Hereditary breast and ovarian cancer (HBOC) syndrome, which is caused by a germline mutation in the high-penetrance breast cancer genes BRCA1 or BRCA2, is characterized by an increased risk for breast cancer.3 An increased likelihood of a BRCA1 or BRCA2 mutation can be suspected on the basis of certain personal and family history characteristics and clinical criteria. The lifetime risk for breast cancer in individuals with a mutation in BRCA1 or BRCA2 is estimated to be 40% to 80%.4

The prognosis for patients with BRCA1– or BRCA2-related breast cancer depends on the stage at which the cancer is diagnosed, and early diagnosis may depend on a patient’s awareness of increased familial or genetic risk. Similarly, patients with mutations in other high-penetrance genes such as tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), serine/threonine kinase 11 (STK11), and cadherin 1, type 1 (CDH1) may develop cancer predisposition syndromes associated with the development of several types of cancer, and they have a higher likelihood of developing breast cancer in their lifetimes. Moderate-penetrance breast cancer susceptibility genes that can increase breast cancer risk during a woman’s lifetime include checkpoint kinase 2 (CHEK2), ataxia telangiectasia mutated serine/threonine kinase (ATM), nibrin (NBN), RAD50 homolog, double strand break repair protein (RAD50), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and partner and localizer of BRCA2 (PALB2).5 In men, 3 classes of genetic susceptibility to breast cancer (high-, moderate-, and low-penetrance) are recognized, but the genes that are involved and their impact do not exactly overlap in female and male breast cancer.6

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An increased likelihood of a genetic mutation in moderate- and high-penetrance genes can be suspected on the basis of certain personal and family history characteristics and clinical criteria. Clinicians may then be able to advise patients who carry a genetic mutation or know of their increased risk of management strategies that might mitigate their breast cancer risk. 

Even if no hereditary susceptibility is suggested by the family history, individuals having one or more close relatives with breast cancer may benefit from beginning cancer surveillance at a younger age and/or with more intensive screening than those in the general population. National guidelines recommend that individuals with hereditary breast cancer susceptibility be screened earlier and consider more sensitive screening tests, risk-reducing medications, and/or risk-reducing surgery.7

Risk of sporadic, familial, and hereditary breast cancer may be modified by lifestyle and environmental factors, breast imaging, chemoprevention, and/or prophylactic surgery,8 but awareness and knowledge about techniques to reduce breast cancer risk varies tremendously among individuals, providers, and populations nationwide. It has been hypothesized that when individuals are made aware of the level of their breast cancer risk and are given appropriate tools, support, and screenings, they would take proactive steps to mitigate their risk of developing cancer and increase their odds of survival if breast cancer does occur.9 It is also thought that if patients are informed of their elevated risk for breast cancer, their compliance with breast cancer prevention measures is greater.9 Of note, tools to identify women at elevated risk of developing breast cancer have been validated.10

The National Comprehensive Cancer Network (NCCN),11 a not-for-profit alliance of 26 of the world’s leading cancer centers that is devoted to patient care, research, and education, has developed breast cancer risk-reduction guidelines that can be used in clinical practice. Individuals at elevated risk of developing breast cancer can be identified and encouraged to follow these clinical guidelines to reduce their risk.

Indications for referral to genetic counseling 

It is important for clinicians in primary care to recognize when referral to a genetic counselor is recommended. A cancer risk assessment should be conducted at every primary care visit, and the patient’s family cancer history should be updated as appropriate at every visit. 

NCCN guidelines7 recommend referral to a cancer genetics professional when there is a history involving either side of the family—maternal or paternal—of any of the following:

  • A known mutation in a cancer susceptibility gene in the family

  • A first- or second-degree relative with breast cancer at age 45 or younger (includes ductal carcinoma in situ). First-degree relatives include siblings, parents, and children; second-degree relatives include grandparents, aunts, uncles, half-siblings, nieces, and nephews; third-degree relatives include cousins, half-aunts and uncles, great aunts and uncles, great grandparents, and great grandchildren.

  • A close family member with at least two primary breast cancers. Close blood relatives include first-, second-, and third-degree relatives.

  • At least two closely related individuals on the same side of the family with breast cancer

  • At least one woman in the family with invasive ovarian cancer (including fallopian tube and primary peritoneal cancer)

  • Breast cancer in a male family member

  • Three or more individuals on the same side of the family with pancreatic or prostate cancer (Gleason score ≥ 7)

  • Ashkenazi (Eastern European) Jewish ancestry and breast, ovarian, or pancreatic cancer at any age