How to improve timing and duration of adjuvant chemotherapy

The efficacy of adjuvant systemic therapy for early breast cancer depends on tumour, patient, and treatment-related features. Selection of treatment is based upon tumour characteristics such as oestrogen receptor (ER) and progesterone receptor (PgR) status, and patient characteristics such as age and menopausal status. Three retrospective analyses of the International Breast Cancer Study Group (IBCSG) database were performed to assess the influence of tumour-related features and patient characteristics on timing of adjuvant chemotherapy, on the efficacy of a short perioperative course of chemotherapy, and on the shorter rather than longer duration of chemotherapy. Timing: Early initiation (between 1 and 3 weeks from surgery) of adjuvant chemotherapy improved disease-free survival in patients whose tumours did not express ER, compared with typical timing to start of chemotherapy (between 4 and 6 weeks after surgery). Outcome was not related to start of chemotherapy for those patients whose tumours expressed ER. This analysis was conducted in premenopausal patients with node-positive disease. Perioperative therapy: A single course of adjuvant perioperative chemotherapy (PeCT) was particularly effective for postmenopausal patients with node-negative ER and PgR-negative breast cancer. Indeed the absence of expression of ER, PgR or both was the most important factor predicting improved outcome with PeCT among postmenopausal patients. No significant effect of PeCT was observed for premenopausal patients with similar characteristics of disease presentation. Duration of chemotherapy: Three courses of adjuvant chemotherapy with cyclosphosphamide, methotrexate, and 5-fluorouracil (CMF) were as effective as six courses for an older cohort of premenopausal patients (age ≥40 years), while younger patients (<40 years old), or those at any age, but with tumours classified as ER-negative, six courses of the CMF appeared superior to three courses of the same regimen. Thus, information on endocrine responsiveness and menopausal status is important for focusing on best choice of timing and duration of adjuvant chemotherapy.