Interpreting breast pathology in the setting of neoadjuvant chemotherapy

Neoadjuvant therapy (NAT) was originally used as a standard treatment for inflammatory and inoperable locally advanced breast cancers. Diagnosis was typically made by fine-needle aspiration biopsy (FNAB). Therefore, pathologic information about the carcinoma (e.g., type, grade, and tumor markers) and information for staging (e.g., size and lymph node status) was limited. The combination of image-guided core needle biopsy of breast cancers, sentinel lymph node biopsy (SLNB), or needle biopsy of lymph nodes, and new breast imaging modalities have substantially increased the ability to accurately classify and stage carcinomas prior to surgical excision. Currently, increasing numbers of women are being treated with chemotherapy or hormonal agents prior to surgery for earlier-stage operable breast cancers. Although clinical trials have shown that systemic treatment before or after surgery gives identical results in locoregional control and metastasis-free survival for patients), major advantages for NAT are that the efficacy of systemic therapy can be assessed during the treatment of patients (with the opportunity to change therapy if a cancer does not respond); tumor response is a major prognostic factor; tumor response can be used as a short-term endpoint for clinical trials; pre and posttreatment tumor samples with known treatment susceptibility are powerful research tools; and more women become eligible for breast conservation. This chapter reviews the special skills needed to properly evaluate and understand breast tissue specimens, including formal surgical resections, by the pathologist and breast clinician following NAT for breast cancer in order to better understand treatment effect and assess for residual disease.