Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization

Cancer Cell International

Svasti Haricharan¹  Elham Sajjadi²  Konstantinos Venetis²  Roberto Piciotti²  Nicola Fusco²  Elena Guerini-Rocco²  Marco Invernizzi³ 

[1] Department of Tumor Microenvironment and Cancer Immunology, Sanford Burnham Prebys Medical Discovery Institute, 10901 N Torrey Pines Rd, 92037, La Jolla, CA, USA;Division of Pathology, IEO, European Institute of Oncology IRCCS, University of Milan, Via Giuseppe Ripamonti 435, 20141, Milan, Italy;Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy;Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont, Viale Piazza D’Armi, 1, 28100, Novara, Italy;

关键词: Breast cancer;    Mismatch repair;    DNA repair;    Immune checkpoint;    Immunotherapy;   

DOI  :  10.1186/s12935-021-01976-y

来源: Springer

【 摘 要 】

The clinical outcome of patients with a diagnosis of hormone receptor (HR)+ breast cancer has improved remarkably since the arrival of endocrine therapy. Yet, resistance to standard treatments is a major clinical challenge for breast cancer specialists and a life-threatening condition for the patients. In breast cancer, mismatch repair (MMR) status assessment has been demonstrated to be clinically relevant not only in terms of screening for inherited conditions such as Lynch syndrome, but also for prognostication, selection for immunotherapy, and early identification of therapy resistance. Peculiar traits characterize the MMR biology in HR+ breast cancers compared to other cancer types. In these tumors, MMR genetic alterations are relatively rare, occurring in ~3 % of cases. On the other hand, modifications at the protein level can be observed also in the absence of gene alterations and vice versa. In HR+ breast cancers, the prognostic role of MMR deficiency has been confirmed by several studies, but its predictive value remains a matter of controversy. The characterization of MMR status in these patients is troubled by the lack of tumor-specific guidelines and/or companion diagnostic tests. For this reason, precise identification of MMR-deficient breast cancers can be problematic. A deeper understanding of the MMR biology and clinical actionability in HR+ breast cancer may light the path to effective tumor-specific diagnostic tools. For a precise MMR status profiling, the specific strengths and limitations of the available technologies should be taken into consideration. This article aims at providing a comprehensive overview of the current state of knowledge of MMR alterations in HR+ breast cancer. The available armamentarium for MMR testing in these tumors is also examined along with possible strategies for a tailored pathological characterization.

【 授权许可】

CC BY