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BRCA1 gene

Associated Syndrome Name: Hereditary Breast and Ovarian Cancer syndrome (HBOC)

BRCA1 Summary Cancer Risk Table

Cancer	Genetic Cancer Risk
Breast	High Risk
Ovarian	High Risk
Male Breast	Elevated Risk
Pancreatic	Elevated Risk
Prostate	Elevated Risk

BRCA1 gene Overview

Hereditary Breast and Ovarian Cancer syndrome (HBOC) 1, 2

Individuals with mutations in BRCA1 have Hereditary Breast and Ovarian Cancer syndrome (HBOC).
Women with HBOC have a risk for breast cancer that is greatly increased over the 12.5% lifetime risk for women in the general population of the United States. Most breast cancers in women with BRCA1 mutations are Triple Negative Breast Cancer (TNBC), a type of breast cancer lacking estrogen and progesterone receptors, and not expressing Her2.
Women with HBOC also have high risks for ovarian, fallopian tube, and primary peritoneal cancer.
Men with HBOC due to mutations in BRCA1 have an elevated risk for breast and prostate cancer. The increased risk for prostate cancer may be most significant at younger ages. Additionally, men with a BRCA1 mutation have a higher risk for an aggressive prostate cancer.
Male and female patients with HBOC due to mutations in BRCA1 have an elevated risk for exocrine pancreatic cancer. These are cancers developing in the enzyme-secreting cells of the pancreas.
Some studies have found that women with BRCA1 mutations have an increased risk for uterine cancer, but other studies have found no increased risk. There are currently no medical management recommendations for uterine cancer risk in women with mutations in BRCA1. If hysterectomy is considered, there is the option for hormone replacement therapy (HRT) with estrogen alone, which is associated with a lower risk of breast cancer than HRT with estrogen and progesterone.
Although there are high cancer risks for patients with HBOC, there are interventions that have been shown to be effective at reducing many of these risks. Guidelines from the National Comprehensive Cancer Network (NCCN) for the medical management of patients with HBOC are listed below. It is recommended that patients with BRCA1 mutations and a diagnosis of HBOC be managed by a multidisciplinary team with experience in the prevention and treatment of the cancers associated with HBOC.

BRCA1 gene Cancer Risk Table

Cancer Type	Age Range	Cancer Risk	Risk for General Population
Female Breast	To age 503, 4, 5, 6	28%-51%	2.0%
	To age 704, 5, 6, 7	46%-87%	7.4%
	Second primary within 5 years of first breast cancer diagnosis8, 9, 10, 11	8.9%-20%	2%
Ovarian	To age 503, 5, 6, 10	8%-23%	0.2%
	To age 703, 4, 5, 6	39%-63%	0.6%
	Ovarian cancer within 10 years of a breast cancer diagnosis11, 12	12.7%	<1.0%
Prostate	To age 706, 13, 14	Up to 16%	6.1%
Male Breast	To age 706, 15	1.2%	<0.1%
Pancreatic	To age 806, 16	Elevated risk	1.1%

BRCA1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type	Procedure	Age to Begin	Frequency (Unless otherwise indicated by findings)
Female Breast	Breast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.2	18 years	NA
	Clinical breast examination2	25 years	Every 6 to 12 months
	Breast MRI with contrast and/or mammography with consideration of tomosynthesis2	Age 25 for MRI, or if MRI is unavailable, mammography with consideration of tomosynthesis. Age 30 for both MRI and mammography. Individualize to a younger age if a relative has been diagnosed younger than age 30.	Annually
	Consider investigational screening studies within clinical trials.2	Individualized	NA
	Consider risk-reducing mastectomy.2	Individualized	NA
	Consider options for breast cancer risk-reduction agents (i.e. tamoxifen).2	Individualized	NA
Ovarian	Bilateral salpingo-oophorectomy2	35 to 40 years, upon completion of childbearing	NA
	Consider transvaginal ultrasound and CA-125 measurement. Consider investigational screening studies within clinical trials.2	30 to 35 years	Individualized
	Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).2, 22	Individualized	NA
Prostate	Consider prostate cancer screening.1, 2	40 years	Individualized, consider annually
	Since mutation carriers are at an increased risk for more aggressive prostate cancer this information may be included as part of the risk and benefit discussion about prostate cancer screening.1, 23	NA	NA
	Since mutation carriers are at an increased risk for more aggressive prostate cancer this information may be considered when choosing management options for men with a diagnosis of prostate cancer.1, 23	NA	NA
Male Breast	Breast self-examination2	35 years	Monthly
	Clinical breast examination2	35 years	Annually
	Consider mammography in men with gynecomastia (enlarged breasts)2	50 years, or 10 years earlier than the youngest male breast cancer diagnosis in the family	Annually
Pancreatic	For patients with a family history of pancreatic cancer, consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in screening for pancreatic cancer, preferably within research protocols.24	Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family	Annually
	Provide education about ways to reduce pancreatic cancer risk, such as not smoking and losing weight.21	Individualized	Individualized
For Patients With A Cancer Diagnosis	For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., platinum chemotherapy, PARP-inhibitors)17, 18, 19, 20, 21	NA	NA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the BRCA1 gene.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

