Postmenopausal women who take hormone therapy - estrogen plus progestin - not only have an increased risk of developing breast cancer, but also of a faster progressing one, researchers from the Los Angeles Biomedical Research Institute reveal in an article published in the peer-reviewed journal JAMA (Journal of the American Medical Association). Taking into account both risks, the risk of breast cancer death is also higher, the investigators report after following-up participants in the Women's Health Initiative (WHI) for approximately 11 years.
Hormone therapy, often referred to when treating women for perimenopausal symptoms as hormone replacement therapy (HRT), is a system of medical treatment for surgically menopausal, premenopausal and also postmenopausal women to a lesser extent. It is aimed at preventing discomfort caused by falling levels of circulating estrogen and progesterone hormones. Hormone therapy involves using one or more of a group of drugs designed to artificially increase hormone levels, mainly levels of estrogens, progesterone (pregostins), and occasionally testosterone. In this text, the researchers focused on women receiving combination estrogen plus progestin.
The researchers looked at the outcomes of a Women's Health Initiative randomized, placebo-controlled clinical trial of estrogen plus progestin hormone therapy. They found that following an intervention period of 5.6 years and 7.9 years of average follow-up, the incidence of breast cancer was significantly higher among participants in the hormone therapy group compared to those on placebo.
The scientists wrote:
..questions of clinical relevance remain, including the cumulative, long-term effect of estrogen plus progestin on breast cancer incidence and whether breast cancer mortality is increased by combined hormone therapy use.
Rowan T. Chlebowski, M.D., Ph.D., not only examined data and revised information on the incidence of breast cancer, but also cancer mortality details of women in the WHI trial who received combined hormone therapy, which had never been done before.
The WHI trial consisted of 16,608 females from 40 clinical centers in the USA, all were postmenopausal, none of them had had a hysterectomy - they were aged between 50 and 79 years. They were randomly selected to receive either equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d or a placebo - in both groups they were given identically-looking pills. The trial was completed on March 31 2005, after which 83% of them (12,788) consented to follow-up monitoring for breast cancer.
The investigators found that the invasive breast cancer rate among those on combined hormone therapy was 0.43% compared to 0.34% for those on placebo. 23.7% of the hormone therapy group women who developed breast cancer had positive lymph nodes versus 16.2% in the placebo group.
Put simply, not only did more hormone therapy participants develop breast cancer compared to those on placebo, but a higher percentage of hormone therapy patients also had more advanced breast cancer.
The authors wrote:
More women died of breast cancer in the combined hormone therapy group compared with the placebo group (25 deaths [0.03 percent per year] vs. 12 deaths [0.01 percent per year]), representing 2.6 vs. 1.3 deaths per 10,000 women per year, respectively. Consideration of all-cause mortality after breast cancer diagnosis provided similar results; among women in the combined hormone therapy group, there were 51 deaths (0.05 percent per year) compared with 31 deaths (0.03 percent per year) among women in the placebo group, representing 5.3 vs. 3.4 deaths per 10,000 women per year, respectively.
With some exceptions, the preponderance of observational studies have associated combined hormone therapy use with an increase in breast cancers that have favorable characteristics, lower stage, and longer survival compared with breast cancers diagnosed in nonusers of hormone therapy. However, in the WHI randomized trial, combined hormone therapy increased breast cancer risk and interfered with breast cancer detection, leading to cancers being diagnosed at more advanced stages. Now, with longer follow-up results available, there remains a cumulative, statistically significant increase in breast cancers in the combined hormone therapy group, and the cancers more commonly had lymph node involvement. The observed adverse influence on breast cancer mortality of combined hormone therapy can reasonably be explained by the influence on breast cancer incidence and stage.
The researchers note that there was a considerable drop in breast cancer incidence in the USA after significantly fewer women were on hormone therapy following the initial reports from the WHI trial linking such therapy with breast cancer risk.
The authors add:
The adverse influence of estrogen plus progestin on breast cancer mortality suggests that a future reduction in breast cancer mortality in the United States may be anticipated as well.
Accompanying EditoriaPeter B. Bach, M.D., M.A.P.P., of Memorial Sloan-Kettering Cancer Center, New York, commented:
..the available data dictate caution in the current approach to use of hormone therapy, particularly because one of the lessons from the WHI is that physicians are ill-equipped to anticipate the effect of hormone therapy on long-term health. Clinicians who prescribe brief courses of hormone therapy for relief of menopausal symptoms should be aware that this approach has not been proven in rigorous clinical trials and that the downstream negative consequences for their patients are of uncertain magnitude. One option - discussing with patients the risk-benefit tradeoffs in pursuit of an informed patient decision - may seem at first blush to be a reasonable approach given this lack of evidence. But the reality is that informed patient decisions are not valid when the information underlying the decision is itself speculative.
"Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women"
Rowan T. Chlebowski, MD, PhD; Garnet L. Anderson, PhD; Margery Gass, MD; Dorothy S. Lane, MD; Aaron K. Aragaki, MS; Lewis H. Kuller, MD; JoAnn E. Manson, MD, DrPH; Marcia L. Stefanick, PhD; Judith Ockene, MD; Gloria E. Sarto, MD; Karen C. Johnson, MD, MPH; Jean Wactawski-Wende, PhD; Peter M. Ravdin, MD, PhD; Robert Schenken, MD; Susan L. Hendrix, DO; Aleksandar Rajkovic, MD, PhD; Thomas E. Rohan, PhD; Shagufta Yasmeen, MD; Ross L. Prentice, PhD; for the WHI Investigators
JAMA. 2010;304(15):1684-1692. doi:10.1001/jama.2010.1500
Written by Christian Nordqvist