Beyond BRCA1 and BRCA2 – evaluation of 123 carriers of pathogenic variants in other HBOC associated genes

Objective In panel studies of familial breast and ovarian cancer, pathogenic variants in additional HBOC-associated risk genes (BARD1, BRIP1, CDH1, CHEK2, PTEN, RAD51C, RAD51D, STK11, PALB2, TP53) beyond BRCA1/2 are detected in approximately 5% of families. This evaluation examines clinicopathological data on 123 mutation carriers from this risk group.

Material and methods Data were collected retrospectively. Healthy individuals and those with breast carcinoma with evidence of a pathogenic alteration in an HBOC-associated core gene with concomitant exclusion of a BRCA1/2 mutation (observation period 4 years) were included.

Results Carriers of a pathogenic alteration in the CHEK2 (44), PALB2 (29), and ATM (19) gene were the most numerous. Of a total of 123 confirmed female mutation carriers, 47% (58/123) had developed breast carcinoma so far, 38% (47/123) unilateral and 9% (11/123) bilateral. The age of first disease from breast carcinoma varied between 23-64 years; in 36% (21/58) the date of diagnosis was before 41 years of age, and in 12% (7/58) before 31 years of age. Complete pathologic data were available for the 58 diseased individuals. 60% (35/58) had ductal subtype, 13% (8/58) pure DCIS. The tumors of 74% (43/58) were estrogen and progesterone receptor positive; the Her2 receptor was overexpressed in 13% of tumors. 12% (7/58) had a triple negative (TNBC) subtype, of which 4 were carriers of a pathogenic PALB2 variant.

Summary PALB2-associated tumors have the highest proportion of TNBC tumors in this study population. Further characterization of this heterogeneous genetic group will help optimize clinical care.

Interessenskonflikt

Ich erkläre als korrespondierender Autor, dass meine Koautoren mir mitgeteilt haben, dass sie während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne hatten. Auch ich selbst hatte keine derartigen Verbindungen in den letzten 3 Jahren.

Publikationsverlauf

Artikel online veröffentlicht:
21. Juni 2022