Newer Anti-Estrogen Treatment May Benefit Younger Breast Cancer Survivors

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A new type of anti-estrogen drug appears to work better than the estrogen-blocking drug tamoxifen in preventing recurrences of breast cancer in certain women, a new study reports.

Exemestane (Aromasin), which belongs to a class of drugs called aromatase inhibitors, reduced the relative risk of breast cancer recurrence by nearly a third compared to tamoxifen. But, for exemestane to work in premenopausal women, the drug can only be given when ovarian function is being suppressed.

“For years, tamoxifen has been the standard hormone therapy for preventing breast cancer recurrences in young women with hormone-sensitive disease. These results confirm that exemestane with ovarian function suppression constitutes a valid alternative,” study lead author Dr. Olivia Pagani, clinical director of the Breast Unit at the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland, said in a prepared statement.

Findings from the study were scheduled to be presented Sunday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. The study was also published simultaneously in the New England Journal of Medicine. Funding for the study was provided by drug makers Pfizer and Ipsen, as well as the International Breast Cancer Study Group and the U.S. National Cancer Institute.

Aromatase inhibitors, such as exemestane, work by preventing other hormones from changing into estrogen, which is the female hormone that often fuels breast cancer growth.

By comparison, tamoxifen blocks estrogen from being used by cancer cells.

Tamoxifen has been the default standard of care for premenopausal women because aromatase inhibitors are not effective in women whose ovaries are functioning, said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

“The amount of estrogen in their bodies is too great for it to have a beneficial function,” Lichtenfeld said.

But doctors wondered whether aromatase inhibitors could be used to better protect young women against breast cancer if their ovary function was suppressed, essentially putting them through menopause and reducing their estrogen levels.

This study analyzed treatment outcomes of almost 4,700 breast cancer survivors who participated in two worldwide clinical trials aimed at answering that question.

The women, average age 43, all underwent treatment to stop their ovaries from functioning. Each chose one of three methods, Lichtenfeld said — they could take medication to suppress ovary function, have their ovaries exposed to radiation, or have their ovaries surgically removed.

On top of ovary suppression, the women were randomly assigned to take either exemestane or tamoxifen to help prevent a recurrence of their breast cancer.

The cancer-free survival rate at five years ended up 91.1 percent in the exemestane group versus 87.3 percent in the tamoxifen group. That amounts to a 28 percent lower risk of subsequent invasive cancer, the researchers reported.

There was a 34 percent reduction in the risk of breast cancer recurrence in the exemestane group compared to the tamoxifen group. The study also found a 22 percent decrease in the risk of cancer spreading to other parts of the body.

“This definitely does show that using an aromatase inhibitor is clearly superior than using tamoxifen,” said Dr. Larry Norton, deputy physician-in-chief for Breast Cancer Programs and medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center in New York City. “It provides an important option for these patients.”

Reported side effects were similar to those in previous studies that compared aromatase inhibitors and tamoxifen in postmenopausal women, and differed depending on the drug.

Despite the side effects, only 14 percent of the participants completely stopped the treatments early in the five-year trials. That’s an adherence rate higher than what is seen in everyday practice, the researchers said. Previous studies suggest that many breast cancer survivors stop taking preventive hormone therapy before the recommended time.

Norton noted that younger breast cancer survivors might be more likely to take their post-treatment medications as directed if they had an alternative to tamoxifen, which is known to increase a woman’s risk of endometrial cancer.

The five-year overall survival rates were high in both groups — 95.9 percent in the exemestane group and 96.9 percent in the tamoxifen group. Longer follow-up is needed to get a better idea of the impact these two treatments will have on long-term survival, the researchers noted.

“Where the study stands right now, the women who got the Aromasin have had a delay in the recurrence of the disease, but they haven’t necessarily had an improvement in survival,” Lichtenfeld said.

Lichtenfeld and Norton said follow-up research needs to compare exemestane plus ovarian suppression directly with tamoxifen alone, since tamoxifen can be used without ovarian suppression to treat younger breast cancer survivors.

“My sense is in terms of practical implications, I suspect some physicians will change their treatment plans based on this, but I don’t expect widespread change,” Lichtenfeld said. “It’s going to take more time, more understanding, and a comparison of the newer approach to the standard approach.”

A second study, also scheduled to be presented on Sunday at the ASCO meeting, looked at using a combination of two treatments — trastuzumab and lapatinib — after surgery for a certain type of breast cancer. The study found that for breast cancers known as HER2 positive breast cancers, the drug lapatinib didn’t make a significant difference in disease-free survival after four years.

In addition, the combination therapy led to an increased risk of side effects.

The researchers were surprised that lapatinib didn’t add any benefit, but were encouraged that trastuzumab appears to work well on its own in women with early HER2 positive breast cancers after surgery.

More information

For more information on tamoxifen, visit the American Cancer Society.

Source: HealthDay

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