title: Breast Cancer and Menopausal Hormone Therapy by Race/Ethnicity and Body Mass Index.
abstract: In analyses combining estrogen with or without progestin, some observational studies describe minimal breast cancer risk in obese and black women. Therefore, we examined these suggested interactions in the two Women's Health Initiative (WHI) randomized hormone therapy trials. The estrogen plus progestin trial entered 16 608 postmenopausal women with a uterus, while the estrogen trial entered 10 736 postmenopausal women with prior hysterectomy. Hazard ratios (HRs), 95% confidence intervals (CIs), and P values from log-rank x(2) statistics were estimated from Cox proportional hazards models with subgroup analyses based on tests of interaction. All statistical tests were two-sided. Estrogen plus progestin statistically significantly increased breast cancer incidence (HR = 1.28, 95% CI = 1.11 to 1.48, P < .001), with hazard ratios greater than 1 in all body mass index (BMI) subgroups (P interaction = .58) and hazard ratios greater than 1 in black and white women (P interaction = .96). In contrast, estrogen alone statistically significantly decreased breast cancer incidence (HR = 0.79, 95% CI = 0.65 to 0.90, P = .02), with hazard ratios lower than 1 in all BMI subgroups (P interaction = .86) and hazard ratios lower than 1 in black and white women, where analyses with limited numbers suggest somewhat greater reduction in black women (P interaction = .09). In summary, estrogen plus progestin and estrogen alone have opposite effects on breast cancer incidence, with no statistically significant interactions by race/ethnicity or BMI. Therefore, observational studies should not combine these two regimens when examining breast cancer risk.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, AKA, RP). rowanchlebowski@gmail.com.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, AKA, RP).
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, AKA, RP).
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, AKA, RP).
authors.forename: Ross
authors.initials: R
authors.lastname: Prentice
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000139:chemically induced / Q000208:ethnology* / Q000209:etiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D009765:Obesity / Q000150:complications*; D016017:Odds Ratio; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000191:economics; D012109:Research Support as Topic; D012306:Risk; D014481:United States / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data; D016387:Women's Health
chemical_list: D004967:Estrogens; D011372:Progestins