2652 - Analysis of Failure Risk Factors in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy: A Large Cohort Retrospective Study

H. Ababneh¹, G. E. Naoum², A. Niemierko³, and A. G. Taghian⁴; ¹Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ²Northwestern University McGaw Medical Center, Chicago, IL, ³Massachusetts General Hospital, Boston, MA, ⁴Harvard Medical School, Boston, MA

Purpose/Objective(s): To identify different risk factors associated with achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC), risk factors related to any failure after pCR, and to calculate the median time to any failure after pCR with and without regional nodal radiation (RNI) Materials/

Methods: Between 2000 and 2021, we retrospectively reviewed 1115 consecutive patients in a single institution database following NAC. Multivariable analysis was performed using the Cox proportional hazards model to identify the independent predictors of invasive disease-free survival (IDFS). IDFS was defined as the time from the date of diagnosis to the first event, either loco-regional failure (LRF) or distant failure. LRF includes ipsilateral recurrence in the breast, chest wall, or axilla. No cases received neoadjuvant RT. Whenever adjuvant RNI was indicated, conventional fractionation (45-50.4 Gy in 25-28 fractions) was used.
Results: The median follow-up was 8.0 years (IQR 4.1 – 12.4 years). After NAC, 274 patients (25%) achieved pCR in the breast, 750 (67%) had a partial response (PR), and 91 (8%) experienced disease progression (DP). For 552 patients with clinically node-positive disease confirmed by LN biopsy pre-NAC, 227 patients (41%) achieved pCR in the axilla, and 325 (59%) showed PR or DP. Notably, 209 patients (19%) achieved pCR in both the breast and axilla. Invasive ductal carcinoma (IDC) patients were more likely to achieve pCR than those with any invasive lobular carcinoma (ILC) in either the breast or axilla. The rates of pCR for IDC patients vs ILC patients were 25.8% vs 9.6% (p < 0.001) in the breast and 46% vs. 33.9% (p = 0.01) in the axilla, respectively. On multivariable analysis, the number of clinically positive LNs pre-NAC (HR= 1.09, p< 0.001) was identified as a significant predictor of IDFS among patients who achieved pCR in both the breast and axilla. Triple-negative disease was associated with higher hazards of IDFS; however, this did not achieve statistical significance (HR= 1.35, p = 0.08). Subgroup analysis of patients with clinically node-positive disease confirmed by LN biopsy pre-NAC, who achieved pCR in both the breast and axilla (n=117), revealed that the median time to IDFS after achieving pCR was 7.1 years for those receiving RNI (n=95) versus 7.8 years for those without RNI (n=22) (p=0.8).
Conclusion: In patients achieving pCR, our analysis revealed that a higher clinical nodal stage pre-NAC significantly predicts inferior IDFS. Our data also reveals that IDC patients are more likely to achieve a pCR in the breast or axilla post-NAC compared to those with any ILC. Additionally, we have shown that the median time to failure after achieving pCR, with or without adjuvant RNI, is approximately 7 years. This indicates the need to wait for mature results from the B51 trial, and further follow-up is required.