Sharp Decline in Breast Cancer Linked to HRT, Study Shows

Allison Gandey

April 18, 2007

April 18, 2007 — Researchers have observed a dramatic fall in breast cancer incidence that perfectly mirrors the decline in the use of hormone replacement therapy (HRT). Many women stopped taking hormones at the end of 2002, when the pivotal Women's Health Initiative study was prematurely stopped and the safety of the drugs was called into question. The combination of estrogen and progestin appeared to significantly increase the risk for invasive breast cancer. While these latest data, reported in the April 19 issue of the New England Journal of Medicine, cannot establish a cause-and-effect relationship, researchers show a 6.7% fall in breast cancer
in 2003 — a decline that has never before been seen in a single year.

"I was surprised by the precipitous drop in breast cancer incidence that started immediately after the announcement of the Women's Health Initiative results and the consequent decrease in the use of HRT," senior author Donald Berry, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, told Medscape. "But when I realized that stopping a cancer's fuel could slow its growth, it seemed quite reasonable."

As previously reported by Medscape, the researchers first presented their findings at the 29th Annual San Antonio Breast Cancer Symposium (San Antonio Breast Cancer Symposium: Abstract 5. Presented December 14, 2006). "Something went right in 2003," lead investigator Peter Ravdin, MD, also from MD Anderson, told reporters attending the December meeting. The findings made international headlines and were widely reported by media. Those attending the session called the results "fascinating" and "provocative."

Another research team reporting last year in the November 20, 2006 issue of the Journal of Clinical Oncology came to similar conclusions (Clarke CA et al. J Clin Oncol. 2006;24:e49-50). "Hormone therapy use dropped 68% between 2001 and 2003, and shortly thereafter we saw breast cancer rates drop by 10% to 11%," lead author Christina Clarke, MD, from the Northern California Cancer Center, in Fremont, said in a news release. "This drop was sustained in 2004, which tells us that the decline wasn't just a fluke."

Ahmedin Jemal, PhD, an epidemiologist at the American Cancer Society, who has studied in this area, told Medscape that he agrees the recent decline in breast cancer is probably linked to the decline in HRT use. "It is likely related," he said during an interview. "We know that estrogen-positive cancers tend to increase when HRT is used." Dr. Jemal does not rule out the possibility that other factors may also be contributing to the trend. His research team is working on another soon-to-be-published breast cancer study examining the clinical implications.

Affects Women Aged 50 Years or Older


In the present analysis, the researchers looked at data from the Surveillance Epidemiology and End Results (SEER) database, a program of the National Cancer Institute (NCI). They collected information from 9 cancer registries, representing 9% of the US population.

The decline in breast cancer was seen only in women aged 50 years or older and was more evident in cancers that were estrogen-receptor-positive than in those that were estrogen-receptor-negative. Other potential explanations for the trend include changes in reproductive factors, in mammographic screening, in environmental exposures, and in diet. "Of these factors," the researchers write, "only the use of hormone-replacement therapy changed substantially between 2002 and 2003."

The investigators point out that other medications can also influence the incidence of breastcancer. These drugs include tamoxifen
and raloxifene
, and there is some evidence for beneficial effects of nonsteroidal anti-inflammatory drugs, statins, and calcium and vitamin D
supplements. "However," they note, "none of these agents were used by a substantial portion of postmenopausal women or showed substantial change in use during the period from 2000 to 2004. Therefore, the drugs are unlikely candidates for causing the decrease in incidence."

Women participating in the Women’s Health Initiative hormone trial were asked to discontinue their study medications but were encouraged to continue undergoing annual mammography
. These women continue to be followed, and a report of the combined estrogen-plus-progestin trial is anticipated later this year. These much-anticipated results will help shed light on the effect of stopping HRT and its potential role in breast cancer.

Many important questions remain. "Can we expect only a delay in the appearance of clinically detectable tumors, with no reduction in long-term incidence, or will there be a long-term reduction?" the researchers wonder. "A change in the hormonal milieu may have slowed the growth of tumors slightly or temporarily. If this is the case, as the use of hormone-replacement therapy stabilizes, breast-cancer incidence should rise again," they hypothesize. "Alternatively, the change in hormonal milieu may have a more profound effect similar to that of hormonal adjuvant therapy."

Responding to the study findings, Steven Ory, MD, president of the American Society for Reproductive Medicine, told reporters today, "Whether or not this phenomenon is an anomaly in an otherwise increasing trend will become clearer as we continue to follow breast cancer rates and HRT usage in women in different age groups." He noted, "Hormone replacement does offer the most effective way to manage the symptoms of menopause
for women in the menopausal transition. While these data from the SEER registry show a possible trend, other studies have failed to show an increase in breast cancer incidence in younger women with 5 years or less of HRT use. Whether or not a woman should use HRT is an individual decision she must make after discussing her own needs and risk factors with her physician.”

Dr. Berry told Medscape that he agrees that HRT may be a reasonable option for women struggling with the effects of menopause. But he emphasized the importance of short-term therapy. He noted, "There are no benefits and there may be harms for long-term use."

N Engl J Med
2007;356:1670-1674.

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