Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.

BACKGROUND: Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families. PATIENTS AND METHODS: A prospective study involving women seen at a single family history clinic in Manchester, UK. Patients were excluded if they had ovarian cancer or oophorectomy prior to clinic. Follow-up was censored at the latest date of: 31/12/2010; ovarian cancer diagnosis; oophorectomy; or death. We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population. RESULTS: We studied 8005 women from 895 families. Women from BRCA2 mutation families showed a 17-fold increased risk of invasive ovarian cancer (relative risk (RR) 16.67; 95% CI 5.41 to 38.89). This risk increased to 50-fold in women from families with BRCA1 mutations (RR 50.00; 95% CI 26.62 to 85.50). No association was found for women in families tested negative for BRCA1/2, where there was 1 observed invasive ovarian cancer in 1613 women when 2.74 were expected (RR 0.37; 95% CI 0.01 to 2.03). There was no association with ovarian cancer in families untested for BRCA1/2 (RR 0.99; 95% CI 0.45 to 1.88). DISCUSSION: This study showed no increased risk of ovarian cancer in families that tested negative for BRCA1/2 or were untested. These data help counselling women from BRCA1/2 negative families with breast cancer that their risk of invasive ovarian cancer is not higher than the general population.

Assessing individual breast cancer risk within the U.K. National Health Service Breast Screening Program: a new paradigm for cancer prevention.

The aim of this study is to determine breast cancer risk at mammographic screening episodes and integrate standard risk factors with mammographic density and genetic data to assess changing the screening interval based on risk and offer women at high risk preventive strategies. We report our experience of assessing breast cancer risk within the U.K. National Health Service Breast Screening Program using results from the first 10,000 women entered into the "Predicting Risk Of breast Cancer At Screening" study. Of the first 28,849 women attending for screening at fifteen sites in Manchester 10,000 (35%) consented to study entry and completed the questionnaire. The median 10-year Tyrer-Cuzick breast cancer risk was 2.65% (interquartile range, 2.10-3.45). A total of 107 women (1.07%) had 10-year risks 8% or higher (high breast cancer risk), with a further 8.20% having moderately increased risk (5%-8%). Mammographic density (percent dense area) was 60% or more in 8.3% of women. We collected saliva samples from 478 women for genetic analysis and will extend this to 18% of participants. At time of consent to the study, 95.0% of women indicated they wished to know their risk. Women with a 10-year risk of 8% or more or 5% to 8% and mammographic density of 60% or higher were invited to attend or be telephoned to receive risk counseling; 81.9% of those wishing to know their risk have received risk counseling and 85.7% of these were found to be eligible for a risk-reducing intervention. These results confirm the feasibility of determining breast cancer risk and acting on the information in the context of population-based mammographic screening.