Ten-Year Outcomes of Patients With Breast Cancer With Cytologically Confirmed Axillary Lymph Node Metastases and Pathologic Complete Response After Primary Systemic Chemotherapy

Abstract

Importance: The long-term effect of axillary pathologic complete response (pCR) on survival among women with breast cancer treated with primary systemic chemotherapy (PST) is unknown.

Objective: To assess the long-term effect of axillary pCR on relapse-free survival (RFS) and overall survival (OS) in women with breast cancer with cytologically confirmed axillary lymph node metastases treated with PST.

Design, setting, and participants: We retrospectively analyzed the effect of axillary pCR on 10-year OS and RFS among all women who received a diagnosis of breast cancer stages II to III with cytologically confirmed axillary metastases between 1989 and 2007 who received PST at a large US comprehensive cancer center. Women were stratified by post-PST axillary status, and survival outcomes were estimated and compared according to response in the breast and axilla.

Main outcomes and measures: Outcomes of interest were RFS and OS.

Results: Of 1600 women treated, median (range) age at diagnisis was 49 (21-86) years. A total of 454 (28.4%) achieved axillary pCR. These patients were more likely to have human epidermal growth factor receptor 2 (HER2)-positive and triple-negative disease (P < .001), pCR in the breast (P < .001), high-grade tumors (P < .001), and lower clinical and pathologic T stage (P = .002). Ten-year OS rates were 84% (95% CI, 79%-88%) and 57% (95% CI, 54%-61%) (P < .001) and 10-year RFS rates 79% (95% CI, 74%-83%) and 50% (95% CI, 46%-53%) (P < .001) for patients with axillary pCR and residual axillary disease, respectively. For patients with axillary pCR, 10-year OS rates were 90% (95% CI, 84%-94%) for those with breast pCR and 72% (95% CI, 61%-80%) for those with residual breast disease (P < .001). For patients with residual axillary disease, 10-year OS rates were 66% (95% CI, 56%-74%) for patients with and 56% (95% CI, 52%-60%) for patients without breast pCR (P = .02). Of patients receiving HER2-targeted therapy for HER2-positive disease, 67.1% (100 of 149) achieved axillary pCR; 10-year OS rates were 92% (95% CI, 84%-96%) and 57% (95% CI, 20%-82%) (P = .003) and 10-year RFS rates 89% (95% CI, 81%-94%) and 44% (95% CI, 18%-68%) (P < .001) for those with axillary pCR and residual axillary disease, respectively.

Conclusions and relevance: Axillary pCR was associated with improved 10-year OS and RFS. Patients with axillary and breast pCR after PST had superior long-term survival outcomes. Patients undergoing HER2-targeted therapy for HER2-positive disease had high rates of axillary pCR, and those with axillary pCR had excellent 10-year OS.

Figure 1

A. Overall Survival in all patients by pathologic lymph node status. Overall survival in all patients stratified by response to primary systemic therapy (PST) in the axilla. Pathologic complete response (pCR) in the axilla is in green, and residual axillary disease is in red. The number of patients at risk is indicated under the x-axis. B. Relapse Free Survival in all patients by pathologic lymph node status. Relapse-free survival in all patients stratified by response to PST in the axilla. pCR in the axilla is in green, and residual axillary disease is in red. The number of patients at risk is indicated under the x-axis.

Figure 2

A. Overall Survival by pathologic response to PST in axilla and breast. Overall survival in patients stratified by response to PST in the axilla and the breast. pCR in both the axilla and breast is in green, pCR in the axilla but residual disease in the breast is in red, residual disease in the axilla but pCR in the breast is in blue, and residual disease in both the breast and axilla is in black. The number of patients at risk is indicated under the x-axis. B. Relapse Free Survival by pathologic response to PST in axilla and breast. Relapse-free survival in patients stratified by response to PST in the axilla and the breast. pCR in both the axilla and breast is in green, pCR in the axilla but residual disease in the breast is in red, residual disease in the axilla but pCR in the breast is in blue, and residual disease in both the breast and axilla is in black. The number of patients at risk is indicated under the x-axis.

Figure 3

A. Overall Survival by pathologic lymph node status for HER2-positive breast cancer receiving HER2-targeted therapy Overall survival in patients with HER2-positive breast cancer receiving HER2-targeted therapy. pCR in the axilla is in green, and residual axillary disease is in red. The number of patients at risk is indicated under the x-axis. B. Relapse Free Survival by pathologic lymph node status for HER2-positive breast cancer receiving HER2-targeted therapy Relapse-free survival in patients with HER2-positive breast cancer receiving HER2-targeted therapy. pCR in the axilla is in green, and residual axillary disease is in red. The number of patients at risk is indicated under the x-axis.

Figure 3

A. Overall Survival by pathologic lymph node status for HER2-positive breast cancer receiving HER2-targeted therapy Overall survival in patients with HER2-positive breast cancer receiving HER2-targeted therapy. pCR in the axilla is in green, and residual axillary disease is in red. The number of patients at risk is indicated under the x-axis. B. Relapse Free Survival by pathologic lymph node status for HER2-positive breast cancer receiving HER2-targeted therapy Relapse-free survival in patients with HER2-positive breast cancer receiving HER2-targeted therapy. pCR in the axilla is in green, and residual axillary disease is in red. The number of patients at risk is indicated under the x-axis.