The Association of Neoadjuvant Systemic Treatment on Hormone Receptor and Her2 Expression in Breast Cancer
Abstract
Background:Â Pathological complete response (pCR) following neoadjuvant systemic treatment(NAST) for breast cancer is associated with improved prognosis; however, a large proportion of patients have residual disease. Oestrogen Receptor (ER) and HER2 status have been shown to affect likelihood of achieving pCR, with ER positive tumors being more treatment resistant. As hormone receptor status is heterogeneous within tumors, we postulated that, following NAST, ER expression would change in patients with residual disease, as the ER negative cells within the tumor are more treatment sensitive.
Methods: A retrospective case series of patients treated with NAST prior to surgery at our institution was conducted. Information collected included demographic data, tumor grade, hormone receptor and HER2 status both before and after treatment, and pCR rates.
Results: Of the 44 patients included, half achieved pCR. HER2 status (P=0.01), and subtype (P=0.008) were significantly associated with pCR. HER2 positive/ER negative tumors were most likely to undergo pCR. Approximately 80% of residual disease was ER positive. Higher levels of ER expression were also associated with increasing residual cancer burden (RCB) class (P=0.037). There was no trend between change in ER or HER2 expression following NAST. Median change in ER expression was 80% to 90% (P= 0.89), HER2 intensity changed from 3.0 to 2.2 (P=0.67) following treatment.
Conclusion: Consistent with the literature, we have shown associations between ER and HER2 status and PCR, and between ER expression and residual disease burden. Our study was not able to demonstrate a significant trend in hormone and HER2 expression.
Full text article
References
Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61-70.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
Killelea BK, Yang VQ, Mougalian S, Horowitz NR, Pusztai L, et al. Neoadjuvant chemotherapy for breast cancer increases the rate of breast conservation: results from the National Cancer Database. J Am Coll Surg. 2015;220(6):1063-9.
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72.
Gavila J, Oliveira M, Pascual T, Perez-Garcia J, Gonzalez X, et al. Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial. BMC Med. 2019;17(1):8.
Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, et al. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. J Clin Oncol. 2016;34(6):542-9.
Jones RL, Salter J, A'Hern R, Nerurkar A, Parton M, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010;119(2):315-23.
Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800.
Zujewski JA, Rubinstein L. CREATE-X a role for capecitabine in early-stage breast cancer: an analysis of available data. NPJ Breast Cancer. 2017;3:27.
Gluz O NU, Liedtke C et al. No survival benefit of chemotherapy escalation in patients with pCR and "high-immune" triple-negative early breast cancer in the neoadjuvant WSG-ADAPT-TN trial. Cancer Res 2018;79S:SABCS #GS5.
Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784-95.
Amin MB ES, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, et al. AJCC Cancer Staging Manual (8th edition): Springer International Publishing: American Joint Commission on Cancer; 2017.
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(28):4414-22.
van de Ven S, Smit VT, Dekker TJ, Nortier JW, Kroep JR. Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev. 2011;37(6):422-30.
Colleoni M, Viale G, Zahrieh D, Pruneri G, Gentilini O, et al. Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res. 2004;10(19):6622-8.
Piper GL, Patel NA, Patel JA, Malay MB, Julian TB. Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status. Am Surg. 2004;70(12):1103-6.
Makris A, Powles TJ, Allred DC, Ashley SE, Trott PA, et al. Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: a pilot study. Breast Cancer Res Treat. 1999;53(1):51-9.
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, 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(1):25-32.
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-84.
Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016;17(3):345-56.
Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, et al. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2012;132(3):1049-62.
Nahta R, O'Regan RM. Therapeutic implications of estrogen receptor signaling in HER2-positive breast cancers. Breast Cancer Res Treat. 2012; 135(1):39-48.
Gluck S, Arteaga CL, Osborne CK. Optimizing chemotherapy-free survival for the ER/HER2-positive metastatic breast cancer patient. Clin Cancer Res. 2011;17(17):5559-61.
Bhargava R, Dabbs DJ, Beriwal S, Yildiz IA, Badve P, et al. Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer. Mod Pathol. 2011;24(3):367-74.
Authors
Copyright (c) 2021 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.