HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer

被引:20
作者
Cherifi, Francois [1 ,2 ]
Da Silva, Angelique [2 ]
Johnson, Alison [2 ]
Blanc-Fournier, Cecile [3 ]
Abramovici, Olivia [4 ]
Broyelle, Antonin [5 ]
Levy, Christelle [1 ,2 ]
Allouache, Djelila [2 ]
Hrab, Ioana [2 ]
Segura, Carine [2 ]
Morel, Adeline [2 ]
Villemin, Maud [2 ]
Boscher, Clemence [2 ]
Dubot-Poitelon, Coraline [2 ]
Rottier, Pauline [2 ]
Lequesne, Justine [1 ]
Emile, George [1 ,2 ]
机构
[1] CLCC Francois Baclesse, Dept Clin Res, Caen, France
[2] Inst Normand Sein, Breast Canc Unit, CLCC Francois Baclesse, Caen, France
[3] CLCC Francois Baclesse, Dept Pathol, Caen, France
[4] CLCC Oscar Lambret, Dept Pathol, Lille, France
[5] CLCC Oscar Lambret, Breast Canc Unit, Lille, France
关键词
Antibody-drug conjugates; HER2-low; Breast cancer; Trastuzumab-deruxtecan; Neoadjuvant treatment; Lymphocytes; Neutrophils; PROGNOSTIC-FACTOR; CLINICAL ONCOLOGY/COLLEGE; AMERICAN SOCIETY; EXPRESSION; SURVIVAL; IMMUNOHISTOCHEMISTRY; AMPLIFICATION; NEUTROPHIL; RATIO;
D O I
10.1186/s12885-022-10163-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification). Methods We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed. Results We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15-0.84] and HR = 0.24 [0.07-0.81], respectively). NLR was not associated with worse DFS or OS. Conclusion In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.
引用
收藏
页数:10
相关论文
共 47 条
[1]   Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer [J].
Andrikopoulou, Angeliki ;
Zografos, Eleni ;
Liontos, Michalis ;
Koutsoukos, Konstantinos ;
Dimopoulos, Meletios-Athanasios ;
Zagouri, Flora .
CLINICAL BREAST CANCER, 2021, 21 (03) :E212-E219
[2]  
[Anonymous], R Project for Statistical Computing (Version 3.0.2)
[3]   Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer [J].
Bardia, A. ;
Hurvitz, S. A. ;
Tolaney, S. M. ;
Loirat, D. ;
Punie, K. ;
Oliveira, M. ;
Brufsky, A. ;
Sardesai, S. D. ;
Kalinsky, K. ;
Zelnak, A. B. ;
Weaver, R. ;
Traina, T. ;
Dalenc, F. ;
Aftimos, P. ;
Lynce, F. ;
Diab, S. ;
Cortes, J. ;
O'Shaughnessy, J. ;
Dieras, V ;
Ferrario, C. ;
Schmid, P. ;
Carey, L. A. ;
Gianni, L. ;
Piccart, M. J. ;
Loibl, S. ;
Goldenberg, D. M. ;
Hong, Q. ;
Olivo, M. S. ;
Itri, L. M. ;
Rugo, H. S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (16) :1529-1541
[4]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[5]   Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021 [J].
Burstein, H. J. ;
Curigliano, G. ;
Thurlimann, B. ;
Weber, W. P. ;
Poortmans, P. ;
Regan, M. M. ;
Senn, H. J. ;
Winer, E. P. ;
Gnant, M. .
ANNALS OF ONCOLOGY, 2021, 32 (10) :1216-1235
[6]   Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].
Cardoso, F. ;
Kyriakides, S. ;
Ohno, S. ;
Penault-Llorca, F. ;
Poortmans, P. ;
Rubio, I. T. ;
Zackrisson, S. ;
Senkus, E. .
ANNALS OF ONCOLOGY, 2019, 30 (08) :1194-1220
[7]   Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].
Cortazar, Patricia ;
Zhang, Lijun ;
Untch, Michael ;
Mehta, Keyur ;
Costantino, Joseph P. ;
Wolmark, Norman ;
Bonnefoi, Herve ;
Cameron, David ;
Gianni, Luca ;
Valagussa, Pinuccia ;
Swain, Sandra M. ;
Prowell, Tatiana ;
Loibl, Sibylle ;
Wickerham, D. Lawrence ;
Bogaerts, Jan ;
Baselga, Jose ;
Perou, Charles ;
Blumenthal, Gideon ;
Blohmer, Jens ;
Mamounas, Eleftherios P. ;
Bergh, Jonas ;
Semiglazov, Vladimir ;
Justice, Robert ;
Eidtmann, Holger ;
Paik, Soonmyung ;
Piccart, Martine ;
Sridhara, Rajeshwari ;
Fasching, Peter A. ;
Slaets, Leen ;
Tang, Shenghui ;
Gerber, Bernd ;
Geyer, Charles E., Jr. ;
Pazdur, Richard ;
Ditsch, Nina ;
Rastogi, Priya ;
Eiermann, Wolfgang ;
von Minckwitz, Gunter .
LANCET, 2014, 384 (9938) :164-172
[8]   HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer [J].
de Moura Leite, Luciana ;
Cesca, Marcelle Goldner ;
Tavares, Monique Celeste ;
Santana, Debora Maciel ;
Saldanha, Erick Figueiredo ;
Guimaraes, Paula Tavares ;
Sa, Daniella Dias Silva ;
Simoes, Maria Fernanda Evangelista ;
Viana, Rafael Lima ;
Rocha, Francisca Giselle ;
Loose, Simone Klog ;
Silva, Sinara Figueiredo ;
Pirolli, Rafaela ;
Fogassa, Camilla Albina Zanco ;
Mattos, Bruna Raphaeli Silva ;
Campos, Fernando Augusto Batista ;
Sanches, Solange Moraes ;
de Lima, Vladmir Claudio Cordeiro ;
Ponde, Noam Falbel .
BREAST CANCER RESEARCH AND TREATMENT, 2021, 190 (01) :155-163
[9]   Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials [J].
Denkert, Carsten ;
Seither, Fenja ;
Schneeweiss, Andreas ;
Link, Theresa ;
Blohmer, Jens-Uwe ;
Just, Marianne ;
Wimberger, Pauline ;
Forberger, Almuth ;
Tesch, Hans ;
Jackisch, Christian ;
Schmatloch, Sabine ;
Reinisch, Mattea ;
Solomayer, Erich F. ;
Schmitt, Wolfgang D. ;
Hanusch, Claus ;
Fasching, Peter A. ;
Luebbe, Kristina ;
Solbach, Christine ;
Huober, Jens ;
Rhiem, Kerstin ;
Marme, Frederik ;
Reimer, Toralf ;
Schmidt, Marcus ;
Sinn, Bruno, V ;
Janni, Wolfgang ;
Stickeler, Elmar ;
Michel, Laura ;
Stoetzer, Oliver ;
Hahnen, Eric ;
Furlanetto, Jenny ;
Seiler, Sabine ;
Nekljudova, Valentina ;
Untch, Michael ;
Loibl, Sibylle .
LANCET ONCOLOGY, 2021, 22 (08) :1151-1161
[10]   Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer [J].
Eggemann, Holm ;
Ignatov, Tanja ;
Burger, Elke ;
Kantelhardt, Eva Johanna ;
Fettke, Franziska ;
Thomssen, Christoph ;
Costa, Serban Dan ;
Ignatov, Atanas .
ENDOCRINE-RELATED CANCER, 2015, 22 (05) :725-733