Pathology Issues Related to Neoadjuvant Treatment and the Evaluation of Pathological Response

Tumor response to neoadjuvant therapy for breast carcinoma has been validated as an excellent intermediate endpoint for disease-free survival and overall survival. Pathological complete response (pCR) is the typical endpoint to assess tumor response, and most studies define pCR as absence of invasive carcinoma in the breast. The assessment of pCR poses a challenge to the pathologist. Patients with a complete clinical response may not have a grossly identifiable lesion in the breast, and the delineation of the tumor bed in consultation with radiologist/surgeon is essential in these cases for appropriate sampling; determination of size of microscopic foci of residual carcinoma also requires careful mapping of the tumor bed; modified Bloom and Richardson system may be difficult to apply on the residual carcinoma due to paucity of cells and therapy effect in neoplastic cells. Some authors have included absence of metastases to axillary lymph nodes in the definition of pCR. The biological significance of microscopic foci of residual invasive carcinoma in the breast, lymphovascular invasion, and isolated tumor cells in lymph nodes is unclear. AJCC TNM system can be used to assess tumor response after neoadjuvant therapy and has been shown to be superior than other response classification systems in predicting survival. The relative simplicity, ease of use, and familiarity by the practicing pathologist with this system make this system both user-friendly and reproducible. A modification of the AJCC TNM system is proposed to assess pCR.