OBJECTIVE To retrospectively determine the relationship of age to toxicity from adjuvant chemotherapy for breast cancer. METHODS We identified 1,405 consecutive patients age 65 or older with primary invasive breast cancer who were seen at Memorial Sloan-Kettering Cancer Center from January 1998 to December 2000. Patients selected from this cohort for analysis were aged 65 or older at diagnosis; received their follow-up care at Memorial Sloan-Kettering Cancer Center; had stage I, II, or III breast cancer; and received adjuvant chemotherapy consisting of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil), an anthracycline-based regimen (AC [doxorubicin and cyclophosphamide], or AC-T [AC and paclitaxel or docetaxel]). Exclusion criteria included prior chemotherapy or previous breast cancer. RESULTS One hundred thirty-two patients were included in this study, with a mean age of 70 (range 65--79). Comorbidity measured by the Charlson comorbidity index was low: score 0 (83%), 1 (12%), 2 (5%); with stages: I(18%), IIA (41%), IIB (27%), IIIA (8%), IIIB (6%), T1Nx (1%). Patients receiving an anthracycline-based regimen were more likely to experience grade 3 or 4 toxicity (p=0. 01), require hospitalization (p<0.001), and/or develop febrile neutropenia (p<0.001). Treatment delays due to myelosuppression occurred more frequently in patients receiving CMF (p<0.001). The type of chemotherapy regimen (anthracycline compared to CMF) was a better predictor for toxicity than increased age or comorbidity score. CONCLUSIONS In this cohort of older patients with breast cancer, the risk for toxicity from adjuvant chemotherapy depended more on the type of regimen (anthracycline vs. CMF) than the patient's chronological age.