Menopausal hormone therapy in women with hysterectomy lowers breast cancer incidence:
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.