2009 Supplements

In metastatic breast cancer (MBC), lapatinib (Tykerb) + letrozole (Femara) delayed disease progression in HER2+, HR+ patients, according to initial results from a phase III trial (EGF30008) presented by Stephen Johnston, MD (abstract 46).

SUPPLEMENT
The use of engineered monoclonal antibodies as antineoplastic therapy has been a significant advance within the past 15 years. These agents target various receptors and ligands required for the proliferation, survival, or maintenance of angiogenesis of tumors.

Based on 2 meta-analyses of nearly 20,000 HR+ early breast cancer patients, AIs are superior to tamoxifen in reducing recurrences, whether as initial monotherapy or given in a “switching” strategy (abstract 12). As initial monotherapy, AIs reduced the risk of recurrence by 23% over tamoxifen; for patients who switched to AIs after 2–3 yr of tamoxifen, AIs reduced the risk by 29%, relative to those who continued on tamoxifen, James Ingle, MD, reported.

SUPPLEMENT
The phenomenon of anaphylaxis was discovered by Portier and Richet in 1903. They injected dogs with toxins from sea anemone with the intent of generating protective antibodies. Unexpectedly, they found that certain dogs became ill with a rapid heartbeat and collapse. Because this syndrome was the precise opposite of protection or prophylaxis, they termed it anaphylaxis.

There is evidence that higher doses of fulvestrant (Faslodex) may have greater activity than the approved dose of 250 mg/mo. The FIRST trial (Fulvestrant First-Line Study) compared 500 mg vs anastrozole 1 mg/d in the first-line advanced disease setting, finding that a dose of 500 mg/mo achieved response rates and clinical benefit rates similar to those obtained with anastrozole 1 mg/d but gave a significantly longer time to progression (abstract 6126).

EXPERT’S CORNER—Nearly three quarters of breast cancer patients have tumors that express estrogen receptors (ERs) or progesterone receptors (PRs); approximately half of these patients are postmenopausal. We look to endocrine therapy, therefore, to prevent recurrences and save lives in the majority of early breast cancer patients and to prolong survival in the advanced disease setting. We are fortunate to have several means of targeting the estrogen signaling pathway. The third-generation aromatase inhibitors (AIs)—anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin)—are increasingly being found to improve upon the efficacy we observed for decades with tamoxifen.

ABCSG Trial: Survival Benefit for Tamoxifen → Anastrozole Updated results from Austrian Breast and Colorectal Cancer Study Group Trial 8 confirmed a survival difference for the sequencing strategy of tamoxifen followed by anastrozole (Arimidex), compared to 5 years of tamoxifen (abstract 14). Preliminary results (median follow-up 55 mo) had previously revealed a 24% reduction in recurrence in favor of the sequencing strategy, although the difference was not statistically significant.