Observational studyBreast cancerOvarian cancer

Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

JAMA · 20179856 women carrying a mutation (6036 BRCA1 carriers and 3820 BRCA2 carriers)

Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. JAMA. 2017. 317:2402

Study type: Observational study
Study name: BRCA1/2 Cohort Consortium
Design: Prospective cohort study
Sample size: 9856 women carrying a mutation (6036 BRCA1 carriers and 3820 BRCA2 carriers)
Source: JAMA · 2017

In plain words

This large study followed women with a BRCA1 or BRCA2 gene mutation to find out how likely they are to develop breast or ovarian cancer. By age 80, about 72% of BRCA1 carriers and 69% of BRCA2 carriers had developed breast cancer. The risk of ovarian cancer was much higher in BRCA1 carriers (44%) than in BRCA2 carriers (17%). Having relatives with breast cancer, and where the mutation sits in the gene, can also change the risk. Be sure to discuss decisions about screening or preventive steps with your doctor and a genetic counsellor.

Key results

72% in BRCA1 carriers and 69% in BRCA2 carriers

Cumulative breast cancer risk to age 80

95% CI 65–79% for BRCA1 and 61–77% for BRCA2

Rapid increase until ages 30 to 40 in BRCA1 and 40 to 50 in BRCA2; then constant incidence (20 to 30 per 1000 person-years) until age 80

Pattern of breast cancer incidence by age

44% in BRCA1 carriers and 17% in BRCA2 carriers

Cumulative ovarian cancer risk to age 80

95% CI 36–53% for BRCA1 and 11–25% for BRCA2

40% in BRCA1 carriers and 26% in BRCA2 carriers

Cumulative contralateral breast cancer risk 20 years after breast cancer diagnosis

Hazard ratio BRCA2 vs BRCA1: 0.62 (95% CI 0.47–0.82); P=0.001

BRCA1: hazard ratio 1.99; BRCA2: hazard ratio 1.91

Effect of the number of relatives with breast cancer (≥2 vs 0) on breast cancer risk

95% CI 1.41–2.82 (P<0.001 for trend) in BRCA1 and 1.08–3.37 (P=0.02 for trend) in BRCA2

BRCA1 (outside c.2282-c.4071): hazard ratio 1.46; BRCA2 (outside c.2831-c.6401): hazard ratio 1.93

Breast cancer risk for mutations outside versus inside the specified region

95% CI 1.11–1.93 (P=0.007) for BRCA1 and 1.36–2.74 (P<0.001) for BRCA2

426 breast cancers, 109 ovarian cancers and 245 contralateral breast cancers

Number of cancers diagnosed during follow-up

Among 3886 women eligible for the breast cancer analysis, 5066 women eligible for the ovarian cancer analysis and 2213 women eligible for the contralateral breast cancer analysis

Treatment arms and regimens

1BRCA1 mutation carriers

Observational study with no drug intervention. 6036 women carrying a BRCA1 mutation were followed.

2BRCA2 mutation carriers

Observational study with no drug intervention. 3820 women carrying a BRCA2 mutation were followed.

Source of the regimen details: Abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Women carrying a BRCA1 or BRCA2 mutation enrolled between 1997 and 2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Of these, 5046 were unaffected at baseline and 4810 had breast cancer, ovarian cancer or both at baseline. Participants were identified mainly through family clinics (94%) and less often through population-based studies (6%). Most participants came from large national studies in the UK (EMBRACE), the Netherlands (HEBON) and France (GENEPSO).

Endpoints

Main outcome measures: annual incidence, standardised incidence ratio and cumulative risk of breast cancer, ovarian cancer and contralateral breast cancer. Exposures examined: BRCA1/2 mutations, family history of cancer and mutation location. Follow-up continued until December 2013, with a median follow-up of 5 years.

Safety and side effects

This is an observational study estimating cancer risk; treatment-related adverse events are not reported in the abstract.

Clinical significance and place in guidelines

This study provides prospective, age-specific estimates of the risks of breast, ovarian and contralateral breast cancer in BRCA1 and BRCA2 carriers, which can be used in counselling and clinical management of these individuals. According to the abstract, family history and mutation location may matter in risk assessment. The abstract does not comment on any direct change to guidelines or on their endorsement, and the status of clinical guidelines should be checked separately.

Limitations

Median follow-up was 5 years. Most participants (94%) were identified through family clinics and only 6% came from population-based studies, so the results should be generalised to all carriers with caution. Further details on limitations are in the full paper.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.