Published online: 2020-12-14

Suryavanshi, et al.: Clinical utility of DDPCR in breast cancer

Criterion values and coordinates of the receiver operating characteristic curves Criterion Sensitivity 95% CI Specificity 95% CI +LR −LR >0.41126071 86.67 69.3-96.2 75.00 53.3-90.2 3.47 0.18 >0.436551724 83.33 65.3-94.4 75.00 53.3-90.2 3.33 0.22 >0.477777778 83.33 65.3-94.4 79.17 57.8-92.9 4.00 0.21 >0.510869565 83.33 65.3-94.4 83.33 62.6-95.3 5.00 0.20 >0.524793388 80.00 61.4-92.3 83.33 62.6-95.3 4.80 0.24 >0.536912752 76.67 57.7-90.1 83.33 62.6-95.3 4.60 0.28 >0.635658915 73.33 54.1-87.7 83.33 62.6-95.3 4.40 0.32 >0.657894737 70.00 50.6-85.3 83.33 62.6-95.3 4.20 0.36 >0.7 70.00 50.6-85.3 87.50 67.6-97.3 5.60 0.34 >0.829268293 70.00 50.6-85.3 91.67 73.0-99.0 8.40 0.33 >0.903553299 66.67 47.2-82.7 91.67 73.0-99.0 8.00 0.36 >0.904494382 63.33 43.9-80.1 91.67 73.0–99.0 7.60 0.40 >0.990066225 63.33 43.9-80.1 95.83 78.9–99.9 15.20 0.38 >1.018276762 63.33 43.9-80.1 100.00 85.8–100.0 0.37 >1.317307692 60.00 40.6-77.3 100.00 85.8–100.0 0.40 >1.444444444 56.67 37.4-74.5 100.00 85.8–100.0 0.43 >1.552083333 53.33 34.3-71.7 100.00 85.8–100.0 0.47 >1.695833333 50.00 31.3-68.7 100.00 85.8–100.0 0.50 >2.107843137 46.67 28.3-65.7 100.00 85.8–100.0 0.53 >2.387267905 43.33 25.5-62.6 100.00 85.8–100.0 0.57 >2.449275362 40.00 22.7–59.4 100.00 85.8–100.0 0.60 >2.777777778 36.67 19.9-56.1 100.00 85.8–100.0 0.63 >3.108108108 33.33 17.3-52.8 100.00 85.8–100.0 0.67 >4.887323944 30.00 14.7-49.4 100.00 85.8–100.0 0.70 >5.266304348 26.67 12.3-45.9 100.00 85.8–100.0 0.73 >7.01863354 23.33 9.9-42.3 100.00 85.8–100.0 0.77 >7.80952381 20.00 7.7-38.6 100.00 85.8–100.0 0.80 >13.62068966 16.67 5.6-34.7 100.00 85.8–100.0 0.83

>13.85714286 13.33 3.8-30.7 100.00 85.8–100.0 0.87 >20.41666667 10.00 2.1-26.5 100.00 85.8–100.0 0.90 >24.92857143 6.67 0.8-22.1 100.00 85.8–100.0 0.93 >90.6779661 3.33 0.08-17.2 100.00 85.8–100.0 0.97 >366.1764706 0.00 0.0-11.6 100.00 85.8–100.0 1.00 CI=Confidence interval

Letter to the Editor from the Food and Drug Administration in 2013. The The evolving role of pathologic complete corresponding adjuvant trial (APHINITY) demonstrated only a marginal improvement in disease‑free survival (94.1% vs. response in breast cancer 93.2%, P = 0.045) in its early analysis, and further maturing DOI: 10.4103/sajc.sajc_67_19 of data is awaited. Along similar lines, addition of Dear Editor, improved pCR rates significantly; however, in the adjuvant [4,5] The concept of pathologic complete response (pCR) has been setting, it failed to impact survival outcomes. The CTNeoBC [6] an enigmatic one, often at the center of much debate and meta‑analysis funded by the US‑FDA confirmed the prognostic value of pCR, especially in aggressive tumor subtypes; however, controversy. While most researchers would agree that the it could not validate pCR as a surrogate endpoint for survival. absence of residual invasive carcinoma in the breast and axilla is imperative in defining pCR, the impact of residual in situ Following this, pCR continued to simmer for a while and found its tumor is still debated. The current AJCC 8th Edition defines clinical application in its ability to prognosticate aggressive subtypes. [7] pCR as the absence of any residual invasive carcinoma in the However, the recent turn of events, specifically the CREATE‑X and KATHERINE[8] trials, has demonstrated, a hitherto unexplored, breast/axilla/lymph vessels. The presence of in situ tumor in the predictive capability of pCR. The CREATE‑X study suggested a absence of invasive carcinoma still constitutes a pCR.[1] survival benefit with the addition of capecitabine, in women with From the early studies onward, pCR showed great promise triple‑negative breast cancer, with residual disease post‑neoadjuvant in its ability to predict outcomes after . This chemotherapy (NACT). Likewise, the early analysis of KATHERINE association was strongest in aggressive biology tumors, such points toward a benefit in invasive disease‑free survival with as triple‑negative and HER2‑positive cancers.[2] Researchers emtansine over trastuzumab, in HER2‑positive breast surmised that pCR could potentially be a surrogate marker cancers with residual disease post‑NACT. In both these studies, pCR, for survival. Based on its ability to improve pCR rates,[3] or more specifically, the lack of it, was used as a marker to tailor was the first drug to receive accelerated approval adjuvant therapy, with improved outcomes. 210 South Asian Journal of Cancer ♦ Volume 8 ♦ Issue 4 ♦ October-December 2019 Suryavanshi, et al.: Clinical utility of DDPCR in breast cancer

