Time from Completion of Neo‐adjuvant Chemotherapy to Surgery: Effects on Outcomes in Breast Cancer Patients

Abstract

There is no consensus on the ideal time interval between the completion of neo‐adjuvant chemotherapy (NAC) and definitive surgery for patients with breast cancer. This study sought to determine the ideal time interval from completion of systemic therapy to surgery in an attempt to define a best practice. A retrospective analysis of all patients undergoing NAC for Stage I‐III breast cancer from 1998‐2010 was undertaken. Analysis of all demographic and clinical information was performed, with emphasis on interval from completion of systemic therapy to definitive surgical management. Three hundred and eighty eight patients met the inclusion criteria with a median age of 50 (61.9% white, 33.8% black and 4.3% other). Overall, 2.8% of patients were Stage I, 57.2% Stage II and 40% Stage III. Median follow‐up was 85 months. Pathologic response to systemic therapy was complete in 20.6%, partial in 67.8% and no response or progression in 11.6%; responders (pCR or pPR) were noted to have significantly improved Disease free survival (DFS) and Overall survival (OS). Patients undergoing surgical intervention 4‐6 weeks after completion of NAC were noted to have a trend towards improved DFS and OS on multivariable analysis. These findings were also observed in the nonlinear relationship between survival risk and surgery time window using martingale residual plots. Timing of surgical intervention following the receipt of NAC may not appear to affect DFS or OS.

The relationship between time to surgery after neoadjuvant chemotherapy and survival in breast cancer patients:a meta-analysis

“…In our subgroup analysis ,patients who received surgery with TTS > 4 weeks had a worse prognosis.Using TTS < 4 weeks as a reference time interval,the pooled HRs for OS and DFS/RFS were 1.39 (95%CI:1.18-1.63) and1.33(95%CI:1.16-1.53),respectively. In terms of DFS/RFS, as shown in gure 5, there was no different in the patients who underwent surgery in 4-6weeks or > 6 weeks,the combined HRs were 1.24 (95CI%:0.69-2.22,I 2 =92.8%) and 1.84 (95CI%:0.89-3.79,I 2 =81.2%),respectively,and the differences did not reach statistical signi cance.As for OS,the pooled HRs for the breast cancer patients who underwent surgery with TTS 4-6weeks and > 6 weeks were 0.87(95%CI: 0.67-1.10) and 1.34 ((95%CI:1.04-1.71),respectively.As can be seen,two studies explored the relationship between TTS 4-6 weeks and OS [13,18], the pool HR revealed that patients with TTS 4-6 weeks reduced in the risk of death by 13%,with no signi cant heterogeneity(I 2 =0%,P=0.69),while the difference was not statistically signi cant,so the results should be interpreted cautiously.The pooled HR for the breast cancer patients who underwent surgery with TTS > 8 weeks were 1.49(95%CI: 1.05-2.12,I 2 =0%),and this difference was statistically signi cant( gure 4).…”

“…Data synthesis:A total of four hundred and ve potentially relevant publications were found according to our initial search strategy,one hundred and sixteen publications from PubMed/Medline,two hundred and eighty-nine publications from Embase.There were three hundred and one publications after duplicate publications were removed;of these,we excluded two hundred and sixty-eight articles because the title or abstract did not meet the eligibility criteria.Eight systematic reviews,four studies on metastatic breast cancer,and eleven non-neoadjuvant chemotherapy were further excluded. Eventually,nine studies were identi ed as eligible for our analysis,including nine independent studies for OS [11][12][13][14][15][16][17][18][19],six studies for RFS [11,12,[15][16][17][18],and three for DFS [13,14,19].The ow chart of the literature search and study selection is shown in gure 1. Subsequently,subgroup analysis was performed based on different time intervals.…”

“…Previous guidelines indicated that 2-4 weeks after NAC might be the best timing of surgery [25],the studies by Cletus Arciero [13]and RachelA.Sanford [18] demonstrated that a longer TTS was connected with a worse prognosis,compared with TTS < 8 weeks,the combined HR for OS was 1.49 (95%CI:1.05-2.12,P=0.025, gure 4),whether these conclusions were related to a longer waiting time would lead to tumor growth.Ladd J. Turner and his colleagues compared the size of the tumor on USS-6 and the pathology report to explore whether delayed surgery after NAC would lead to an increase in tumour size,and then they found that there were not apparent growth in tumor size between TTS< 6-weeks and TTS > 6-weeks [26],Wagner, Jamie L et al also found the same conclusion in their study [27].…”

Management of early-stage breast cancer patients during the coronavirus disease 2019 (COVID-19) pandemic: The experience in China from a surgical standpoint

“…Another important issue is the management of patients who have currently completed neoadjuvant therapy and are waiting for surgery. Although many studies have suggested that delayed surgical treatment could lead to poor prognosis in breast cancer patients, the delay between neoadjuvant therapy and surgery has been ignored by many prospective clinical trials of neoadjuvant chemotherapy [31,34]. At present, the physical condition of patients receiving neoadjuvant therapy needs 2 to 3 weeks to recover from the toxic reactions of neoadjuvant regimens, therefore surgery is typically performed during this time.…”

“…However, the influence of delayed surgery on prognosis of breast cancer patients was unclear. Retrospective studies showed that an interval of less than 3 weeks tended to improve the prognosis of breast cancer patients, and an interval of less than 6 weeks did not affect RFS (relapse-free survival), LRFS (locoregional recurrence-free survival) or OS in breast cancer patients [34][35][36]. Therefore, patients receiving neoadjuvant chemotherapy should undergo surgery as soon as possible.…”