Breast cancer is influenced by a complex interplay of factors, including genetics. While a family history of breast cancer is often associated with increased risk, only a specific portion of cases directly stems from inherited gene mutations. Understanding the role genetics plays helps individuals and their healthcare providers make informed decisions about screening and prevention. This article will cover the types of breast cancer, the genes involved, genetic counseling and testing, and medical management options.
Hereditary Versus Sporadic Breast Cancer
Breast cancer is broadly categorized into sporadic, familial, and hereditary forms. Sporadic breast cancer is the most common, representing 85-90% of cases, and occurs due to random genetic changes over a person’s lifetime. Familial breast cancer accounts for a smaller percentage, affecting multiple family members without an identifiable inherited gene mutation. This clustering might be due to a combination of shared lifestyle factors, common environmental exposures, or as-yet-undiscovered genetic predispositions.
Hereditary breast cancer, by contrast, results from specific inherited gene mutations passed down through families. These inherited forms represent about 5-10% of all breast cancers, but often involve a significantly higher lifetime risk of developing breast cancer and can occur at younger ages compared to sporadic cases. For instance, genetic factors may account for about 25% of breast cancers in women under 30 years of age.
The Role of Key Genes
The most recognized genes linked to hereditary breast cancer are BRCA1 and BRCA2, abbreviated as “BRCA” (BReast CAncer gene). These genes function as tumor suppressor genes, repairing damaged DNA and preventing uncontrolled cell growth. Everyone inherits two copies, one from each parent. A harmful mutation in one of these genes impairs DNA repair, increasing the likelihood of genetic errors that contribute to cancer.
Women who inherit a harmful BRCA1 variant have an estimated 55-72% chance of developing breast cancer by age 70-80, and those with a harmful BRCA2 variant have a 45-69% chance. Men with a BRCA2 mutation also face an increased risk of breast cancer (around 6%), compared to 1% for men with a BRCA1 mutation.
Other genes can also increase breast cancer risk, though generally to a lesser extent. These include PALB2, CHEK2, ATM, and TP53. For example, a PALB2 mutation, which works with BRCA2 in DNA repair, is associated with an estimated 35% risk of developing breast cancer by age 70. CHEK2 mutations can approximately double the risk for breast cancer in women.
Genetic Counseling and Testing
Genetic counseling is an important first step for individuals concerned about breast cancer risk. A genetic counselor reviews personal and family medical histories to determine if testing is appropriate and which genes to analyze. The counselor also explains the benefits, risks, and limitations of genetic testing.
When to Consider Genetic Testing
Certain family history “red flags” might prompt a recommendation for genetic testing:
Breast cancer diagnosed at a younger age (typically under 50).
Multiple relatives on the same side of the family with breast cancer.
A personal history of more than one primary breast cancer.
A family history of ovarian, pancreatic, male breast, or triple-negative breast cancer.
A known gene mutation already identified in a family member.
The genetic testing process is straightforward, often involving a blood or saliva sample sent for DNA analysis. Results typically take several weeks to months.
Understanding Test Results
Understanding genetic test results is important, as there are generally three main possibilities.
Positive Result
A “positive” result indicates a known pathogenic, or harmful, gene mutation was found. This means the individual has an increased risk of developing certain cancers, including breast cancer, guiding future medical management.
Negative Result
A “negative” result means no known mutation was detected in the genes tested. While this significantly reduces the likelihood of a high hereditary risk, it does not eliminate the general population risk of developing cancer. Current tests may not identify all possible genetic changes, or other genes not yet understood might contribute to risk.
Variant of Uncertain Significance (VUS)
A VUS means a gene change was found, but it is not currently known if this specific change increases cancer risk. VUS results are common, especially with multi-gene panel testing, and their clinical significance is unclear. These variants are re-evaluated over time as more research becomes available, and some may be reclassified as benign or pathogenic.
Medical Management for Gene Carriers
Upon receiving a positive genetic test result for a high-risk mutation, such as in BRCA1 or BRCA2, individuals work with their healthcare team to develop a personalized medical management plan. These strategies aim to reduce cancer risk or detect cancer at its earliest, most treatable stages.
Enhanced Surveillance
This involves more frequent and specialized screenings. For instance, women with BRCA1 or BRCA2 mutations are typically advised to begin annual mammograms and breast magnetic resonance imaging (MRI) at a younger age, often starting between 25 and 30 years old. MRI is particularly sensitive for detecting breast cancer in high-risk women and can identify cancers at earlier stages, which is important for prognosis.
Risk-Reducing Medications (Chemoprevention)
Drugs like tamoxifen and raloxifene, which are selective estrogen receptor modulators (SERMs), have been approved to reduce breast cancer risk in women with an elevated risk. While their efficacy in preventing breast cancer in healthy BRCA gene carriers is still being studied, tamoxifen has shown promise in reducing the risk of new cancer in the opposite breast for BRCA1 and BRCA2 variant carriers previously diagnosed with breast cancer. These medications work by interfering with estrogen’s effects on breast tissue, thereby reducing cancer cell growth.
Risk-Reducing Surgeries
Risk-reducing surgeries represent a more definitive approach to managing elevated cancer risk. A bilateral risk-reducing mastectomy, which involves the surgical removal of both breasts, can reduce breast cancer risk by at least 95% in women with BRCA1 or BRCA2 mutations. This procedure significantly lowers the chance of developing breast cancer, though it cannot eliminate all risk because some breast tissue may remain. For ovarian cancer risk, a bilateral risk-reducing salpingo-oophorectomy, the removal of both ovaries and fallopian tubes, is often recommended, as it can substantially reduce the risk of both ovarian and, potentially, breast cancer. These surgical decisions are highly personal and are made after thorough discussions with a medical team, considering individual risk, family planning, and quality of life.