Agreement: 
I Agree
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Dear Editor

With regard to the results of the meta-analysis reported by Conforti et al.[1], whether pathological complete response could serve as a surrogate endpoint in regulatory neoadjuvant trials of early-stage breast cancer is a meaningful issue worthy of attention and discussion. In this meta-analysis of 54 studies with 32611 participants, the authors found that pathological complete response (pCR) should not be used as a primary endpoint in regulatory neoadjuvant trials of early-stage breast cancer. The authors are to be praised for their research included a substantial number of patients, which provided sufficient statistical power to detect associations. Nevertheless, there are still some issues that need to be further explored.

Potential effects of histological type and tumour grade on the correlation between pCR and long-term patients’ outcomes should not be ignored. A previous meta-analysis reported that the association between pCR and the long-term outcome was stronger in patients with high-grade tumours than in those with low-grade tumours [2]. Another pooled analysis of 6,377 patients also highlighted the potential effect of histological type and tumour grade on the correlation between the two [3]. They observed that pCR was predictive for DFS and OS in ductal or other histologic types and grade 2 or 3 tumours, but neither DFS nor OS in subgroups associated with lobular type and grade 1 tumours [3]. Given this, we suggest that the authors divide the included patients into different subgroups based on tumour histological type and grade and then perform a meta-analysis of each subgroup.

Nevertheless, we are grateful to the authors for their efforts in studying the association between pCR and long-term outcomes in patients with early-stage breast cancer.

Competing interests: None declared.

1. Conforti F, Pala L, Sala I, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ 2021;375:e066381. doi: 10.1136/bmj-2021-066381
2. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8 [published Online First: 2014/02/18]
3. von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595 [published Online First: 2012/04/18]

No competing Interests: 
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The following competing Interests: 
Electronic Publication Date: 
Wednesday, December 29, 2021 – 11:56
Workflow State: 
Released
Full Title: 

Re: Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis

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Last Name: 
Wang
First name and middle initial: 
Bolin
Address: 
Chengdu, 610041, China
Occupation: 
PhD student
Other Authors: 
Jimming Yu
Affiliation: 
Lung Cancer Center, West China Hospital, Sichuan University
BMJ: Additional Article Info: 
Rapid response