|LETTER TO EDITOR
|Year : 2022 | Volume
| Issue : 1 | Page : 150-151
Pathological complete response in locally advanced breast cancer after neoadjuvant chemotherapy: Hope or hype
Reshu Agarwal1, Vijaykumar Dehannathparambil Kottarathil2
1 Prakhar Cancer Clinic, Kanpur, Uttar Pradesh, India
2 Amrita Centre for Breast Diseases, Amrita Institute of Medical Science, Kochi, Kerala, India
|Date of Submission||15-Jan-2022|
|Date of Decision||25-Jan-2022|
|Date of Acceptance||25-Jan-2022|
|Date of Web Publication||31-Mar-2022|
Vijaykumar Dehannathparambil Kottarathil
Amrita Centre for Breast Diseases, Amrita Institute of Medical Sciences and Research Center, Kochi - 682 041, Kerala
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Agarwal R, Kottarathil VD. Pathological complete response in locally advanced breast cancer after neoadjuvant chemotherapy: Hope or hype. Cancer Res Stat Treat 2022;5:150-1
|How to cite this URL:|
Agarwal R, Kottarathil VD. Pathological complete response in locally advanced breast cancer after neoadjuvant chemotherapy: Hope or hype. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 21];5:150-1. Available from: https://www.crstonline.com/text.asp?2022/5/1/150/341284
Choudhary et al. have presented the clinicopathological factors associated with pathological complete response (pCR) and its effect on disease-free survival (DFS) and overall survival (OS) in Indian women with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT). The authors have extensively documented the variation in pCR rate by hormone receptor and human epidermal growth factor receptor 2 (HER2) status of the tumor, and the improvement in the survival outcomes with the achievement of pCR. The results of the study by Chaudhary et al. are similar to earlier studies. As stated by Badwe et al., this study only provides additional confirmation of what we already know about the role of NACT in LABC. However, the authors have not attempted to test the strength of correlation of pCR as a surrogate for survival.
Choudhary et al. have stated that very few Indian studies have assessed the response to NACT in patients with LABC. The authors further go on to state that factors predictive of pCR and the role of pCR as a prognostic factor for survival are yet to be identified. In addition to the studies cited by Choudhary et al., other large studies have reported the predictors for pCR and the factors that determine prognosis in LABC in the Indian population.
The study by Agarwal et al. is one of the few Indian studies which has not only evaluated the survival outcomes in patients with pCR in LABC after NACT but has also discussed the relevance of using pCR as the surrogate endpoint.
It is well established that the achievement of pCR at the time of surgery reported as ypT0/is ypN0 is associated with a favorable outcome. However, its use as a surrogate endpoint is still controversial. von Minckwitz et al. demonstrated pCR to be a reasonable surrogate endpoint in luminal B/HER2−, ER/PR/HER2+, and TNBC subtype but not in luminal B/HER2+ or luminal A tumors. Agarwal et al. demonstrated that although pCR is a good prognosticator, its accuracy is not 100% even in luminal B/HER2−, ER/PR/HER2+, and TNBC subtypes. They reported that at recurrence, the survival was similar in the pCR and non-pCR cohorts, reflecting the failure of NACT in these patients despite achieving pCR.
Agarwal et al. evaluated the validity of using pCR as a surrogate endpoint using regression analysis. The R2 value for pCR as a surrogate for DFS was 0.006 (P = 0.294) and OS was 0.004 (P = 0.407) suggesting minimal association between pCR and survival. Conforti et al. also reported a weak association between the pCR rate and both DFS (R2 = 0.14, 95% confidence interval [CI], 0.00–0.29) and OS (R2 = 0.08, 95% CI, 0.00–0.22). The authors demonstrated similar results across all subgroups evaluated, independent of the definition used for pCR, treatment type in the experimental arm, and biological features of the disease.
Thus, we conclude that although pCR is a favorable prognostic factor and helps clinicians in tailoring (escalating/de-escalating) treatment in individual patients, its use as a surrogate endpoint in clinical trials is still a debatable issue. The current evidence does not demonstrate a strong association between the pCR and survival. This issue should be addressed in future studies on pCR.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Choudhary P, Gogia A, Deo SV, Sharma D, Mathur SR, Batra A, et al.
Correlation of pathological complete response with outcomes in locally advanced breast cancer treated with neoadjuvant chemotherapy: An ambispective study. Cancer Res Stat Treat 2021;4:611-20. [Full text]
Conforti F, Pala L, Sala I, Oriecuia C, De Pas T, Specchia C, 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.
Badwe RA, Parmar V, Nair NS. Predicting pathological complete response post neoadjuvant chemotherapy and personalizing therapy in breast cancer. Cancer Res Stat Treat 2021;4:726-7. [Full text]
Agarwal R, Unnikrishnan UG, Keechilat P, Rajanbabu A, Jose W, Vijaykumar DK. Pathological complete response in locally advanced breast cancer after neoadjuvant chemotherapy: Survival outcome and its relevance as a surrogate end point. South Asian J Cancer 2020;9:136-40.
von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al.
Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012;30:1796-804.