Abstract P6-08-33: A remarkably high yield of identified hereditary breast cancer cases in a single oncology center, followed by inversely proportional rate of cascade testing in family relatives
Authors: Fostira Florentia , Rapti Vasiliki , Apostolou Paraskevi , Delimitsou Angeliki , Papamentzelopoulou Myrto , Yannoukakos Drakoulis , Misitzis Ioannis , Koumakis Georgios , Demiri Stamatina , Konstantopoulou Irene , Tryfonopoulos Dimitrios 
Published: March 2020

Background: Individuals carrying pathogenic, cancer-predisposing, variants face an increased lifetime risk for various diagnoses, depending on the gene and maybe, variant. Traditionally, germline genetic testing is ordered for a cancer patient who fulfills certain eligibility criteria; mainly based on early age at diagnosis and family history for cancer. Although the test results provide useful information for the clinical management of the patients themselves, this information is pivotal for the primary disease prevention of their blood relatives. Targeted testing for the causative variant (so-called cascade testing), already identified in an affected individual, provide valuable information, while minimizing testing cost. Asymptomatic carriers who are at elevated risk may be offered risk-reducing measurements or early-stage diagnoses, resulting in improved outcomes or even no cancer diagnosis.

Methods: In a single breast oncology clinic, with a turnaround of ~200 new breast cancer patients annually, and throughout years 2014-2019, a total of ninety-five cancer patients fulfilled the NCCN criteria, agreed and consented to genetic testing. Of these, eighty-nine were breast cancer patients, of which two were males, while six were ovarian cancer patients. A comprehensive cancer-gene panel was implemented, which targets a total of 94 genes.

Results: Overall, 25.2% (24/95) of the tested patients carried a loss-of-function variant in a breast/ovarian cancer susceptibility gene (BRCA1, BRCA2, PALB2, TP53, ATM, RAD51C and PMS2), while secondary findings were identified in 5.2% (5/95) of the patients. All carriers in the first group were counselled and were informed to notify their blood relatives. Of these, thirty-nine family relatives from fourteen different families (range 1-6 per family), actually pursued cascade testing based on their relatives’ genetic test result, contributing in a rate of 56%. Interestingly, all the aforementioned were first-degree relatives and no second-degree relative came forward. Of these, twenty individuals (51.2%; 20/39) tested positive, five males and fifteen females.

Conclusion: Although cascade testing for high penetrant pathogenic variants can provide primary prevention options for asymptomatic carriers, as well as assurance in non-carriers, patients with a positive genetic test result are reluctant to inform their family relatives. The rate of notification is inversely proportional to the degree of relation, with individuals in our study being restricted only to their first degree relatives. Changes in law and health policies will maximize the benefits of targeted testing. Considering the clinical actionability and the potential for preventing tumor diagnoses through cascade testing, raising awareness and educating our patients seems inevitable.

Citation Format: Florentia Fostira, Vasiliki Rapti, Paraskevi Apostolou, Angeliki Delimitsou, Myrto Papamentzelopoulou, Drakoulis Yannoukakos, Ioannis Misitzis, Georgios Koumakis, Stamatina Demiri, Irene Konstantopoulou, Dimitrios Tryfonopoulos. A remarkably high yield of identified hereditary breast cancer cases in a single oncology center, followed by inversely proportional rate of cascade testing in family relatives [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-33.