Abstract P3-09-01: BRCAsearch - results of population-based screening of BRCA1 and BRCA2 germline mutations in incident breast cancer in South Sweden
Authors: Loman N , Borg Å , Henriksson K , Kristoffersson U , Kvist A , Silfverberg B , Törngren T , Brandberg Y , Nilsson M 
Published: March 2017

Increasing evidence supports the benefit of identifying the BRCA1 and BRCA2 germline mutation status in early breast cancer. Germline mutations in these two genes are treatment predictive for the benefit of risk reducing surgical interventions of the contralateral breast and the ovaries and fallopian tubes, in early breast cancer (Metcalf 2014; Domchek 2010). Furthermore, they may possibly also be treatment predictive for the effect of certain types of medical interventions (Tutt SABCS 2014).

In order to provide the patient with the opportunity to take BRCA test results into account already when planning primary treatment, BRCA testing and cancer genetic counseling needs to be initiated and performed early during the diagnostic and treatment related process in newly diagnosed breast cancer cases. Special attention needs to be taken to the fact that the test results may affect not only the patient, but also her or his relatives. We have observed that the clinical efficacy of BRCA-screening criteria may be surprisingly low, leaving a substantial number of BRCA-carriers undetected in spite of intense contacts with health care providers (Unpublished results).

BRCAsearch (ClinicalTrials.gov Identifier: NCT02557776) is a population based study including new invasive breast cancer cases at three hospitals in the South of Sweden. Patients are invited to perform BRCA1 and BRCA2 germline mutation analysis at time of primary treatment after written study information and written genetic counseling, irrespective of family history, age or clinical phenotype. The primary end-points of the study include the rate of BRCA mutations in newly diagnosed breast cancer in South Sweden, the fraction of patients that accept inclusion in the study, and the rate of mutation positive patients that do not fulfill clinical criteria for BRCA mutation screening. Secondary end-points include the perception among patient of the intervention and testing procedures, the types of questions the patients present during the process and psychosocial outcome among carriers and non-carriers.

In May 2016 about 400 patients have been included in the study, whereof 333 have been analyzed for BRCA germline mutations. The accrual target of the study is 500 patients, which will be reached during the fall of 2016. At the meeting, the BRCA1 and BRCA2 mutation rates will be presented, as well as the acceptance rate of the study among patients approached, and the fraction of mutation positive patients that do not fulfill current BRCA1 and BRCA2 mutation screening criteria, and whose positive mutation status therefore would have been missed if clinical selection criteria had been applied.

The results of the study will be used to define selection criteria for BRCA-mutation screening in new breast cancer cases, and the design of screening procedures with an appropriate clinical effectiveness.Increasing evidence supports the benefit of identifying the BRCA1 and BRCA2 germline mutation status in early breast cancer. Germline mutations in these two genes are treatment predictive for the benefit of risk reducing surgical interventions of the contralateral breast and the ovaries and fallopian tubes, in early breast cancer (Metcalf 2014; Domchek 2010). Furthermore, they may possibly also be treatment predictive for the effect of certain types of medical interventions (Tutt SABCS 2014).

In order to provide the patient with the opportunity to take BRCA test results into account already when planning primary treatment, BRCA testing and cancer genetic counseling needs to be initiated and performed early during the diagnostic and treatment related process in newly diagnosed breast cancer cases. Special attention needs to be taken to the fact that the test results may affect not only the patient, but also her or his relatives. We have observed that the clinical efficacy of BRCA-screening criteria may be surprisingly low, leaving a substantial number of BRCA-carriers undetected in spite of intense contacts with health care providers (Unpublished results).

BRCAsearch (ClinicalTrials.gov Identifier: NCT02557776) is a population based study including new invasive breast cancer cases at three hospitals in the South of Sweden. Patients are invited to perform BRCA1 and BRCA2 germline mutation analysis at time of primary treatment after written study information and written genetic counseling, irrespective of family history, age or clinical phenotype. The primary end-points of the study include the rate of BRCA mutations in newly diagnosed breast cancer in South Sweden, the fraction of patients that accept inclusion in the study, and the rate of mutation positive patients that do not fulfill clinical criteria for BRCA mutation screening. Secondary end-points include the perception among patient of the intervention and testing procedures, the types of questions the patients present during the process and psychosocial outcome among carriers and non-carriers.

In May 2016 about 400 patients have been included in the study, whereof 333 have been analyzed for BRCA germline mutations. The accrual target of the study is 500 patients, which will be reached during the fall of 2016. At the meeting, the BRCA1 and BRCA2 mutation rates will be presented, as well as the acceptance rate of the study among patients approached, and the fraction of mutation positive patients that do not fulfill current BRCA1 and BRCA2 mutation screening criteria, and whose positive mutation status therefore would have been missed if clinical selection criteria had been applied.

The results of the study will be used to define selection criteria for BRCA-mutation screening in new breast cancer cases, and the design of screening procedures with an appropriate clinical effectiveness.

Citation Format: Loman N, Borg Å, Henriksson K, Kristoffersson U, Kvist A, Silfverberg B, Törngren T, Brandberg Y, Nilsson M. BRCAsearch - results of population-based screening of BRCA1 and BRCA2 germline mutations in incident breast cancer in South Sweden [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-09-01.