Genetic Disorder Reference Sheet: BRCA1 and BRCA2 Hereditary Cancers

May 06, 2021 by Suzanne M. Mahon DNS, RN, AOCN®, AGN-BC, FAAN

Risks Associated With Pathogenic BRCA1 or BRCA2 Variants

Cancer	Risk in General Population	Risk With Pathogenic Variant
Female breast	12%	38%–84%
Male breast	Less than 1%	Up to 8.9% (higher risk in BRCA2)
Ovary, fallopian tube, primary peritoneal cancer	1%–2%	39%–63% (BRCA1) 16%–27% (BRCA2)
Prostate	12%	20%–34%
Melanoma	2%	Increased (especially in BRCA2)
Pancreas	0.5%	Up to 7% (higher risk in BRCA2)

Note. Based on information from NCCN (https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf) and Petrucelli et al (https://www.ncbi.nlm.nih.gov/books/NBK1247).

BRCA1- or BRCA2-associated hereditary breast and ovarian cancer is the most common form (https://www.ncbi.nlm.nih.gov/books/NBK1247) of hereditary breast and ovarian cancer. The prevalence of BRCA1 and BRCA2 pathogenic variants in the general population is estimated at 1 in 400–500 people, although it increases to 1 in 40 for those of Ashkenazi Jewish ancestry, which is linked to three founder pathogenic variants (BRCA1 c.68_69delAG, BRCA1c.5266dupC, and BRCA2 c.5946delT).

Cancer Risks

Understanding whether an individual carries a pathogenic BRCA1 or BRCA2 variant has implications for cancer prevention, early detection, and treatment strategies in BRCA1- or BRCA2-related malignancies. Key indicators (https://doi.org/10.1136/gutjnl-2019-319352) for referral to genetics professionals for evaluation (https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf) of BRCA1- or BRCA2-associated cancer risk and possible testing (https://www.ncbi.nlm.nih.gov/books/NBK1247) include:

Breast cancer diagnosed at age 45 or younger
Ovarian cancer
Multiple primary breast cancers in one or both breasts
Male breast cancer
Pancreatic cancer
Triple-negative (ER-negative, PR-negative, and HER2/neu-negative) breast cancer, diagnosed before age 60
Combination of pancreatic cancer or prostate cancer (Gleason score ≥ 7) with breast cancer or ovarian cancer
Breast cancer diagnosed at any age with Ashkenazi Jewish ancestry
Two or more relatives with breast cancer, one younger than age 50
Three or more relatives with breast cancer at any age
BRCA1 or BRCA2 pathogenic variant previously identified in the family

Recommendations for Cancer Prevention and Early Detection Increased Screening

Increased Screening

Women should have annual breast magnetic resonance imaging (MRI) beginning at age 25–29, depending on family history. At age 30 and beyond, alternate annual mammography and breast MRI every six months, depending on family history.

Obtain a clinical breast exam every 6–12 months, starting at age 25 for women and 35 for men.

Practice breast self-awareness, with prompt evaluation of any change, starting at age 18 for women and 35 for men.

Men should have prostate screening with a digital rectal exam and prostate-specific antigen test starting at age 40.

Obtain annual full-body skin examinations for melanoma, and conduct monthly skin self-examination with prompt evaluation of any changes.

Obtain annual pancreatic screening starting at age 40 or 10 years prior to the age of the youngest pancreatic cancer diagnosis in the family, with MRI/magnetic resonance cholangiopancreatography, endoscopic ultrasound, fasting blood glucose, and HbA1c.

Risk-Reducing Surgery

Bilateral risk-reducing mastectomy with an option of breast reconstruction

Surgery to remove the ovaries and fallopian tubes at age 35–45, when childbearing is complete

Other Prevention Strategies

Tamoxifen and raloxifene, used for five years, may reduce the risk for certain types of breast cancer by up to 50%.

Hormonal contraceptive pills following risk-reducing mastectomies may reduce the risk of ovarian cancer by up to 60%.

Individuals should avoid artificial tanning and use broad-spectrum sunscreen of SPF 30 or higher, seek shade, cover up with clothing (including hats), and wear UV-blocking sunglasses.

Note. Based on information from Goggins et al. (https://doi.org/10.1136/gutjnl-2019-319352), NCCN (https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf), and Petrucelli et al (https://www.ncbi.nlm.nih.gov/books/NBK1247).

Both men and women are at increased risk for developing multiple cancers if they have a pathogenic BRCA1 or BRCA2 variant. Not every individual with a pathogenic variant develops cancer because of incomplete penetrance, cancer risk reduction from prophylactic surgery, or early death, and risk differs slightly between BRCA1 or BRCA2 pathogenic variants. See the table for specific risk increases for each cancer and variant.

People who have a pathogenic BRCA1 or BRCA2 variant should follow recommended guidelines for increased cancer prevention and early detection strategies.

Nursing Implications

Identifying a pathogenic BRCA1 or BRCA2 variant may also influence the choice of targeted therapy or the appropriateness of adding a PARP inhibitor to therapy. For example, olaparib has been approved in various settings (https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s001lbl.pdf) for breast, ovarian, prostate, and pancreatic cancer in people with pathogenic BRCA1 or BRCA2 variants.

Women of childbearing age should be informed that Fanconi anemia is associated with having two copies of a BRCA2 pathogenic variant (one from each parent). The chance of having a child with Fanconi anemia is 25% for every pregnancy (https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf) if both parents have a pathogenic variant.

Individuals and families with a known BRCA1 or BRCA2 pathogenic variant are often overwhelmed by the risk information and complex recommendations for cancer prevention and early detection. Oncology nurses can direct patients to the many organizations that offer support, including:

Bright Pink (http://brightpink.org/) has resources for women to know their risk and manage their health proactively.
Familial Ovarian Cancer Registry (http://ovariancancer.com/) connects patients to resources that advance research for ovarian cancer.
FORCE: Facing Our Risk of Cancer Empowered (http://facingourrisk.org/) provides support and educational resources for individuals with hereditary breast and ovarian cancer syndromes.
Sharsheret (http://sharsheret.org/) has information for Jewish women and families with breast and ovarian cancer.

Resources and interprofessional, coordinated care for the entire family offer the best hope for successful prevention, early detection, and management of BRCA1- or BRCA2-related malignancies.

Editor’s note: For definitions of many of the genetics and genomics terms used in this article, visit ons.org/genomics-taxonomy (http://ons.org/genomics-taxonomy).

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