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    SUMMARIES OF NEWSWORTHY CLINICAL TRIAL RESULTS  
 
    Posted: 02/27/2006
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Age, Type of Chemotherapy Affect Women's Chances of Menstruating after Breast Cancer Treatment

Key Words

Breast cancer, menstruation, fertility. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

This observational study found that premenopausal breast cancer patients were more likely to return to their normal menstrual cycles after chemotherapy-induced amenorrhea if they were younger than 35 and if their chemotherapy had been an anthracycline-based regimen. The breast cancer hormone treatment tamoxifen also disrupted some women’s menstruation, but the modest effect disappeared after three years.

Source

Journal of Clinical Oncology, published online Feb. 13, 2006; in print March 1, 2006 (see the journal abstract).
(J Clin Oncol. 2006 Feb 13; [Epub ahead of print])

Background

The most common treatment for breast cancer is surgery, followed by chemotherapy to kill any lingering cancer cells and to reduce the risk that the disease will return. But chemotherapy can disrupt a woman’s menstrual cycle, causing it to stop (amenorrhea), at least temporarily. This is a potentially serious problem for younger patients still hoping to become pregnant.

The scope of the problem isn’t well understood. Rates of amenorrhea caused by chemotherapy have varied widely depending on the study, from 21 percent to 100 percent. The study described here is the most authoritative to date on the impact of breast cancer drug and hormone treatments on menstrual cycling.

The Study

Researchers in this multicenter observational study enrolled 595 women between January 1998 and July 2002 who had been diagnosed with breast cancer within the previous eight months. All of the women were premenopausal, though about ten percent were not menstruating at the time of diagnosis. All were between 18 and 45 years old and had had surgery to remove their cancer.

The women were followed during the normal course of their treatment, as determined by their doctors. After surgery, 523 (87 percent) received some kind of chemotherapy, usually a combination of drugs. These drugs included doxorubicin (Adriamycin®), cyclophosphamide, paclitaxel (Taxol®), and others. Women on the same regimens received similar doses on similar schedules.

Three hundred and forty (57 percent) women also received hormone treatments. Of these, most (329) got tamoxifen.

Researchers asked the patients to keep track of their own menstrual bleeding during this time and continued to check on the women’s medical condition. The women were followed for a median of 45 months.

The study’s lead author was Jeanne A. Petrek, M.D., from the Memorial Sloan Kettering Cancer Center in New York City.

Results

Overall, menstrual cycling dropped dramatically when chemotherapy began, though less so in women under age 40. After chemotherapy ended, the number of women who resumed their monthly cycle rose for 15 months, to nearly 55 percent, and then eventually declined to about 35 percent five years after they were diagnosed. (Because the average age of women at diagnosis was 39.5 and the study follow-up period continued for another five years, many of these women might well have experienced natural menopause during this time, regardless of their cancer treatment.)

Women under age 35 recovered most rapidly, with 85 percent resuming their menstrual cycle within six months of ending chemotherapy and continuing monthly bleeding throughout the follow-up period.

Though age was the biggest factor, the results also differed depending on which chemotherapy drugs the women took. Nearly half (48 percent) of the 83 women receiving the CMF regimen (cyclophosphamide, methotrexate, and fluorouracil) had menstrual bleeding the month after chemotherapy ended, compared to just 16 percent of the 307 women receiving one of three AC-based regimens (Adriamycin and cyclophosphamide, whether or not followed by paclitaxel or docetaxel).

However, over time the number of CMF-treated women who were menstruating continued to decline (to about 18 percent by the end of the study) while many women who had received an AC-based treatment began to recover their menstrual cycles. By the end of the study about half of the women in the AC-based group were menstruating.

As for hormone treatment, about 15 percent of the women receiving tamoxifen experienced amenorrhea, mostly between one and two years after starting the drug. This was true regardless of what (if any) chemotherapy they received. Three years after starting the drug, women on tamoxifen were just as likely to be menstruating as those not on tamoxifen. The authors state that “the effect on the ovary [of tamoxifen] is assumed to be reversible and temporary.”

Comments

“This study reaffirmed that older age is strongly related to decreased menstrual bleeding” after breast cancer treatment, wrote the authors. The other major finding, they noted, was that, regardless of age, women’s menstrual cycles were affected differently depending on which chemotherapy regimen they received.

This and other studies, they said, suggest that “[a]menorrhea seems most related to the cumulative dosage of cyclophosphamide…almost all programs based on anthracyclines [such as Adriamycin] have less premature ovarian failure.”

These are very welcome results, said Jennifer Eng-Wong, M.D., a clinical physician with the National Cancer Institute’s Center for Cancer Research. “The risk of losing fertility is a big part of the chemotherapy discussion with premenopausal women. Compared to 30 years ago, many such women are older and have childbearing hopes and plans. While this study doesn’t tell us exactly what to do, it provides some important scientific evidence of the risks to fertility.”

Limitations

The researchers did not classify women’s actual ovarian function by analyzing hormones from the blood and urine. The authors noted that “there are no clinical parameters for defining chemotherapy-related amenorrhea . . .[and] direct assessment of menopausal status is often difficult.”

This is an important limitation, according to NCI’s Eng-Wong, “because bleeding per se is not a proxy for fertility.” That is, some women can still get pregnant even though their menstrual cycle has been disrupted and others can fail to get pregnant even though they’re still menstruating.

Also, the women in the study did not represent the general population, especially in terms of race and education, so the findings might not be widely applicable.

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