Anastrozole Use After Tamoxifen Tx Beneficial


Postmenopausal women with hormone-sensitive early breast cancer who were switched to anastrozole after 2 years of tamoxifen treatment were 40% less likely to experience disease recurrence, compared with those who remained on tamoxifen, according to a combined analysis of two large European studies.

“There are two possible explanations for this finding: tamoxifen resistance might be overcome by a change in treatment; or aromatase inhibitors might simply be a better treatment option, since they reduce peripheral estrogen concentrations to extremely low levels, whereas tamoxifen is a partial agonist,” wrote the investigators, who were led by Raimund Jakesz, M.D., of Vienna Medical University, Austria.

He and his associates studied the combined results of the Austrian Breast and Colorectal Cancer Study Group trial and the German Adjuvant Breast Cancer Group trial, which were both randomized, prospective, open-label trials with similar inclusion criteria.

Eligible patients were postmenopausal women with locally radically treated invasive or minimally invasive breast cancer without previous chemotherapy, hormone therapy, or radiotherapy. The cancers were hormone sensitive (Lancet 2005;366:455–62).

Of the 3,224 women who participated in both trials and who had completed at least 2 years of adjuvant oral tamoxifen 20–30 mg daily, 1,618 went on to receive 1 mg of the aromatase inhibitor anastrozole daily while 1,606 continued to receive 20–30 mg of tamoxifen daily for the remainder of their adjuvant therapy. The primary end point was event-free survival, which was defined as time to relapse at any site or incidence of contralateral breast cancer.

After a median follow-up of 28 months, there were 67 events in women who were switched to anastrozole, compared with 110 in those patients who remained on tamoxifen. This translates into a 40% decrease in the risk of an event for those women who were switched to anastrozole, compared with those who remained on tamoxifen.

“We noted significantly more fractures and significantly fewer thromboses in patients treated with anastrozole than in those who received only tamoxifen,” Dr. Jakesz and his associates wrote. “However, we also noted a nonsignificant tendency toward fewer emboli and endometrial cancers in women on anastrozole.”

The researchers also pointed out that the results of their investigation “apply only to those women who have successfully completed 2–3 years' adjuvant therapy for early breast cancer.

They added that the results are not applicable to newly diagnosed patients, and should not be used to support a treatment strategy of starting with tamoxifen with the intention of changing to an aromatase inhibitor after 2 or more years.

“Overall, however, the results of these studies show the efficacy advantages attached to treatment with an aromatase inhibitor. …”

Dr. Jakesz and his associates concluded that further investigation of aromatase inhibitors is needed in order to more accurately “ascertain the ideal sequence and duration” of therapy.

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