Tumor Biology Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients Presenting with Locally Advanced Breast Cancer

Abstract

Background Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset. The purpose of this study was to determine rates of pathologic complete response (pCR) in LABC patients and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery. Methods From 2006-2016, 1522 patients received NAC followed by surgery; 321 had advanced disease in the breast (cT4) and/or in the nodes (cN2/N3). pCR rates were assessed by T and N stage, and receptor subtype. Results Of 321 LABC patients, 223 were cT4, 77 cN2, and 82 cN3. 43% were hormone receptor (HR)+/HER2-, 23% triple negative, and 34% HER2+. The overall pCR rate was 25% and differed by receptor subtype (HR+/HER2- 7%; triple negative 23%; HER2+ 48%;p<0.001). Breast pCR occurred in 27% and was similar in T4 vs. non-T4 disease (29% vs. 22%,p=0.26). Nodal pCR was achieved in 38% of cN+ patients and did not differ by nodal stage (cN1 43%, cN2 36%, cN3 32%; p=0.23). Nodal pCR was significantly more common than breast pCR (p=0.014) across all tumor subtypes. Receptor subtype was the only predictor of overall pCR (p<0.001). Conclusion In patients with LABC, pCR after NAC was seen in 25%, and did not differ by T or N stage. Tumor biology, but not extent of disease, predicted pCR. Studies assessing feasibility of surgical downstaging with NAC in LABC patients are warranted.

Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: Are we ready to endorse axillary conservation?

“…On multivariate analysis, receptor subtype remained the only significant predictor of overall pCR ( P = 0.02). In line with recent reports the highest pCR rates in our series were achieved in Her2+ and TN tumors (59.5% and 29% respectively). In light of the impact of tumor subtype on the achievement of pCR, the need for breast surgery is being questioned in Her2+ and TN tumors, when a post NAC biopsy indicates a breast pCR, and clinical trials are currently ongoing, in which breast surgery is omitted in patients with these tumor subtypes and documented breast pCR .…”

“…We confirm a correlation between BC subtypes and axillary pCR in a consecutive series of cN+ patients who received NAC and surgery at our Institutions. Overall pCR was achieved in almost one third of patients, in line with recent reports . Luminal A tumors never achieved a pCR.…”

“…An important issue is the influence of tumor biology on pCR. Receptor subtype, as assessed by immunohistochemistry on pre‐NAC biopsies, can predict the response of BC to NAC . In our series, the overall pCR rate was significantly correlated only with receptor subtype and nuclear grading of the tumors ( P = 0.01).…”

“…According to literature, pathologic complete response (pCR) rates have improved, occurring in 33%‐37% of cases in the breast and in 20%‐61% in the nodes, with variation based on tumor subtypes. While the achievement of breast pCR improves the rate of breast‐conserving surgery, it has been suggested that nodal pCR could reduce the need for axillary dissection (ALND) in pre‐NACT clinically node‐positive patients, particularly in HER2+ disease …”

Neo‐adjuvant chemotherapy and axillary de‐escalation management for patients with clinically node‐negative breast cancer

“…The research of our center22 found that the rates of axillary lymph node pCR (apCR) after NAC in clinically node positive (cN + ) patients with HER2+ (with targeted therapy) and TN were 58.6% and 53.2%, respectively, which were significantly higher than that in HR+/HER2− patients (21.2%, P < 0.001). Gentile et al23 and Kantor et al 24 also reached the same results. According to apCR situation in cN + patients, we deduced that ALNs occult metastasis had lower ypN0 after NAC in the initial cN0 patients with HR+/HER2− subtype than those with TN and HER2+ (with targeted therapy) subtypes.…”