Real-world prevalence, treatment and survival of "high risk" early breast cancer, with mandatory testing of gBRCA1/2 mutation according to the OlympiA trial inclusion criteria: Data from a population-based registry

Abstract

Background: The results of the OlympiA study led to the approval of a PARP inhibitor (olaparib) as adjuvant treatment for early breast cancer (eBC) at high risk of relapse in patients with a germline BRCA1/2 mutation (gBRCAm). However, the proportion of patients in routine practice who meet the "high-risk" criteria applied in the OlympiA study, and for whom gBRCAm testing would now be mandatory, remains unknown.

Patients and methods: In this population-based study, we use unique data from the French specialized Côte d'Or Breast and Gynecological Cancer Registry, to assess the real-life proportion, and long-term prognosis of patients treated for eBC between 2005 and 2015 with standard treatment, and at "high risk" of relapse according to the OlympiA trial criteria.

Results: We included 3483 patients treated for HER2-negative eBC (N = 380 with ER-, and N = 3103 with ER + tumor). We found N = 62 (1.8 %) patients with gBRCA1/2 mutations. A total of 494 patients (14.2 %) were classified as "high risk" according to the Olympia criteria; 55 % with ER-tumors, and 9.1 % with ER + tumors, respectively. Despite more intensive systemic treatments in "high risk" patients, 10-year overall survival was much worse in these "high risk" patients compared to the others: 60.1 % vs 83.8 % in ER-tumors, and 55.4 % vs 84.1 % in ER + tumors. Our estimates of net survival show an even greater difference.

Conclusion: This study provides real-life insights into the prevalence and prognosis of patients with high-risk eBC, in a context where the approval of adjuvant olaparib requires careful reorganization of care, so as not to overlook a patient with gBRCAm who could benefit from adjuvant olaparib.

Keywords: Adjuvant; BRCA; Breast cancer; Epidemiology; High risk; Olaparib; Olympia.

Fig. 1

Flow chart of patients with “high risk” early breast cancer (OlympiA study criteria) included in our registry, according to the type of treatment received: A: ER-negative early breast cancers (triple negative breast cancers); B: ER-positive early breast cancer (ER+/HER2-breast cancers).

Fig. 2

Kaplan-Meier estimates for overall survival (OS) according to “high risk” (Olympia study criteria; red curves), or “non high risk” (blue curves) early breast cancer. A: ER-negative early breast cancers (triple negative breast cancers); B: ER-positive early breast cancer (ER+/HER2-breast cancers). Median OS, median follow-up, number of events (deaths), and OS at 2, 3, 5 and 10 years are shown in the tables below each survival curve.

Fig. 3

Pie charts depicting the percentage of “high risk” (OlympiA study criteria) and “non high risk” early breast cancer patients included in our registry according to the type of treatment received (primary surgery, followed by adjuvant treatment (adjuvant cohort), or neoadjuvant chemotherapy followed by breast surgery (neoadjuvant cohort)). A: ER-negative early breast cancers (triple negative breast cancers); B: ER-positive early breast cancer (ER+/HER2-breast cancers). For ER+/HER2-breast cancer, percentages are shown according to both the OlympiA trial high risk criteria (inner circle), and the monarchE trial high risk criteria (outer circle).