Pathologic findings from the National Surgical Adjuvant Breast Project. VIII. Relationship of chemotherapeutic responsiveness to tumor differentiation.

The possible influence of histologic grade, necrosis and size of invasive breast cancers on the five year survival rate of women treated in NSABP clinical trials with regimens of L-PAM (P) and L-PAM + 5-FU (PF) and for four years in those receiving L-PAM + 5-FU + methotrexate (PMF) was investigated. Generally, all regimens effected an increased survival when compared to controls that did not receive adjuvant therapy. However, this favorable response was statistically more pronounced in those women whose cancers were histologically evaluated to be poorly differentiated (histologic grade 3) and exhibited four or more regional axillary nodal metastases. Patients whose cancers were associated with 1-3 nodal metastases were not found to exhibit statistically significant responsiveness to any regimen regardless of tumor grade. Possible reasons for this dichotomy are presented. Tumor necrosis, although paralleling the results noted with histologic grade, failed to further discriminate patients who might respond to chemotherapeutic agents. Tumor size was not found to be a consistently significant indicator of chemotherapeutic responsiveness. Generally, the PF and PMF regimens were more effective than P alone in those patients exhibiting a response. These findings indicate the importance of identifying subsets of patients with breast cancer not only from a biologic but also therapeutic perspective.