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BRCA Gene Test - Indications, Uses, Drawbacks, and Role

Published on Jan 03, 2023 and last reviewed on Feb 16, 2023   -  6 min read


BRCA gene testing helps to confirm the diagnosis of hereditary breast and ovarian cancer. Read the article to find out more.

What Is the BRCA Gene Test?

The BRCA gene is a tumor gene mainly found in breast and ovarian cancers. Clinical genetics practitioners commonly perform BRCA1 and BRCA2 genetic testing for cancer risk prediction and management. The BRCA gene test identifies individuals with a personal or family history of BRCA1 and BRCA2 associated with hereditary breast and ovarian cancer (HBOC). The BRCA gene testing also detects uncommon variations whose clinical significance cannot be determined solely based on sequence information. It is also essential for clinical geneticists to communicate BRCA test results in a clinically understandable and consistent style.

What Are the Indications for BRCA Gene Testing?

The following are the indications for germline genetic testing for BRCA1 and BRCA2:

  • For breast cancer diagnosis in those over the age of 50.

  • One or both breasts have many primary breast cancers.

  • Triple-negative breast cancer (lacking the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor).

  • BRCA gene testing is to be done if breast, ovarian, pancreatic, and prostate cancer (metastatic or Gleason score 7) is found.

  • Planning chemotherapy treatments and making informed decisions on the extent of therapeutic surgery.

What Is the Use of the BRCA Gene Test?

The BRCA gene helps to diagnose:

  • Hereditary breast and ovarian cancer (HBOC) in females and males with breast cancer.

  • Ovarian cancer of the fallopian tube and primary peritoneal cancers.

  • Other cancers, such as prostate cancer and pancreatic cancer.

  • Melanoma with a BRCA2 pathogenic variant.

BRCA gene testing provides the safe integration of genetic counseling and testing for detecting hereditary breast and ovarian cancer. The growing use of BRCA gene testing for cancer treatment and testing of tumor tissue for somatic mutations is bringing BRCA1/2 mutation screening genetic services into general oncology practice. Thus, clinicians, patients, and their families benefit from increased genetic knowledge.

What Is the Role of the BRCA Gene in Breast Cancer?

BRCA1-Related Tumors-

  • They usually overlap with basal-like breast cancers.

  • They are estrogen and progesterone receptor-positive.

BRCA2-Related Tumors-

  • The histologic characteristics of BRCA2-related tumors have been inconsistent but appear more heterogeneous and less characterized than BRCA1-related tumors.

  • They show higher histologic grades with an excess of medullary histopathology.

  • They are estrogen receptor-negative and progesterone receptor-negative.

  • They are less likely to demonstrate human epidermal growth factor receptors.

Contralateral Breast Cancer (CBC)-

1) Several studies have found that women treated conservatively had a higher incidence of contralateral breast cancer (CBC).

2) The risk factors for contralateral breast cancer (CBC) are:

  • Women were diagnosed with their first breast cancer at a young age.

  • A family history of early-onset breast cancer.

  • The damaged BRCA gene.

3) Most studies suggest an increased risk of contralateral breast cancer (CBC) in people with a BRCA1 pathogenic variant compared to people with a BRCA2 pathogenic variant.

4) Prophylactic oophorectomy reduces the risk of contralateral breast cancer in women (CBC).5) There was no apparent link between radiation therapy and increased contralateral breast cancer (CBC) incidence in people with BRCA1 or BRCA2 mutations.

Ipsilateral Cancer-

Various studies have identified a considerably greater rate of ipsilateral breast cancer in adults with a germline BRCA1 or BRCA2 pathogenic variation than in sporadic controls. Radiation therapy has shown a significant reduction in ipsilateral breast cancer risk.

What Are the Challenges for BRCA Gene Testing?

Genetic testing has numerous challenges, but the key is genetic knowledge and the interpretation and reporting of genetic test results. Variability in individuals' genetic codes is ubiquitous in the general population and among people of different ethnic backgrounds. This inherent variability can make analyzing some types of sequence changes challenging. Variants of unknown clinical significance (VUS) pose a unique difficulty because clinical relevance cannot be derived solely from sequence information. VUS misinterpretation can result in severe clinical consequences for both patients and families. Up to 20 % of BRCA1/2 tests will detect hereditary VUS, although, in a well-characterized ethnic population, the proportion may be as low as five percent.

What Are the Mutations of the BRCA Gene?

