steven R. 
Published: January 2011

Abstract
Background: New onset of hot flashes with anti-estrogen therapy was found to predict breast cancer prognosis. Hot flashes were also observed to modify the effects of dietary interventions on breast cancer risk and prognosis. We investigated whether hot flashes 1) predict breast cancer risk (Aim 1), and 2) modify the effects of estrogen plus progestin (E+P) and E-alone therapy on breast cancer risk (Aim 2).
Methods: We performed a prospective analysis within the Women's Health Initiative randomized, placebo-controlled clinical trials of E+P (0.625 mg/day conjugated equine estrogens [CEE] plus 2.5 mg/day medroxyprogesterone acetate) and E-alone (0.625 mg/day CEE). The cohort included 27,347 postmenopausal women (mean age: 63.4 ± 7.2 years; 81% white; no history of breast cancer). During an average follow-up of 7.8 years, 752 incident breast cancer cases were diagnosed and confirmed. The occurrence of hot flashes (HF-status) was self-reported at the baseline visit and categorized as: none, mild (symptom not interfering with usual activities), and moderate (interfering somewhat with usual activities) or severe (so bothersome that usual activities could not be performed). Cox proportional hazards regression was used for analysis. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained. Models were adjusted for the following confounders: age, race, age at menarche, body mass index, prior breast needle aspiration, and prior use of oral contraceptives or E+P therapy. For Aim 1, the analysis combined the placebo groups of both trials and the cohort was followed through September 2005. For Aim 2, the E+P and E-alone trials were analyzed separately and the cohort was followed through each trial's termination date.
Results: Twenty one percent of participants reported mild hot flashes, and 11% reported moderate/ severe symptoms. Aim 1: Baseline HF-status was not significantly associated with breast cancer risk (HRs [95% CIs]: mild HF= 1.06 [0.79-1.42]; moderate/severe HF= 0.96 [0.64-1.44]; no HF= reference).
Aim 2: No significant interactions were observed for HF-status with E+P or E-alone therapy. Breast cancer risk associated with E+P or E-alone treatment did not vary significantly according to baseline HF-status (effect of E+P in: no HF= 1.14 [0.87-1.50], mild HF= 1.26 [0.76-2.09], moderate/severe HF= 1.86 [0.87-3.97]. Effect of E-alone in: no HF=0.73 [0.52-1.03], mild HF= 0.61 [0.32-1.16], moderate/severe HF= 1.02 [0.46-2.26]).
Conclusion: Among postmenopausal women, hot flashes were not associated with breast cancer risk, and they did not significantly modify the effects of E+P or E-alone therapy on breast cancer risk. The possibility that women with moderate/severe hot flashes have different effects of hormone therapy needs to be investigated in a larger study.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B99.