BRCA1 Hereditary Breast and Ovarian Cancer Syndrome (BRCA1 HBOC) is an inherited condition that is characterized by an increased risk for a variety of different cancers. Women with this condition have a 57-60% risk of developing breast cancer, a 40-59% risk of developing ovarian cancer and an 83% risk of developing contralateral breast cancer by age 70. Men have a 1% lifetime risk of breast cancer and an increased risk for prostate cancer. BRCA1 HBOC may also be associated with an elevated risk for cancers of the cervix, uterus, pancreas, esophagus, stomach, fallopian tube, and primary peritoneum; however, these risks are not well defined. This condition is caused by mutations in the BRCA1 gene and is inherited in an autosomal dominant manner. A diagnosis of HBOC is considered when there are multiple cases of breast cancer and/or ovarian cancer on the same side of the family.
Other Names: BROVCA1, Familial susceptibility to breast-ovarian cancer 1
Pathophysiology and Epidemiology
The chance that a family has HBOC increases in any of these situations:
- One or more women are diagnosed at age 45 or younger
- One or more women are diagnosed with breast cancer before age 50 with additional family history of cancer, such as prostate cancer, melanoma, and pancreatic cancer
- There are breast and/or ovarian cancers in multiple generations on the same side of the family, such as having both a grandmother and an aunt on the father’s side both diagnosed with these cancers
- A woman is diagnosed with a second breast cancer in the same or the other breast or has both breast and ovarian cancers
- A male relative is diagnosed with breast cancer
- There is a history of breast cancer, ovarian cancer and/or pancreatic cancer on the same side of the family
- There is a history of breast and/or ovarian, pancreatic, or male breast cancer in a family of Ashkenazi Jewish ancestry
HBOC is an inherited genetic condition. Two genes are associated with the majority of HBOC families: BRCA1 and BRCA2. Other, less common genes have also been associated with an increased risk of developing breast and other cancers, such as mutations in the TP53, PTEN, CDH1, ATM, CHEK2 or PALB2 tumor suppression genes and many others. Blood tests now include many of these genes in a single, multiple-gene panel test. A mutation in either BRCA1 or BRCA2 gives a woman an increased lifetime risk of developing breast and ovarian cancers. Men with these gene mutations also have an increased risk of breast cancer and prostate cancer.
Prevention
Prevention strategies may include high risk cancer screening, chemoprevention and/or prophylactic surgeries.
Some studies have shown prophylactic oophorectomy, salpingectomy, tubal ligation, and oral contraceptives have been efficacious in preventing ovarian cancer and fallopian tube cancer.
Signs and Symptoms
Common symptoms of HBOC include:
- Abnormal fallopian tube morphology
- Ovarian neoplasm
- Primary peritoneal carcinoma
Diagnosis
HBOC should be suspected in individuals with a personal or family history of any of the following characteristics :
- Breast cancer diagnosed at or before age 50 years
- Ovarian cancer
- Multiple primary breast cancers either in one or both breasts
- Male breast cancer
- Triple-negative (estrogen receptor-negative, progesterone receptor-negative, and HER2/neu [human epidermal growth factor receptor 2]-negative) breast cancer, particularly when diagnosed before age 60 years
- The combination of pancreatic cancer and/or prostate cancer (Gleason score ≥7) with breast cancer, and/or ovarian cancer
- Breast cancer diagnosed at any age in an individual of Ashkenazi Jewish ancestry
- Two or more relatives with breast cancer, one under age 50
- Three or more relatives with breast cancer at any age
- A previously identified BRCA1 or BRCA2 pathogenic variant in the family
The diagnosis of BRCA1- and BRCA2-associated HBOC is established in a proband by identification of a heterozygous germline pathogenic variant in BRCA1 or BRCA2 on molecular genetic testing.
Management and Treatment
Individuals with a BRCA1 HPOC pathogenic variant might consider bilateral mastectomy as a primary surgical treatment of breast cancer because of their elevated rate of ipsilateral and contralateral breast cancer.
FDA approved treatments for BCRA1 HPOC include:
Clinical Trials
For a full list of clinical trials relating to BRCA1 HPOC, go here.
Resources
To learn more about rare cancers, visit our Rare Cancers page