JCO abstract: Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers (185delAG, 5382insC, 6174delT)

Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers

Purpose 

Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. 

Methods 

Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. 

Results 

Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers. No significant difference was seen in cancer risk reduction after RRSO among subgroups. 

Conclusion 

Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.

Jan 2012 abstract: Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening

Blogger's Note: in this study longterm followup = 2 years

Abstract

There are two mutations in BRCA1 and one in BRCA2, which are present in up to 2.5% of Jewish women. Population genetic testing for Jewish women has been proposed; however, it is unclear how this would impact the uptake of cancer prevention options and psychosocial functioning in women with a positive result. Two thousand and eighty unselected Jewish women were tested for the Jewish BRCA mutations, and 1.1% were positive. Cancer-related distress was measured before testing, and at 1 and 2 years post-testing. Information on uptake of cancer risk reduction options was collected at 2 years. Breast and ovarian cancer risks were estimated using BRCAPRO. Within 2 years of receiving a positive result, 11.1% of women had prophylactic mastectomy, and 89.5% had a prophylactic oophorectomy. The mean breast cancer risk was estimated to be 37.2% at time of testing, compared to 20.9% at 2 years post-testing. The mean ovarian cancer risk was estimated to be 24.5% at time of testing, compared to 7.5% at 2 years following testing. Distress decreased between 1 and 2 years for women with prophylactic mastectomy and oophorectomy (P = 0.02), and for women with prophylactic oophorectomy only (P = 0.04) but not for those with neither surgery. The majority of Jewish women with a BRCA mutation identified through a population screening elected prophylactic oophorectomy, but a few had a prophylactic mastectomy. Uptake of either surgery resulted in decreased distress. Provision of population BRCA testing resulted in reduced risks of breast and ovarian cancers in women with a mutation.

Keywords  BRCA1 – BRCA2 – Breast cancer – Genetic testing – Jewish

clinical trial: Anonymous Testing of Pathology Specimens for BRCA (and Lynch Syndrome MSH2) Mutations in Ashkenazi Jewish Individuals Who Have Cancer

Purpose

The intent of the proposed study is to describe the prevalence of the most common recurring mutations

in BRCA1 and BRCA2, blmAsh , and the A636P MSH2  (Lynch Syndrome) mutation among Ashkenazi Jewish individuals with a variety of cancer diagnoses. If a substantial proportion of these samples contain such mutations, future patients presenting with these diseases may wish to undergo genetic counseling and, if appropriate, formal genetic testing. The benefit from such a process would pertain mainly to the families of these individuals.

Condition
Extrahepatic Bile Duct Cancer Gallbladder Cancer Gastric Cancer Lung Cancer Melanoma Non-Hodgkin's Lymphoma Uterine Cancer CORPUS UTERI,ENDOMETRIUM LUNG OVARY

The rate of the predominant Jewish mutations in the BRCA1, BRCA2, MSH2 and MSH6 genes in unselected Jewish endometrial cancer patients (study number 289 patients)

Note: MSH2/MSH6 are 2 of the Lynch Syndrome genes

Objectives

The genes associated with familial Endometrial Cancer (EC) are largely unknown. While EC is an integral part of Hereditary Non-Polyposis Colon Cancer, there is an ongoing debate if EC is indeed overrepresented in hereditary breast/ovarian cancer families.

Conclusions

Our data do not support screening for BRCA1/2 mutations in consecutive EC patients.

AACR Hosts Cancer Disparities Conference in Miami, Fla. abstract online Sept

This year, the American Association for Cancer Research will host its third conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved at the Loews Miami Beach Hotel in Miami, Fla.

Findings presented at this year’s meeting will include:

• proven communication methods for reaching minority populations;
• strategies to increase enrollment in clinical trials;
• prognosis in lung cancer affected by race;
• breast cancer trends in Arab and Israeli Jewish women;
• the importance of social support and physical activity in survivors; and,
• socioeconomics and access to health care.
To help you plan your coverage of the conference, the program schedule is available online at
http://www.aacr.org/disparities2010

abstracts will be available on Sept. 22, 2010

Preventing Future Cancers by Testing Women With Ovarian Cancer for BRCA Mutations -- University of British Columbia/MD Anderson

"BRCA testing of women with ovarian cancer based on personal/family history of cancer or Ashkenazi Jewish ancestry is a cost-effective strategy to prevent future breast and ovarian cancers among FDRs (first degree relatives). More inclusive testing strategies prevent additional cancer cases but at significant cost."

press release: Women's College Hospital (Toronto) offers Jewish women genetic screening for breast cancer

“Our study identified two major concerns with current breast cancer screening guidelines,” says Dr. Kelly Metcalfe, adjunct scientist at the Women’s College Research Institute and associate professor at the University of Toronto. “The first is that over half of the women we identified with a mutation would never have known that they were at an increased risk of cancer because they were not eligible for genetic testing outside of this study. The second concern was that although 45 per cent of the women with mutations were eligible for genetic testing based on their family history of cancer, none were referred by their health-care provider for screening. "