Last updated:
9/1/2025
Years published: 2018, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Jennifer Litton, MD, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, for assistance in the preparation of this report.
Hereditary breast and ovarian cancer (HBOC) syndrome is an inherited condition that significantly increases the risk of developing certain cancers (cancer-predisposition syndrome). People with HBOC syndrome have a greater risk of developing certain cancers, particularly breast cancer, in both males and females, and ovarian cancer in females.
Affected individuals tend to develop cancer earlier in life, usually before the age of 50. Additionally, to a lesser degree, there is also an increased risk of developing other types of cancer including prostate cancer, melanoma and pancreatic cancer. HBOC syndrome is associated with changes (variants) in either the BRCA1 gene or the BRCA2 gene. In HBOC syndrome, there is usually a family history of cancer, and the gene variants are inherited.
The underlying causes of cancer are not completely understood, and it is important to understand that while inheriting a variant in the BRCA1 or BRCA2 gene greatly increases a person’s risk of developing certain cancers, it does not mean that the person will definitely develop cancer. Some people with variants in these genes never develop cancer. There may be other factors that influence whether and how cancer develops including other genetic variants, lifestyle and environmental exposures. For example, factors like smoking, alcohol use and reproductive history can all influence cancer risk.
In contrast to hereditary cancers, most cancers occur sporadically, meaning they arise from genetic changes that develop over a lifetime rather than being inherited. Sporadic cancers typically affect people older than 60, with no strong family pattern. A familial pattern may be present when multiple relatives develop the same cancer, often after age 50, but without a single identifiable high-risk gene. These cases may involve shared environmental factors or multiple low- to moderate-risk genetic variants.
HBOC syndrome differs from both sporadic and familial cancer in that it involves a single, high-impact gene variant and often leads to early-onset cancer affecting multiple family members. Most commonly, the variants are found in the BRCA1 or BRCA2 genes, though other genes are now also recognized as causes of HBOC syndrome.
If a person develops a specific cancer, treatment is standard for that particular cancer.
HBOC syndrome is a cancer predisposition syndrome in which people are at a greater risk of developing certain cancers, particularly breast or ovarian cancer. Signs and symptoms are associated with the development of cancer and depend upon the type and location of cancer. HBOC syndrome can cause cancer in multiple family members over several generations. It can also be associated with more than one cancer in the same person.
The exact risk for specific types of cancer in HBOC syndrome varies greatly depending on the specific gene that is altered and the specific variant that is present. Some people with a variant in an HBOC syndrome gene never develop cancer.
Female breast cancer is the most common type of cancer associated with variants in BRCA1 or BRCA2 genes. The risk for breast cancer in the general population is about 12%, but for females with a BRCA1 gene variant it can be between 46%-87%, and between 38%-84% for females with a BRCA2 gene variant. There is also an increased risk of having a second primary breast cancer.
In HBOC syndrome, ovarian cancer includes cancer of the fallopian tubes. Primary peritoneal cancers can also occur. These are cancers that develop in the thin layer of tissue that lines the abdomen (peritoneum). The risk for ovarian cancer in the general population is about 1%-2%, but for people with a BRCA1 gene variant the risk is about 39%-63% and 16.5%-27% for people with a BRCA2 gene variant.
There is an increased risk for male breast cancer, which affects about 0.1% of the population. In males with a BRCA1 gene variant, there is a 1.2% risk and an 8.9% risk in males with a BRCA2 gene variant. In general, the relative risk for male breast cancer is greatest in males in their 30s and 40s and decreases with advancing age.
There is a risk of prostate cancer of 6% before the age of 69 in the general population. There is an 8.9% risk by 65 years of age in males with a BRCA1 gene variant and a 15% risk by age 65 in males with a BRCA2 gene variant. The lifetime risk for prostate cancer is about 20%-25%.
The risk of pancreatic cancer in the general population is about 0.5%. or people with a BRCA1 gene variant the risk is about 1%-3% and with a BRCA2 gene variant the risk is about 2%-7%.
