Additional Research on Menopausal Hormone Therapy and Breast Cancer

A recent study of menopausal hormone therapy and risk of breast cancer reported that risk may vary by body weight and the type of hormone therapy. These results were published in Cancer Epidemiology, Biomarkers, & Prevention.

As women reach menopause and beyond, more than 80% will experience symptoms such as hot flashes, night sweats, sleep disturbance, and vaginal dryness. Estrogen, with or without progestin, is an effective treatment for many of these symptoms. Over the last several years, however, studies have raised important concerns about the health effects of menopausal hormone therapy.

Use of estrogen plus progestin has been linked with an increased risk of heart disease, breast cancer, stroke, and blood clots and a decreased risk of fractures and colorectal cancer. Use of estrogen alone, which is generally reserved for women who have had a hysterectomy, has been linked with an increased risk of strokes and a decreased risk of fractures.

Although it is now well established that menopausal hormone therapy with estrogen plus progestin increases the risk of breast cancer, researchers continue to explore the question of which subgroups of women are at greatest risk. This information would help personalize messages about the risks and benefits of hormone therapy.

The current study evaluated information from the California Teachers Study. Of the more than 56,000 perimenopausal or postmenopausal women in the study, 2,857 developed invasive breast cancer during 10 years of follow-up.

Compared with women who had never used hormone therapy, women who had used estrogen alone for 15 years or longer had a 19% increased risk of breast cancer (A 19% increase in risk means that if a woman has a 5% risk of getting breast cancer in the next 20 years, the risk goes up to 6%.). Women who had used estrogen plus progestin for 15 years or longer had an 83% increased risk of breast cancer (An 83% increase means that if a woman has a 5% risk over 20 years, the risk goes up to approximately 9%).For users of estrogen plus progestin, risk varied by the specific type of regimen used. Continuous regimens (progestin every day of the month) appeared to increase breast cancer risk to a greater extent than sequential regimens (progestin only some days of the month).The increased risk of breast cancer among users of hormone therapy was most apparent among thinner women.Use of hormone therapy increased the risk of cancers that were estrogen receptor-positive and progesterone receptor-positive.

These results provide additional evidence regarding the links between menopausal hormone therapy and risk of breast cancer. Women who are considering hormone therapy to manage menopausal symptoms are advised to talk with their doctor about the risks and benefits.

Reference: Saxena T, Lee E, Henderson K et al. Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study. Cancer Epidemiology, Biomarkers, & Prevention [early online publication]. August 10, 2010.

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Hormone Use Near Menopause May Pose Greatest Breast Cancer Risk

A large study conducted in the UK has reported that early use of menopausal hormone therapy (use before or soon after menopause) may increase breast cancer risk to a greater extent than later use. These results were published in the Journal of the National Cancer Institute. A limitation of this study, however, is that it is an observational study (not a randomized clinical trial), and therefore susceptible to certain types of bias.

For many years, hormone therapy with estrogen (with or without progestin) has provided an effective way for women to manage menopausal symptoms such as hot flashes. Studies over the last several years, however, have raised some concerns about the health effects of hormone therapy. In the Women’s Health Initiative (WHI) clinical trial of estrogen plus progestin, hormone use decreased the risks of fracture and colorectal cancer, but increased the risks of heart disease, breast cancer, stroke, and blood clots.[1] More recent reports suggest that combined hormone therapy may also increase lung cancer mortality.[2] Estrogen alone did not increase the risk of breast or lung cancer in the WHI trial, but did increase risk of stroke.[3]

As research into hormone therapy has continued, there has been growing interest in whether the health effects vary by a woman’s age and proximity to the time of menopause. In the WHI study of combined estrogen plus progestin, for example, the risk of heart disease among hormone users appeared to be greater among women who were farther past menopause.[4] ?The risk of breast cancer among hormone users didn’t clearly vary by time since menopause, although there was a suggestion that earlier hormone use posed a greater risk than later hormone use.[5]

To further explore the timing of menopausal hormone therapy and risk of breast cancer, researchers evaluated information from the UK Million Women Study.[6] Unlike the WHI hormone trials, the Million Women Study is an observational study. In an observational study, scientists do not control the medications that women take. Rather, they observe what happens to women after the women themselves decide whether or not to take a particular medication. A limitation of this type of study is that the women who take a particular medication (such as hormones) are likely to differ from women who do not take the medication; these differences between groups can affect the study results. Researchers attempt to account for differences between groups when they analyze the data, but some differences may be difficult to identify or measure.

