Is mastectomy (MRM) still needed for a patient with stage 3A HER2 (Human Epidermal growth factor Receptor 2)-positive breast cancer with a non-delineated mass after 8 cycles of chemotherapy?

Management of Stage 3A HER2-Positive Breast Cancer with Non-delineated Mass After Chemotherapy

Modified radical mastectomy (MRM) is still recommended for stage 3A HER2-positive breast cancer with a non-delineated mass after neoadjuvant chemotherapy to ensure complete removal of residual disease and optimize survival outcomes.

Rationale for Mastectomy in This Case

The presence of a non-delineated mass after 8 cycles of chemotherapy indicates:

1. Residual disease persistence: Non-delineated masses represent incomplete response to neoadjuvant therapy, suggesting chemoresistant disease that requires definitive surgical removal 1.

2. Stage 3A disease characteristics: Stage 3A HER2-positive breast cancer is considered locally advanced, and the NCCN guidelines recommend mastectomy with axillary lymph node dissection for optimal local control in such cases 1.

3. Limited breast conservation options: Breast-conserving surgery is not considered a standard approach for stage 3A disease, particularly when the mass remains non-delineated after chemotherapy 1.

Treatment Algorithm for This Patient

1. Complete surgical removal via MRM

   • Modified radical mastectomy with axillary lymph node dissection is the preferred approach
   • Non-delineated masses after chemotherapy indicate poor response and higher risk of local recurrence if less aggressive surgery is attempted

2. Post-mastectomy adjuvant therapy

   • Complete 1 year of HER2-targeted therapy (trastuzumab) if not completed preoperatively 1
   • Consider trastuzumab emtansine (T-DM1) if there is residual invasive disease after neoadjuvant therapy 2
   • Post-mastectomy radiation therapy to chest wall and regional lymph nodes 1

3. Continued HER2-targeted therapy

   • If the patient has already received pertuzumab/trastuzumab in the neoadjuvant setting, continue HER2-targeted therapy to complete a full year 1
   • Consider switching to T-DM1 if significant residual disease is found at surgery 2

Evidence Supporting This Recommendation

The NCCN guidelines specifically state that for stage 3A disease, "local therapy after a complete or partial response to preoperative systemic therapy is usually mastectomy" when lumpectomy is not possible 1. The non-delineated nature of the mass indicates that lumpectomy would not be feasible in this case.

For HER2-positive disease with residual tumor after neoadjuvant therapy, the KATHERINE trial demonstrated that switching to T-DM1 significantly improved invasive disease-free survival compared to continuing trastuzumab (HR 0.50; 95% CI, 0.39-0.64) 2.

Important Considerations

• Residual disease assessment: The pathological evaluation of the mastectomy specimen will guide further treatment decisions, particularly whether to switch to T-DM1 2.

• Radiation therapy requirement: Post-mastectomy radiation therapy is strongly recommended for stage 3A disease to reduce local recurrence risk 1.

• Continued systemic therapy: HER2-targeted therapy should be continued for a total of one year to optimize survival outcomes 1.

• Common pitfall: Attempting breast conservation in the setting of a non-delineated mass after neoadjuvant therapy may lead to positive margins and increased risk of local recurrence.

In conclusion, while breast-conserving approaches are increasingly used in breast cancer treatment, the presence of a non-delineated mass after neoadjuvant chemotherapy in stage 3A HER2-positive disease strongly indicates the need for mastectomy to ensure complete tumor removal and optimize long-term survival outcomes.