Definitions Related to Cancer Genetics and Risk Assessment

All definitions are written in the context of this glossary of terms are specific to concepts related to the NCBC Cancer Genetics and Risk Assessment Certification.

Breast cancer risk assessment ‐ The process of evaluating the likelihood of developing breast cancer in a specific individual by utilizing personal medical history, personal and reproductive factors, family history, breast cancer risk assessment models (i.e. Tyrer‐Cuzick, Gail, BOIDACEA, Claus, for example), as well as genetic test results (when available and appropriate). This includes identification and appropriate referral of patients at risk for other hereditary cancer syndromes for further cancer genetic risk assessment and/or counseling.

Breast density – The comparison of the relative amounts of fibroglandular opacity (white) versus background fat density (black) seen by mammography in the breast. Increased density is associated with increased risk for the development of breast cancer, as well as decreased sensitivity of mammography. Breast density is not currently included in any of the commonly accepted breast cancer risk assessment models. BI‐RADS categories for breast density include:

1 – fatty (<25% glandular)
2 – scattered fibroglandular densities (25‐50% glandular)
3 – heterogeneously dense (51‐75% glandular)
4 – extremely dense (>75% glandular)

Cancer genetics ‐ The study of changes in genes that contribute to cancer risk. These may be hereditary or familial and contribute to familial risk (germline mutations) or acquired genetic mutations in cancer cells that contribute to cancer initiation or progression (somatic mutations).

Cancer genetic counseling – The integration of cancer genetic risk assessment, appropriate genetic testing, and thorough discussion regarding the impact of such assessment and test results. Cancer Genetic counseling includes risk assessment for all types of cancer appearing in the family history, as well as evaluation for all potential hereditary cancer syndromes indicated by the family history, including coordination of all types of hereditary cancer genetic testing and interpretation of results of these tests. Cancer genetic counseling also addresses the impact of the cancer risk and/or hereditary syndrome to the individual and family, both medically and psychosocially.

Cancer genetics professional – A board‐certified (and oftentimes licensed) individual who has completed advanced education in cancer genetics and has been certified by one of several organizations, such as the American Board of Genetic Counseling (ABGC), the American College of Medical Genetics (ACMG), the American Nurses Credentialing Center (ANCC), the Genetic Nursing Credentialing Commission (GNCC), the Nurse Portfolio Credentialing Commission (NPCC), or other similar organizations.

Cancer genetic risk assessment – The process of evaluating a patient’s likelihood to develop hereditary cancer by utilizing personal medical history, family history, risk assessment models and genetic test results.

Chemoprevention – The use of medications to decrease the risk of developing breast cancer. The most common methods utilize endocrine therapy. They can be used as primary prevention in women with a 5‐year breast cancer risk of 1.67% or greater, as determined by the Gail model. These medications can also be prescribed to women who have been diagnosed with estrogen receptor positive breast cancer, to prevent a recurrence.

Collaborative approach ‐ The process by which healthcare providers with different areas of specialty and focus work together to effectively and efficiently provide comprehensive care related to breast cancer risk assessment, pre- and post-test genetic counseling, genetic testing, and the resulting recommendations for personalized medical management.

Cowden syndrome – A rare autosomal dominant syndrome caused by a mutation in the PTEN gene. This syndrome is characterized by breast cancer, uterine cancer, thyroid cancer, benign hamartomatous polyps and macrocephaly.

Familial cancer – The occurrence of cancer within a family more often than would be expected by chance without being attributed to a specific, known genetic mutation for which genetic testing is available. These cancers often occur at an early age, and may indicate the presence of a gene mutation that increases the risk of cancer. They may also be a sign of shared genetic, environmental or lifestyle factors. About 15-20% of common cancers are familial.

Family history ‐ Details about the presence of cancer in a patient’s first‐, second‐, and third‐ degree (and possibly higher degree) relatives, including, but not limited to, type of cancer, gender and age at cancer diagnosis.

Genetic Testing for Inherited Cancer Susceptibility:  – A laboratory analysis (typically a blood or saliva sample) that attempts to identify a gene mutation related to hereditary cancer susceptibility.  Genetic counseling by a specially trained professional knowledgeable in the genetics of cancer risk can help people consider the risks, benefits, alternatives to, and limitations of genetic testing in their individual situations.

People considering genetic testing should understand that their results may become known to other people or organizations that have legitimate, legal access to their medical records, such as their insurance company or employer, if their employer provides the patient’s health insurance as a benefit. Legal protections are in place to prevent genetic discrimination, including the Genetic Information Nondiscrimination Act of 2008 and the Privacy Rule of the Health Information Portability and Accountability Act of 1996.

Genetics Tests Available for Cancer Risk Assessment – There are more than 50 hereditary cancer syndromes. Most are caused by harmful variants that are inherited in an autosomal dominant fashion, though some are inherited in an autosomal recessive pattern or can occur “de novo”. For the majority of these syndromes, genetic tests for cancer susceptibility variants are available. Examples of hereditary cancer syndromes include Birt-Hogg-Dube Syndrome, Cowden Syndrome, Familial Adenomatous Polyposis, Hereditary Breast, Ovarian and Pancreatic Cancer Syndrome (previously Hereditary Breast and Ovarian Cancer or HBOC), Hereditary Diffuse Gastric Cancer, Familial Medullary Thyroid Cancer, Li-Fraumeni Syndrome, Lynch Syndrome, Melanoma-Pancreatic Cancer Syndrome, Multiple Endocrine Neoplasia (Type 1, Type 2A and 2B), Peutz-Jeghers Syndrome, and, Von Hippel-Lindau syndrome.  A full list can be found on the NIH website at

Tests are also available for several inherited genetic variants that have been found to increase cancer risk though are not associated with named syndromes. Examples include inherited variants in genes such as ATM (associated with increased risks of breast, pancreatic, prostate cancer) BARD1 (breast and ovarian cancer), PALB2 (breast and pancreatic cancers), CHEK2 (breast and colorectal cancers), BRIP1 (ovarian cancer), HOXB13 (prostate cancer) and RAD51C and RAD51D (ovarian cancer).


