Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance)

Abstract

Background. De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2? and triple-negative breast cancer (TNBC), respectively. Patients and Methods. A total of 760 patients with stage II-III HER2? or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status. Results. In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P \ 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P \ 0.0001). Conclusions. Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with \ 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials.

De-escalating Surgery Among Patients with HER2 + and Triple Negative Breast Cancer

“…In the study by Tadros et al, among patients with TN and HER2 positive breast cancer who achieved a pCR in the breast no disease was identified in the axillary lymph nodes [ 51 ]. Similar results of low risk of nodal positivity have also been shown in other reports [ 52 , 53 ]. In the largest of these studies by Barron et al, using the National Cancer Database and analyzing data from over 13,000 patients, the risk of nodal disease in patients with TN and HER2 positive cancer achieving pCR in the breast was 1.6% [ 54 •].…”

Triple negative breast cancer: Pitfalls and progress

“…Among the most important recent advances for TNBC patients is the use of neoadjuvant chemotherapy, which increases the percentage of patients eligible for breast cancer conservation surgery and for de-escalation of axillary surgery 55 . In CALGB 40603, among TNBC patients with pre-treatment clinically positive nodes, 67% had pathologic nodal clearance, potentially avoiding axillary node dissection 56 . The benefit of neoadjuvant chemotherapy is not only in surgical outcomes but also in the ability to tailor therapy based on pCR.…”

Persistent EGFR/K-RAS/SIAH pathway activation drives chemo-resistance and early tumor relapse in triple-negative breast cancer

“…Pathology following completion of NACT/NST, with or without immunotherapy (pembrolizumab), produces a binary response: pathologic complete response (pCR) or pathologic incomplete response (pIR) [40,41] . pCR is a reliable prognostic marker that correlates with tumor remission and long-term survival, whereas pIR is associated with an increased risk of early tumor relapse and poor prognosis [36,[42][43][44][45][46][47] .…”

“…pCR is a reliable prognostic marker that correlates with tumor remission and long-term survival, whereas pIR is associated with an increased risk of early tumor relapse and poor prognosis [36,[42][43][44][45][46][47] . Incomplete responders can be further classified by the residual cancer burden (RCB classes I-III); the higher the RCB classification, the higher the likelihood of tumor relapse and mortality [21,40,41,[48][49][50][51] . TNBC patients with high-risk and high-grade residual disease are now commonly treated with additional adjuvant chemotherapy, including capecitabine, which may be combined with immunotherapy (pembrolizumab) post-operatively [35,36,38,[52][53][54] .…”

“…Pathology following completion of NACT/NST, with or without immunotherapy (pembrolizumab), produces a binary response: pathologic complete response (pCR) or pathologic incomplete response (pIR) [ 40 , 41 ] . pCR is a reliable prognostic marker that correlates with tumor remission and long-term survival, whereas pIR is associated with an increased risk of early tumor relapse and poor prognosis [ 36 , 42 - 47 ] . Incomplete responders can be further classified by the residual cancer burden (RCB classes I-III); the higher the RCB classification, the higher the likelihood of tumor relapse and mortality [ 21 , 40 , 41 , 48 - 51 ] .…”