Other cancers including melanoma, cervical and uterine cancer have all been reported as having higher rates in affected individuals. Further studies are needed to confirm which additional cancers are definitively associated with variants in these genes.
For people who go on to develop cancer, the symptoms depend on the specific type of cancer.
Depending on the type of cancer, other signs and symptoms may develop.
HBOC syndrome is usually caused by variants in a single major cancer-related gene, either BRCA1 (breast cancer susceptibility gene 1) or BRCA2 (breast cancer susceptibility gene 2). These genes provide instructions for making proteins that help suppress tumors by repairing damaged DNA and regulating cell growth. When a disease-causing variant occurs in either of these genes, the resulting protein may not function properly or may be absent altogether. This can increase the likelihood of cells growing uncontrollably, leading to cancer.
The variant responsible for HBOC syndrome is usually a germline variant, meaning it is present in all cells of the body from birth and inherited through reproductive cells, either the egg or sperm. Germline variants can be passed from parent to child. In contrast, sporadic variants arise later in life, after fertilization, and are not inherited. These can result from environmental exposures, random errors during DNA replication, or other unknown factors.
Not all gene variants cause disease. When a gene variant does cause disease, it is called a pathogenic variant. In some people, a variant is discovered in BRCA1 or BRCA2, but its effect on health is unclear, this is known as a variant of unknown significance (VUS). A pathogenic BRCA1 or BRCA2 gene variant significantly raises a person’s lifetime risk of developing certain cancers, most notably breast and ovarian cancer. However, not everyone with a pathogenic variant will develop cancer. Even within the same family, people who carry the same variant may experience different cancer types, onset ages, or never develop cancer at all. This variability is known as penetrance, the degree to which a gene variant leads to disease. Other genetic or environmental factors likely influence whether and when cancer develops in individuals with BRCA1 or BRCA2 variants.
BRCA1 and BRCA2 are tumor suppressor genes, meaning their normal function is to control cell division and prevent unchecked growth. When working correctly, they help protect against cancer by repairing breaks in DNA. When variants in these genes occur, cells can accumulate genetic damage and begin to proliferate uncontrollably.
Inheritance
HBOC syndrome follows an autosomal dominant inheritance pattern. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
HBOC syndrome can affect both males and females and occurs across all racial and ethnic backgrounds. It is the most common cause of hereditary breast and ovarian cancer. While the exact prevalence of HBOC syndrome is unknown, the estimated frequency of pathogenic BRCA1 or BRCA2 gene variants in the general population ranges from about 1 in 200 to 1 in 800 individuals. In certain populations, the prevalence is significantly higher. Among individuals of Ashkenazi Jewish descent, approximately 1 in 40 people carry a BRCA1 or BRCA2 variant. This increased frequency is largely due to a “founder effect”, a phenomenon where a small ancestral population passes down a specific gene variant through multiple generations, leading to a higher prevalence within that group. Similar founder variants have also been identified in other populations, including some groups in the Netherlands, Iceland and certain French-Canadian communities.
Several medical organizations have developed guidelines for identifying individuals who may benefit from genetic testing for HBOC syndrome, particularly BRCA1 and BRCA2 gene variants. One of the most frequently cited and clinically applied sources is the National Comprehensive Cancer Network (NCCN), which regularly publishes and updates evidence-based recommendations for healthcare providers. These guidelines help determine who should be offered genetic counseling and testing. Information on these guidelines for physicians can be found at: NCCN guidelines detection, prevention, and risk reduction. Registration is needed to see these guidelines.
HBOC syndrome may be suspected in people with breast cancer diagnosed before age 50, people with multiple primary breast cancers, males with breast cancer, or anyone diagnosed with ovarian, fallopian tube, or primary peritoneal cancer at any age. It’s also considered when there is a personal or family history that includes both breast and either prostate or pancreatic cancer, or when multiple close relatives have had breast cancer, especially if diagnosed before age 50. A confirmed BRCA1 or BRCA2 gene variant in the family is a strong reason for testing. People of Ashkenazi Jewish descent with a personal history of breast cancer are at higher risk and are typically offered testing regardless of age at diagnosis. Testing is also recommended for people diagnosed with triple-negative breast cancer before age 60.
