Gene mutation associated with 10%-13% of breast cancers under the age of 35 years.

Comprises only 5% of breast cancers or fewer than 10,000 cases per year in the United States.

17q21 chromosome disorder.

This gene is responsible for inherent DNA damage-sensing processes and DNA repair mechanisms.

About 25% of all triple negative breast cancers and 10 to 20% of high-grade serous ovarian cancers harbor BRCA 1 promoter methylation.

Involved in cell cycle check-point control, chromatin remodeling, transcriptional regulation and mitosis.

BRCA1 gene plays a role in interstrand DNA crosslink repair through several mechanisms including homologous recombination.

In families with four or more cases of breast cancer the prevalence of BRAC1 mutations 13-18%.

Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely

BRCA1  carriers in men are related to one percent risk of breast cancer.

Mutations in this gene confer an approximate 80% lifetime risk of breast cancer among carriers.

Patients carry a four fold higher risk for colon cancer than the general female population.

May confer a 44% risk of ovarian cancer by age 73.

By age 80 BRCA1 carriers have a 44-45%  cumulative risk of developing ovarian cancer.

Women with BRCA1 mutations have a 39-54% cumulative lifetime risk of developing oh varying cancer.

0.1% of the general population and between 3-5% of breast cancer patients.

50% of mutations account for missense alterations and intronic variations of unknown significance.

A large majority BRCA1 associated breast cancers express a triple negative phenotype, and basal-like cytokeratins five, 14, 17 and HER1.

Triple Negative Breast Cancer and BRCA1 gene are strongly associated.

More than 75% of the BRCA1 mutation patients have a triple negative phenotype, a basal-like phenotype or both.

BRCA1 gene an important tumor suppressor gene responsible for DNA damage sensing and DNA repair mechanisms.

BRCA1 gene results in deficiencies in proteins encoded for DNA damage repair and genetic instability.

Most BRCA1 gene expression analyses indicate that most BRCA-1 associated brest cancers have a basal-like phenotype and are likely to be triple negative (Sorlie T, Irvin WJ).

Because about 15% of TNBC are not basal-like, a smaller proportion of TNBC tumors compared to basal-like cancers are BRCA-1 positive (Nofech-Mozes S).

BRCA-1, TNBC and basal-like tumors tend to express basal markers including EGFR, cytokeratinsd 5,14 and 17 (Irvin WJ).

Compared with luminal tumors TNBC more likely to arise among younger women, women with early menarche, higher parity, younger age at full term pregnancy, shorter duration of breast feeding, use of medications that suppress lactation, higher BMI, and waist-hip ratio and metabolic syndrome (Millikan RC, Dolle JM, Maiti B Vona-Davis L).

Increased risk of TNBC in premenopausal women and in African-American women.

BRCA1 mutation status clusters with basal-like subtype breast cancers.

80% of cases associated breast cancers display the basal-light molecular subtype.

Mutations are associated with occult primary ovarian insufficiency and may, in part, explained a link between infertility and breast/ovarian cancer risks (Oktay K ).

Prophylactic oophorectomy following diagnosis of breast cancer among women with BRCA1 or BRCA2 mutation reduces the risk of dying of breast cancer: In a study of 676 women with the above mutations 345 underwent bilateral oophorectomy the adjusted hazard ratio was 0.38 for BRCA1 carriers. and 0.57 for BRCA2 carriers. (Metcalfe K et al).

Women with ER negative receptor breast cancer and BRCA1 mutation should undergo oophorectomy shortly after diagnosis of breast cancer.

Among women with a BRCA1 sequence variation, MRI surveillance is associated with a significant reduction in breast cancer mortality compared with no MRI surveillance.

Cisplatin effective in BRCA1 mutations with a 72% pathologic complete remission in neoadjuvant therapy (Gronwald J).

Leave a Reply

Your email address will not be published. Required fields are marked *