The results of the Million Women Study suggest that hormone use that begins close to the time of menopause may increase breast cancer risk to a greater extent than hormone use that begins later:

Among current users of estrogen only, women who began hormone use more than five years after menopause did not have a significantly increased risk of breast cancer. In contrast, women who began hormone use within five years of menopause had a 43% increased risk of breast cancer compared with women who had never used menopausal hormones.Among current users of estrogen plus progestin, women who began hormone use more than five years after menopause had a 53% increased risk of breast cancer, and women who began hormone use within five years of menopause had a roughly two-fold increase in breast cancer risk.

The finding that early use of estrogen alone may increase the risk of breast cancer differs from what was observed in the WHI trial of estrogen alone. Questions remain about whether estrogen alone affects breast cancer risk.

For combined estrogen plus progestin, the finding that earlier use may have a greater effect on breast cancer risk than later use is generally consistent with what was observed in the WHI trial, although the WHI trial did not find strong evidence that risk varied by the timing of hormone use.

Because many factors may influence a woman’s decision about use of hormone therapy to manage menopausal symptoms, women who have questions about the risks and benefits are advised to talk with their healthcare provider.

References:

[1] Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321-33

[2] Chlebowski RT, Schwartz AG, Wakelee H et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374:1243-1251.

[3] Anderson GL, Limacher M, Assaf AR et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004; 291:1701-1712.

[4] Toh S, Hernandez-Diaz S, Logan R, Rossouw JE, Hernan MA. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: does the increased risk ever disappear? A randomized trial. Annals of Internal Medicine. 2010;152:211-217.

[5] Chlebowski RT, Anderson GL, Gass M et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. Journal of the American Medical Association. 2010;304:1684-1692.

[6] Beral V, Reeves G, Bull D, and Green J for the Million Women Study Collaborators. Breast cancer risk in relation to the interval between menopause and starting hormone therapy. Journal of the National Cancer Institute. Early online publication January 28, 2011.

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Hormone Replacement Therapy after Ovary Removal May be Safe for BRCA1/BRCA2 Carriers

For women with BRCA1 or BRCA2 gene mutations, use of hormone replacement therapy after preventive removal of the ovaries and fallopian tubes does not appear to increase the risk of breast cancer. These results were presented at the 2011 annual meeting of the American Society of Clinical Oncology.???

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.??

Options to manage this increased cancer risk include regular cancer screening, chemoprevention (use of medications to reduce risk), or preventive surgery (surgery to remove the breasts and/or ovaries before cancer is diagnosed).?

When performed by the time a woman is in her mid-30s or early 40s, preventive removal of the ovaries can substantially reduce the risk of both ovarian cancer and breast cancer. This reduction in cancer risk, however, comes at the cost of an early menopause and symptoms such as hot flashes, sleep disturbances, and vaginal dryness.??

Hormone replacement therapy (HRT) can effectively manage these symptoms, but it’s been uncertain whether this is safe for women with BRCA1/BRCA2 mutations. Studies in women without these mutations have indicated the combined (estrogen plus progestin) hormone therapy increases the risk of breast cancer.?

To evaluate the risk of breast cancer among BRCA1/BRCA2 carriers who have undergone preventive removal of their ovaries and fallopian tubes, researchers collected information from 795 women with a BRCA1 mutation and 504 women with a BRCA2 mutation. ?

????After ovary removal, breast cancer was diagnosed in 14% of the women who took HRT and 12% of the women who did not take HRT. This difference between groups was not statistically significant, suggesting that it could have occurred by chance alone. By comparison, risk of breast cancer was 22% among women who did not have their ovaries removed and did not take HRT.??

These results suggest that short-term use of HRT to manage menopausal symptoms may be an option for BRCA1/BRCA2 carriers who have had their ovaries removed. HRT did not significantly increase the risk of breast cancer in this population.????

Reference: Domchek SM, Friebl T, Neuhausen SL et al. Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1) and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer? Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 1501.?

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