Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.

The computerized analysis of mammograms suggests that mammographic patterns in carriers of BRCA1 and BRCA2 mutations differ from those of women at low risk for breast cancer. Our computer-extracted features may be useful as radiographic markers for identifying women at high risk for breast cancer.

Purpose: To evaluate prophylactic salpingo-oophorectomy uptake and timing among BRCA1/2 mutation carriers in a cancer risk assessment program. Methods: Clinical records of female BRCA1/2 mutation carriers who received cancer genetic counseling between 1996 and 2003 were reviewed to determine the completion and the timing of prophylactic salpingo-oophorectomy. Logistic regression models evaluated associations between subject characteristics and surgery. Survival analysis methods were used to estimate the distribution of time to surgery. Results:Among 88 women, 70% underwent prophylactic salpingo-oophorectomy. Prophylactic salpingo-oophorectomy was associated with older age, white race, having children, and a family history of ovarian cancer. Many women waited more than 12 months to undergo surgery and some delayed by several years. Younger age and not having children were associated with delays to surgery. Conclusion: Prophylactic salpingo-ooporectomy is an acceptable risk reduction measure for many BRCA1/2 mutation carriers. Some women make this decision many years after genetic testing. Continued discussion of the risks and benefits of risk reduction options may facilitate the uptake of recommended risk reduction interventions among BRCA mutation carriers. Genet Med 2008:10(3):161-166. Key Words: BRCA1, BRCA2, prophylactic salpingo-oophorectomyWomen who carry a BRCA1 or BRCA2 mutation have a 31-87% risk of developing breast cancer and a 15-40% risk of developing ovarian cancer 1-4 compared with the risk in the general population of 12.5% and 1.5%, respectively. 5 In light of these risks, BRCA mutation carriers are counseled regarding available risk reduction methods, including prophylactic surgery, increased surveillance, and chemoprevention. One of these options, bilateral prophylactic salpingo-oophorectomy (BSO), has been shown to decrease the risk of ovarian cancer in BRCA mutation carriers by 85-96% and the risk of breast cancer by 50%. 6 -8 In addition, surgical morbidity and mortality has decreased with the advent of laparoscopic surgical techniques. 9 Thus, BSO is currently recommended to BRCA mutation carriers between 35 and 40 years of age or at completion of childbearing. 5,10 Despite this, many women and clinicians are concerned about the effects of premature menopause after surgical prophylaxis. 11,12 Although there is some evidence suggesting that short-term hormone replacement therapy (HRT) does not increase breast cancer risks in BRCA mutation carriers, long-term prospective data are not available and many physicians are reluctant to provide, and many women are reluctant to consider postsurgical HRT. 13 Thus, some women elect not to undergo BSO and receive ovarian cancer surveillance with transvaginal ultrasound, serum CA-125, and clinical pelvic examination, although studies have suggested that the ability to detect early cancers with such screening is poor. 14,15 Despite these recommendations and considering the controversy surrounding postsurgical HRT, the acceptability of BSO as a risk reduc...

Children of BRCA mutation carriers learn of their parents genetic test results many years before preventive interventions are indicated. Further research is needed to examine how young individuals understand this information and its psychosocial impact and influence on subsequent lifestyle and health behaviors.

Age, type of initial breast cancer surgery, and prophylactic oophorectomy are all predictive of prophylactic contralateral mastectomy in women with breast cancer and a BRCA mutation. The acceptance of contralateral preventive mastectomy was much higher in North America than in Europe.

Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. There is a recent report that BRCA2 carriers with prostate cancer have poorer survival than noncarrier prostate cancer patients. In this study, we compared survival of men with a BRCA2 mutation and prostate cancer with that of men with a BRCA1 mutation and prostate cancer. We obtained the age at diagnosis, age at death or current age from 182 men with prostate cancer from families with a BRCA2 mutation and from 119 men with prostate cancer from families with a BRCA1 mutation. The median survival from diagnosis was 4.0 years for men with a BRCA2 mutation vs 8.0 years for men with a BRCA1 mutation, and the difference was highly significant (Po0.01). It may be important to develop targeted chemotherapies to treat prostate cancer in men with a BRCA2 mutation. British Journal of Cancer (2008) BRCA2 is a multisite cancer gene. It is generally thought that BRCA2 mutations primarily affect women, but men with mutations are also at elevated cancer risk. The two most important cancer sites for males who carry a mutation are the prostate and the pancreas (Liede et al, 2004). The risk of prostate cancer is elevated approximately fivefold in BRCA2 carriers, compared to noncarriers. Genetic counselors and urologists advise men with BRCA2 mutations to undergo surveillance with annual PSA testing from the age of 40 years -a recommendation based on the perceived effectiveness of prostate screening. It is hoped that screening leads to early diagnosis, when cure rates are high. A recent study from Iceland suggests that prostate cancers in men with a BRCA2 mutation may be unusually aggressive (Tryggvadottir et al, 2007). Tryggvadottir et al (2007) identified the Icelandic founder mutation (BRCA2 999 del5) in 30 of the 527 prostate cancer patients studied (5.7%). Men with a BRCA2 mutation had a median survival of only 2.1 years, compared with 12.4 years for noncarriers (Po0.01). The survival difference could not be explained by stage or grade. It is important that these findings be replicated because of the implications for the screening of men with a BRCA2 mutation. We identified the prostate cancer patients in a panel of 2673 families with a BRCA1 or a BRCA2 mutation and estimated survival of the men in the two subgroups. METHODSMen with prostate cancer were included in the survival analysis if they were from a family with a BRCA mutation and if they were (a) known to carry the familial BRCA mutation, or (b) if they were a first-degree relative of a known carrier, or (c) if they were a firstdegree relative of a woman diagnosed with breast or ovarian cancer. For each eligible man with prostate cancer, information was collected on age at diagnosis, age at death (if deceased) or age when last known alive (if alive). Information was collected by the

Sensitivity for identifying BRCA gene mutation carriers is similar for experienced risk counselors and the computer model BRCAPRO. Because the computer model consistently demonstrated superior specificity, overall discrimination between BRCA gene mutation carriers and BRCA gene mutation noncarriers was slightly better for BRCAPRO.

Cowden syndrome (CS) (OMIM 158350) is a multiple hamartoma syndrome associated with germline mutations in the PTEN tumour suppressor gene. While CS is characterised most commonly by noncancerous lesions (mucocutaneous trichilemmomas, acral and palmoplantar keratoses, and papillomatous papules), it is also associated with an increased susceptibility to breast cancer (in females) and thyroid cancer, as well as noncancerous conditions of the breast and thyroid. Here we report two cases of male breast cancer occurring in patients with classical CS phenotypes and germline PTEN mutations. The first subject was diagnosed with CS indicated primarily by mucocutaneous papillomatosis, facial trichilemmomas, and macrocephaly with frontal bossing at the age of 31 years. He developed breast cancer at 41 years and subsequently died of the disease. A PTEN mutation, c.802delG, was identified in this subject, yet none of his family members showed evidence of a CS phenotype, suggesting that this PTEN mutation may be a de novo occurrence. The second subject had a CS phenotype including multiple trichilemmomas and thyroid adenoma, developed male breast cancer at 43 years, and died of the disease at 57 years. He was a carrier of a PTEN mutation c.347-351delACAAT that cosegregated with the CS phenotype in aVected family members. These two cases of male breast cancer associated with germline PTEN mutations and the CS phenotype suggest that CS may be associated with an increased risk of early onset male as well as female breast cancer. (J Med Genet 2001;38:159-164)