Estrogen plus progestin increased incidence of breast cancer, mortality

Issue: May 25, 2013

New data suggest that estrogen plus progestin use is linked to increased breast cancer incidence and mortality. These findings are consistent with results from the Women’s Health Initiative randomized trial.

Perspective from Robert W. Rebar, MD

“This study shows that women who begin the hormonal therapy of estrogen plus progestin closer to menopause are at greater risk of breast cancer than those who started the therapy earlier. Because menopause usually is the reason for women to undergo hormonal therapy, this is a very significant finding,” researcher Rowan T. Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute, said in a press release.

Rowan T. Chlebowski

To examine the differences, Chlebowski and colleagues studied a cohort of patients from the Women’s Health Initiative (WHI) observational study (n=41,449). The postmenopausal women had no prior hysterectomy or negative mammogram within 2 years and were not hormone users (n=25,328) or estrogen and progestin users (n=16,121).

“The study also showed that all categories of breast cancer are increased — not just those with favorable prognosis — among women using estrogen plus progestin. This finding suggests higher mortality from breast cancer among women who use this combined hormonal therapy. As always, women should consult with their physicians and consider the potential risks of any hormonal therapy to help relieve the symptoms of menopause,” Chlebowski said.

According to data, after a mean of 11.3 years, with 2,236 breast cancers identified, researchers reported that the incidence was greater among patients administered estrogen plus progestin vs. nonusers (0.6% vs. 0.42%; HR=1.55; 95% CI, 1.41-1.70).

In women who began HT closer to menopause, the risk for breast cancer was greater with linear diminishing influence as time from menopause increased (P<.001), the researchers wrote. Moreover, researchers reported that survival after breast cancer, measured from the time of diagnosis, was similar in combined HT users and nonusers (HR=1.03; 95% CI, 0.79-1.35).

On a population basis, data suggest that more deaths from breast cancer, measured from cohort entry (HR=1.32; 95% CI, 0.90-1.93), and more all-cause deaths after breast cancer (HR=1.65; 95% CI, 1.29-2.12), they added.

In an accompanying editorial, Catherine Schairer, PhD, and Louise A. Brinton, PhD, MPH, of the National Cancer Institute, wrote that lingering questions remain.

“In general, tumors in estrogen plus progestin users in the WHI Observational Study were not significantly different from those in nonhormone users with regard to number of positive lymph nodes or tumor size, but were more likely to be well differentiated and positive for hormone receptors, findings which are similar to other observational studies,” Schairer and Brinton wrote.

Additionally, they suggest further analysis of the dataset in conjunction with other observational studies with updated information on several characteristics to appropriately identify biological differences between tumors.

For more information:

Chlebowski RT. J Natl Cancer Inst. 2013;doi:10.1093/jnci/djt043.

Schairer C. J Natl Cancer Inst. 2013;doi:10.1093/jnci/djt058.

Perspective

Robert W. Rebar, MD

Investigators now report the effects of use of combined estrogen and progestin (so-called hormone therapy) in women in the Women’s Health Initiative Observational Study on breast cancer incidence and mortality after follow-up of a mean of 11.3 years. Utilizing data from over 41,000 enrolled women with no prior hysterectomy and mammogram negative within two years of enrollment who were either using HT or not, Chlebowski and colleagues report that the incidence of breast cancer was higher (HR=1.55; 95% CI, 1.41-1.70) in HT users. The risk of breast cancer was increased when HT was initiated close to menopause and decreased linearly with time of onset of use after menopause (P<.001). There were somewhat more deaths from breast cancer after study enrollment (HR=1.32; 95% CI, 0.90-1.93) and more all-cause deaths after breast cancer (HR=1.65; 95% CI, 1.29-2.12) in the HT users. Because prognosis after diagnosis for those on HT and those not using HT, the authors conclude that increased breast cancer mortality can be expected.

The authors stress that this study adds to the literature in the field and caution against recommending HT use in women who are not debilitated by their menopausal symptoms because widespread use would likely increase deaths from breast cancer. What they do not say is that once more the increased risk is quite modest. For women who clearly would benefit from use of HT, the risks are increased very little – especially compared to other risk factors for breast cancer. Yet the press is once more likely, as are most clinicians,

Robert W. Rebar, MD

Endocrine Today Editorial Board Member

Executive Director of the American Society for Reproductive Medicine

Disclosures: Rebar reports serving on the NIH Data and Safety Monitoring Board and being an editor for Journal Watch from the Massachusetts Medical Society.