Which Patients Do We Need to Test for BRCA1/2 Mutation? Feasibility of Adjuvant Olaparib Treatment in Early Breast Cancer–Real-World Data from Two Large German Breast Centers

Abstract

Background: Approximately 6% of women with breast cancer carry pathogenic germline variants in predisposition genes such as BRCA1 and BRCA2. Depending on personal and family cancer history, it is therefore recommended to test for hereditary breast cancer. Moreover, as shown by the phase III OlympiA trial, olaparib significantly improves overall survival in patients with HER2 negative (HER2−) early breast cancer who (1) carry a BRCA1 or BRCA2 germline mutation (gBRCA1/2-positive), (2) have received (neo)adjuvant chemotherapy and (3) are at high clinical risk. The objective of the current analysis was to determine the number of patients with early HER2- breast cancer who are at high clinical risk, according to the inclusion criteria of OlympiA, and to estimate how many of these patients would meet the criteria for hereditary cancer testing in a real-world analysis. Methods: All patients included in this retrospective analysis were treated for early breast cancer (eBC) at the Department of Gynecology and Obstetrics, Ulm University Hospital, Germany, and the Department of Women’s Health at Tuebingen University Hospital, Germany, between January 2018 and December 2020. Patients were identified as high risk, in line with the clinicopathological determiners used in the OlympiA trial. The criteria of the German Consortium for Hereditary Breast and Ovarian Cancer were used to identify patients who qualify for hereditary cancer testing. Results: Of 2384 eligible patients, 1738 patients (72.9%) showed a hormone receptor positive (HR+)/HER2- tumor biology, 345 patients (14.5%) displayed HER2+ breast cancer and 301 patients (12.6%) suffered from HR-/HER2- breast cancer (TNBC). Of 2039 HER2- breast cancer patients, 271 patients (13.3%) were at high clinical risk. This cohort encompassed 130 of the 1738 patients with HR+/HER2− breast cancer (7.5%) and 141 of 301 patients with TNBC (46.8%). A total of 121 of 271 patients (44.6%) with high clinical risk met the criteria for hereditary cancer testing (34 of 130 (26.2%) HR+/HER2− patients and 87 of 141 (61.7%) patients with TNBC). Conclusion: Approximately one in ten patients with HR+/HER2−, and half of the patients with TNBC, meet the high-risk criteria according to OlympiA. Half of these patients do not meet the criteria for hereditary cancer testing and should therefore be tested for the presence of gBRCA1/2 mutations, irrespective of their own or family cancer history. The overall number of patients with early breast cancer benefiting from olaparib needs to be investigated in future studies.

Feasibility of targeted therapies in the adjuvant setting of early breast cancer in men: real-world data from a population-based registry

“…In this analysis, we were able to show that 21.2% and 47.6% of male patients with HR + /Her2− eBC met the high-risk criteria of the monarchE and NATALEE trial, respectively, and that 12.6% of male patients with eBC met the high-risk clinicopathological criteria of the OlympiA study. This is a much higher percentage of patients than has been reported in the real-world data for women [ 13 , 14 ], which might be due to the fact that men tend to be diagnosed at a more advanced stage [ 15 – 18 ].…”

The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers

“…Adjuvant therapy with Olaparib is available to a small patient population with high-risk HR+/HER2− eBC in the presence of a germline BRCA1/2 mutation [42]. Recently, we were able to demonstrate that approximately 8% of patients with HR+/HER2− eBC meet the clinical-pathological inclusion criteria of the OlympiA study [26,43]. Even though the frequency of a BRCA1/2 mutation is low in the HR+/HER2− cohort, ranging from 1.5% to 5.0%, testing should be strongly recommended in this context, regardless of individual or familial risk, to determine the therapeutic indication for Olaparib [44,45].…”

The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients—a multicenter real-world analysis

“…HR and HER2 receptor expression was assessed by board-certified pathologists according to local standards as previously described. 27 , 28 , 29 …”

“…Data processing and statistical analyses were carried out using Jupyter Notebook on Anaconda, with the Python extension packages pandas, numeric Python, and lifelines as previously described. 27 , 28 , 29 Comparative statistics of survival analyses were carried out using the log-rank test with a significance level of α = 0.05. Affinity Publisher 2 (Serif Europe Ltd., Nottingham, UK) was used for data visualization.…”