Women With Lower Pretreatment Estrogen Levels at Greater Risk of Breast Cancer During Estrogen-Plus-Progestin Therapy
In a study reported in the Journal of the National Cancer Institute, Ghada N. Farhat, PhD, of University of Balamand in Beirut, and colleagues found that women with lower pretreatment endogenous estrogen levels are at greatest risk of breast cancer during estrogen-plus-progestin therapy.
Study Details
The investigation consisted of a nested case-control study within the Women’s Health Initiative randomized trial of estrogen-plus-progestin therapy, which enrolled 16,608 postmenopausal women aged 50 to 79 years with an intact uterus and no history of breast cancer. During a mean follow-up of 5.6 years, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Patients had estrogens, testosterone, progesterone, and sex hormone–binding globulin measured at baseline and estrogens and sex hormone–binding globulin measured at year 1.
Increased Risk With Higher Baseline Levels
Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels by quartile (highest vs lowest quartile) for total estradiol (odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.12–5.63; P = .04 for trend), bioavailable estradiol (OR = 2.82, 95% CI = 1.25–6.36; P = .03 for trend), estrone (OR = 3.01, 95% CI = 1.34–6.76; P = .007 for trend), and estrone sulfate (OR = 2.38, 95% CI = 1.20–4.72; P = .007 for trend).
Greatest Effect on Risk
Estrogen-plus-progestin therapy increased all measured estrogens and sex hormone–binding globulin at year 1 (all P < .001) compared with placebo. Women with pretreatment levels of total estradiol, bioavailable estradiol, and estrone in the lowest quartiles had the greatest risk of breast cancer with combined hormone therapy: odds ratios for breast cancer for estrogen plus progestin vs placebo for the lowest vs highest quartile were 2.47 (95% CI = 1.28–4.79) vs 0.96 (95% CI = 0.44–2.09) for estradiol (P =.04 for interaction), 2.35 (95% CI = 1.20–4.64) vs 0.75 (95% CI = 0.34–1.64) for bioavailable estradiol (P = .02 for interaction), and 3.06 (95% CI = 1.52–6.17) vs 0.95 (95% CI = 0.45–2.03) for estrone (P = .02 for interaction).
Absolute changes in sex hormone levels (total and bioavailable estradiol, estrone, estrone sulfate, and sex hormone–binding globulin) between baseline and year 1 were not significantly associated with breast cancer risk.
The investigators concluded: “[T]he risk of breast cancer associated with [estrogen-plus-progestin] therapy is greatest for postmenopausal women who have the lowest circulating estradiol and estrone levels. Thus, pretreatment determination of estradiol and estrone levels may be helpful in identifying women at particularly elevated risk for breast cancer with combined hormone therapy. Further studies are warranted to confirm these findings and extend them to other clinical conditions under [estrogen-plus-progestin] influence.”
The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute at the National Institutes of Health.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
