Residual Tumor Characteristics Following Neoadjuvant Chemotherapy in Breast Cancer

Neoadjuvant chemotherapy for breast cancer leaves behind a residual tumor that is substantially different in its characteristics from the original tumor. The histological changes and receptor changes have been systematically evaluated in large studies. However, the nucleolar morphology of the residual cancer has not been well characterized. This study evaluated the nucleolar morphology in the residual cancer using haematoxylin eosin for evaluation of nucleolar number and size in relation to mitotic index, mAgNOR assessment, and an immunohistochemistry panel consisting of Ki-67, p53, CCND1, E-Cad, ER, PR, Her2Neu, CD3, CD8 and CD68. Another sample of patients were studied by exome analysis of a 344 candidate cancer gene panel. The results were collated to infer the nature of the residual tumor. There was an increase in nucleolar number and size following neoadjuvant chemotherapy. The mitotic rate, and positive staining for Ki-67 and CCND1 were reduced in the residual tumor. 344 candidate cancer gene panel exome analyses showed residual tumor with fewer mutations and the more common known driver mutation in breast cancer such as CREBP, ERBB2, PARP, TOP2A, P53 etc. COL1A1 was the only gene mutation demonstrated in the residual tumor that was not found in the untreated primary surgical group.