Neoadjuvant aromatase inhibitors valuable against some breast cancers

NEW YORK (Reuters Health) - Low-toxicity neoadjuvant therapy with the aromatase inhibitors (AIs) letrozole (Femara), anastrozole (Arimidex) and exemestane (Aromasin) led to "marked improvements" in surgical outcomes in certain women with breast cancer, U.S. researchers reported online on May 9 in the Journal of Clinical Oncology.

Neoadjuvant AI therapy should become a standard of care for postmenopausal women with clinical stage 2 or 3 breast cancer that is strongly estrogen receptor-positive and HER2-negative when the patient is at risk for mastectomy, Dr. Matthew J. Ellis of Washington University in St. Louis told Reuters Health by e-mail.

"A 50% breast conservation rate for patients who otherwise would have undergone mastectomy is impressive," Dr. Ellis added.

Of the 159 women who had been candidates for mastectomy before neoadjuvant therapy, 51% received breast-conserving surgery.

The randomized, phase II screening study found that "the biologic activities of the three AIs studied are closely equivalent, therefore predicting similar activity as adjuvant therapies."

Similar findings have been seen in earlier studies of AIs and surgical outcomes, but "this is the only trial that has compared these three agents directly," Dr. Ellis said.

He said that had this been known previously, "we would not have activated large trials involving thousands of patients that made the same comparison...we really must change the way we develop endocrine drugs for breast cancer and demand evidence from a neoadjuvant trial involving hundreds of patients that an agent is biologically superior before we activate a trial involving thousands of patients."

The study involved 374 menopausal women with clinical stage T2-T4c, N0-3, M0, ER-rich (Allred score 6-8) breast cancer and ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 2. Participants were randomized to receive daily exemestane 25 mg, letrozole 2.5 mg, or anastrozole 1 mg for 16 to 18 weeks before surgery.

Clinical response rates (complete and partial responses as defined by WHO criteria) were 62.9% in the exemestane group, 74.8% in the letrozole group and 69.1% in the anastrozole group.

Data from Ki67 assessments and the Preoperative Endocrine Prognostic Index (PEPI) model, which combines Ki67 data with pathologic stage and estrogen-receptor levels, established the biologic equivalence of the three agents.

The authors say patients with LumA-subtype breast cancer may be particularly suitable for neoadjuvant endocrine therapy, because about a quarter of such patients have a PEPI of 0, "implying that a prognosis with adjuvant endocrine therapy may be sufficient without adjuvant chemotherapy treatment."

The study was supported in part by Pfizer, the maker of exemestane/Aromasin, and Novartis, the maker of letrozole/Femara.

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