TY - JOUR
T1 - Genetic Risk of Second Primary Cancer in Breast Cancer Survivors
T2 - The Multiethnic Cohort Study
AU - Chen, Fei
AU - Park, Sungshim L.
AU - Wilkens, Lynne R.
AU - Wan, Peggy
AU - Hart, Steven N.
AU - Hu, Chunling
AU - Yadav, Siddhartha
AU - Couch, Fergus J.
AU - Conti, David V.
AU - de Smith, Adam J.
AU - Haiman, Christopher A.
N1 - Funding Information:
A.J. de Smith reports grants from Concern Foundation Marni Levine Memorial Breast Cancer Research Fund during the conduct of the study. No disclosures were reported by the other authors.
Funding Information:
This work was supported by the NCI at the NIH (grant nos. T32CA229110 to F. Chen, U01CA164973 to C.A. Haiman and L.R. Wilkens, and R01CA192393 and R35CA253187 to F.J. Couch), the Concern Foundation Marni Levine Memorial Breast Cancer Research Fund (to A.J. de Smith), and the Breast Cancer Research Foundation (to F.J. Couch).
Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2022/9/15
Y1 - 2022/9/15
N2 - Women who have had breast cancer in the past are at increased risk of developing a second primary cancer (SPC), including second primary breast cancer (SPBC) or a second primary non-breast cancer (SPNBC). In the Multiethnic Cohort (MEC) Study, we conducted a prospective cohort analysis in 3,223 female breast cancer survivors from five racial/ethnic populations (White, African American, Japanese American, Latino, and Native Hawaiian) to assess the association of rare pathogenic variants (PV) in 37 known cancer predisposition genes with risk of SPC. A total of 719 (22.3%) women developed SPC, of which, 323 (10.0%) were SPBC. Germline PVs in BRCA1 (HR, 2.28; 95% CI, 1.11–4.65) and ERCC2 (HR, 3.51; 95% CI, 1.29–9.54) were significantly enriched in women with SPC. In the subtype analysis for SPBC, a significant association of ERCC2 PVs (HR, 5.09; 95% CI, 1.58–16.4) and a suggestive association of BRCA2 PVs (HR, 2.24; 95% CI, 0.91–5.55) were observed. There was also a higher risk of SPNBC in carriers of BRCA1 PVs (HR, 2.98; 95% CI, 1.21–7.36). These results provide evidence that germline PVs in BRCA1, BRCA2, and ERCC2 contribute to the development of SPC in breast cancer survivors. These findings also suggest that compromised DNA repair mechanisms could be a predisposition factor for SPC in patients with breast cancer, supporting the need for closer monitoring of SPC in women carrying PVs in these genes.
AB - Women who have had breast cancer in the past are at increased risk of developing a second primary cancer (SPC), including second primary breast cancer (SPBC) or a second primary non-breast cancer (SPNBC). In the Multiethnic Cohort (MEC) Study, we conducted a prospective cohort analysis in 3,223 female breast cancer survivors from five racial/ethnic populations (White, African American, Japanese American, Latino, and Native Hawaiian) to assess the association of rare pathogenic variants (PV) in 37 known cancer predisposition genes with risk of SPC. A total of 719 (22.3%) women developed SPC, of which, 323 (10.0%) were SPBC. Germline PVs in BRCA1 (HR, 2.28; 95% CI, 1.11–4.65) and ERCC2 (HR, 3.51; 95% CI, 1.29–9.54) were significantly enriched in women with SPC. In the subtype analysis for SPBC, a significant association of ERCC2 PVs (HR, 5.09; 95% CI, 1.58–16.4) and a suggestive association of BRCA2 PVs (HR, 2.24; 95% CI, 0.91–5.55) were observed. There was also a higher risk of SPNBC in carriers of BRCA1 PVs (HR, 2.98; 95% CI, 1.21–7.36). These results provide evidence that germline PVs in BRCA1, BRCA2, and ERCC2 contribute to the development of SPC in breast cancer survivors. These findings also suggest that compromised DNA repair mechanisms could be a predisposition factor for SPC in patients with breast cancer, supporting the need for closer monitoring of SPC in women carrying PVs in these genes.
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U2 - 10.1158/0008-5472.CAN-21-4461
DO - 10.1158/0008-5472.CAN-21-4461
M3 - Article
C2 - 35834270
AN - SCOPUS:85138447269
VL - 82
SP - 3201
EP - 3208
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 18
ER -