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Table of Contents
EDITORIAL
Year : 2021  |  Volume : 4  |  Issue : 4  |  Page : 726-727

Predicting pathological complete response post neoadjuvant chemotherapy and personalizing therapy in breast cancer


Department of Surgical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission04-Dec-2021
Date of Decision07-Dec-2021
Date of Acceptance08-Dec-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Rajendra A Badwe
Tata Memorial Center, Homi Bhabha National Institute, Dr. E. Borges Road, Parel, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_310_21

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How to cite this article:
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

How to cite this URL:
Badwe RA, Parmar V, Nair NS. Predicting pathological complete response post neoadjuvant chemotherapy and personalizing therapy in breast cancer. Cancer Res Stat Treat [serial online] 2021 [cited 2022 May 28];4:726-7. Available from: https://www.crstonline.com/text.asp?2021/4/4/726/334232



Locally advanced cancers constitute 40%–45% of new breast cancer cases in India. Neoadjuvant chemotherapy (NACT) is often the first line of treatment to downstage the tumor making it amenable to resection or breast conserving surgery in few patients. However, NACT has had no known impact on survival. Over the years, many studies have shown that responsiveness to chemotherapy in specific subtypes such as HER2/neu-positive and triple-negative breast cancer (TNBC), also offers prognostic information. Predicting pathological complete response (pCR) may thus help utilize resources efficiently, avoid expensive chemotherapy and result in appropriate treatment planning. Although pCR is often considered a surrogate marker for outcome after NACT, this is not true for all subtypes of breast cancer.

A study reported by Choudhary et al.[1] aimed to identify the clinicopathological factors associated with pCR and the factors, including pCR, affecting disease-free survival (DFS) and overall survival (OS) among 425 Indian women with locally advanced breast cancer (LABC) diagnosed and treated between 2013 and 2019. The study reported that following NACT, pCR was achieved in 99 (23.3%) cases, with the highest rates achieved among patients with TNBC and HER-2/neu positive tumors, compared to those with hormone receptor-positive tumors. TNBC had an adjusted odds ratio (aOR) of 4.58 (95% confidence interval [CI], 2.20–9.53); hormone receptor-negative and HER2-positive tumors had aOR of 3.93 (95% CI, 1.66–9.27); hormone receptor-positive and HER2-positive tumors had aOR of 2.78 (95% CI, 1.20–6.44). Attainment of pCR after NACT within a subtype was associated with an improvement in the DFS and OS, particularly in patients with HER-2/neu positive and TNBC tumors.

The authors go on to state that very few Indian studies have reported the response to NACT in patients with LABC; they also state that the reported pCR rates have varied widely from 8%-36%.[2],[3],[4],[5],[6] They also mention that factors predictive of pCR and the role of pCR as a prognostic factor for survival have yet to be identified. In addition to studies cited by Choudhary et al., some other large cohorts have reported the predictors for pCR and prognostic information in LABC in the Indian population.[7],[8] What emerges uniformly from all studies is that response rate is inversely proportional to the tumor size, hormone receptor negativity and HER-2/neu positivity (provided the patients are treated with trastuzumab). It is also evident that hormone receptor positive tumors fall short in responding to chemotherapy. Since there is no survival advantage with chemotherapy (when compared to primary surgery with adjuvant chemotherapy), it may be most appropriate to limit chemotherapy cycles to a number just enough to make the tumor amenable to desired surgery and to continue chemotherapy until completion in responders or until maximum response is achieved.

Various clinical, biological, imaging, and molecular factors, as well as gene-expression signatures have been evaluated as the effective predictors of chemotherapy response. It is interesting to note that not much has changed over the past decade despite the changing landscape of systemic therapy. The authors present results similar to those published previously, wherein, younger age, younger age, lower clinical stage and estrogen and progresterone- negative tumors, and the use of targeted therapy have been shown to better the response rates. This study only revalidates and confirms what we already know about the response to NACT in LABC.

The authors have also reported on the impact of pCR on DFS and OS in Indian women with LABC with a 5-year DFS of 52.7%. Improvement in systemic therapy over time has led to a remarkable change in the 5-year DFS from hormone receptor-positive and HER2-positive tumors 37% as reported by previous studies[7] to 52.7% in the current study. However, the results reported by the authors are a projected estimate of DFS and OS, as the median follow-up in this cohort was only 16.2 months.

Although pCR within a subtype has a good correlation with clinical outcomes and prognosis, the association between pCR and survival between various subtypes is not yet clear. For instance, patients with TNBC with residual disease after NACT have worse survival than those with luminal subtypes, yet some of them do not relapse for a long time. Yu et al.[9] reported on the 7-gene signature for patients with TNBC with residual disease and different prognosis to molecularly define the clinically relevant subgroups.

So where do we stand today? There is irrefutable randomized evidence that NACT is no different compared to adjuvant chemotherapy and pCR is a good prognosticator but not the evidence of efficacy of NACT. Additionally, a poor response to chemotherapy in patients with hormone responsive tumors further confirms that NACT and duration of time to complete NACT may be detrimental to the outcome and we should rethink on wasting time and resources on ineffective treatment in hormone responsive tumors.



 
  References Top

1.
Choudhary P, Gogia A, Deo SVS, 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.  Back to cited text no. 1
  [Full text]  
2.
Mukherjee P, Sharma S, Sheikh ZA, Vijaykumar DK. Correlation of clinico-pathologic and radiologic parameters of response to neoadjuvant chemotherapy in breast cancer. Indian J Cancer 2014;51:25-9.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK, Sharma DN. Taxane and anthracycline based neoadjuvant chemotherapy for locally advanced breast cancer: Institutional experience. Asian Pac J Cancer Prev 2014;15:1989-92.  Back to cited text no. 3
    
4.
Agrawal S, Banswal L, Saha A, Arun I, Datta SS, Chatterjee S, et al. Progesterone receptors, pathological complete response and early outcome for locally advanced breast cancer – A single centre study. (PPLB-01). Indian J Surg Oncol 2016;7:397-406.  Back to cited text no. 4
    
5.
Sivasanker M, Sistla SC, Manwar SA, Vivekanandam S. Clinical and pathologic response following taxane based neoadjuvant chemotherapy in locally advanced breast cancer patients in a tertiary care centre in India. Indian J Cancer 2016;53:220-5.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Narendra H, Thomas J, Ray S, Fernandes DJ. An analysis of response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer with emphasis on pathological complete response. Indian J Cancer 2014;51:587-92.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Parmar V, Krishnamurthy A, Hawaldar R, Nadkarni MS, Sarin R, Chinoy R, et al. Breast conservation treatment in women with locally advanced breast cancer – Experience from a single centre. Int J Surg 2006;4:106-14.  Back to cited text no. 7
    
8.
Parmar V, Nair NS, Badwe RA, Hawaldar R, Shet T, Desai S. Pathological complete response in locally advanced breast cancer: Determinants and predictive significance. Natl Med J India 2012;25:132-6.  Back to cited text no. 8
    
9.
Yu KD, Zhu R, Zhan M, Rodriguez AA, Yang W, Wong S, et al. Identification of prognosis-relevant subgroups in patients with chemoresistant triple-negative breast cancer. Clin Cancer Res 2013;19:2723-33.  Back to cited text no. 9
    



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