麻豆传媒

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

According to the American Cancer Society, about will develop breast cancer during their lifetime. However, the risk increases precipitously for those with a genetic mutation, also known as a pathogenic variation. Therefore, assessment of a person's individual breast cancer risk and whether or not genetic testing is indicated is crucial.

for breast cancer is usually considered when there is a strong family history of the disease -- specifically in cases of early-onset breast cancer (diagnosed before age 50) or when multiple family members have been diagnosed with cancer.

It is important to emphasize to patients, however, that not all people with a pathogenic variation that increases breast cancer risk will be diagnosed with breast cancer.

Pathogenic Variations

BRCA1 and BRCA2 are associated with an increased risk of breast cancer in both women and men. BRCA1 and BRCA2 pathogenic variations can be inherited from both sexes on either side of a family and are seen at a higher incidence in those of Ashkenazi Jewish ancestry.

Pathogenic variations in these genes substantially elevate the risk of developing breast and ovarian cancers, and also increase the risk of pancreatic cancer, melanoma, and prostate cancer. Anywhere from 55% to 72% of women who carry a BRCA1 pathogenic variation will develop breast cancer, while 45-69% of women who inherit a BRCA2 pathogenic variation will develop breast cancer, according to the National Cancer Institute (.

Other inherited pathogenic variations for breast cancer include the following:

• Women: TP53, PTEN, STK11, ATM, BARD1, BRIP1, CHEK2, CDH1, NF1, PALB2, RAD51C, and RAD51D

• Men: BRCA1, BRCA2, CHEK2, and PALB2

Tumor protein 53 () is a gene involved with tumor suppression; the pathogenic variation is linked to increased cancer risk. People with the inherited TP53 pathogenic variation have an increased risk of premenopausal breast cancer, as well as other cancers; are more likely to be diagnosed with cancer at a younger age; and have a lifetime risk rate of about 90% for any type of cancer.

The phosphatase and tensin homolog () gene has been identified as a tumor suppressor, and its pathogenic variation may cause an increased risk of both non-cancerous and cancerous tumors (Cowden syndrome). The gene has been linked to breast, uterine, thyroid, colorectal, and kidney cancers.

The serine/threonine kinase 11 () gene stops cells from growing and dividing too quickly; pathogenic variations in the gene are rare and can promote carcinogenesis, including breast cancer.

People with the ataxia-telangiectasia mutated () gene have an estimated 40% risk of developing cancer, and the gene has been linked to an increased risk of breast cancer as well as poorer outcomes. It has also been shown to be associated with an increased risk for prostate, pancreatic, and stomach cancers.

A , or pathogenic variation increases the risk for ovarian cancer, and may increase the risk for breast cancer. A pathogenic variation may increase the risk for breast cancer. Research is ongoing as to the role that each of these pathogenic variations have in the development of breast cancer.

The checkpoint kinase 2 () pathogenic variation is more frequently found in Eastern and Northern European population groups and has been linked to breast cancer. CHEK2 increases breast cancer risk approximately 1.5 to 3.0 times, with the highest risk for those with a .

Pathogenic variations in the cadherin 1 () gene have been linked to an up to 60% lifetime risk of female invasive lobular carcinoma -- which begins in the milk glands -- with an average diagnosis at age 53. CDH1 has also been identified as conferring an up to 80% lifetime risk of diffuse gastric cancer for those who express this gene.

Neurofibromatosis type 1 () affects around 1 in every 3,000 people and is one of the most common genetic disorders. It can cause a variety of symptoms and complications, as well as a predisposition toward certain types of tumors, including breast cancer.

, a partner and localizer of BRCA2, is a genetic pathogenic variation associated with BRCA2 that causes an increased risk of breast, ovarian, and pancreatic cancers and is linked to breast cancer in men. PALB2 is found in about patients, according to the NCI.

The Specifics of Testing

Patients considering genetic testing should be referred to a genetic counselor who can provide detailed information about the testing process, the implications of test results, and potential management options.

Genetic testing for breast cancer can be used to identify pathogenic variations that may increase a patient's risk of cancer, and may help patients understand their cancer risk.

If a patient has already been diagnosed with breast cancer, genetic testing may aid in making appropriate treatment decisions. This information also may give a patient the information they need to investigate strategies for risk reduction, along with other lifestyle changes.

The National Comprehensive Cancer Network (NCCN) recommends pathogenic variation or a first-degree relative who has a BRCA1 or BRCA2 pathogenic variation.

A patient who tested negative for either a BRCA1 or BRCA2 pathogenic variation may need to be retested, because assays have improved since then and are capable of detecting pathogenic variations involving a larger area of each gene.

BRCA1 and BRCA2 tests are considered a single or limited gene panel test; it is less comprehensive, however, and other high-risk gene pathogenic variations are not included.

testing, in addition to testing for BRCA1 and BRCA2, also check for pathogenic variations in genes such as TP53, CHEK2, ATM, PALB2, and others, thus providing a more comprehensive evaluation of genetic risk. The test can be fully customized by the ordering physician, and can provide results on multiple genes in a relatively quick time.

Multigene panel testing may identify pathogenic variations for which the cancer risk or management strategies are not known; in these instances, it may not be helpful in making treatment decisions. Testing may also identify a even when there is no hereditary cancer syndrome history.

Numerous professional and expert groups offer guidelines for genetic testing -- for example:

• American Society of Clinical Oncology ()

Managing Results

Positive results to either a single-gene test or multigene panel indicate the presence of a genetic pathogenic variation, suggesting that the patient be referred to a breast cancer specialist to assess the patient's overall risk profile and develop the appropriate management plan. This could include surveillance, prophylactic surgery, or chemoprevention.

Patients who test positive for a breast cancer gene pathogenic variation should be encouraged to share the results with family members since this can help identify other individuals who may benefit from breast cancer risk-reduction strategies.

Getting a positive test for a breast cancer gene pathogenic variation can be emotionally and psychologically challenging, as can sharing the results with family members. Clinicians should be prepared to provide or refer these patients to appropriate counseling and support services.

Read previous installments in this series:

Part 1: Breast Cancer -- The Basics of Diagnosis, Staging, and Treatment

Part 2: Breast Cancer: Making the Diagnosis With Breast Biopsy

Part 3: What to Know About Management of Early-Stage Breast Cancer

Part 4: New Treatment Options for Locally Advanced and Metastatic Breast Cancer