Checkpoint Inhibitors in the Treatment of Breast Cancer

被引:12
作者
Lyons, Tomas G. [1 ]
Dickler, Maura N. [1 ,2 ]
Comen, Elizabeth E. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Breast Med Serv, 300 E 66th St, New York, NY 10065 USA
[2] Cornell Univ, Dept Med, Weill Cornell Med Coll, New York, NY 10021 USA
关键词
Breast cancer; Triple-negative breast cancer; Immunotherapy; Checkpoint inhibitors; PD-1; PD-L1; TUMOR-INFILTRATING LYMPHOCYTES; MICROSATELLITE INSTABILITY; PEMBROLIZUMAB; TRASTUZUMAB; PHASE-2;
D O I
10.1007/s11912-018-0701-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The treatment landscape for many cancers has dramatically changed with the development of checkpoint inhibitors. This article will review the literature concerning the use of checkpoint inhibitors in breast cancer. The histological subtype of BC with the strongest signal of efficacy has been triple-negative breast cancer (TNBC). Early trials of single-agent checkpoint inhibitors did not demonstrate a uniformly positive signal. Clinical studies suggest response rates between 5 and 10% in pretreated patients and roughly 20-25% for untreated advanced TNBC. However, in the small subset of patients who do respond, the response is often durable. More encouraging results have been reported with their use in combination with chemotherapy in the neoadjuvant setting. Larger phase III studies are underway to confirm these earlier findings. An immune-directed therapeutic approach for the management of BC is underway, and it is likely that combination therapy will be required to achieve a level of efficacy worthy of use in the BC treatment paradigm. These agents are not without both economic and clinical toxicity; therefore, it is imperative that we identify patients most likely to benefit from these therapies through well-designed biologically plausible clinical studies and by evaluating novel combinatorial approaches with informative biomarker driven correlative studies.
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页数:10
相关论文
共 41 条
[1]   Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. [J].
Adams, Sylvia ;
Schmid, Peter ;
Rugo, Hope S. ;
Winer, Eric P. ;
Loirat, Delphine ;
Awada, Ahmad ;
Cescon, David W. ;
Iwata, Hiroji ;
Campone, Mario ;
Nanda, Rita ;
Hui, Rina ;
Curigliano, Giuseppe ;
Toppmeyer, Deborah ;
O'Shaughnessy, Joyce ;
Loi, Sherene ;
Paluch-Shimon, Shani ;
Card, Deborah ;
Zhao, Jing ;
Karantza, Vassiliki ;
Cortes, Javier .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35
[2]   Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple negative breast cancer (mTNBC). [J].
Adams, Sylvia ;
Diamond, Jennifer Robinson ;
Hamilton, Erika Paige ;
Pohlmann, Paula Raffin ;
Tolaney, Sara M. ;
Molinero, Luciana ;
He, Xian ;
Waterkamp, Daniel ;
Funke, Roel Peter ;
Powderly, John D. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (15)
[3]   Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].
Adams, Sylvia ;
Gray, Robert J. ;
Demaria, Sandra ;
Goldstein, Lori ;
Perez, Edith A. ;
Shulman, Lawrence N. ;
Martino, Silvana ;
Wang, Molin ;
Jones, Vicky E. ;
Saphner, Thomas J. ;
Wolff, Antonio C. ;
Wood, William C. ;
Davidson, Nancy E. ;
Sledge, George W. ;
Sparano, Joseph A. ;
Badve, Sunil S. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+
[4]   Microsatellite instability in hereditary and sporadic breast cancers [J].
Adem, C ;
Soderberg, CL ;
Cunningham, JM ;
Reynolds, C ;
Sebo, TJ ;
Thibodeau, SN ;
Hartmann, LC ;
Jenkins, RB .
INTERNATIONAL JOURNAL OF CANCER, 2003, 107 (04) :580-582
[5]   Signatures of mutational processes in human cancer [J].
Alexandrov, Ludmil B. ;
Nik-Zainal, Serena ;
Wedge, David C. ;
Aparicio, Samuel A. J. R. ;
Behjati, Sam ;
Biankin, Andrew V. ;
Bignell, Graham R. ;
Bolli, Niccolo ;
Borg, Ake ;
Borresen-Dale, Anne-Lise ;
Boyault, Sandrine ;
Burkhardt, Birgit ;
Butler, Adam P. ;
Caldas, Carlos ;
Davies, Helen R. ;
Desmedt, Christine ;
Eils, Roland ;
Eyfjord, Jorunn Erla ;
Foekens, John A. ;
Greaves, Mel ;
Hosoda, Fumie ;
Hutter, Barbara ;
Ilicic, Tomislav ;
Imbeaud, Sandrine ;
Imielinsk, Marcin ;
Jaeger, Natalie ;
Jones, David T. W. ;
Jones, David ;
Knappskog, Stian ;
Kool, Marcel ;
Lakhani, Sunil R. ;
Lopez-Otin, Carlos ;
Martin, Sancha ;
Munshi, Nikhil C. ;
Nakamura, Hiromi ;
Northcott, Paul A. ;
Pajic, Marina ;
Papaemmanuil, Elli ;
Paradiso, Angelo ;
Pearson, John V. ;
Puente, Xose S. ;
Raine, Keiran ;
Ramakrishna, Manasa ;
Richardson, Andrea L. ;
Richter, Julia ;
Rosenstiel, Philip ;
Schlesner, Matthias ;
Schumacher, Ton N. ;
Span, Paul N. ;
Teague, Jon W. .
NATURE, 2013, 500 (7463) :415-+
[6]  
Anbazhagan R, 1999, CLIN CANCER RES, V5, P839
[7]  
[Anonymous], 2017, SAN ANT BREAST CANC
[8]  
[Anonymous], ANN ONCOLOGY S5
[9]  
[Anonymous], IMMUNITY
[10]  
[Anonymous], SAN ANT BREAST CANC