乌鸦传媒

CHICAGO -- For premenopausal women, exemestane (Aromasin) cut breast cancer recurrence compared with tamoxifen when given atop ovarian suppression, two trials showed.

A 5-year course of the for hormone receptor-positive early breast cancer patients with hormones suppressed by triptorelin, oophorectomy, or ovarian irradiation (91.1% versus 87.3%, P<0.001).

Disease recurrence drove the difference, without a difference in overall survival at a median 68 months of follow-up, Olivia Pagani, MD, of the Institute of Oncology of Southern Switzerland in Bellinzona, and colleagues found.

Their pooled analysis of the phase III TEXT and SOFT trials appeared online in the New England Journal of Medicine in conjunction with a late-breaking presentation at the American Society of Clinical Oncology meeting.

The results were very , which led to a shift in practice due to better prevention with the AI anastrozole (Arimidex) than tamoxifen, commented , of the University of California Los Angeles.

It wasn't surprising that the results were replicated for younger women when suppressing estrogen akin to menopause, she told 乌鸦传媒.

These results are likely to change practice, too, although not by establishing a new standard of care, noted , medical director of the breast center at Memorial Sloan Kettering Cancer Center in New York City.

"It's another option," he said in an interview. "There are reasons why someone might not want to take tamoxifen, just as there are reasons why somebody might want to take tamoxifen. Those are going to enable individualized decisions."

However, the key question is whether the ovarian suppression is really necessary and worthwhile, Ganz said.

"While it's a potential advance, the quality of life data are going to be important," she said.

Ovarian suppression is no small matter for women, agreed , co-director of the breast cancer program at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

"It renders women menopausal with the attendant side effects of menopause, including symptoms such as hot flashes, vaginal dryness, and bone loss, and possible increased risk for heart disease," she said.

To make sure that shutting off the ovaries actually boosted the benefit of tamoxifen -- as suspected and as recommended in some countries -- the SOFT trial also included a tamoxifen without ovarian suppression arm to mimic the current U.S. standard of care.

Those results are expected later this year, perhaps at the San Antonio Breast Cancer Symposium.

Ovarian suppression is already bad for quality of life and symptoms, and an AI makes it worse, Ganz said, noting that even in postmenopausal women, only about 60% of women stick it out to 5 years of tamoxifen or AI therapy.

The fact that the trial arm without ovarian suppression hasn't been halted may suggest that the difference between groups isn't that great for efficacy, Ganz speculated.

Women would have to individually weigh whether to accept early menopause for a few absolute percentage points in survival, she noted.

One strategy may be to discuss treatment with the option that "if it doesn't agree with you, we'll stop," she suggested.

The TEXT and SOFT trials included a total of 4,690 patients for joint analysis in arms randomized to tamoxifen versus exemestane atop ovarian suppression. Separate analysis is expected later.

Together, they showed a 34% relative reduction in breast cancer recurrence with the AI at 5 years (92.8% 88.8%, P<0.001).

Exemestane-treated patients also were 22% less likely to have a distant recurrence.

While no difference was seen in the high survival rate across groups (95.9% exemestane and 96.9% on tamoxifen, P=0.37), the researchers called for longer follow-up to accurately assess impact.

Adverse event profiles were as expected from postmenopausal populations.

The rate of selected grade 3 and 4 events was 30.6% with exemestane and 29.4% with tamoxifen, and followed patterns expected from studies in postmenopausal women.

Study withdrawal was more common with exemestane (16% versus 11%).

"Between-group differences were observed with respect to specific symptoms, but the overall quality of life assessment did not favor either treatment," Pagani's group noted.

The results likely generalize across AIs as a class, Norton noted, which can help with side effects.

"Very often if someone gets muscle aches and pains from one, they don't get muscle aches and pains from another one, so you can switch and find the one that works best for that individual patient," he said. "Giving us lots of options is the answer."

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