Prospective study of breast cancer risk for mutation negative women from BRCA1 or BRCA2 mutation positive families

• Published in: Breast cancer research and treatment Vol. 130; no. 3; pp. 1057 - 1061
• Main Authors: Harvey, S. L., Milne, R. L., McLachlan, S. A., Friedlander, M. L., Birch, K. E., Weideman, P., Goldgar, D., Hopper, J. L., Phillips, K. A.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-12-2011; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Brief Report; Cancer; Cancer research; Family; Female; Gene mutations; Genes, BRCA1; Genes, BRCA2; Genetic aspects; Genetic Predisposition to Disease; Genetics; Gynecology. Andrology. Obstetrics; Humans; Incidence; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Oncology, Experimental; Prospective Studies; Risk Assessment; Risk factors; Tumors; Young Adult; Australia; Phenocopy; Risk; Breast cancer; BRCA1; BRCA2; Human; Breast disease; Malignant tumor; Prospective; Mammary gland diseases; BRCA2 gene; Risk factor; Adult; Female; Genetics; Mutation; Woman; BRCA1 gene; Cancer; Tumor suppressor gene
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-011-1733-6

Published studies have reached contradictory conclusions regarding breast cancer risk for women from families segregating a
BRCA1
or
BRCA2
mutation who do not carry the family-specific mutation. Accurate estimation of breast cancer risk is crucial for appropriate counselling regarding risk management. The aim of this study is to prospectively assess whether breast cancer risk for mutation negative women from families segregating
BRCA1
or
BRCA2
mutations is greater than for women in the general population. Eligible women were 722 first-, second- and third-degree relatives of a
BRCA1
or
BRCA2
mutation carrier from 224 mutation positive (128
BRCA1
, 96
BRCA2
) families, had no personal cancer history at baseline, and had been tested and found not to carry the family-specific mutation. Self-reported family history of cancer, preventive interventions and verified cancer diagnoses were collected at baseline, and every 3 years thereafter. Median follow-up was 6.1 years (range 0.1–12.4 years). Time at risk of breast cancer was censored at cancer diagnosis or risk-reducing surgery. Standardised incidence ratios (SIR) were estimated by comparing observed to population incidences of invasive breast cancer using Australian Cancer Incidence and Mortality Books. Six cases of invasive breast cancer were observed. The estimated SIRs were 1.14 (95% CI: 0.51–2.53) overall (
n
 = 722), 1.29 (95% CI: 0.58–2.88) when restricted to first- and second-degree relatives of an affected mutation carrier (
n
 = 442) and 0.48 (95% CI: 0.12–1.93) when restricted to those with no family history of breast cancer in the non-mutation carrying parental lineage (
n
 = 424). There was no evidence that mutation negative women from families segregating
BRCA1
or
BRCA2
mutations are at increased risk of breast cancer. Despite this being the largest prospective cohort to assess this issue, moderately increased breast cancer risk (2-fold) cannot be ruled out.