Estrogen-Only Therapy May Reduce Breast Cancer Risk --Doctors Lounge

Medpage: LaCroix A, et al "Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial" JAMA 2011; 305: 1305-1314.

Blogger's Note: also see website for video

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New WHI Estrogen Analysis Shows Lower Breast Ca Risk

By John Gever, Senior Editor, MedPage Today

Published: April 05, 2011

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points

• Explain that post-intervention follow-up of the WHI Estrogen-Alone Trial showed that both risks and benefits of unopposed estrogen largely disappeared after therapy stopped.
• Note that while the risk of breast cancer remained decreased for the intervention and post-intervention period combined, the decreased risk during the post-intervention period itself was not statistically significant.

In contrast to other studies of unopposed postmenopausal estrogen therapy, long-term follow-up of Women's Health Initiative (WHI) Estrogen-Alone Trial participants showed a persistent reduction in breast cancer risk, researchers said.

But other benefits and risks associated with use of conjugated equine estrogens (CEE) quickly dissipated after the therapy was stopped, according to Andrea Z. LaCroix, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

"Considering the entire follow-up period, rates of total mortality and the global index of chronic diseases were essentially the same in the conjugated equine estrogen and placebo groups," LaCroix and co-authors wrote in the April 6 issue of the Journal of the American Medical Association.
"Statistically significant age interactions for conjugated equine estrogen use, suggesting greater safety and possible benefit among women in their 50s and potential harm among older women, were observed for coronary heart disease, total MI, colorectal cancer, total mortality, and the global index of chronic diseases," they added.

An editorial in the same issue suggested more caution in interpreting the breast cancer results.

abstract: Unopposed estrogen and estrogen plus progestin menopausal hormone therapy and lung cancer risk in the NIH-AARP Diet and Health Study Cohort

Abstract

PURPOSE:

Previous studies have reported that lung cancer risk may be decreased, increased, or unaffected by prior use of menopausal hormone therapy (MHT).

CONCLUSIONS:

Our results failed to support any substantial alterations in lung cancer risk associated with use of either unopposed estrogen or estrogen plus progestin MHT, even when detailed exposure measures and other risk predictors were considered.

Hormone therapy for menopausal symptoms | BMJ

 Editorial

Hormone therapy for menopausal symptoms

BMJ 2012; 344 doi: 10.1136/bmj.e815 (Published 8 February 2012)

Cite this as: BMJ 2012;344:e815

Access to the full text of this article requires a subscription or payment. 

"Recent evaluations of the methods of key studies should not change how we advise wome.

A recently published and much publicised paper by Shapiro and colleagues, the last in a series of four, evaluated the effects of hormone therapy on the risk of breast cancer.1 

The authors of the four review articles applied epidemiological principles to the findings of two randomised placebo controlled studies from the Women’s Health Initiative (WHI; 27 347 women) and two observational studies—the Collaborative Reanalysis (53 865 women) and the Million Women Study (MWS). Shapiro and colleagues concluded in their fourth paper that the MWS had design defects, that it contained multiple biases, and that its findings were thus not robust enough to show that hormone therapy increased the risk of breast cancer.

All observational studies are inherently biased because subjects are not randomly assigned to treatment or control. Adjustment for confounders and careful design of observational studies help to reduce bias. However, because there is no independent variable, such studies can tell us only about association not causation.

The MWS was published in the Lancet in August 2003,2 and a flurry of letters was published in a print issue later that year, many …"

HRT Post Oophorectomy Adds No Breast Cancer Risk : Internal Medicine News

"....The PROSE database was developed by 20 centers in the United States and Europe who identified and prospectively followed women with a deleterious BRCA1 or BRCA2 mutation. For the study, the investigators focused on those who at ascertainment had at least one ovary, no prior breast or ovarian cancer, no prior bilateral mastectomy, and at least 6 months of follow-up. ...."

press release International Menopause Society - Global expert review confirms that Hormone Replacement Therapy needs to be customised but is safe for most women.

University of Pennsylvania School of Medicine - Women with BRCA mutations can take hormone-replacement therapy safely after ovary removal

CHICAGO) ––

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania which will be presented Monday, June 6 during the American Society for Clinical Oncology's annual meeting (Abstract #1501). Results of the prospective study indicated that women with BRCA mutations who had their ovaries removed and took short-term HRT had a decrease in the risk of developing breast cancer...............

Domchek says some of the confusion about the role of HRT in cancer risk elevation comes from the fact that the risks and benefits associated with HRT depend on the population of women studied. In this group of women – who have BRCA1/2 mutations and who have had their ovaries removed while they are quite young – HRT should be discussed and considered an option for treating menopausal symptoms. "People want to make hormone replacement therapy evil, so they can say 'Don't do it,'" she says. "But there isn't one simple answer. The devil is in the details of the studies."

By contrast, Penn researchers and their collaborators in the PROSE consortium have shown definitively that oophorectomy reduces ovarian and breast cancer incidence in these women, and reduces their mortality due to those cancers. But paying attention to the role that hormone depletion following preventive oophorectomy plays in women's future health (blogger's note: eg. cardiovascular) is also important............"

abstract: The effect of estrogen vs. combined estrogen-progestogen therapy on the risk of colorectal cancer

"While literature for the association between ET and CRC risk is heterogeneous, our analyses suggest only current use of ET is associated with a decreased CRC risk."