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Purpose: To evaluate the safety and efficacy of oral everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in two different schedules in minimally pretreated patients with metastatic breast cancer and to explore for possible biologic correlates of response., Patients and Methods: Patients who received no or one prior chemotherapy regimen for metastatic breast cancer were entered onto this multicenter, noncomparative, randomized phase II study of everolimus 10 mg daily versus 70 mg weekly; the multinomial end points of response and progression were evaluated at 8 weeks. A two-stage accrual design was used, with 15 evaluable patients in each schedule in stage 1. Only daily therapy met criteria for continuing, and another 15 patients were added. pAKT, PTEN, carbonic anhydrase 9, estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were evaluated for possible correlation with response., Results: The most common drug-related toxicities were fatigue, rash, anorexia, diarrhea, stomatitis, cough, and pneumonitis. Pneumonitis occurred at higher than expected rates and seemed to be schedule dependent, with the highest incidence on the daily schedule. Response rate with daily therapy was 12% (95% CI, 3.4% to 28.2%) compared with 0% (95% CI, 0.0% to 20.6%) for weekly therapy. Twenty-seven percent of patients on daily therapy discontinued treatment compared with 13% on weekly therapy (16% v 6% with pneumonitis, respectively). No biologic correlates of response could be identified, although there were trends favoring benefit in ER-positive and HER2-negative metastatic breast cancer., Conclusion: Oral everolimus has activity in metastatic breast cancer that is schedule dependent. Daily therapy with 10 mg is worthy of further study in this patient population.

Purpose: After National Cancer Institute of Canada trial MA.17 demonstrated benefits with letrozole after 5 years of tamoxifen, oncologists needed to identify and offer therapy to patients in community follow-up who were eligible for extended adjuvant hormone therapy. In British Columbia (BC), letters about extended letrozole therapy were sent to eligible BC women, their primary care physicians (PCPs), and their oncologists. We evaluated the effectiveness of this communication strategy., Patients and Methods: Eight hundred eighty-five women with stage I-III breast cancer who completed 4 to 6 years of tamoxifen in 2004 with no documented recurrence were sent letters describing extended adjuvant letrozole in February 2005. Treatment uptake and characteristics for women who did or did not receive a subsequent letrozole prescription were described., Results: Among 838 eligible women, 305 (36%) received a letrozole prescription before April 2006. More women in the letrozole cohort had tumors larger than 2.0 cm (44.2% v 30.8%); node-positive disease (52.5% v 22.5%); prior radiotherapy (71.1% v 58.5%); and prior chemotherapy (51.5% v 20.8%; all P