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LETTER TO THE EDITOR
Year : 2019  |  Volume : 8  |  Issue : 4  |  Page : 210-211

The evolving role of pathologic complete response in breast cancer


Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

Date of Web Publication22-Oct-2019

Correspondence Address:
Dr. Nisha Hariharan
Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sajc.sajc_67_19

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How to cite this article:
Hariharan N, Rao T S. The evolving role of pathologic complete response in breast cancer. South Asian J Cancer 2019;8:210-1

How to cite this URL:
Hariharan N, Rao T S. The evolving role of pathologic complete response in breast cancer. South Asian J Cancer [serial online] 2019 [cited 2019 Dec 9];8:210-1. Available from: http://journal.sajc.org/text.asp?2019/8/4/210/269709

Dear Editor,

The concept of pathologic complete response (pCR) has been an enigmatic one, often at the center of much debate and controversy. While most researchers would agree that the absence of residual invasive carcinoma in the breast and axilla is imperative in defining pCR, the impact of residual in situ tumor is still debated. The current AJCC 8th Edition defines pCR as the absence of any residual invasive carcinoma in the breast/axilla/lymph vessels. The presence of in situ tumor in the absence of invasive carcinoma still constitutes a pCR.[1]

From the early studies onward, pCR showed great promise in its ability to predict outcomes after chemotherapy. This association was strongest in aggressive biology tumors, such as triple-negative and HER2-positive cancers.[2] Researchers surmised that pCR could potentially be a surrogate marker for survival. Based on its ability to improve pCR rates,[3] pertuzumab was the first drug to receive accelerated approval from the Food and Drug Administration in 2013. The corresponding adjuvant trial (APHINITY) demonstrated only a marginal improvement in disease-free survival (94.1% vs. 93.2%, P = 0.045) in its early analysis, and further maturing of data is awaited. Along similar lines, addition of lapatinib improved pCR rates significantly; however, in the adjuvant setting, it failed to impact survival outcomes.[4],[5] The CTNeoBC meta-analysis [6] funded by the US-FDA confirmed the prognostic value of pCR, especially in aggressive tumor subtypes; however, it could not validate pCR as a surrogate endpoint for survival.

Following this, pCR continued to simmer for a while and found its clinical application in its ability to prognosticate aggressive subtypes. However, the recent turn of events, specifically the CREATE-X [7] and KATHERINE [8] trials, has demonstrated, a hitherto unexplored, predictive capability of pCR. The CREATE-X study suggested a survival benefit with the addition of capecitabine, in women with triple-negative breast cancer, with residual disease post-neoadjuvant chemotherapy (NACT). Likewise, the early analysis of KATHERINE points toward a benefit in invasive disease-free survival with Trastuzumab emtansine over trastuzumab, in HER2-positive breast cancers with residual disease post-NACT. In both these studies, pCR, or more specifically, the lack of it, was used as a marker to tailor adjuvant therapy, with improved outcomes.

Since its inception, the role of pCR is now entering an exciting phase. It may lack the ability to be a surrogate marker for survival on the scale of a clinical trial, but it does remain a crucial marker for prognosis on an individual patient level and is an emerging predictive marker for tailoring adjuvant therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Giuliano AE, Edge SB, Hortobagyi GN. Ann Surg Oncol 2018;25:1783.  Back to cited text no. 1
    
2.
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.  Back to cited text no. 2
    
3.
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012;13:25-32.  Back to cited text no. 3
    
4.
Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): A randomised, open-label, multicentre, phase 3 trial. Lancet 2012;379:633-40.  Back to cited text no. 4
    
5.
Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: Results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol 2016;34:1034-42.  Back to cited text no. 5
    
6.
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet 2014;384:164-72.  Back to cited text no. 6
    
7.
Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 2017;376:2147-59.  Back to cited text no. 7
    
8.
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380:617-28.  Back to cited text no. 8
    




 

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