Abstract P1-10-18: Serum protein expression predicts neoadjuvant chemotherapy response in patients with locally advanced breast cancer
Authors: Kim Ji-Yeon , Park Kyunghee , Jung Hae Hyun , Lee Se Kyung , Yu Jonghan , Lee Jeong Eon , Kim Seok Won , Nam Seok Jin , Park Yeon Hee 
Published: March 2020

Introduction: Neoadjuvant chemotherapy (NAC) enables curative surgery and deprives micrometastasis in locally advanced breast cancer (LABC). Indeed, response of NAC, representatives of pathologic complete response (pCR) as well as residual cancer burden (RCB) class, is the most powerful indicator to predict BC prognosis. Therefore, NAC has been commonly used to treat LABC especially for HER2+ and TNBC subtype. While BC was treated with NAC, BC pathologic characteristics could be switched as a consequence of NAC. However, serial tumor biopsies are not feasible in clinical practiceeven though NAC has been used “in vitro vehicle” for translational research. Therefore, plasma biomarker is unmet need for treatment response prediction. In this study, we aimed to identify potential plasma biomarkers using multiplex immunoassay in BC patients with NAC. In total, we evaluated 45 plasma biomarkers and analyzed the association between the level of biomarkers and clinical outcomes.

Methods: This study was prospectively conducted for LABC patients with NAC. Patients were treated with a standard NAC protocol for 6 months, consisting of four cycles of adriamycin/cyclophosphamide (AC) (60/600 mg/m2) combination chemotherapies followed by four cycles of docetaxel(D) (80mg/ m2) chemotherapy. HER2+ BC patients were treated with docetaxel plus trastuzumab (DH) combination therapies after AC. Surgical response was evaluated according to pathologic complete remission (pCR) defined as no residual invasive carcinoma in primary tumor bed and axillary lymph node. We also calculated residual cancer burden (RCB) score based on surgical pathology report. For each patient, blood sampling were prospectively taken 3times; before treatment (T1), three weeks after the first cycle of AC (T2) and at surgery following six months of treatment (T3). Plasma samples were assayed by multiplex immunoassays for 45 biomarkers, including growth factor, cytokines and chemokines using 45-Plex Human ProcartaPlexTM Panel (Thermo Fisher Scientific, Inc. Carlsbad, CA, USA).

Results: In total, 167 patients diagnosed with LABC were participated in serial plasma sampling. Fifty eight patients were diagnosed with HER2+ BCs (34.7%) and 63 of TNBCs (37.7%). Clinical stage at BC diagnosis was variate; 59 of stage II (35.3%), 108 of stage III (64.7%). After BC surgery, pCR (RCB class 0) was observed in 53 BCs (6 hormone receptor positive and HER2- BCs (13.0%), 27 HER2+ BCs (46.6%) and 20 TNBCs (31.7%)). In terms of RCB class, 20 BCs were class I, 63 of class II and 28 of class III. Two patients diagnosed with LABC had undergone disease progression during NAC. Among clinical variables, RCB class after NAC in LABC patients has the highest predictive value for relapse free survival (RFS) (c-index: 0.787, 95% confidence interval [CI]:0.690, 0.884, p-value &lt;0.001). Of 45 proteins, seven (epidermal growth factor [EGF], interleukin-6 [IL-6], granulocyte-macrophage colony-stimulating factor [GM-CSF], Interferon-gamma, IL-12p70, IL-17A, IL-5) expression profile at initial diagnosis predict RCB class after NAC (Accuracy 0.598, area under curve [AUC] 0.792). Further survival analysis based on predicted RCB class according to seven protein expression profile was showed similar results compared with RCB class according to clinical result of curative surgery (c-index: 0.611, 95% CI: 0.453, 0.768, p-value 0.006).

Conclusion: Seven plasma protein expressions predict RCB class in LABC patients with NAC and predicted RCB class also has a similar predictive value for RFS compared with RCB class based on the result of curative surgery.

Citation Format: Ji-Yeon Kim, Kyunghee Park, Hae Hyun Jung, Se Kyung Lee, Jonghan Yu, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Yeon Hee Park. Serum protein expression predicts neoadjuvant chemotherapy response in patients with locally advanced breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-18.