Earlier age of onset of BRCA mutation‐related cancers in subsequent generations

BACKGROUND: 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 earli...

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Bibliographic Details
Published in:Cancer 2012-01, Vol.118 (2), p.321-325
Main Authors: Litton, Jennifer K., Ready, Kaylene, Chen, Huiqin, Gutierrez‐Barrera, Angelica, Etzel, Carol J., Meric‐Bernstam, Funda, Gonzalez‐Angulo, Ana M., Le‐Petross, Huong, Lu, Karen, Hortobagyi, Gabriel N., Arun, Banu K.
Format: Article
Language:English
Subjects:
Adult
Age of Onset
Aged
anticipation
Biological and medical sciences
BRCA1
BRCA2
breast cancer
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Female
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Gynecology. Andrology. Obstetrics
hereditary breast and ovarian cancer syndrome
Humans
Mammary gland diseases
Medical sciences
Middle Aged
Mutation
Ovarian Neoplasms - genetics
Risk
Tumors
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Summary:BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Women with mutations in the breast cancer (BRCA) genes BRCA1 or BRCA2 have a high lifetime risk of developing breast cancer, and more intense screening and prophylactic measures are used. The results of this study indicated that, in families with a known deleterious BRCA mutation, women were being diagnosed overall 7.9 years earlier than in the preceding generation.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.26284