Pathogenic variants among females with breast cancer and a non-breast cancer reveal opportunities for cancer interception.

Autor: Bychkovsky BL; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA. Brittany_Bychkovsky@dfci.harvard.edu.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA. Brittany_Bychkovsky@dfci.harvard.edu.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA. Brittany_Bychkovsky@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. Brittany_Bychkovsky@dfci.harvard.edu., Lo MT; Ambry Genetics, Aliso Viejo, CA, USA., Yussuf A; Ambry Genetics, Aliso Viejo, CA, USA., Horton C; Ambry Genetics, Aliso Viejo, CA, USA., Hemyari P; Ambry Genetics, Aliso Viejo, CA, USA., LaDuca H; Ambry Genetics, Aliso Viejo, CA, USA., Garber JE; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Scheib R; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Rana HQ; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.; Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2023 Jul; Vol. 200 (1), pp. 63-72. Date of Electronic Publication: 2023 Mar 01.
DOI: 10.1007/s10549-023-06870-x
Abstrakt: Purpose: Herein, we report the frequency and distribution of germline pathogenic variants (PVs) among females with breast cancer (BC) and at least one other non-BC who underwent multi-gene panel testing (MGPT). Among females with PVs diagnosed first with BC or ovarian cancer (OC), we sought to enumerate the frequency of subsequent PV-associated cancers.
Methods: Females with BC and cancer of ≥ 1 other site (multiple primary cancers, MPC) who underwent MGPT through Ambry Genetics from March 2012 to December 2016 were included if they had testing of at least 21 genes of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53). Phenotypic data were abstracted from test requisition forms and clinical notes.
Results: Of 6,617 evaluable patients, most were White (70.8%) and median age at first cancer, second cancer, and MGPT was 49 (interquartile range [IQR]: 18), 59 (IQR: 16), and 63 (IQR: 16) years, respectively. PVs were found among 14.1% (932/6617) of the overall cohort and in 16.4% (440/2687) of females who were diagnosed first with BC. Among those, 55.2% (243/440) had an actionable PV associated with a subsequent cancer diagnosis including 150 OCs. Of the 2443 females with breast and ovarian cancer, few (n = 97, 9.5%) were diagnosed first with OC, limiting our analysis.
Conclusions: Females with MPC, including BC, have a high frequency of germline PVs (14.1%). These data delineate the opportunities for intercepting subsequent cancers associated with genetic risk among females diagnosed first with BC.
(© 2023. The Author(s).)
Databáze: MEDLINE
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