WHI Trial Suggests Possible Reduction in Breast Cancer Risk with Estrogen Alone

Postmenopausal women who take hormone therapy consisting of estrogen alone may have a somewhat reduced risk of breast cancer. These findings—from longer-term follow-up of the Women’s Health Initiative trial of estrogen alone—were published in the Journal of the American Medical Association. It should be noted that this report addressed only estrogen alone; it did not include combined estrogen plus progestin, which has previously been linked with an increased risk of breast cancer.

Menopause—when menstrual cycles end and ovarian hormone production drops dramatically—produces symptoms such as hot flashes and night sweats in up to 80% of women. When these symptoms are severe, they can have a profound effect on a woman’s quality of life and ability to function.

For many years, hormone therapy with estrogen (with or without progestin) has provided an effective way for women to manage menopausal symptoms. 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]

Initial reports from the WHI study of estrogen alone found that estrogen alone did not appear to increase the risk of breast or lung cancer, but did increase risk of stroke.[3] Because estrogen alone increases the risk of endometrial (uterine) cancer, it is generally only used in women who have had a hysterectomy.

Treatment with hormone therapy was stopped in both of the WHI hormone trials after these early reports, but study participants continue to be followed in order to document longer-term health effects. The current report addressed a range of health outcomes among women who had participated in the study of estrogen alone.[4] Information was available for 7,645 of the original 10,739 women.

Overall, risk of breast cancer was 0.27% among women who had been assigned to the estrogen group compared with 0.35% among women who had been assigned to the placebo group. The increased risk of stroke that was observed during estrogen treatment was no longer apparent after treatment stopped.Younger women (those in their 50s) tended to have more favorable health outcomes with estrogen than older women. Among younger women, for example, estrogen alone was linked with a decreased risk of heart attack; no such decrease was observed among older women.

The researchers note that their results “emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status.”

The finding that estrogen alone may decrease the risk of breast cancer was questioned in an accompanying editorial, which noted that this finding is “inconsistent with a longstanding, corroborated body of evidence…”[5]

Women who are considering using hormone therapy to manage menopausal symptoms are advised to discuss the risks and benefits with their physician.

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] LaCroix AZ, Chlebowski RT, Manson JE et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305:1305-1314.

[5] Jungheim ES, Colditz GA. Short-term use of unopposed estrogen: a balance of inferred risks and benefits. JAMA. 2011;305:1354-1355.

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Phase III Trial Fails to Find Benefit of PARP Inhibitor for Triple-Negative Breast Cancer

In a Phase III clinical trial, the addition of the PARP inhibitor iniparib to chemotherapy did not improve outcomes among women with metastatic triple-negative breast cancer. These results—which differ from those of a prior Phase II clinical trial—were presented at the 2011 annual meeting of the American Society of Clinical Oncology.??

Breast cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.??

Iniparib belongs to a class of drugs called PARP inhibitors. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy. Because many triple-negative breast cancers are thought to have defects in DNA repair, researchers have hypothesized that triple-negative breast cancers may be particularly vulnerable to PARP inhibition.???

A Phase II clinical trial provided hope that iniparib would indeed provide a valuable new treatment option for triple-negative breast cancer. Results published in the New England Journal of Medicine early in 2011 suggested that the addition of iniparib to chemotherapy with GemzarR (gemcitabine) and carboplatin delayed cancer progression and improved overall survival.?[1] Median overall survival was 7.7 months among women treated with chemotherapy alone and 12.3 months among women treated with chemotherapy plus iniparib.?

?A subsequent Phase III clinical trial, however, did not find a benefit. The study enrolled a larger group of women (519 versus 123 in the Phase II trial), and once again compared chemotherapy alone with chemotherapy plus iniparib for the treatment of metastatic triple-negative breast cancer. According to results presented at the 2011 annual meeting of the American Society of Clinical Oncology, the addition of iniparib did not significantly improve overall or progression-free survival.?[2] ?

Although the Phase III results were a great disappointment, it remains possible that iniparib could still provide a benefit to women whose cancer has progressed (worsened) on other treatments. Researchers are continuing to explore whether there are particular subsets of women who respond well to this treatment.?

References:?

[1] O’Shaughnessy J, Osborne C, Pippen JE et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. New England Journal of Medicine. 2011;364:205-214.?

[2] O’Shaughnessy J, Schwartzberg LS, Danso MA et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). Presented at the 2011 annual meeting of the American Society of Clinical Oncology. Chicago, IL. June 3-7, 2011. Abstract 1007.?

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