BRCA mutation

Methods to diagnose the likelihood of a patient with mutations in BRCA1 and BRCA2 getting cancer were covered by patents owned or controlled by Myriad Genetics.

[8] Biallelic and homozygous inheritance of a BRCA gene leads to a severe form of Fanconi anemia, and is embryonically lethal in the majority of the cases.

[11][12][13] BRCA-related ovarian and fallopian tube cancer is more treatable than average because it is unusually susceptible to platinum-based chemotherapy like cisplatin.

[14] BRCA1-related ovarian cancer appears at younger ages, but the risk for women with BRCA2 climbs markedly at or shortly after menopause.

Compared to that, a woman with a high-risk BRCA1 mutation, if she had breast cancer screening but no prophylactic medical or surgical intervention, would have only 59% chance to reach age 70, twenty-five percentage points lower than normal.

[15] Women with high-risk BRCA2 mutations, with screening but with no prophylactic medical or surgical intervention, would have only 71% chance to reach age 70, thirteen percentage points lower than normal.

[15] The likelihood of surviving to at least age 70 can be improved by several medical interventions, notably prophylactic mastectomy and oophorectomy.

Medical imaging is not usually recommended, but because male BRCA2 carriers have a risk of breast cancer that is very similar to the general female population, the standard annual mammogram program can be adapted to these high-risk men.

[20] [21] BRCA mutation carriers may be more likely to give birth to girls than boys,[22] however this observation has been attributed to ascertainment bias.

[9]: 82–85 Each pregnancy in genetically typical women is associated with a significant reduction in the mother's risk of developing breast cancer after age 40.

[18] Although some studies have produced different results, women with BRCA mutations are generally not expected to receive these significant protective benefits.

[18] However, the following general trends have been identified: Reports of patients biallelic or homozygous for a deleterious BRCA allele conferring a greatly increased risk of breast cancer are rare.

[26] For live cases, inheriting both mutations lead to a grave prognosis, characterized by Wilms tumors, leukemias, and early-onset brain malignancies.

Genetic counseling is recommended in women whose personal or family health history suggests a greater than average likelihood of a mutation.

In some cases, because of the founder effect, Jewish ethnicity can be used to narrow the testing to quickly check for the three most common mutations seen among Ashkenazi Jews.

[9]: 51–74 A positive test result for a known deleterious mutation is proof of a predisposition, although it does not guarantee that the person will develop any type of cancer.

Mammograms are typically used only at advanced age as there is reason to believe that BRCA carriers are more susceptible to breast cancer induction by X-ray damage than general population.

Birth control pills are associated with substantially lower risk of ovarian cancer in women with BRCA mutations.

Raloxifene (Evista), which has a reduced risk of side effects, is used as an alternative, but it has not been studied in BRCA mutation carriers specifically.

[9]: 113–142 Several type of preventive surgeries are known to substantially reduce cancer risk for women with high-risk BRCA mutations.

They may choose to focus on total cancer prevention, psychological benefits, current quality of life, or overall survival.

The possible impact of future medical developments in treatment or prognosis may also be of some importance for very young women and family planning.

The risk of ovarian cancer is low before this age, and the negative effects of oophorectomy are less serious as the woman nears natural menopause.

Research has looked into the effects of risk-reducing surgery on the psychological and social wellbeing of women with a BRCA mutation.

[47] Due to limited evidence, a 2019 meta analysis was unable to draw conclusions on whether interventions can help with the psychological effects of surgery in female BRCA carriers.

[9]: 275–302  Salpingo-oophorectomy is the single most effective method of preventing ovarian and fallopian tube cancer in women with a BRCA mutation.

[9]: 113–142 Having her first child at a younger age, having more children than average, and breastfeeding for more than one year decreases the risk of breast cancer for an average-risk woman.

[9]: 113–142  The only dietary intervention that is generally accepted as preventing breast cancer in BRCA mutation carriers is minimizing consumption of alcoholic beverages.

[49] A patent application for the isolated BRCA1 gene and cancer-cancer promoting mutations discussed above, as well as methods to diagnose the likelihood of getting breast cancer, was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics in 1994;[5] over the next year, Myriad, in collaboration with investigators from Endo Recherche, Inc., HSC Research & Development Limited Partnership, and University of Pennsylvania, isolated and sequenced the BRCA2 gene and identified key mutations, and the first BRCA2 patent was filed in the US by Myriad and other institutions in 1995.

In effect, the United States is the only jurisdiction where Myriad's strong patent position has conferred sole-provider status.

BRCA mutations are inherited in a genetically dominant fashion, from either parent.
The BRCA genes are tumour suppressor genes pictured here on their respective chromosomes. BRCA 1 has the cytogenetic location 17q21 or the q arm of Chromosome 17 at position 21. BRCA 2 has the cytogenetic location 13q12.3 or the q arm of Chromosome 13 at position 12.3. Both genes produce proteins that help repair damaged DNA, keeping the genetic material of the cell stable. A damaged BRCA gene in either location can lead to increased risk of cancer, particularly breast or ovarian in women.