Molecular genetic testing is the only way to confirm a diagnosis of HBOC syndrome. This typically involves analyzing a blood or saliva sample to look for pathogenic variants in the BRCA1 and BRCA2 genes. If a known variant is found, family members may be offered predictive testing to determine their own risk. Genetic testing is widely accessible through clinical providers and laboratories, but results should be interpreted with the help of a genetic counselor, especially when dealing with variants of uncertain significance (VUS). A VUS is a change in a gene’s DNA sequence where the effect on a person’s health is currently unknown.
Even if a BRCA1 or BRCA2 variant is not found, an individual may still develop cancer from other hereditary syndromes or sporadic causes. Therefore, a negative test does not eliminate cancer risk entirely.
For people with a confirmed BRCA1 or BRCA2 gene variant, regular cancer surveillance is recommended. Females are typically advised to have annual breast MRI and mammography, beginning at an earlier age than the general population. Combining both imaging methods increases the likelihood of detecting cancer early. MRI is especially useful for identifying dense or otherwise hard-to-image tissue and can help define the extent of disease if cancer is found. Mammography uses low-dose X-rays to screen for tumors and is a well-established component of breast cancer screening protocols.
Treatment
The treatment of HBOC syndrome is highly individualized, which means that the specific treatment options and recommendations vary among affected individuals. The best management may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who use radiation to treat cancer (radiation oncologists), oncology nurses, psychiatrists and other healthcare specialists. Emotional and psychological support (psychosocial support) for the entire family is essential as well.
Genetic counseling is extremely important in HBOC syndrome. Understanding the risk of cancer based on variants in the BRCA1 and BRCA2 genes is critical to allow affected people, along with their medical team, to make the best decisions concerning their health. Genetic counseling by appropriately trained medical personnel including genetic counselors is recommended by multiple organizations that support people with cancer.
Today, multigene panel testing is the standard type of testing, since many people at risk carry variants other than BRCA1 and BRCA2 such as variants in the PALB2, CHEK2 and ATM genes. Multigenic panels are genetic tests that simultaneously examine multiple genes to identify inherited variants linked to a specific disease, such as cancer. While panels identify more carriers, they also produce more uncertain results (variants of uncertain significance), which require careful interpretation.
Certain populations, such as Ashkenazi Jewish individuals, have higher rates of founder variants, leading to debates about routine population screening. Founder variants are gene variants that are unusually common in a specific population because they originated from a single ancestor or a small number of founders who established that group. Direct-to-consumer (DTC) testing is available but limited, and results need confirmation in a clinical setting. DTC tests are medical tests that individuals can order, pay for, and receive results for directly, without involving a healthcare provider.
A positive result for HBOC syndrome can help determine treatment, screening and prevention strategies, while negative or uncertain results still require assessment in the context of family history.
Several organizations have published guidelines for the surveillance, screening and treatment of HBOC syndrome. Information on the guidelines published by the National Comprehensive Cancer Network (NCCN) can be found at: NCCN guidelines for professionals on treatment of HBOC syndrome.
Specific therapies and interventions may vary, depending upon numerous factors, such as the type of cancer, disease stage, tumor size, specific cancer subtype, the presence or absence of certain symptoms, an individual’s age and general health and/or other factors. Decisions concerning the use of drug regimens, surgery and/or other treatments should be made by physicians, genetic counselors and other members of the health care team in careful consultation with the patient based upon the specifics of their case, a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects, patient preference and other appropriate factors.
Specific surveillance recommendations have been made for females with intact breast tissue and a known hereditary risk of breast cancer. Other females, especially those with a confirmed disease-causing variant in the BRCA1 or BRCA2 gene, may choose to have their breasts surgically removed as a preventive measure. This is called prophylactic mastectomy. This surgery may be recommended after counseling involving the specific cancer risk, degree of protection, and issues involving breast reconstruction (surgical rebuilding of the breast). Doctors estimate that the cancer risk in unaffected women is reduced 90–95% following preventive mastectomy.
