Decline in Use of Menopausal Hormones Linked with Lower Breast Cancer Rates

According to the results of a study conducted in Canada, the sharp drop in use of combined (estrogen plus progestin) hormone therapy that occurred between 2002 and 2004 was accompanied by a decrease in breast cancer incidence. These results were published in the Journal of the National Cancer Institute.

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.

In 2002, a report from the Women’s Health Initiative indicated that combined hormone therapy increased the risk of breast cancer, heart disease, stroke, and blood clots.? Use of combined hormone therapy decreased the risk of fractures and colorectal cancer, but these benefits were thought to be outweighed by the risks for most women.

After this report, use of combined hormone therapy declined markedly. Studies from several countries—including the United States—suggest that this decline in hormone use was followed by a decline in breast cancer incidence rates.

To evaluate trends in hormone use and breast cancer in Canada, researchers collected information about women between the ages of 50 and 69 who participated in the National Population Health Survey between 1996 and 2006.

Between 2002 and 2004, the percent of women who used combined hormone therapy decreased from 12.7% to 4.9%. During this same period, the rate of breast cancer declined.Since 2005 there has been some rebound in breast cancer rates. This suggests that avoidance of hormone therapy may act primarily by slowing the growth of breast cancer (rather than preventing breast cancer). Mammography rates remained stable throughout the study period.The study did not have information about the hormone receptor status of the breast cancers that were diagnosed, nor was information available about duration of hormone use.

The researchers conclude that between 2002 and 2004, a decline in hormone therapy use in Canada was accompanied by a decline in breast cancer incidence.

Additional research is warranted to determine the biologic link between hormone therapy and breast cancer. The results of the current study suggest that combined hormone therapy may speed the growth of breast cancers.

Reference: De P, Neutel I, Olivotto I, Morrison H. Breast cancer incidence and hormone replacement therapy in Canada. Journal of the National Cancer Institute [early online publication]. September 23, 2010.

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Avastin May Improve Breast Cancer Response Rates

Among women with HER2-negative breast cancer that has not spread to distant sites in the body, the addition of Avastin to neoadjuvant (before-surgery) chemotherapy may increase the likelihood of a complete response to treatment (a disappearance of detectable cancer). These results were published in the New England Journal of Medicine.

Avastin is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin is used in the treatment of several types of cancer, but its approval for breast cancer was revoked by the US Food and Drug Administration (FDA) in November, 2011.??

Avastin was originally for breast cancer in 2008 under the FDA’s accelerated approval program. The accelerated approval program provides earlier access to promising drugs for life-threatening health conditions while confirmatory studies are conducted. The approval was for use of Avastin in combination with chemotherapy for women with metastatic, HER2-negative breast cancer. The approval was based on the finding that Avastin delayed the progression (worsening) of metastatic breast cancer. There was no evidence that Avastin improved overall survival.??

After 2008, additional studies were reported to the FDA. These studies found that Avastin had only a small effect on rate of cancer progression and no effect on overall survival. The FDA concluded that the potential benefits of Avastin for breast cancer did not outweigh the risks, and revoked Avastin’s approval for breast cancer. Risks of Avastin include severe high blood pressure; bleeding problems; the development of perforations (holes) in the nose, stomach, and intestines; and heart attack or heart failure. It remains possible that Avastin will be found to benefit specific subgroups of breast cancer patients, and the FDA noted that it is open to considering data from additional studies that address this question.???

Results from Avastin clinical trials continue to be reported. Two of these were published in the New England Journal of Medicine and address the use of Avastin in women with earlier-stage (nonmetastatic), HER2-negative breast cancer.?

The first study—the Phase III GeparQuinto trial—enrolled 1,948 women with nonmetastatic, HER2-negative breast cancer.[1] Study participants received neoadjuvant treatment with chemotherapy alone or in combination with Avastin. The primary outcome of interest was a complete response, which was defined in this study as no detectable cancer in the breast or axillary (under-the-arm) lymph nodes.????