Since its inception, the role of pCR is now entering an exciting 4. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, phase. It may lack the ability to be a surrogate marker for Aura C, et al. Lapatinib with trastuzumab for HER2‑positive early breast cancer (NeoALTTO): A randomised, open‑label, multicentre, phase 3 trial. survival on the scale of a clinical trial, but it does remain a Lancet 2012;379:633‑40. crucial marker for prognosis on an individual patient level and 5. Piccart‑Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, is an emerging predictive marker for tailoring adjuvant therapy. Viale G, et al. Adjuvant lapatinib and trastuzumab for early human epidermal 2‑positive breast cancer: Results Financial support and sponsorship from the randomized phase III adjuvant lapatinib and/or trastuzumab Nil. treatment optimization trial. J Clin Oncol 2016;34:1034‑42. Conflicts of interest 6. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. There are no conflicts of interest. Pathological complete response and long‑term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet 2014;384:164‑72. Nisha Hariharan, T. Subramanyeshwar Rao 7. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant Department of Surgical Oncology, Basavatarakam Indo American Cancer capecitabine for breast cancer after preoperative chemotherapy. N Engl Hospital and Research Institute, Hyderabad, Telangana, India J Med 2017;376:2147-59. Correspondence to: Dr. Nisha Hariharan, 8. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, E‑mail: [email protected] et al. for residual invasive HER2‑positive breast References cancer. N Engl J Med 2019;380:617‑28. 1. Giuliano AE, Edge SB, Hortobagyi GN. Ann Surg Oncol 2018;25:1783. 2. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which on prognosis after neoadjuvant chemotherapy in various intrinsic breast allows others to remix, tweak, and build upon the work non‑commercially, as long as cancer subtypes. J Clin Oncol 2012;30:1796‑804. appropriate credit is given and the new creations are licensed under the identical terms. 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 How to cite this article: Hariharan N, Rao TS. The evolving role of pathologic with locally advanced, inflammatory, or early HER2‑positive breast complete response in breast cancer. South Asian J Cancer 2019;8:210-1. cancer (NeoSphere): A randomised multicentre, open‑label, phase 2 © 2019 The South Asian Journal of Cancer | Published by Wolters Kluwer - Medknow trial. Lancet Oncol 2012;13:25‑32.

Letter to the Editor Table 1: Baseline characteristics of patients treated with Use of lorlatinib subsequent to lorlatinib Demographic (n=10) Patients (n=10) in anaplastic ‑positive Median age, years (range) 52 (23‑67) non‑small cell lung cancer: Indian experience Gender, n (%) DOI: 10.4103/sajc.sajc_169_19 Female 5 (50) Dear Editor, Male 5 (50) History of smoking/tobacco use, n (%) Lung cancer treatment is a rapidly evolving and an excellent Yes 2 (20) example of precision medicine. The outcome of anaplastic No 8 (80) lymphoma kinase (ALK)‑positive non‑small cell lung Histopathology, n (%) cancer (NSCLC) has improved significantly with recent report Adenocarcinoma 6 (60) [1] showing the survival of 56% at 4 years. This has been Adenosquamous carcinoma 2 (20) possible due to the availability of effective sequential treatment. Adenocarcinoma with neuroendocrine 2 (20) One of the important drugs has been lorlatinib. This has found Comorbidities, n (%) to be effective in second‑line setting after crizotinib.[2] There Diabetes mellitus 1 (10) has been no data from India. We retrospectively analyzed the Hypertension 1 (10) data of patients receiving lorlatinib in our hospital. Patients Chronic lung disease 1 (10) diagnosed with ALK‑positive advanced NSCLC who have Multiple 1 (10) received lorlatinib between January 2018 and February None 6 (60) 2019 patients who have progressed on crizotinib were included ALK positivity, n (%) FISH alone 1 (10) in the study. Lorlatinib ( Oncology, Groton, CT, USA) IHC alone 1 (10) was administered orally in a tablet form at a starting dose of Both 8 (80) 100 mg once daily continuously in 21‑day cycles. Line of lorlatinib use, n (%) The details of these patients were obtained from the prospective 3 4 (40) lung cancer audit database that is maintained in the department 4 4 (40) of medical oncology. Demography (age, gender, comorbidity, 5 1 (10) and smoking status), disease status, and therapy details were 6 1 (10) recorded. ALK amplified status was ascertained either by Best responses (total evaluable ‑ 9), n (%) immunohistochemistry (monoclonal antibody D5F3 [Ventana Complete response 2 (20) Partial response 5 (50) Medical Systems, Tucson, AZ, USA]) or fluorescent in situ Stable disease 2 (20) hybridization analysis (Abbott Molecular platform). Response ALK=Anaplastic lymphoma kinase, FISH=Fluorescent in situ hybridization, assessment was performed every 2–4 months as per the IHC=Immunohistochemistry (Continue on page 217...) South Asian Journal of Cancer ♦ Volume 8 ♦ Issue 4 ♦ October-December 2019 211