In rare instances, an individual may inherit mutations in both copies of the BRCA1 gene, leading to the condition Fanconi Anemia, Complementation Group S (FANCS). This condition is rare and may include physical abnormalities, developmental delay, and a high risk for cancer. The children of this patient are at risk of inheriting FANCS only if the other parent is also a carrier of a BRCA1 mutation. Screening the other biological parent of any children for BRCA1 mutations may be appropriate.2, 25

Parents who are concerned about the possibility of passing on a BRCA1 mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).2

References

Giri VN, et al. Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol. 2020 38:2798-2811. PMID: 32516092.

Daly M et al. NCCN Clinical Practice Guidelines in Oncology^®: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic. V 1.2022. Aug 11. Available at https://www.nccn.org.

Easton DF, et al. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995 56:265-71. PMID: 7825587.

Mavaddat N, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013 105:812-22. PMID: 23628597.

Chen S, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006 24:863-71. PMID: 16484695.

SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from https://seer.cancer.gov/explorer/.

Ford D, et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 343:692-5. PMID: 7907678.

Verhoog LC, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet. 1998 351:316-21. PMID: 9652611.

Engel C, et al. Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance. Int J Cancer. 2020 146:999-1009. PMID: 31081934.

Kuchenbaecker KB, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017 317:2402-2416. PMID: 28632866.

Curtis RE, et al. New Malignancies Following Breast Cancer. 2006 In: Curtis RE, et al., editors. New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000. National Cancer Institute. NIH Publ. No. 05-5302.

Metcalfe KA, et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol Oncol. 2005 96:222-6. PMID: 15589605.

Struewing JP, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997 336:1401-8. PMID: 9145676.

Liede A, et al. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004 22:735-42. PMID: 14966099.

Tai YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 99:1811-4. PMID: 18042939.

Lynch HT, et al. BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet. 2005 158:119-25. PMID: 15796958.

Gradishar WJ et al. NCCN Clinical Practice Guidelines in Oncology^®: Breast Cancer. V 5.2021. June 28. Available at https://www.nccn.org.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209115s000lbl.pdf

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s002lbl.pdf

Armstrong DK, et al. NCCN Clinical Practice Guidelines in Oncology^®: Ovarian Cancer. V 1.2021. Feb 26. Available at https://www.nccn.org.

Tempero MA, et al. NCCN Clinical Practice Guidelines in Oncology^®: Pancreatic Adenocarcinoma. V 2.2021. Feb 25. Available at https://www.nccn.org.

Gupta S, et al. NCCN Clinical Practice Guidelines in Oncology^® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2021. May 11. Available at https://www.nccn.org.

Schaeffer E, et al. NCCN Clinical Practice Guidelines in Oncology^®: Prostate Cancer. V 2.2021. Feb 17. Available at https://www.nccn.org.

Goggins M, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 69:7-17. PMID: 31672839.

Keupp K, et al. Biallelic germline BRCA1 mutations in a patient with early onset breast cancer, mild Fanconi anemia-like phenotype, and no chromosome fragility. Mol Genet Genomic Med. 2019 7:e863. PMID: 31347298.

Last Updated on 29-Sep-2022

Gene Results