Neoadjuvant pertuzumab: the exception that proves the rule?

The original impetus for neoadjuvant therapy for breast cancer was to render patients with locally advanced breast cancer operable. In subsequent clinical trials, the key goals of neoadjuvant treatment were to improve surgical options for patients, and to determine whether earlier administration of systemic therapy would lower the risk of breast cancer recurrence. In the end, that latter objective was not realized—but neoadjuvant therapy nonetheless emerged as a treatment option that could enable less extensive surgery and provide effective “adjuvant” treatment. The identification of pathologic complete response (pCR) as a prognostic marker for outcomes following neoadjuvant chemotherapy made neoadjuvant treatment a favorite model for clinical investigators, since neoadjuvant treatment allowed for rapid ascertainment of clinical activity without the time required for long-term follow-up, made every patient an “event” (permitting smaller study sample sizes), and facilitated extensive correlative studies using serial imaging or tissue biopsies. This enthusiasm led to hundreds of trials of neoadjuvant therapy for breast cancer.