Relationship Between Breast and Axillary Pathologic Complete Response According to Clinical Nodal Stage: A Nationwide Study From Korean Breast Cancer Society

Abstract

Purpose We evaluated the relationship between breast pathologic complete response (BpCR) and axillary pathologic complete response (ApCR) after neoadjuvant chemotherapy (NACT) according to nodal burden at presentation. As the indications for NACT have expanded, clinicians have started clinical trials for the omission of surgery from the treatment plan in patients with excellent responses to NACT. However, the appropriate indications for axillary surgery omission after excellent NACT response remain unclear. Methods Data were collected from patients in the Korean Breast Cancer Society Registry who underwent NACT followed by surgery between 2010 and 2020. We analyzed pathologic axillary nodal positivity after NACT according to BpCR stratified by tumor subtype in patients with cT1-3/N0-2 disease at diagnosis. Results A total of 6,597 patients were identified. Regarding cT stage, 528 (9.5%), 3,778 (67.8%), and 1,268 (22.7%) patients had cT1, cT2, and cT3 disease, respectively. Regarding cN stage, 1,539 (27.7%), 2,976 (53.6%), and 1,036 (18.7%) patients had cN0, cN1, and cN2 disease, respectively. BpCR occurred in 21.6% (n = 1,427) of patients, while ApCR and pathologic complete response (ypCR) occurred in 59.7% (n = 3,929) and ypCR 19.4% (n = 1,285) of patients, respectively. The distribution of biologic subtypes included 2,329 (39.3%) patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease, 1,122 (18.9%) with HR-positive/HER2-positive disease, 405 (6.8%) with HR-negative/HER2-positive disease, and 2,072 (35.0%) with triple-negative breast cancer . Among the patients with BpCR, 89.6% (1,122/1,252) had ApCR. Of those with cN0 disease, most (99.0%, 301/304) showed ApCR. Among patients with cN1-2 disease, 86.6% (821/948) had ApCR. Conclusion BpCR was highly correlated with ApCR after NACT. In patients with cN0 and BpCR, the risk of missing axillary nodal metastasis was low after NACT. Further research on axillary surgery omission in patients with cN0 disease is needed.

Factors Associated with Axillary Lymph Node Status in Clinically Node-Negative Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

“…Differences in the way subjects clinically defined cN0 and the biological subtypes included in subjects, the proportions achieving breast pCR varied widely for the overall ypN+ rates observed in each cN0 breast cancer patient undergoing NAC [ 25 , 26 , 27 , 34 , 35 , 36 , 37 , 38 ]. Murphy et al reported a ypN+ rate of 22% in patients registered in the National Cancer Database, without knowing whether axillary ultrasound was routinely performed [ 34 ].…”

“…A lower ypN+ rate of only 3.4% was observed in a prospective cohort study by Tadros et al in the cN0 subgroup that included only triple-negative and HER2-positive breast cancers [ 26 ]. In a study conducted by Ryu et al using the Korean Breast Cancer Society Registry database, all patients with cT1-3N0 were found to have a breast pCR rate of 19.7% and a ypN+ rate of 16.7% regardless of the biological subtype [ 38 ]. In our study, the low ypN+ rate of 7.7% could be explained by routine axillary ultrasound combined with ultrasound-guided fine needle aspiration or core needle biopsy to confirm cN0 status; nearly 60% of patients had triple-negative or HER2-positive breast cancer and all populations had a high probability of achieving breast pCR of 40.5% regardless of biological subtype.…”

“…Several studies have demonstrated a strong correlation between breast pCR and ALN negativity [ 26 , 27 , 35 , 36 , 37 , 38 ]. Extremely low ypN+ rates were consistently observed in a cohort of cN0 breast cancer patients with HER2-positive or triple-negative breast cancer who achieved breast pCR after NAC.…”

“…As for the ypN+ rate of the HR-postive/HER2-negative subtype, some related studies have shown that it is slightly higher than that of HER-2 and triple-negative subtypes, but this is still controversial. Barron et al and Samiei et al observed that the ypN+ rate of HR-postive/HER2-negative subtype was 4.5% and 6.7%, respectively [ 27 , 37 ]; in contrast, Ryu et al found that the ypN+ rate in the same subtype population was 0% [ 38 ]. In a retrospective study by Ryu et al, there were 647 cases of cT1-3 and cN0 breast cancer with HR-postive/HER2-negative subtype, of which 96 cases with breast pCR were confirmed to have no ALN metastasis, which is consistent with our findings [ 38 ].…”

“…Barron et al and Samiei et al observed that the ypN+ rate of HR-postive/HER2-negative subtype was 4.5% and 6.7%, respectively [ 27 , 37 ]; in contrast, Ryu et al found that the ypN+ rate in the same subtype population was 0% [ 38 ]. In a retrospective study by Ryu et al, there were 647 cases of cT1-3 and cN0 breast cancer with HR-postive/HER2-negative subtype, of which 96 cases with breast pCR were confirmed to have no ALN metastasis, which is consistent with our findings [ 38 ]. However, the inconsistency in results on HR-positive/HER2-negative subtype breast cancer could be caused by the lack of prospective studies so far.…”