Knowledge about BRCA

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What are BRCA1 and BRCA2?

BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. Specific inherited mutations in BRCA1 and BRCA2 most notably increase the risk of female breast and ovarian cancers. A harmful BRCA1 or BRCA2 mutation can be inherited from a person’s mother or father with 50% chance to pass it on to child.

  • Breast cancer

    About 12% of women will develop during life. About 72% of women who inherit a harmful BRCA1 mutation and about 69% of women who inherit a harmful BRCA2 mutation will develop breast cancer by the age of 80.

  • Ovarian cancer

    About 1.3% of women will develop during life. About 44% of women who inherit a harmful BRCA1 mutation and about 17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by the age of 80

  • Other cancer

    Fallopian tube cancer and peritoneal cancer;

    Men with BRCA2 mutations, and to a lesser extent BRCA1 mutations, are also at increased risk of breast cancer and prostate cancer ;

    Both men and women with harmful BRCA1 or BRCA2 mutations are at increased risk of pancreatic cancer;

    Certain mutations in BRCA2 (also known as FANCD1), if they are inherited from both parents, can cause a rare form of Fanconi anemia (subtype FA-D1) ;

    certain mutations in BRCA1 (FANCS), if they are inherited from both parents, can cause another Fanconi anemia subtype

Certain racial/ethnic populations

People of Ashkenazi Jewish descent have a higher prevalence of harmful BRCA1 and BRCA2 mutations than people in the general U.S. . Also, Norwegian, Dutch, and Icelandic peoples have a higher prevalence.

About genetic sequencing tests

  • Do not benefit every patient. They might not identify the “driver” DNA alteration or cannot be targeted by existing therapies
  • Heterogeneous :tumors are composed of cancer cells with varied. A small sample of cancer cells obtained from a biopsy may not accurately represent a heterogeneous tumor. The tests act against some, but not all, of your cancer cells.
  • Genetic alterations in a tumor can change over time, but a sequencing test only captures a “snapshot”

Genetic test result

  • Positive

    A person has inherited a known harmful mutation in BRCA1 or BRCA2, but cannot tell whether or when an individual will actually develop cancer. This indicates that his or her siblings has a 50% chance of having inherited

  • Negative

    • True negative: If a close (fisrt- or second-degree) relative of the tested person is known to carry a harmful BRCA1 or BRCA2 mutation, the result means that this person doesn’t carry the gene responsible for family’s cancer risk
    • False negative: The tested person has a family history that suggests the possibility of having a harmful mutation in BRCA1 or BRCA2 but complete gene testing identifies no such mutation in the family,
  • Uncertain/Ambiguous

    Change in BRCA1 or BRCA2 that has not been previously associated with cancer (about 10% of women had this type )

Other gene factors

Mutations in the genes TP53, CDH1, and CHEK2, which increase the risk of breast cancer, and in RAD51C, RAD51D, and STK11, which increase the risk of ovarian cancer.

Genetic testing for these other mutations is available as part of multigene (panel) testing

Implications of harmful BRCA1 or BRCA2 mutation

  • Higher possibility of developing a second cancer in either the same (ipsilateral) breast or the opposite (contralateral) breast. Some women chose a bilateral mastectomy or breast-conserving surgery.
  • Tend to be “TNBC (triple-negative cancers)" (that is, the breast cancer cells do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein), which generally have poorer prognosis than other breast cancers.
  • A class of drugs called PARP inhibitors [e.g. olaparib (Lynparza™) and rucaparib (Rubraca®)], which block the repair of DNA damage, have been found to arrest the growth of cancer cells that have BRCA1 or BRCA2 mutations. Olaparib is also approved for HER2-negative metastatic breast cancers

Reed Liu created on 18.12.28

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Understanding the Biology of Triple Negative Breast Cancer and Breast Cancer Stem Cells in Patients of Diverse Ethnicities.

Breast cancer burden

  • 1.7 million new cases worldwide in 2012
  • 2.4 million incident cases in 2015, making it the most common cancer. As fifth leading cause of cancer deaths for both men and women. For women, breast cancer was the leading cause of death in 2015.
  • In U.S., approximately one in eight women (12%) will develop. In 2016, more than 3.5 million women have a breast cancer history. Additional 246,660 new cases are expected to be diagnosed and approximately 40450 would die
  • Median age at diagnosis of breast cancer is 61 years, lung cancer is 70 years and colorectal cancer is 68 years. About 19% diagnosed in women aged 30 to 49 years.

Breast cancer sub-type

Yunze Liu
Yunze Liu
Bioinformatics Sharer

Co-founder of Bioinfoplanet(生信星球)