Menopausal hormone therapy in women with hysterectomy lowers breast cancer incidence: JAMA
USA: The prior use of conjugated equine estrogen (CEE) alone in women having a previous hysterectomy, lowered the incidence and mortality of breast cancer, according to a recent study in the journal JAMA. Further, prior use of CEE+medroxyprogesterone acetate (MPA) versus placebo in women having an intact uterus increased the incidence of breast cancer but did not have any significant difference in breast cancer mortality.
The association between menopausal hormone therapy and breast cancer remains unclear with discordant findings from randomized controlled trials and observational studies. Rowan T. Chlebowski, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, and colleagues assessed the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women's Health Initiative clinical trials.
The researchers conducted a long-term follow-up of 2 placebo-controlled randomized clinical trials involving 27 347 postmenopausal women aged 50-79 years. The women had no prior breast cancer and a negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017.
In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of CEE plus 2.5 mg/d of MPA and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years' median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years' median intervention duration.
The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer.
Key findings of the study include:
- Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%.
- CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78) and was associated with statistically significantly lower breast cancer mortality with 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60).
- In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28) and no significant difference in breast cancer mortality with 71 deaths (annualized mortality rate, 0.045%) vs 53 deaths (annualized mortality rate, 0.035%; HR, 1.35).
"In this long-term follow-up study of 2 randomized trials, prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy, was significantly associated with lower breast cancer incidence and lower breast cancer mortality, whereas prior randomized use of CEE plus MPA, compared with placebo, among women who had an intact uterus, was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality," concluded the authors.
The study, "Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women's Health Initiative Randomized Clinical Trials," is published in the journal JAMA.