Another treatment option is chemoprevention. Chemoprevention involves using certain drugs, such as tamoxifen (a medication that blocks estrogen receptors in breast tissue) to lower the risk of developing breast cancer. One large clinical trial demonstrated an almost 50% decrease in the risk of breast cancer in unaffected females.
In 2018, the U.S. Food and Drug Administration (FDA) approved the drug olaparib (Lynparza) for the treatment of BRCA-associated breast cancer that has spread (metastasized) to other areas of the body. Lynparza is a PARP inhibitor, a type of medication that blocks poly (ADP-ribose) polymerase (PARP), an enzyme that helps repair damaged DNA. Researchers think that stopping the activity of PARP keeps cancer cells from repairing themselves, which helps stop their growth. This is a type of targeted therapy, meaning it targets specific cancer-related molecules instead of attacking all rapidly dividing cells, like traditional chemotherapy does. As a result, targeted therapies often have fewer side effects.
Lynparza has also been approved by the FDA for females who have ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (a cancer of the lining inside the abdomen) who have responded to treatment with a platinum-based chemotherapy medication (such as cisplatin or carboplatin), but in whom the cancer has returned. Lynparza is also approved for advanced ovarian cancer in females who have received treatment with three or more prior chemotherapy medications.
As of 2025, PARP inhibitors like olaparib are used more often as maintenance therapy, to help prevent cancer from returning, especially after platinum chemotherapy in ovarian and related cancers. Use in breast cancer remains approved but is less common in real-world practice.
In 2018, talazoparib (Talzenna) was approved to treat patients with pathogenic or suspected pathogenic germline BRCA gene variants and HER2-negative, locally advanced or metastatic breast cancer. Patients must be selected for therapy based on a companion diagnostic test for talazoparib. The FDA approved the BRACAnalysis CDx test to identify eligible patients.
In 2018, the FDA approved the drug rucaparib (Rubraca) for the treatment of recurrent epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer in individuals who are in a complete or partial response to platinum-based chemotherapy.
In 2017, the FDA approved the drug niraparib (Zejula) for the same types of cancers in similar patients. As of 2025, niraparib is recommended even for patients without BRCA gene variants if they test positive for homologous recombination deficiency (HRD), a broader category of DNA repair problems. HRD means that a cell has lost its ability to properly repair broken DNA using its most accurate repair system, called homologous recombination. Normally, this repair pathway acts like a skilled mechanic that can fix serious DNA damage and keep cells healthy. When HRD is present, the cell’s repair system is broken, so DNA mistakes build up over time, which can lead to cancer. Variants in genes such as BRCA1 or BRCA2 are common causes of HRD, but other genes can also be involved.
Because cancer cells with HRD are already missing their main repair tool, they are especially vulnerable to PARP inhibitor drugs, which block another backup repair pathway. Without either repair system, cancer cells cannot survive, which makes HRD an important marker doctors look for when deciding on treatment.
A procedure called risk-reducing salpingo-oophorectomy may be recommended for females with ovarian cancer and for people who carry a BRCA1 or BRCA2 variant but have not yet developed cancer. This is the surgical removal of the ovaries and fallopian tubes. It significantly reduces the risk of ovarian cancer and may also reduce breast cancer risk somewhat. After this surgery, females cannot become pregnant, and those who are premenopausal will experience early menopause, which can bring symptoms like hot flashes, mood swings and bone loss. The decision to have this surgery should follow careful counseling on reproductive options, the level of cancer risk and the effects of early menopause.
Some studies have shown that birth control pills (oral contraceptives) have a duration-dependent protective effect against ovarian cancer. This means the longer a person takes them, the more protection they offer, but this protection ends when they stop using them. However, oral contraceptive use may be linked to a slightly increased risk of breast cancer.
