Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage
breast cancer. Response, in the form of pathological complete response, is a validated and evaluable
surrogate end point of survival after
neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, there is a current lack of uniformity in the definition of pathological complete response. A review of standard operating procedures used by 28 major neoadjuvant
breast cancer trials and/or 25 sites involved in such trials identified marked variability in specimen handling and histologic reporting. An international working group was convened to develop practical recommendations for the pathologic assessment of residual disease in neoadjuvant clinical trials of
breast cancer and information expected from pathology reports. Systematic sampling of areas identified by informed mapping of the specimen and close correlation with radiological findings is preferable to overly exhaustive sampling, and permits taking tissue samples for translational research. Controversial areas are discussed, including measurement of lesion size, reporting of lymphovascular space invasion and the presence of isolated
tumor cells in lymph nodes after
neoadjuvant therapy, and retesting of markers
after treatment. If there has been a pathological complete response, this must be clearly stated, and the presence/absence of residual
ductal carcinoma in situ must be described. When there is residual invasive
carcinoma, a comment must be made as to the presence/absence of
chemotherapy effect in the breast and lymph nodes. The
Residual Cancer Burden is the preferred method for quantifying residual disease in neoadjuvant clinical trials in
breast cancer; other methods can be included per trial protocols and regional preference. Posttreatment
tumor staging using the
Tumor-Node-
Metastasis system should be included. These recommendations for standardized pathological evaluation and reporting of neoadjuvant
breast cancer specimens should improve prognostication for individual patients and allow comparison of treatment outcomes within and across clinical trials.