Rare Endocrinology News

Disease Profile

Familial breast cancer

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Breast cancer, familial; Heritable breast cancer; Genetic breast cancer;

Categories

Congenital and Genetic Diseases; Female Reproductive Diseases; Rare Cancers

Summary

Familial breast cancer is a cluster of breast cancer within a family. Most cases of breast cancer occur sporadically in people with little to no family history of the condition. Approximately 5-10% of breast cancer is considered "hereditary" and is thought to be caused by an inherited predisposition to breast cancer that is passed down through a family in an autosomal dominant manner. In some of these families, the underlying genetic cause is not known; however, many of these cases are caused by changes (mutations) in the BRCA1, BRCA2, PTEN, TP53, CDH1, or STK11 genes (which are each associated with a unique hereditary cancer syndrome). Additional genes, such as CHEK2BRIP1RAD51, and ATM, are associated with breast and/or gynecologic cancers in some cases. About 15-20% of women diagnosed with breast cancer have a significant family history of breast cancer (two or more first-degree or second-degree relatives with breast cancer) but have no identifiable mutation in a gene known to cause a hereditary predisposition to breast cancer. These clusters of breast cancer are likely due to a combination of gene(s) and other shared factors such as environment and lifestyle.[1][2][3]

High-risk cancer screening and other preventative measures such as chemoprevention and/or prophylactic surgeries are typically recommended in women who have an increased risk for breast cancer based on their personal and/or family histories.[4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Breast carcinoma
Breast cancer
0003002
Somatic mutation
0001428

Cause

Most cases of breast cancer occur sporadically in people with little to no family history of the condition. They are due to random changes (mutations) that occur only in the cells of the breast. These mutations (called somatic mutations) accumulate during a person's lifetime and are not inherited or passed on to future generations.[1]

Approximately 15-20% of women diagnosed with breast cancer have a significant family history of breast cancer (two or more first-degree or second-degree relatives with breast cancer) but have no identifiable mutation in a gene known to cause a hereditary predisposition to breast cancer. These clusters of breast cancer are likely due to a combination of gene(s) and other shared factors such as environment and lifestyle.[3]

An additional 5-10% of breast cancer is considered "hereditary." These cases are thought to be caused by an inherited predisposition to breast cancer that is passed down through a family in an autosomal dominant manner. In some of these families, the underlying genetic cause is not known. However, many of these cases are part of a hereditary cancer syndrome. The following cancer syndromes are associated with an increased risk of breast cancer and several other types of cancer:[1][2][3]

Of note, some research suggests that inherited mutations in several other genes (including CHEK2, BRIP1, ATM, PALB2, RAD51, BARD1, MRE11A, NBN, and RAD50) may also be associated with an increased risk for breast cancer. However, the risk associated with many of these genes is not well understood. Most are termed "moderateor low-penetrant" genes which means that, on their own, they would be expected to have a relatively small effect on breast cancer risk. However, in combination with other genes and/or environmental factors, these genes may lead to a significant risk of breast cancer.[1][3][2]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Management of familial breast cancer is generally focused on high-risk cancer screening to allow for early detection and treatment of cancer. In general, the National Comprehensive Cancer Network recommends high-risk breast cancer screening for women who have: (1) a personal and family history suggestive of a hereditary cancer syndrome that is associated with breast cancer or (2) a greater than 20% risk of developing breast cancer in their lifetime based largely on family history. The recommended screening protocol includes:[4]

    • Breast awareness and breast self-exams
    • Clinical breast exams every 6-12 months beginning at age 30 or individualized based on the earliest breast cancer diagnosis in the family
    • Annual mammogram and breast MRI beginning at age 30 or individualized based on the earliest breast cancer diagnosis in the family
    • Discussion of other risk reduction strategies such as chemoprevention and/or prophylactic surgeries

    If the familial breast cancer is part of a known hereditary cancer syndrome, management will also include screening for the other associated cancers. Please click on the following links for more information regarding the treatment and management of each condition:

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus Genetics contains information on Familial breast cancer. This website is maintained by the National Library of Medicine.
        • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
        • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.

          In-Depth Information

          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Familial breast cancer. Click on the link to view a sample search on this topic.

            References

            1. Genetics of Breast and Gynecologic Cancers (PDQ®). National Cancer Institute. 2017; https://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional.
            2. Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann Oncol. January 2015; [Epub ahead of print]:
            3. Economopoulou P, Dimitriadis G, Psyrri A. Beyond BRCA: new hereditary breast cancer susceptibility genes. Cancer Treat Rev. January 2015; 41(1):1-8.
            4. Bevers T. Breast Cancer Screening and Diagnosis. National Comprehensive Cancer Network. January 2014;

            Rare Endocrinology News