The BOLERO-2 trial demonstrated that adding everolimus to exemestane substantially improved clinical benefit with acceptable safety in postmenopausal women with HR + breast cancer relapsing/progressing on a nonsteroidal aromatase inhibitor. Incidences and severities of everolimus-related toxicity were consistent with other oncology settings, and were manageable using established strategies.

This retrospective analysis supports a starting dose of 2000 mg/m2/day because of its superior therapeutic index; however, patients may still have toxic effects and individualization of dosing is necessary. A phase III, multicenter, randomized study to establish the safety and efficacy of different doses of capecitabine is urgently needed.

To our knowledge, this is the largest study examining tamoxifen-related toxic effects among male breast cancer patients. Among male patients, there is a high rate of discontinuation of tamoxifen. Prospective studies of antihormonal agents in male breast cancer are warranted.

Prolonged treatment with the potent bisphosphonates pamidronate and zoledronic acid seems to be well tolerated and should be studied in prospective, randomized studies to document prolonged skeletal efficacy.

#6077 Background
 The purpose of this study was to determine the incidence of brain metastases in a cohort of women with early stage triple-receptor negative breast cancer and to evaluate the survival outcomes of these patients.
 Method
 Six hundred and seventy nine patients with early stage triple-receptor negative breast cancer diagnosed between 1980 and 2006 were identified. Cumulative incidence of brain metastases at 2- and 5-years following a diagnosis of early-stage triple receptor-negative breast cancer considering death as a competing risk was computed. Time to brain metastases was computed from the date of breast cancer diagnosis to the date of development of brain metastases. Cox proportional hazards models, adjusted for various patient and tumor characteristics, were then fitted to explore factors that could predict for the subsequent development of brain metastases in this cohort. Survival following a diagnosis of brain metastases was measured from the date of brain metastases diagnosis to the date of death from any cause. All survival outcomes were computed using the Kaplan – Meier product limit method and compared across groups using log rank statistic.
 Results
 Median age was 50 years (range 22 to 97 years) and median follow-up was 26.9 months (range 1.1 to 321.3 months. Overall 42 (6.2%) patients developed brain metastases of whom 16 (38.1%) had 3 brain lesions or less, 19 (45.2%) had more than 3 brain lesions and number of brain lesions was unknown in 7 (16.7%) patients. Overall cumulative incidence at 2- and 5-years was 5.6% (95% CI 3.8%-7.9%) and 9.6% (95% CI 6.8% - 13%) respectively. Twenty –four (3.5%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 2- and 5-years observed to be 2.0% (95% CI 2.6% -6.0%) and 4.9% (95% CI 3.2%-7.0%) respectively. In the multivariable model factors such as age at primary tumor diagnosis, initial clinical stage, histological tumor grade, number of lymph nodes examined and tumor lymph-vascular invasion were not significantly associated with time to brain metastases. For the whole group of patients who developed brain metastases median survival was 2.9 months (95% CI 2.0 – 7.6 months). Among those who developed brain metastases as the first site of recurrence median survival was 5.8 months (95% CI 1.7 – 11.0 months).
 Conclusion
 Data from published studies have reported a 5-year cumulative incidence of brain metastases of approximately 5 % in an unselected breast cancer population. In our large single institutional study patients with triple-receptor-negative breast tumors we report higher early cumulative incidence compared to historical controls associated with poor survival. Patients with triple-receptor negative breast tumors may be an ideal cohort to target brain metastases preventive strategies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6077.