CORRECTION: Letrozole/goserelin is effective hormone therapy for premenopausal breast CA

NEW YORK (Reuters Health) - For premenopausal women with hormone-receptor positive metastatic breast cancer, combination therapy with goserelin and letrozole appears to be an effective new option, Korean researchers report in the April 26th online issue of the Journal of Clinical Oncology

In their phase II trial, first-line treatment with this combination yielded outcomes that are comparable to what postmenopausal women have with letrozole alone, they say.

Many oncologists have already been treating premenopausal hormone-responsive metastatic breast cancer patients with aromatase inhibitors plus a gonadotropin releasing hormone (GnRH) agonist after tamoxifen, with or without GnRH agonist failure, co-author Dr. Jungsil Ro told Reuters Health by e-mail. "Our data support this practice."

He added that the study's impact is likely to be greater in Asian countries, where more than half of the patients are premenopausal at diagnosis.

In their paper, Dr. Ro from the National Cancer Center in Goyang-si and colleagues compare the response rates and clinical benefit of first-line therapy with goserelin (3.6 mg every 4 weeks) plus letrozole (2.5 mg/day) in 35 premenopausal patients versus letrozole alone in 38 postmenopausal women.

All women in the study had estrogen receptor-positive and/or progesterone receptor-positive metastatic breast cancer.

Serum estradiol levels in the premenopausal group fell markedly during the first 4 weeks after the first goserelin injection and, along with FSH levels, remained suppressed throughout treatment.

Objective response rates (complete remission plus partial remission) were numerically but not statistically higher in the premenopausal group (46%) than in the postmenopausal group (27%), and the clinical benefit rate was comparable between the two groups (77% versus 74%, respectively).

The median time to progression didn't differ significantly between the groups, either overall (9.5 vs 8.9 months for pre- and postmenopausal women, respectively) or among the patients with clinical benefit (10.9 vs 12.2 months, respectively).

On Kaplan-Meier analysis, 2-year survival rates were also similar for the premenopausal (82.5%) and postmenopausal (82.1%) groups.

Both treatments were well tolerated, with hot flashes and arthralgias representing the most common adverse events in both groups. Premenopausal patients were more likely than postmenopausal patients to experience hot flashes, weight gain, and vaginal dryness.

Bone mineral density declined significantly and markers of bone metabolism tended to increase in patients who didn't receive bisphosphonate treatment during the study. On the other hand, when patients did receive bisphosphonates, markers of bone resorption and bone formation declined significantly over time.

Excessive ovarian estrogen production in premenopausal women means that aromatase inhibitors (AIs) are not useful, Dr. Ro said -- but these women can use AIs when ovarian function is suppressed by GnRH agonists.

"This strategy of combining GnRH agonists could be utilized in any treatment plan containing AIs, such as AIs plus anti-HER2 therapy or biological therapy," Dr. Ro said.

He added that even when there is no bone metastasis, prophylactic use of bisphosphonate following Dexa bone testing could help bone health in all women on AIs.

http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.26.5884v1

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