HRT and breast cancer: better prognosis more likely due to frequent screening than hormone use

While women with breast cancer who have used hormone-replacement therapy are known to have better survival odds than those who’ve never taken hormones, the advantage is due, most likely, to more-frequent mammography screening rather than the effect of the hormones on tumor biology, according to new findings by researchers at Fred Hutchinson Cancer Research Center.

“Most of the good prognostic factors that have been ascribed to HRT – such as smaller tumor size and earlier cancer stage at diagnosis – may simply be an artifact of screening,” said Janet Daling, Ph.D., lead author of the paper, which appears in the current (November) issue of Cancer Epidemiology, Biomarkers and Prevention.

“In many cases probably the HRT itself is doing nothing, other than getting women to the doctor once a year for a prescription renewal – and a mammogram,” said Daling, a member of Fred Hutchinson’s Public Health Sciences Division. Daling and co-authors from five study sites nationwide reported that 90 percent of women who used combination estrogen/progestin HRT had undergone a screening mammogram within two years of breast-cancer diagnosis. In contrast, only 65 percent of women with breast cancer who’d never used HRT had undergone a mammogram during that time period.

The difference in tumor size between the two groups was significant. Among women who’d been screened within two years of diagnosis, 67 percent had tumors smaller than 2 centimeters (about the size of a pea), whereas only about 34 percent of women who hadn’t been screened had tumors that small.

“I was floored when I saw this data,” Daling said, “because tumor size is one of the most important prognostic factors in breast cancer. The difference in the size of the tumors between the two groups was staggering. If that isn’t a good advertisement for mammography screening, then I don’t know what is.”

The findings were based on data from the Women’s CARE (Contraceptive and Reproductive Experience) Study, the first project of its kind to collect detailed information about mammography screening in an attempt to assess markers of breast-cancer prognosis in relation to HRT use, said Daling, the study’s principal investigator.

“Previous studies have shown a link between HRT and improved breast-cancer prognosis, but this is the first to account for screening history as verified by medical records, not just based on the women’s recall,” she said.

The federally funded, multicenter study, which was designed to assess hormonal influences on breast-cancer risk, was based on the analysis of tumors and medical records, as well as in-person interviews, with 2,346 women in Atlanta, Detroit, Los Angeles, Philadelphia and Seattle who were diagnosed with breast cancer between the ages of 50 and 64. About 1,400 of the women had used some form of HRT for six months or more, while the rest had no history of hormone use.

In addition to tumor size, the researchers evaluated the effects of HRT on other markers of prognosis such as tumor stage (how far the cancer has spread), the hormonal sensitivity of the breast tumors (estrogen- and progesterone-receptor status) and tumor histology, or cellular type (ductal versus lobular carcinoma).

“Our goal was to determine whether hormone therapy directly influenced the development of such tumor characteristics at the biological level or whether they were the result of confounding factors such as cancer screening, age and race,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine.

After adjusting for screening history and other factors that can influence breast-cancer outcome, the researchers found several compelling links between HRT use and improved prognosis that did suggest a true impact on tumor biology:

• Among women with a history of continuous-combined HRT, who received estrogen and progestin daily, 73 percent developed estrogen-receptor-positive (ER+) and progesterone-receptor-positive (PR+) breast cancer as compared to 54 percent of women who’d never used HRT. Such hormonally sensitive tumors respond well to estrogen-blocking drugs such as tamoxifen.
• About 20 percent of the women on continuous-combined HRT also developed lobular breast cancer, which tends to be hormonally sensitive, as compared to 12 percent of women who had never used hormones. Such cancer involves the lobules, or chambers in the breast that contain milk-producing glands. While lobular carcinoma accounts for only 10 percent to 15 percent of all breast-cancer cases, it is more treatable than the more common ductal variety, which arises in the ducts that carry milk from the lobules to the nipple. Daling and colleagues earlier this year reported that the incidence of lobular cancer has risen 65 percent during the past decade, a trend that may be due to the increased use of combined HRT.
• After adjusting for screening history, the researchers also found a statistically significant link between the use of unopposed estrogen (estrogen-only therapy) and reduced odds of being diagnosed with more-advanced disease. Women who took estrogen only were 70 percent less likely to be diagnosed with advanced breast cancer as compared to women who’d never taken hormones.

The National Institute of Child Health and Human Development and the National Cancer Institute funded the study. The women in the study were identified through the Surveillance, Epidemiology and End Results, or SEER, program, a national cancer registry operated by the National Cancer Institute. The Centers for Disease Control and Prevention served as the study’s data-coordinating center. Study sites were located at the CDC (Atlanta), Wayne State University (Detroit), University of Southern California (Los Angeles), University of Pennsylvania (Philadelphia) and Fred Hutchinson (Seattle).

The Fred Hutchinson Cancer Research Center, home of two Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center’s four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical partners, the University of Washington Academic Medical Center and Children’s Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 39 nationwide. For more information, visit the center’s Web site at http://www.fhcrc.org.