Breast and ovarian cancer risks increase by inactivating mutations in the tumor suppressor genes BRCA1 and BRCA2. Pathogenic variants are commonly referred to as "mutations" or "deleterious variants" in the context of BRCA genetic testing, and the word "pathogenic variant" is used here for precision. Pathogenic mutations in each gene increase female carriers' lifetime risk of developing ovarian or (another) primary breast cancer, but they account for only 20 % of familial breast cancer cases. The number of malignancies, the age of onset, and the mixing of ovarian and breast cancer among relatives all raise the likelihood that a BRCA gene mutation causes a family cluster. Aside from familial clusters, BRCA mutations are responsible for more than ten percent of patients with early-onset triple-negative breast cancer.

What Are the Variants of Uncertain Clinical Significance (VUS)?

When the scope of sequencing expands to include untranslated sections and when tumor testing is available, the percentage of gene tests that result in a VUS rises. Thus, with laboratory professionals having less BRCA testing experience, the proportion of variants of unknown clinical significance (VUS) is projected to increase. Most variants of uncertain clinical significance (VUS) are not connected with a significant risk of cancer. Still, a mistaken VUS can lead to patient and physician mismanagement. Clinicians who seek BRCA tests must keep these variants in mind when using BRCA test results to manage patients and their families.

What Are the Drawbacks of BRCA Gene Testing?

  • There is currently no globally agreed standard for BRCA testing, reporting and classification systems.

  • Some laboratories report variants without interpretation; others use a narrative approach, and some use locally developed guidelines or published schemes.

  • Additional evidence may be required for types of BRCA gene mutations before a variant can be classified.

  • Since different lines of evidence may contradict one another, an integrated estimation that considers all available information is required to establish a definitive categorization for many variants.

  • Multiple lines of evidence are required to establish pathogenicity. Software systems are available to assist in interpreting genetic variants, each having advantages and disadvantages.

  • There is a lack of understanding of how the many activities of the BRCA1 and BRCA2 proteins connect to cancer risk, and few validated functional tests are available.

How Are BRCA1 And BRCA2 Diagnosed?


  • Breast cancer screening in women consists of a monthly self-exam, an annual or semiannual clinical breast examination, annual mammography, and a breast MRI.

  • Annual transvaginal ultrasound and serum CA-125 concentrations may be investigated for ovarian cancer screening at age 35.

  • Breast cancer screening for males comprises breast self-examination instruction and training and annual clinical breast examinations commencing at age 35.

  • At 45, annual serum prostate-specific antigen and digital rectal exam screening should begin.

  • Doctors should customize melanoma screening for each individual based on family history.

  • Asymptomatic people should not be screened for pancreatic cancer.

Evaluation of Relatives at Risk:

Once a cancer-predisposing BRCA1 or BRCA2 gene has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial pathogenic variant and, as a result, require increased surveillance and specific treatments if cancer is detected.

What Is Genetic Counseling?

Hereditary breast and ovarian cancer (HBOC) associated with BRCA1 and BRCA2 are inherited in an autosomal dominant manner. Most people who carry a BRCA1 or BRCA2 gene inherited it from one of their parents. However, because the penetrance of breast, ovarian, and other cancers associated with the BRCA1 and BRCA2 genes is less than 100 %, not all individuals with a BRCA1 or BRCA2 gene have a cancer-affected parent. The offspring of BRCA1 or BRCA2 genes have a 50 % probability of inheriting the pathogenic variant. Prenatal and preimplantation genetic testing is possible after cancer-predisposing BRCA1 or BRCA2 genes have been detected in a family.

What Is the Management for Breast Cancer?

Prevention of Primary Manifestations:

1) Female carriers with harmful mutations can judge preventive surgery or increased screening.

2) The following preventive measures are taken for breast cancer prevention:

  • Prophylactic bilateral mastectomy (surgical removal of both breasts and nipples).

  • Prophylactic oophorectomy (surgical removal of ovaries and fallopian tubules).

  • Chemoprevention (for example, Tamoxifen)

3) The following preventive measures are taken for ovarian cancer prevention:

  • Prophylactic salpingectomy (removal of healthy fallopian tubules to avoid cancer).

  • Delayed oophorectomy or salpingo-oophorectomy (unilateral or bilateral fallopian tubules).

Treatment of Manifestations:

With the increased rate of ipsilateral and contralateral breast cancer, oncologists may recommend bilateral mastectomy as the primary surgical treatment of breast cancer. PARP inhibitors may be considered in BRCA1- and BRCA2-related malignancies.


BRCA gene testing is a primary method to diagnose breast, ovarian, and, to some extent, other types of cancer. There is a need for it to be wholly accepted in mainstream oncology. An international group of specialists will facilitate the categorization of variations for clinical application by gathering and integrating all available lines of evidence and classifying variants according to an internationally recognized system.

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Last reviewed at:
16 Feb 2023  -  6 min read




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