Breast cancer is a common diagnosis. While various factors contribute to its development, a significant connection exists between an individual’s genetic makeup and their susceptibility. This article explores how inherited genetic changes impact an individual’s lifetime breast cancer risk.
Understanding Genetic Contributions to Breast Cancer
Genetic contributions to breast cancer primarily involve changes in an individual’s DNA passed down through families. These inherited alterations, known as germline mutations, are present in nearly every cell from birth. They differ from acquired (somatic) mutations, which occur later in life in specific cells and are not passed to offspring. While most breast cancers arise from acquired mutations, a notable percentage are linked to these inherited germline changes.
Inherited genetic changes can disrupt normal cellular processes like DNA repair or cell growth regulation. When compromised, cells may be more prone to uncontrolled growth, leading to cancer. Not all breast cancer is hereditary; however, for those with a strong family history, inherited genetic factors play a significant role in their elevated risk. This distinction helps identify individuals who might benefit from specialized screening or prevention.
Key Genes Associated with Inherited Breast Cancer
BRCA1 (Breast Cancer Gene 1) and BRCA2 (Breast Cancer Gene 2) are the most recognized genes linked to inherited breast cancer. These tumor suppressor genes produce proteins that help repair damaged DNA and regulate cell growth. Mutations in BRCA1 or BRCA2 impair these protective functions, increasing the lifetime risk of developing breast, ovarian, and other cancers. For instance, a woman with a BRCA1 mutation has an estimated lifetime breast cancer risk ranging from 60% to 90%, while for BRCA2 mutations, the risk falls between 45% and 85%.
Other genes also contribute to hereditary breast cancer risk, though less commonly than BRCA mutations. PALB2 (Partner and Localizer of BRCA2) works with BRCA2 in DNA repair; mutations can significantly increase breast cancer risk, sometimes approaching that of BRCA2. An estimated 53% of women with a mutated PALB2 gene may develop breast cancer by age 80. CHEK2 (Checkpoint Kinase 2) and ATM (Ataxia-Telangiectasia Mutated) are involved in cell cycle control and DNA damage response; mutations in these genes lead to a moderate increase in breast cancer risk.
Less frequently, mutations in genes like TP53 (tumor protein p53), CDH1 (cadherin 1), and PTEN (phosphatase and tensin homolog) are associated with specific inherited cancer syndromes that include elevated breast cancer risk. TP53 mutations are linked to Li-Fraumeni syndrome, a rare condition with a very high lifetime cancer risk, with breast cancer cumulative incidence reaching 85% by age 60. CDH1 mutations are primarily associated with hereditary diffuse gastric cancer but also increase the risk of invasive lobular carcinoma. PTEN mutations cause Cowden syndrome, which involves increased risks of breast, thyroid, and endometrial cancers.
Genetic Testing for Breast Cancer Risk
Genetic testing for breast cancer risk is considered for individuals with a personal or family history suggestive of an inherited predisposition. This includes:
Diagnosis of breast cancer at a young age.
Triple-negative breast cancer.
Male breast cancer.
Multiple relatives on the same side of the family with breast or ovarian cancer.
A known BRCA mutation in the family.
Ashkenazi Jewish descent, due to a higher prevalence of BRCA mutations.
Before testing, individuals usually participate in genetic counseling. A genetic counselor reviews personal and family medical history, discusses testing benefits and limitations, and helps individuals understand results. This session also covers emotional and psychological aspects of learning about genetic risks. The testing process typically involves providing a blood or saliva sample, from which DNA is extracted and analyzed for specific gene mutations.
Results can indicate a positive result (a mutation known to increase cancer risk was found) or a negative result (no such mutation identified). Sometimes, a variant of uncertain significance (VUS) may be reported, a genetic change whose impact on cancer risk is not yet clear. Multi-gene panel testing, which examines several genes simultaneously, is a common approach to assess hereditary cancer risk.
Managing Genetic Breast Cancer Risk
Individuals identified with an inherited genetic predisposition to breast cancer have various strategies to manage their elevated risk. Enhanced surveillance is a common approach, involving earlier and more frequent screenings. This often includes annual mammograms starting in their 30s and annual breast magnetic resonance imaging (MRI) scans, which are more sensitive in detecting abnormalities in dense breast tissue. These screenings aim to detect cancer at its earliest, most treatable stages.
Risk-reducing medications, also known as chemoprevention, offer another management option. Medications like tamoxifen or raloxifene can reduce the risk of estrogen-receptor-positive breast cancer by blocking estrogen’s effects on breast cells. Healthcare providers consult with individuals to weigh benefits against potential side effects.
Preventive surgeries are the most aggressive risk-reduction strategies. A bilateral prophylactic mastectomy (surgical removal of both breasts) can reduce breast cancer risk by approximately 90% or more in women with BRCA1/2 mutations. For women with BRCA1 or BRCA2 mutations, a prophylactic oophorectomy (surgical removal of the ovaries and fallopian tubes) is often recommended to reduce ovarian cancer risk and further decrease breast cancer risk, particularly for hormone-sensitive cancers, by approximately 50%. Management strategy choice is highly personalized, requiring shared decision-making with the healthcare team, considering the specific genetic mutation, family history, and personal preferences.
References
National Cancer Institute. “Genetics of Breast and Ovarian Cancer (PDQ®)–Health Professional Version.” Accessed August 3, 2025.
Centers for Disease Control and Prevention. “BRCA1 and BRCA2 Genes.” Accessed August 3, 2025.
American Cancer Society. “Risk-Reducing Surgery to Prevent Breast Cancer.” Accessed August 3, 2025.