Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27

Abstract

Purpose: The limited information on predictors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NC) has resulted in controversy about the optimal use of adjuvant radiotherapy and the timing of sentinel lymph node biopsy.

Patients and methods: We examined patterns and predictors of LRR as first event in combined analysis of two National Surgical Adjuvant Breast and Bowel Project (NSABP) neoadjuvant trials. NC was either doxorubicin/cyclophosphamide (AC) alone or AC followed by neoadjuvant/adjuvant docetaxel. Lumpectomy patients received breast radiotherapy alone; mastectomy patients received no radiotherapy. Pathologic complete response was defined as the absence of invasive tumor in the breast. Multivariate analyses were used to identify independent predictors of LRR. The primary end point was time to LRR as first event.

Results: In 3,088 patients, 335 LRR events had occurred after 10 years of follow-up. The 10-year cumulative incidence of LRR was 12.3% for mastectomy patients (8.9% local; 3.4% regional) and 10.3% for lumpectomy plus breast radiotherapy patients (8.1% local; 2.2% regional). Independent predictors of LRR in lumpectomy patients were age, clinical nodal status (before NC), and pathologic nodal status/breast tumor response; in mastectomy patients, they were clinical tumor size (before NC), clinical nodal status (before NC), and pathologic nodal status/breast tumor response. By using these independent predictors, groups at low, intermediate, and high risk of LRR could be identified. Nomograms that incorporate these independent predictors were created.

Conclusion: In patients treated with NC, age, clinical tumor characteristics before NC, and pathologic nodal status/breast tumor response after NC can be used to predict risk for LRR and to optimize the use of adjuvant radiotherapy.

Fig 1.

CONSORT diagram for National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and B-27 trials. AC, doxorubicin/cyclophosphamide; LLR, locoregional recurrence.

Fig 2.

Ten-year cumulative incidence of locoregional recurrence (LRR) in patients (A) age ≥ 50 years treated with lumpectomy plus breast external radiotherapy (XRT) and (B) younger than age 50 years treated with lumpectomy plus breast XRT. IBTR, ipsilateral breast tumor recurrence; pCR, pathologic complete response [after neoadjuvant chemotherapy]; ypN, pathologic nodal status [after neoadjuvant chemotherapy].

Fig 3.

Ten-year cumulative incidence of locoregional recurrence (LRR) in patients with (A) ≤ 5-cm tumors treated with mastectomy and (B) > 5-cm tumors treated with mastectomy. pCR, pathologic complete response [after neoadjuvant chemotherapy]; ypN, pathologic nodal status [after neoadjuvant chemotherapy].

Fig 4.

Nomogram to predict 10-year risk of locoregional recurrence (LRR) in patients treated with (A) lumpectomy plus breast external radiotherapy (XRT) after neoadjuvant chemotherapy or (B) mastectomy after neoadjuvant chemotherapy. cN, clinical nodal status [before neoadjuvant chemotherapy]; pCR, pathologic complete response [after neoadjuvant chemotherapy]; ypN, pathologic nodal status [after neoadjuvant chemotherapy].

Fig A1.

Ten-year cumulative incidence of locoregional recurrence (LRR) in pathologically node-positive patients (A) age ≤ 50 years treated with lumpectomy plus breast external radiotherapy (XRT) according to number of positive nodes; (B) age ≥ 50 years treated with lumpectomy plus breast XRT according to number of positive nodes; (C) with tumors ≤ 5 cm treated with mastectomy according to number of positive nodes; (D) with tumors > 5 cm treated with mastectomy according to number of positive nodes.