BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer

Abstract

BackgroundTriple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.MethodsThe BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens.ResultsOf the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (P = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC.ConclusionsThe 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.

Deep learning and manual assessment show that the absolute mitotic count does not contain prognostic information in triple negative breast cancer

“…Well-known prognostic factors are not yet established for TNBC. Recent work has focused on identifying immune-based and molecular features of TNBC to obtain prognostic [36,37] and predictive [38][39][40] biomarkers. For the TNBC subtype, only scarce literature exists focusing on the prognostic value of proliferation.…”

BRCAness Combined With a Family History of Cancer Is Associated With a Poor Prognosis for Breast Cancer Patients With a High Risk of BRCA Mutations

“…Our previous study found BRCAness is an independent negative prognostic factor for RFS and OS of patients with TNBC. 21 In the present study, multivariate analysis revealed that BRCAness was an independent negative prognostic factor when we included early-onset breast cancer. According to the Japanese Breast Cancer Society, the ratio of breast cancer patients with a positive FH for breast cancer in Japan was 1185/14,749 (8.0%) in 2004 and 10,080/78,897 (12.8%) in 2014 (Supplemental Figure 1; available in the online version).…”

“…The BRCAness of these TNBCs was reported in our previous study. 21 Patients received neoadjuvant or adjuvant treatment according to the following guidelines: National Comprehensive Cancer Network (NCCN) guidelines for the treatment of breast cancer, 23 Clinical Practice Guideline of Breast Cancer by the Japanese Breast Cancer Society, 24 and the recommendations of the St Gallen International Breast Cancer Conference. [25][26][27][28] We conducted a survey to determine the presence of a positive FH for breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer among firstto third-degree e1218 -Clinical Breast Cancer October 2018…”

“…19,20 Also, BRCAness serves as an essential biomarker for predicting the prognosis of those with TNBC. 21 A positive FH of cancer is a strong risk factor for the onset of breast cancer and is dependent on the frequency of breast cancer in the family. For instance, the pooled estimate of RR associated with various FH factors is as follows: mother, RR, 2.0; 95% CI, 1.8-2.1; mother and sister, RR, 3.6; 95% (CI, 2.1-2.4).…”

BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study

“…Mori et al measured the BRCAness of surgical specimens from 262 patients with primary TNBC who had not received neoadjuvant chemotherapy [22]. BRCAness in patients with TNBC was an independent factor for both recurrence and survival in their multivariate analysis.…”