Avis Antel

From the 1970s onwards into the early 2000’s, hormone therapy was routinely recommended to women going through menopause. Hormone therapy was said to relieve hot flashes, promote strong bones, cardiac and brain health, and keep skin youthful-looking. Although related to a small increased risk of breast cancer, the general consensus was that the benefits outweighed the risks.

The Women's Health Initiative (WHI), a major multi-centre clinical trial that began in the U.S. in 1997, was halted in 2002 when experts judged that the risks to health for those on combined estrogen/progestin outweighed any benefits. Although benefits included a 37 percent reduction in colorectal cancer and a one-third reduction in hip fractures, the rate of women experiencing coronary heart disease increased by 29 percent (relative to placebo), stroke rate was 41 percent higher, the incidence of blood clots doubled, and there was a 26 percent increase in invasive breast cancer. The Million Women Study, a similar study conducted in the U.K., soon found similar results.

The findings of these studies belied many of the proclaimed benefits of hormone therapy and also demonstrated a strong statistical link between hormone use and an increase in breast cancer incidence. Also noted with increased use of hormone therapy was a sizeable increase in the proportion of estrogen receptor positive tumours detected. The results of the WHI were highly publicized and women stopped using hormones in droves.

In mid-December of last year, it was announced that breast cancer incidence in the U.S. had plummeted by 7 percent between 2002 and 2003 (6 percent in the first half of 2003 and 9 percent in the second half of the year). The research, carried out by Dr. Peter Ravdin and his colleagues in the Department of Biostatics at the M.D.Anderson Cancer Center in Texas, also found that the rate of decline in breast cancer incidence was greatest among post-menopausal women; in the over-50 group of women, breast cancer rates dropped by 15 percent.

Previously, small declines in breast cancer incidence have occasionally been observed, and have been attributed to earlier detection and/or the use of chemoprevention such as tamoxifen and raloxifene. The most recent large decrease, however, coincided with the sharp decline in the use of hormone therapy by menopausal and post-menopausal women. Although no definitive cause-and-effect has been established, Dr. Christina A. Clarke, from the Northern California Cancer Center in Fremont, California, reported in the Journal of Clinical Oncology that “hormone therapy use dropped 68 percent between 2001 and 2003 and shortly thereafter breast cancer rates dropped 10-11percent, a drop sustained in 2004.”

There is a school of thought that suggests that while the hormones administered to women in perimenopause and/or post-menopause may fuel the surge in breast cancer incidence, they do not directly cause the cancer, but rather lead to the earlier appearance of tumours when screened. If so, it may be that the growth of tumours might have temporarily slowed, but that we may see a surge in breast cancer incidence again in the coming years. Long-term studies are needed to really understand the role of hormones in the etiology of breast cancer.

Supporting the now-presumed link between the decrease in hormone use and the decreased incidence of breast cancer is the information that California (where a higher proportion of women, especially white women, used hormones) also had a more significant decrease in breast cancer incidence, and that this was seen mainly amongst white women.

Devra Lee Davis, director of the Center for Environmental Oncology at the University of Pittsburgh Cancer Institute, and a long-time proponent of prevention, disagrees with those who link the decline in menopausal hormone use to the decline in breast cancer incidence. She claims that the rapidity of the decline of breast cancer incidence following cessation of hormone use is a questionable cause and effect given that tumours grow so slowly. She also notes the difference in the incidence of this decline of breast cancer between the white community and other racial and ethnic groups, and suggests that there might be other explanations -- for example, the increased use of mammograms by white women, the fact that they have nearly 1000 times lower levels of some growth-promoting pesticides and other toxic chemicals in their bloodstreams and breast milk, or that a greater proportion of black and minority women live and work in areas with higher levels of environmental pollution.

Other naysayers question why there has been no similar downward trend in breast cancer incidence in Canada. Barbara Mintzes, of B.C.’s Centre for Health Services & Policy Research, suggests that, because the Society of Obstetricians and Gynecologists of Canada has been so vocal in its continued support of menopausal hormone use, there may not have been such a sharp decline in hormone use in this country.

It would be interesting to know if there has been a decreased incidence of heart disease in the U.S. or Canada, paralleling decreased use of hormones since, as mentioned above, hormone use is associated with higher rates of coronary disease and stroke.

In conclusion, all sides of the discussion seem to agree that more long-term study and research is needed to see if this supposed link is more than an anomaly. In the long run, if a definitive link is established, the pharmaceutical community will have much to answer for. Physicians and their patients must be able to weigh the real risks and benefits associated with various prescription medications, rather than basing their decision on unsubstantiated claims from pharmaceutical companies.

References:

  • Beral V. and Million Women Study Collaborators. “Breast cancer and hormone-replacement therapy in the Million Women Study” Lancet, Aug. 9, 2003; 362 (9382): 419–27
  • “Breast Cancer Drop Tied to Less Hormone Therapy” MSNBC News Services, Dec.14, 2006 http://www.msnbc.msn.com/id/ 16206352/
  • Davis, Devra L. Quoted in e-mail from Liz Armstrong (Jan. 15, 2007)
  • Kolata, Gina. “Reversing Trend, Big Drop Is Seen in Breast Cancer” New York Times, December 15, 2006
  • Kolata, Gina. “Hormones and Cancer: Assessing the Risks” New York Times, December 26, 2006
  • Kondro, Wayne “Decline in breast cancer since HRT study,” Canadian Medical Association Journal, Jan 16, 2007 ;176(2):160-1
  • Moss, Ralph W. “Thoughts on Breast Cancer and HRT,” part one, in Cancer Decisions, at http://www.decisions.com/010707_page.html and part two at http://www.cancerdecisions.com/011407_page.html
  • U.S. National Library of Medicine’s Medline Plus, “Breast Cancer Rates Drop in U.S.” HealthDay, Dec. 14, 2006 and “HRT Debate Not Over Yet,” HealthDay, Dec. 26, 2006 http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html
  • Women & Health Protection, biojest listserv, accessed on December 20, 2006