Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Breast and Ovarian Cancer, familial [C50.9]

OMIM numbers: 604370113705 (BRCA1), 600185 (BRCA2)

Dipl.-Ing. (FH) Tanja Hinrichsen, Dipl.-Biol. Anne Holtorf

Scientific Background

About 5-10% of all breast and ovarian carcinomas are hereditary with autosomal dominant inheritance. Significant characteristics of the hereditary form of this disease are an early age at onset (before the fifth decade of life) and multiple occurrence within a family. The genes BRCA1 and BRCA2 are causal in about 50% of inherited breast and ovarian cancers. The gene products of BRCA1 and BRCA2 are involved in DNA repair of double-strand breaks. Female carriers of a BRCA germline mutation have an increased lifetime risk of developing breast and ovarian cancer. However, a tumor only develops if the second intact allele is inactivated by mutation (loss of heterozygosity, LOH). The risk of developing breast cancer is between 50 and 80%, for contralateral breast cancer it is 60% and between 10 and 40% for ovarian cancer. Male carriers of BRCA mutations also have an increased tumor risk, especially for breast, prostate, pancreatic, stomach and colorectal carcinomas. In male patients, mutations are most often found in the BRCA2 gene.

Older women who develop breast cancer, and do not have any family members affected by the disease, are unlikely to carry genetic mutations. For women that have multiple family members affected by breast or ovarian cancer, or with very early onset of disease, genetic testing may be advisable. In Germany, the German Consortium for Hereditary Breast and Ovarian Cancer created inclusion criteria for those people with at least a 10% probability of having a mutation in the genes BRCA1 and BRCA2 (see Level 3 guidelines for high risk groups, below). A causal mutation can be identified in about 25% of families who meet the criteria.

In Germany, a structured screening program for secondary prevention is recommended for women with a confirmed mutation and women from families tested BRCA1 / 2 negative with a heterozygous risk of > 20%, or a lifetime risk of developing of developing disease of > 30%. Primary prevention includes prophylactic surgery which should be explained to affected patients in the course of interdisciplinary consultation and support.

In predictive genetic testing, at-risk, healthy individuals are tested, being usually first-degree relatives of affected patients. Here, any genetic diagnosis should be combined with the offer of genetic counseling. In the case of predictive genetic testing, genetic counseling must be carried out prior to testing as well as after having received the result (Section 10, paragraph 2 GenDG). An exemption is only possible when a written waiver from the at-risk person is available, to be provided after having received written information on the content of the counseling.

Level 3 Guidelines (for high risk groups)

In accordance with the Level 3 Guidelines for the Diagnosis, Therapy and Follow-up Care of Breast Cancer, genetic counselling and molecular genetic examinations, should be offered when in one line of the family:

  • At least three women have developed breast cancer
  • At least two women have developed breast cancer, one of whom is younger than 51 years old
  • At least one woman has developed breast cancer and one woman has developed ovarian cancer
  • At least two women have developed ovarian cancer
  • At least one woman has developed breast and ovarian cancer
  • At least one women younger than 36 years old has developed breast cancer
  • At least one women has developed bilateral breast cancer before the age of 51
  • At least one man has developed breast cancer and one woman has developed breast or ovarian cancer

Special strategy algorithm modified from the Level 3 Guidelines on Breast Cancer Awareness, DGS (2008)
Breast cancer flow chart from level 3 guidelines