Protective Role Seen for Hormone Therapy in BRCA1 Carriers
TORONTO, Sept. 23 (MedPage Today) -- Hormone therapy did not increase the risk of breast cancer in postmenopausal women with a BRCA1 mutation, according to a case-control study.
Additionally, women who took estrogen alone appeared to have a slightly decreased risk of breast cancer, Steven A. Narod, M.D., of the, University of Toronto, and colleagues reported in the Sept. 23 issue of the Journal of the National Cancer Institute.
Compared with postmenopausal women who were genetically predisposed to breast cancer who never used hormone replacement, women who used hormone replacement had an odds ratio for developing cancer of 0.58 (95% CI 0.35 to 0.96, P =0.03) and women who took only estrogen had an OR of 0.51 (95% CI 0.27 to 0.98 P =0.04).
There was no statistically significant association between the use of estrogen/progesterone, (OR: 0.66, 95% CI 0.34 to 1.27, P =0.21), they wrote.
Dr. Narod and colleagues conducted a matched case-control study of 472 postmenopausal women with a BRCA1 cancer-susceptibility mutation. Cases and controls were matched for chronological age, age at menopause, use of oral contraceptives, smoking, and parity.
A higher percentage of controls (29%) than cases (20%) used hormone therapy (P =0.02).
The average duration of hormone therapy was four years in case patients versus 3.7 years in controls (NS).
The authors said they investigated the relationship between hormone use and breast cancer risk because prophylactic oophorectomy has become a standard of care for women with a BRCA1 or BRCA2 mutation.
In that select population, oophorectomy has been associated with at least a 50% reduction in risk of breast cancer and a reduction of more than 80% in risk for ovarian or peritoneal cancer.
But women might be reluctant to undergo premenopausal oophorectomy because of the effects of surgical menopause and the concern that use of hormone therapy to relieve symptoms could again increase their risk of breast cancer, the authors said.
"We observed an OR below unity, indicative of an inverse association between [hormone therapy] use and breast cancer risk," they wrote.
In an accompanying editorial, Rowan T. Chlebowski, M.D., Ph.D., of Harbor-UCLA Medical Center in Torrance, Calif., and Ross L. Prentice, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle said that the findings from the case-control study provided "some evidence for safety [of hormone replacement] but are insufficient to reliably inform routine clinical practice."
As a result, they noted the editorial comments published four years ago (Garber FJ, Hartman, "Prophylactic oophorectomy and hormone replacement therapy: protection at what price?" J Clin Oncol 2004; 22:978-980) "many aspects of the effects of menopausal hormone therapy on breast cancer risk in mutation carriers are unknown."
Drs. Chlebowski and Prentice specifically questioned the case and control populations, pointing out that "the described methodology suggests that separate and perhaps disparate populations were used to identify case patients and control subjects."
Amos Pines, M.D., , of Ichilov Medical Center in Tel-Aviv, the immediate past president of the International Menopause Society, said in a prepared statement that the results of the study may be relevant for only 3% of women.
Nonetheless, Dr. Pines said the findings show that hormone replacement therapy "in a higher risk population is not necessarily associated with more cases of breast cancer during the first years of hormone use."
He said the data supported his group's view that "hormone therapy in early postmenopausal period is safe and may be prescribed without concerns when needed."
The authors noted several limitations of the study, including the small size and the fact that only prevalent cases were studied. Thus, they pointed out, "if previous hormone therapy use was associated with a decreased survival of breast cancer following a diagnosis of breast cancer, then we may see few hormone therapy users among long- time breast cancer survivors, resulting in a spurious negative association."
The study was funded by the Canadian Research Alliance and the National Institutes of Health.
Dr. Narod reported no financial disclosure. Dr. Chlebowski has been a consultant for AstraZeneca, Novartis Pharmaceuticals, Eli Lilly, Pfizer, and Wyeth and is on the speaker's bureau for AstraZeneca and Novartis. Drs. Prentice and Pines reported no financial disclosure.
Primary source: Journal of the National Cancer Institute Source reference: Eisen A et al "Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers" J Natl Cancer Inst 2008; 100: 1361-1367; Chlebowski RT and Prentice RL "Menopausal Hormone Therapy in BRCA1 Mutation Carriers: Uncertainty and Caution" J Natl Cancer Inst 2008; 100: 1341-1343
What breastcancer.org says about this article…
Protective Role Seen for Hormone Therapy in BRCA1 Carriers
The small study reviewed here found that post-menopausal women who have an abnormal BRCA1 gene who used combination hormone replacement therapy (HRT) had the same risk of developing breast cancer as women with an abnormal BRCA1 gene who didn't use HRT.
Combination HRT includes both estrogen and progesterone. Women with an abnormal BRCA1 gene who used estrogen-only HRT had a slightly lower risk of breast cancer compared to women with an abnormal BRCA1 gene who didn't use HRT.
Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2). Women with an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70. Their risk of ovarian cancer is also increased. Abnormal BRCA1 and BRCA2 genes are found in 5% to 10% of all breast cancer cases in the United States.
Because of their risk of breast cancer is higher, many pre-menopausal women with an abnormal breast cancer gene choose to have their ovaries removed (a procedure called oophorectomy). Oophorectomy can lower the risk of BOTH breast and ovarian cancer by quite a bit. Removing the ovaries causes a sudden drop in estrogen levels. While this helps lower breast cancer risk, it also can cause menopausal symptoms, such as hot flashes. Some women may consider using HRT after oophorectomy to ease menopausal symptoms, but may be concerned that HRT may increase breast cancer risk.
Research has shown that HRT, especially combination HRT, increases the risk of breast and ovarian cancer, as well as heart attack and stroke. Still, the side effects of menopause can dramatically reduce some women's quality of life. These women have to weigh the benefits of HRT against the risks. Using HRT for the shortest time possible is one way to minimize the risks. The women in this study used HRT for 3 to 4 years.
Doctors who reviewed this study said because the study is so small, the results aren't definitive enough to say for certain that women with an abnormal breast cancer gene who use HRT don't increase their breast cancer risk.
If you're pre-menopausal woman with an abnormal breast cancer gene, you may be considering oophorectomy to reduce your risk. And you also may be worried about developing menopausal symptoms after surgery. Those concerns are understandable, but try not to let them shift your focus from making the best decisions for your health. If you've already had your ovaries removed and are having menopausal symptoms, you may be considering HRT but are worried about the risks.
In either case, you and your doctor should carefully consider both the risks and benefits of using HRT. Together you can decide if HRT -- or another treatment to ease menopausal side effects -- might be right for you. If you decide to use HRT, use it for the shortest time possible, consider using estrogen-only HRT, and try to make other healthy lifestyle choices that can lower your breast cancer risk. And remember, during and after HRT make sure to follow the breast cancer screening plan recommended by your doctor for your specific risks and situation.
You can read more about approaches to help ease hot flashes on the Breastcancer.org All About Hot Flashes page.