The use of hormone therapy to treat menopausal symptoms is controversial. It should be evaluated individually based on personal cancer history and prior surgeries. This therapy can help manage symptoms of menopause and prevent bone thinning (osteoporosis). However, long-term hormone therapy (especially with estrogen plus progestin) has been linked to a higher risk of breast cancer in postmenopausal females. For females who go through surgical menopause (menopause caused by removal of the ovaries), symptoms tend to come on suddenly. Some studies suggest that short-term hormone therapy may be helpful in these patients and does not appear to increase breast cancer risk significantly.
The treatment of other forms of cancer associated with HBOC syndrome generally follows the standard guidelines for individuals without BRCA1 or BRCA2 gene variants
As of 2025, many ongoing studies are investigating new uses for PARP inhibitors, both those already approved and newer ones. These include studies of people with cancers other than breast and ovarian, and people with other gene variants that affect DNA repair.
Research has shown that platinum-based chemotherapy (such as cisplatin and carboplatin) is effective for some people with HBOC syndrome. These drugs work by damaging the DNA of cancer cells, which prevents them from dividing and leads to their destruction. However, like all cancer medications, they can have significant side effects. While platinum-based chemotherapy is commonly used in ovarian cancer, it is not yet standard of care in breast cancer, but research continues to explore its benefits for these patients.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Hoang LN, Gilks BC. Hereditary breast and ovarian cancer syndrome: moving beyond BRCA1 and BRCA2. Adv Anat Pathol. 2018;25:85-95. https://www.ncbi.nlm.nih.gov/pubmed/28914618
Committee on Practice Bulletins – Gynecology, Committee on Genetics, Society of Gynecologic Oncology. Practice Bulletin No 182: hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2017;130:e110-e126. https://www.ncbi.nlm.nih.gov/pubmed/28832484
Kuchenbaeker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402-2416. https://www.ncbi.nlm.nih.gov/pubmed/28632866
Iyevleva AG, Imyanitov EN. Cytotoxic and targeted therapy for hereditary cancers. Hered Cancer Clin Pract. 2016;14:17. https://www.ncbi.nlm.nih.gov/pubmed/27555886
Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121:269-275. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293332/
Agarwal R, Liebe S, Turski ML, et al. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome. Discov Med. 2014;18:331-339. https://www.ncbi.nlm.nih.gov/pubmed/25549704
Senter L. Hereditary breast and ovarian cancer syndrome: considering the complexities. Curr Probl Cancer. 2014;38:226-234. https://www.ncbi.nlm.nih.gov/pubmed/25497409
King-Spohn K, Pilarski R. Beyond BRCA1 and BRCA2. Curr Probl Cancer. 2014;38:235-248. https://www.ncbi.nlm.nih.gov/pubmed/25497410
Meaney-Delman D, Bellcross CA. Hereditary breast/ovarian cancer syndrome: a primer for obstetricians/gynecologists. Obstet Gynecol Clin North Am. 2013;40:475-512. https://www.ncbi.nlm.nih.gov/pubmed/24021253
Barks P, Goldgar C. Hereditary breast and ovarian cancer. JAAPA. 2012;25:63-65. https://www.ncbi.nlm.nih.gov/pubmed/22514962
INTERNET
Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2025 Mar 20]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1247/ Accessed August 28, 2025.
American Cancer Society. Family Cancer Syndromes. September 14, 2022. Available at: https://www.cancer.org/cancer/risk-prevention/genetics/family-cancer-syndromes.html Accessed August 28, 2025.
Peshkin BN, Isaacs C. Overview of hereditary breast and ovarian cancer syndromes. UpToDate, Inc. August 1, 2025. Available at: https://www.uptodate.com/contents/overview-of-hereditary-breast-and-ovarian-cancer-syndromes Accessed August 28, 2025.
Genetics of Breast and Gynecologic Cancers (PDQ®)–Health Professional Version. National Cancer Institute (NCI). March 6,2025. https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq Accessed August 28, 2025.
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