Biomarkers of residual disease after neoadjuvant therapy for breast cancer

• Published in: Nature reviews. Clinical oncology Vol. 13; no. 8; pp. 487 - 503
• Main Authors: Penault-Llorca, Frederique, Radosevic-Robin, Nina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2016; Nature Publishing Group
• Subjects: 4040/1892; 692/4028/67/1059; 692/4028/67/1059/602; 692/4028/67/1347; 692/700/565/545; Adjuvant chemotherapy; Biological markers; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Drug therapy; Female; Genetic Markers - genetics; Humans; Identification and classification; Ki-67 Antigen - metabolism; Medicine; Medicine & Public Health; Methods; Mutation - genetics; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm, Residual - diagnosis; Neoplasm, Residual - genetics; Neoplasm, Residual - pathology; Oncology; Patient outcomes; Proteome - genetics; Receptor, ErbB-2 - metabolism; review-article; Treatment Outcome; Tumor Burden; Tumor Microenvironment - immunology
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/nrclinonc.2016.1

Key Points Neoadjuvant therapy (NAT) provides a unique opportunity to assess the response of patients with breast cancer to different treatments Standards for pathological examination need to be standardized in order to enable reproducible evaluation of the residual disease that persists after NAT Residual disease remaining after NAT is different from treatment-naive breast cancer 'Classic' histopathological parameters, such as ypTNM, grade, mitotic index, and hormone-receptor, HER2 and Ki67 status, provide valuable prognostic and predictive information when assessed in residual breast cancer tissue after NAT Genomic and proteomic markers of residual breast cancer are currently under development, and might inform patient stratification for adjuvant treatment Immune markers are among the most-promising biomarkers in the post NAT setting, in which extensive tumour infiltration by lymphocytes indicates a good prognosis, irrespective of residual tumour size The pathobiological features of the breast cancer tissue that remains present after neoadjuvant therapy (NAT) are a major determinant of patient outcome. The decision to further treat this residual disease has traditionally been guided by the features of the tumour at diagnosis, but substantial biological differences exist between treatment-naive breast cancer and the post-NAT residual tissue. In this Review, the authors describe how the evaluation of the response of breast tumours to neoadjuvant treatment should be standardized, and provide an overview of potential biomarkers of prognosis. Nowadays, the decision of which adjuvant treatment should be given to patients with residual breast cancer after neoadjuvant therapy is based on the initial, pretreatment breast cancer molecular subtype and on the estimated residual tumour burden after neoadjuvant therapy. Substantial biological differences exist, however, between treatment-naive breast cancer and the residual tissue that remains after neoadjuvant therapy. In addition, the evaluation of relapse risk in patients is subject to a lack of uniformity in pathological qualification and quantification of remnant breast cancer following neoadjuvant treatment. In this Review, we present the recent recommendations for standardized evaluation of response to neoadjuvant therapy in patients with breast cancer, followed by a comprehensive overview of the pathobiological features of the residual disease after neoadjuvant therapy, which could serve as prognostic biomarkers or guide the choice of targeted adjuvant approaches. These biomarker candidates are at different stages of development, but some already have demonstrated superior prognostic value compared with biomarkers derived from pretreatment breast-cancer characteristics. The evidence presented herein indicates that further research on the biology of breast cancer that persists after neoadjuvant therapy is necessary to improve the management of this disease.