The outlook and treatment plan for breast cancer depend heavily on the tumor’s characteristics. While many cases present with a single lesion, tumors can also manifest in multiple locations within the same breast. Understanding these patterns is important because the presence of more than one tumor focus can alter the surgical approach and the potential for the cancer to return. This article explores how a multifocal presentation compares to a unifocal one in terms of prognosis and therapeutic implications.
Defining Multifocal and Multicentric Breast Cancer
The presence of multiple tumors in the same breast is categorized based on the proximity and origin of the lesions. Unifocal breast cancer involves only a single invasive tumor focus. Multifocal breast cancer is diagnosed when two or more invasive tumors are found within the same quadrant of the breast, often suggesting they arose from a single primary tumor that spread through the ductal system.
This is distinct from multicentric breast cancer, which refers to tumors located in two or more different quadrants of the breast, or those separated by more than two centimeters. Multicentric lesions are considered to have developed independently from separate original tumors. Both presentations are collectively referred to as multifocal/multicentric disease, representing a significant minority of all breast cancer cases.
Prognostic Significance and Recurrence Risk
Clinical data suggests that whether multifocal disease is inherently worse than unifocal disease is complex. Multifocal tumors are frequently associated with factors that indicate a less favorable outlook, such as higher tumor grade and greater involvement of the lymph nodes. However, when comparing multifocal and unifocal disease with the same stage and biological characteristics, overall long-term survival rates often show no significant difference.
The current standard for staging breast cancer, the TNM system, uses the size of the largest tumor focus to determine the T-classification. Multiplicity is noted separately, and the stage is not automatically elevated simply by having multiple lesions. Some studies suggest that if staging were based on the aggregate size of all tumor foci, many multifocal cases would be assigned a higher T-stage, implying the total tumor burden is greater than the largest tumor alone suggests.
The most consistent difference relates to the risk of local recurrence. Patients with multifocal or multicentric disease face a statistically higher risk of the cancer returning to the same breast, even after controlling for the type of surgery performed. For instance, local control rates at ten years have been reported as significantly lower for multifocal/multicentric disease compared to matched unifocal controls. This increased local risk suggests that multiple foci indicate a broader field of cancerous change within the breast tissue.
Impact on Surgical Treatment Strategies
The presence of multiple tumor sites significantly complicates the decision-making process for local treatment. For unifocal disease, breast-conserving surgery (BCS), or lumpectomy, is a widely used option, followed by radiation therapy. Achieving clear surgical margins—removing the entire tumor with a surrounding rim of healthy tissue—is paramount for local control.
In multifocal disease, achieving clear margins around all separate tumor foci across a wider area is much more challenging. When lesions are numerous or spread far apart, removing all of them while maintaining a cosmetic result and sufficient healthy breast tissue is often not feasible. Consequently, extensive multifocal or multicentric disease frequently results in a recommendation for mastectomy, the complete removal of the breast.
Mastectomy remains the more common surgical approach, although some patients with widely separated lesions may still be candidates for BCS if all foci can be excised with clear margins. This choice is primarily driven by the goal of minimizing the elevated risk of local recurrence associated with multiple tumors. Surgical planning requires precise preoperative imaging to map all tumor sites accurately and determine the extent of tissue removal.
Considering Systemic Therapy and Tumor Biology
Systemic therapies, including chemotherapy, hormone therapy, and targeted agents, are determined by the tumor’s biological characteristics, not just the number of foci. The primary challenge in multifocal disease is the potential for discordant biology, where different tumor foci exhibit different receptor statuses. For example, one focus might be estrogen receptor positive (ER+), while another is negative (ER-).
When receptor status is discordant, the treatment plan must account for the most aggressive or largest focus, or involve a strategy to treat for all present biologies. The presence of a triple-negative focus (negative for ER, PR, and HER2) alongside a hormone-positive focus, for instance, mandates a regimen targeting the triple-negative component, as it is typically more aggressive. Pathologists analyze the receptor status of each distinct invasive focus to guide treatment decisions.
This biological heterogeneity means systemic treatments must be highly specific to these receptors. The presence of a multifocal tumor does not automatically change the decision to use systemic therapy, but it does add complexity to selecting the most effective combination of treatments. The goal is to ensure that every population of cancer cells is targeted appropriately to prevent distant spread and recurrence.