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Hereditary breast cancer survival can be equal to sporadic cases | Research article July 16, 2007

Posted by ramunas in breast cancer, cancer genetics, hereditary cancer, research.

In recent article (Title: Clinical Outcomes of Breast Cancer in Carriers of BRCA1 and BRCA2 Mutations) published in New England Journal of Medicine the data of retrospective population-based cohort study of Israeli women to determine the influence of a BRCA1 or a BRCA2 mutation on the prognosis in breast cancer, were presented. The researchers evaluated data obtained between 1987 and 1988, medical records were obtained for 1545 women, DNA was extracted from paraffin-embedded tumor blocks (1794) and analysed for founder mutations: two mutations in BRCA1 (185delAG and 5382insC) and one in BRCA2 (6174delT) genes (approximately 2% of all Ashkenazi women and 12% of Ashkenazi women with breast cancer carry a mutation in one of these two genes). Only 135 mutation carriers were identified and estrogen-receptor status data were available for only 55% of subjects. The study was designed to estimate survival rates for women with a BRCA1 or BRCA2 mutation, as compared with women without a detected mutation, in the 10-year period after diagnosis.

The study concluded [ref.]:

  • Overall, deaths rates from breast cancer were not significantly different among patients with BRCA1 and BRCA2 mutations from those without the mutations.
  • Among patients who underwent treatment with chemotherapy, death rates from breast cancer were not significantly different between patients with BRCA1 and BRCA2 mutations from those without the mutations.

In conclusion, breast cancer–specific rates of death among Israeli women are similar for carriers of a BRCA founder mutationand noncarriers.

These data are important, because little is known about the influence of a BRCA1 or BRCA2 mutation on the natural history of breast cancer or the response to treatment. BRCA1-associated breast cancers tend to occur at younger age, are usually high grade (G3), estrogen receptors negative and have basal-like phenotype. These features normally are associated with a poorer prognosis, but the evidence concerning the effect of BRCA1 or BRCA2 mutation on the prognosis was inconsistive and cotraversive .

In the case of ovarian cancer (which could be a part of hereditary breast-ovarian cancer syndrome (HBOC)), there are some data that BRCA mutations acctually links to longer patient survival and hereditary ovarian cancer can be less deadly than sporadic. It is intriquing observation, which can be explained at least by the two assumptions: the underlying biologic properties of hereditary tumors may make them more indolent, or the hereditary tumors may respond better to chemotherapy [ref.].

However, a small proportion of sporadic breast and ovarian tumors can have inactivating somatic mutations in BRCA1/2 genes , suggesting the role of these genes in the development of sporadic cancer, therefore when analysing tumor DNA it is possible to include sporadic cases as well.

Other BRCA genes mutations and other populations should be studied. Large perspective, randomized trials are now regarded as an ideal research study in clinical cancer genetics [ref.], although they are difficult to conduct.

Bellow is a nice picture of BRCA genes with marked Ashkenazi mutations from E. Passarge “Color Atlas of Genetics”, which I love to show to my students:



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