SAN ANTONIO, TX – Researchers said here that premenopausal women with early stage estrogen receptor positive breast cancer who become menopausal after diagnosis benefit significantly from extended therapy with an aromatase inhibitor.

Investigators from the intergroup NCIC CTG MA17 trial determined that extending therapy beyond five years for these premenopausal women reduced the risk of breast cancer recurrence by about 75% compared with premenopausal women who did not receive extended therapy, said Paul Goss, MD, PhD, professor of medicine at Massachusetts General Hospital Cancer Center/Harvard Medical School, Boston, MA.

Goss noted that, in general practice, based on major clinical trial data, women who are postmenopausal at diagnosis are frequently prescribed extended aromatase inhibitor therapy after 5 years of tamoxifen. In premenopausal women with estrogen receptor-positive breast cancer, however, especially those considered to be at lower risk for recurrence, stopping treatment after 5 years of tamoxifen remains a common standard adjuvant endocrine therapy strategy.

Dr. Goss and colleagues identified 889 premenopausal women from the MA17 trial who were less than 50 years of age at primary diagnosis and who subsequently underwent bilateral oopherectomy when tamoxifen was started or who became amenorrheic during adjuvant chemotherapy or on tamoxifen. In addition, there were 4277 women in MA17 who were 50 years or older and postmenopausal at diagnosis.

The premenopausal women, Dr. Goss noted, compared with postmenopausal women, had poorer prognosis because they had significantly higher likelihood of: Being node positive; being both estrogen receptor positive and progesterone receptor-positive; receiving chemotherapy, and undergoing mastectomy.
“It has been commonplace for women who are premenopausal at diagnosis to discontinue treatment after 5 years of tamoxifen, especially if they are node negative,” Dr. Goss said. “That bothers me, and it is what made me perform this analysis. We showed that not only was there a much stronger proportional benefit, but also a much stronger absolute benefit of extending therapy in the younger patients than in the older ones.”

The absolute improvement in disease free survival at 4 years among women who received extended treatment compared with women who did not receive treatment was 10.1% (P=0.02), Dr Goss said. “That’s the largest absolute treatment benefit I’ve ever seen for a treatment of breast cancer. That’s bigger than trastuzumab, tamoxifen or chemotherapy,” he said.

Of the 424 premenopausal women who received extended aromatase inhibitor therapy after they went through menopause, about 97% achieved disease free survival after four years compared with about 87% of the 465 premenopausal women who did not receive extended aromatase inhibitor therapy. That translated to a 75% reduction in risk of recurrence (p<0.0001).

Dr. Goss said that among the 232 premenopausal women who were node positive and received extended therapy, about 94% achieved disease free survival compared with about 85% of the 269 premenopausal women who did not receive extended therapy, a 67% reduction in risk of recurrence (p=0.008).

He noted that all the 187 premenopausal women who were node negative and received extended aromatase therapy achieved 4-year disease free survival compared with 88.5% of the 188 of the premenopausal node negative patients (p=0.005).

Overall survival did not reach statistical significance. Dr. Goss explained, “Because of a heavy crossover of patients to letrozole it is unlikely that we will ever be able to show a survival benefit. These data are important and, I think, practice-changing,” he commented in an interview.

What explains the large benefit? Dr. Goss speculated that among women in an estrogen receptor-positive premenopausal population are many who have potentially aggressive and estrogen-resistant breast cancer that does not respond to anti-estrogen therapy. These will recur within 5 years, leaving behind those women who have estrogen sensitive disease that will respond to aromatase inhibitor therapy. Traditional dogma based on the fact that premenopausal women are less responsive to tamoxifen is that premenopausal women are less likely to have estrogen-dependent breast cancer—and as a consequence, endocrine therapy is often discontinued after their initial 5 years of treatment.

- MFP Wire Services
- 12-28-2009