A complete response to treatment occurred in 14.9 percent of women treated with chemotherapy alone and 18.4 percent of women treated with chemotherapy plus Avastin.?The greatest benefit of Avastin was observed among women with triple-negative breast cancer (breast cancer that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative). Among these women, the complete response rates were 27.9 percent with chemotherapy alone and 39.3 percent with chemotherapy plus Avastin.?Serious side effects that were more common in the Avastin group included febrile neutropenia (low white-blood cell counts accompanied by fever), mouth sores, hand-foot syndrome, infection, and high blood pressure.?

The second study—the Phase III NSABP B-40 trial—involved 1,206 women with nonmetastatic, HER2-negative breast cancer.[2] Once again, study participants received neoadjuvant treatment with chemotherapy alone or in combination with Avastin. In this study, a complete response was defined as no detectable cancer in the breast; this is a less stringent definition than was used by the GeparQuinto study, which required no detectable cancer in the breast or axillary lymph nodes.????

A complete response to treatment occurred in 28.2 percent of women treated with chemotherapy alone and 34.5 percent of women treated with chemotherapy plus Avastin.?When a more stringent definition of complete response was used (similar to what was used in the GeparQuinto study), the difference between study groups was not statistically significant, suggesting that it could have occurred by chance alone.?The greatest benefit of Avastin was observed among women with estrogen receptor-positive cancer. This differs from what was found in the GeparQuinto study.?Side effects that were more common in the Avastin group included high blood pressure, heart problems, hand-foot syndrome, and mouth sores.?

These results suggest that the addition of Avastin to neoadjuvant chemotherapy may increase the likelihood of a complete response among women with nonmetastatic, HER2-negative breast cancer. Whether this will ultimately translate into improved survival, however, remains uncertain. Overall survival results are not yet available from these studies. The question of whether certain subgroups of patients are more likely to benefit from Avastin than others also remains unanswered, but research is ongoing. Outside of a clinical trial, Avastin should not be used in the preoperative setting; neither of these studies is practice-changing at this time.?

Posted January 30, 2012?

References:?
?[1] von Minckwitz G, Eidtmann H, Rezai M et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. New England Journal of Medicine. 2012;366:299-309.?

?[2] Bear HD, Tang G, Rastogi P et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. New England Journal of Medicine. 2012;366:310-20.?

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Breast Cancer Rates No Longer Declining

After a sharp decline in breast cancer rates between 2002 and 2003 among non-Hispanic white women in the US, overall breast cancer rates did not change significantly between 2003 and 2007. These results were published in Cancer Epidemiology, Biomarkers, & Prevention.

Between 2002 and 2003, breast cancer rates in non-Hispanic white women in the US dropped by 7%. The decrease was most apparent among women between the ages of 50 and 69 and for estrogen receptor-positive (ER+) breast cancers. Non-Hispanic black and Hispanic women did not experience a large decrease in breast cancer rates during this same time period.

Some of the decline in breast cancer rates among non-Hispanic white women was thought to be due to decreasing use of postmenopausal hormones after results from the Women’s Health Initiative (WHI) were published in 2002. The WHI reported that use of combined estrogen plus progestin was linked with an increased risk of breast cancer.

To explore trends in breast cancer rates after 2003, researchers collected information from a large US cancer registry (the Surveillance, Epidemiology, and End Results program). Another database (from the National Health Interview Survey) was used to evaluate trends in postmenopausal hormone use.???

Between 2003 and 2007, overall breast cancer rates did not change significantly among non-Hispanic white women, non-Hispanic black women, or Hispanic women.Use of postmenopausal hormones continued to decrease from 2005 to 2008, but to a lesser extent than it did between 2000 and 2005.

In summary, the decline in overall breast cancer rates that occurred among non-Hispanic white women between 2002 and 2003 did not continue after 2003. Overall breast cancer rates remained fairly stable between 2003 and 2007.

Reference: DeSantis C, Howlader N, Cronin KA et al. Breast cancer incidence rates in US women are no longer declining. Cancer Epidemiology, Biomarkers, & Prevention. Early online publication February 28, 2011.

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