Bilateral breast cancer, the development of cancer in both breasts, depends heavily on an individual’s medical history and genetic makeup. For the general population, the occurrence of two independent cancers is low. However, for those already diagnosed with cancer in one breast, the risk of a new, second primary tumor developing in the opposite breast is significantly higher. Understanding this risk involves distinguishing between the timing of the two diagnoses and identifying specific factors that increase long-term risk.
Understanding Bilateral Breast Cancer
Bilateral breast cancer is defined by the presence of a primary tumor in each breast. Clinicians categorize this occurrence into two distinct types based on the timing of the diagnosis of the second tumor relative to the first. This distinction implies different underlying risk factors and treatment approaches.
The first type is synchronous bilateral breast cancer (SBBC), referring to tumors diagnosed simultaneously or within six to twelve months of the initial diagnosis. This type is relatively rare, accounting for approximately 0.6% to 3% of all breast cancer cases. The second type is metachronous, or contralateral, breast cancer (CBC), which is a new primary tumor developing in the opposite breast more than a year after the first cancer was diagnosed and treated.
The risk calculation for an individual changes drastically once they have been treated for their initial cancer, making the metachronous risk the more common concern for survivors. The occurrence of a metachronous cancer suggests a systemic susceptibility to the disease in the remaining breast tissue.
Statistical Likelihood of Developing Cancer in the Second Breast
For an individual who has completed treatment for cancer in one breast, the annual chance of developing a new, second primary tumor in the opposite breast averages between 0.37% and 1% per year. The risk accumulates over a person’s lifetime following their initial diagnosis, resulting in a higher lifetime probability of developing a second primary tumor than the general population.
The cumulative risk of a second, contralateral breast cancer reaches approximately 10% over the 25 years following the initial diagnosis for the average survivor. For individuals with inherited genetic mutations, however, these statistics escalate dramatically, indicating a much higher baseline susceptibility.
For instance, a woman who carries a pathogenic variant in the BRCA1 gene faces a 10-year cumulative risk of contralateral breast cancer of around 23.1%. Carriers of the BRCA2 variant have a similarly high 10-year cumulative risk, estimated at about 16.9% after their first diagnosis.
Primary Factors Driving Increased Risk
The risk of a second primary tumor is heavily influenced by specific biological and clinical factors. Inherited genetic mutations are the strongest drivers of elevated risk, including pathogenic variants in the BRCA1 and BRCA2 genes.
Other genes, such as CHEK2 and PALB2, also contribute to an increased risk, particularly in cases where the first tumor was estrogen receptor-negative. Age at diagnosis is another factor; women diagnosed at a younger age, especially before age 40, face a higher cumulative risk of a second cancer compared to those diagnosed later in life.
The pathology of the initial tumor also plays a role, with certain types showing a greater tendency toward bilaterality. Invasive lobular carcinoma (ILC) is notably more often bilateral than invasive ductal carcinoma. This tendency is linked to the inactivation of the CDH1 gene, which causes the loss of cell-to-cell adhesion, allowing lobular cells to grow in a dispersed pattern that can easily arise independently in the opposite breast.
Strategies for Monitoring and Risk Management
Medical strategies for monitoring and prevention are tailored to an individual’s specific risk profile.
Enhanced Surveillance
For those classified as high-risk, a strategy known as enhanced surveillance is implemented to catch any potential second cancer at the earliest possible stage. This typically involves alternating annual screening with a mammogram and a magnetic resonance imaging (MRI) scan, often staggered every six months.
Chemoprevention
Chemoprevention, which uses medication to reduce the risk of cancer development, is another option for many survivors. For patients with hormone receptor-positive disease, endocrine therapies such as Tamoxifen and Aromatase Inhibitors (AIs) are effective at lowering the risk of a new primary tumor in the remaining breast. Aromatase Inhibitors, which reduce estrogen levels in postmenopausal women, have shown significant benefit in reducing contralateral cancer risk, particularly in those with BRCA mutations.
Prophylactic Mastectomy
For individuals with the highest genetic risk, such as carriers of BRCA1 or BRCA2 who have already had one breast cancer diagnosis, a surgical option called a prophylactic mastectomy may be considered. This procedure involves the removal of the healthy, unaffected breast to reduce the lifetime risk of developing a second cancer by over 90%. Decisions regarding enhanced surveillance, chemoprevention, or surgery involve careful discussion of the patient’s individual risk factors, tumor characteristics, and personal preferences.