HRT PROMOTION OR CAUSE OF BREAST CANCER?

September 24, 2010 — A dramatic decrease in use of hormone replacement therapy (HRT) during a 2-year period in Canada coincided with lower breast cancer incidence, mirroring what happened in the United States, according to a new study published online September 23 in the Journal of the National Cancer Institute.

The use of HRT, once favored for treating the symptoms of menopause, decreased in the wake of a 2002 report of results from the Women's Health Initiative clinical trial that found that the treatment came with an increased risk for breast cancer, stroke, and myocardial infarction.

In Canada, the proportion of women aged 50 to 69 years who reported using combined HRT — estrogen and progestin — declined from 12.7% in 2002 to 4.9% in 2004, according to the study. The incidence of breast cancer in this age group declined 9.6% during that period, even as mammography rates remained steady.

"The results support the hypothesized link between the use of [HRT] and invasive breast cancer incidence and indicate that the sharp decline in breast cancer incidence in 2002 is likely explained by the concurrent decline in the use of [HRT] among Canadian women," write lead author Prithwish De, PhD, an epidemiologist with the Canadian Cancer Society, and colleagues.

The Canadian researchers note the same trend in the United States, pointing to an 11.8% decline in invasive breast cancer between 2001 and 2004 for women aged 50 to 69 years, as reported by the US Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. During this time, prescriptions for estrogen–progestin and conjugated equine estrogen declined from 60 million to slightly more than 20 million.

Does HRT Promote Rather Than Cause Breast Cancer?

After taking a 2-year dip, the incidence of breast cancer in Canada began to rise again in 2005, except for women aged 40 to 49 years. The Canadian researchers attempt to make sense of this reversal, surmising that such a rebound might be expected "if occult hormone-sensitive tumors were merely slowed by the withdrawal of [HRT,] rather than prevented by it."

If this is true, "[HRT] may be thought to act as a promoter rather than as a putative cause of breast cancer," Dr. Prithwish and colleagues write.

Another statistical wrinkle in the link between HRT and breast cancer is that the incidence of breast cancer among older women had started to decline in 1998, 4 years before the Women's Health Initiative report sounded its alarms about HRT. The authors try to explain that, too. Published research in the late 1990s that downplayed the cardiovascular benefit of HRT may have dampened enthusiasm for the treatment, they write. In addition, an upswing in mammography rates may have caused the number of detectable cases of breast cancer to reach a saturation point.

The authors acknowledge several limitations to their research. Because the study was ecological in design, it looks at trends only at a population level, they write. Self-reported use of HRT is subject to recall bias and does not reflect how long or how frequently women took these hormones. And the authors could not confirm whether changes in breast cancer incidence primarily involved estrogen receptor–positive tumors, because receptor status is not routinely gathered at the national level for Canadian patients with the disease.

The study was conducted with author contributions in-kind. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online September 23, 2010. Abstract