Inherited Cancer Susceptibility Syndromes/Hereditary cancer‐ A type of inherited disorder in which there is a higher-than-average risk of developing certain types of cancer. Hereditary cancer syndromes are caused by mutations (changes) in certain genes passed from a parent to child(ren). In a hereditary cancer syndrome, certain patterns of cancer may be seen within families. These patterns include having several close family members (such as a mother, daughter, and sister) with the same type of cancer, developing cancer at an early age, or having two or more types of cancer develop in the same person. Examples of hereditary cancer syndromes are hereditary breast, ovarian, and pancreatic cancer syndrome, Li-Fraumeni syndrome, Cowden syndrome, and Lynch syndrome. About 5-10% of cancers are hereditary.

Hereditary Breast, Ovarian and Pancreatic Cancer syndrome – An autosomal dominant syndrome caused by a mutation in the BRCA1 or BRCA2 gene that results in an increased risk for breast, ovarian, pancreatic and other cancers. This is the most common cause of hereditary breast cancer.

Hereditary Diffuse Gastric Cancer (HDGC) – is an inherited condition that inherited in an autosomal dominant manner and is caused by a mutation in the CDH1 gene. HDGC is characterized by an increased risk of developing a specific form of stomach cancer called diffuse gastric cancer.  Women with HDGC also have an increased risk for lobular breast cancer. Cancers associated with HDGC generally occur at younger ages than those seen in people who do not have a hereditary predisposition to cancer. Management typically involves high-risk cancer screening and/or prophylactic surgeries.


Informed consent ‐ The process of reviewing key information so that a patient can make a knowledgeable decision about whether to proceed with genetic testing. The American Society of Clinical Oncology outlines 12 basic elements of informed consent for cancer susceptibility testing (J Clin Oncol. 2003 Jun 15;21(12):2397‐406.


Li-Fraumeni syndrome (LFS)– is an inherited cancer syndrome caused by mutations in the TP53 gene. This syndrome is characterized by early onset breast cancer, osteosarcoma, soft-tissue sarcomas, acute leukemia, bran cancer and adrenal cortical tumors. Ant increased risk for melanoma, Wilms’ tumor, stomach, colon, pancreas, esophagus, lung, gonadal germ cell tumors and other types of cancer have been reported in people with this condition.

LFS is characterized by an increased risk for certain types of cancer. Affected people often develop cancer at an earlier age than expected and may be diagnosed with more than one cancer during their lifetime.  Management may include high-risk cancer screening and/or prophylactic surgeries


Lynch Syndrome - a genetic disorder with an autosomal dominant pattern of inheritance caused by a mutation in the mismatch repair genes, (MLH1, MSH2, MSH6, PMS2 or EPCAM) that results in an increased risk of developing certain types of cancer such as colon and rectal cancer, as well as cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women with Lynch syndrome also have a high risk of developing uterine cancer (also called endometrial cancer) and ovarian cancer.

Pedigree ‐ A three to four generation diagram of a patient’s family history of cancer, including types of cancer, gender and ages at diagnosis.

Prevention strategies – The collection of recommendations provided an individual according to their risk level, the goal of which is to decrease the likelihood of developing breast cancer and/or to identify breast cancer at its earliest development. These recommendations are developed as a result of accurate breast cancer risk assessment of the individual. A recommended plan may include specialized imaging or testing, chemoprevention, preventive surgeries, or repeated clinical examinations.

Pre‐test facilitation – The process of obtaining informed consent for a genetic test, as well as coordinating the logistics of sample collection and insurance pre‐authorization and/or writing a letter of medical necessity. This process occurs after risk assessment when deemed appropriate by the healthcare provider and desired by the patient.

Post‐test counseling ‐ The process of disclosing genetic test results to a patient and utilizing those genetic test results to personalize a patient’s cancer risk estimates and/or options for cancer screening and prevention. This includes recognizing and referring to a cancer genetics professional when appropriate for further hereditary cancer risk assessment and/or testing.

Risk levels ‐ A stratification of the lifetime likelihood to develop breast cancer in an individual. According to the American Cancer Society, there are three levels of lifetime breast cancer risk (CA Cancer J Clin 2007;57:75‐89):

  • Average (not elevated) = Below 15% lifetime risk
  • Intermediate (moderately elevated) = Between 15 and 20% lifetime risk
  • High (significantly elevated) = 20% or greater lifetime risk

Tumor DNA Sequencing in Cancer Treatment – Lab tests called DNA Sequencing tests can sequence DNA from tumor cells, either from tissue biopsy or from circulating tumor DNA fragments shed by cancer cells into the bloodstream (liquid biopsy). By comparing the sequence of DNA in cancer cells with that in normal cells, such as blood or saliva, scientists can identify genetic changes in cancer cells that may be driving the growth of an individual’s cancer. This information may help doctors sort out which therapies might work best against a particular tumor. Tumor DNA sequencing can also reveal the presence of inherited mutations. Indeed, in some cases, the genetic testing of tumors has shown that a patient’s cancer could be associated with a hereditary cancer syndrome that the family was not aware of.

As with testing for specific mutations in hereditary cancer syndromes, clinical DNA sequencing has implications that patients need to consider. For example, they may learn incidentally about the presence of inherited mutations that may cause other diseases, in them or in their family members.