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Earlier age of onset of BRCA mutation-related cancers in subsequent generations†
Article first published online: 12 SEP 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 2, pages 321–325, 15 January 2012
How to Cite
Litton, J. K., Ready, K., Chen, H., Gutierrez-Barrera, A., Etzel, C. J., Meric-Bernstam, F., Gonzalez-Angulo, A. M., Le-Petross, H., Lu, K., Hortobagyi, G. N. and Arun, B. K. (2012), Earlier age of onset of BRCA mutation-related cancers in subsequent generations. Cancer, 118: 321–325. doi: 10.1002/cncr.26284
Presented in part at the American Society of Clinical Oncology 2009 Breast Cancer Symposium; San Francisco, California; October 8-10, 2009.
- Issue published online: 5 JAN 2012
- Article first published online: 12 SEP 2011
- Manuscript Revised: 19 APR 2011
- Manuscript Accepted: 19 APR 2011
- Manuscript Received: 3 MAR 2011
- breast cancer;
- hereditary breast and ovarian cancer syndrome
Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations.
Of the 132 BRCA-positive women with breast cancer who participated in a high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families.
The median age of cancer diagnosis was 42 years (range, 28-55 years) in Gen 2 and 48 years (range, 30-72 years) in Gen 1 (P < .001). In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.
Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA-related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages. Cancer 2011. © 2011 American Cancer Society.