Immunotherapy for early triple negative breast cancer: research agenda for the next decade

Paolo Tarantino¹, Chiara Corti^{1

2}, Peter Schmid³, Javier Cortes^{4

5

6

7}, Elizabeth A Mittendorf^{8

9}, Hope Rugo¹⁰, Sara M Tolaney^{11

12}, Giampaolo Bianchini¹³, Fabrice Andrè¹⁴, Giuseppe Curigliano^{15

16}

Affiliations

¹ Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy.
² Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
³ Barts Cancer Institute, Queen Mary University of London, London, UK.
⁴ Oncology Department, International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain.
⁵ Medica Scientia Innovation Research (MedSIR), Barcelona, Spain.
⁶ Breast Cancer Research Program, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.
⁷ Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain.
⁸ Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
⁹ Breast Oncology Program, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁰ University of California San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center Precision Medicine Cancer Building, San Francisco, CA, USA.
¹¹ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹² Harvard Medical School, Boston, MA, USA.
¹³ Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
¹⁴ Department of Medical Oncology, Gustave Roussy, Villejuif, France.
¹⁵ Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy. Giuseppe.curigliano@ieo.it.
¹⁶ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. Giuseppe.curigliano@ieo.it.

PMID: 35181659
PMCID: PMC8857212
DOI: 10.1038/s41523-022-00386-1

Review

Immunotherapy for early triple negative breast cancer: research agenda for the next decade

Paolo Tarantino et al. NPJ Breast Cancer. 2022.

. 2022 Feb 18;8(1):23.

doi: 10.1038/s41523-022-00386-1.

Authors

Affiliations

¹ Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy.
² Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
³ Barts Cancer Institute, Queen Mary University of London, London, UK.
⁴ Oncology Department, International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain.
⁵ Medica Scientia Innovation Research (MedSIR), Barcelona, Spain.
⁶ Breast Cancer Research Program, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.
⁷ Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain.
⁸ Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
⁹ Breast Oncology Program, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁰ University of California San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center Precision Medicine Cancer Building, San Francisco, CA, USA.
¹¹ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹² Harvard Medical School, Boston, MA, USA.
¹³ Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
¹⁴ Department of Medical Oncology, Gustave Roussy, Villejuif, France.
¹⁵ Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy. Giuseppe.curigliano@ieo.it.
¹⁶ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. Giuseppe.curigliano@ieo.it.

PMID: 35181659
PMCID: PMC8857212
DOI: 10.1038/s41523-022-00386-1

Abstract

For decades, the systemic treatment of localized triple negative breast cancer (TNBC) has exclusively relied on chemotherapy. Recent advancements, however, are rapidly reshaping the treatment algorithms for this disease. The addition of pembrolizumab to neoadjuvant chemotherapy has indeed shown to significantly improve event-free survival for stage II-III TNBC, leading to its establishment as new standard of care in this setting. This landmark advancement has however raised several important scientific questions. Indeed, we desperately need strategies to identify upfront patients deriving benefit from the addition of immunotherapy. Moreover, the best integration of pembrolizumab with further recent advancements (capecitabine, olaparib) is yet to be defined. Lastly, extensive efforts are needed to minimize the impact on patients of immune-related adverse events and financial toxicity. The next decade of clinical research will be key to overcome these challenges, and ultimately learn how to optimally integrate immunotherapy in the treatment landscape of TNBC.

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Conflict of interest statement

P.T. served as advisor/consultant for AstraZeneca. P.S. reports research support (grants) to his institution from Genentech, F. Hoffmann-La Roche, OncoGenex and Novartis; reports honoraria from AstraZeneca, F. Hoffmann-La Roche, Medscape and G1 Therapeutics; reports a consulting or advisory role with AstraZeneca, Novartis, F. Hoffmann-La Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Pfizer and Puma; and reports that his spouse has a consulting role for Genentech and F. Hoffmann-La Roche. J.C. has declared consulting role for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MSD, GlaxoSmithKline (GSK), Leuko, Bioasis, and Clovis Oncology; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD, and Daiichi Sankyo; research funding to the institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH–Servier Affaires, Bayer healthcare, Eisai, F Hoffman-La Roche, Guardant Health, MSD, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London and intellectual property for MedSIR. E.A.M. served as advisor/consultant for: Bristol Myers Squib, Exact Sciences (formerly Genomic Health), Genentech/Roche, Lily and Merck. H.S.R. reports the following: Research support for clinical trials through the University of California: Pfizer, Merck, Novartis, Lilly, Roche, Odonate, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, Astra Zeneca, OBI and Immunomedics. Honoraria: Puma, Mylan, Samsung. S.M.T. has served as an advisor/consultant to Novartis, Eli Lilly, Pfizer, Merck, AstraZeneca, Eisai, Puma, Genentech, Immunomedics, Nektar, Tesaro, Daiichi Sankyo, Athenex, Bristol Meyers Squibb, and Nanostring. G.B. received honoraria for speaker, consultancy or advisory rule from Roche, Pfizer, AstraZeneca, Lilly, Novartis, Neopharm Israel, Amgen, MSD, Chugai, Sanofi, Daiichi Sankyo, EISAI, Gilead, Seagen, Exact Science, Gilead, Seagen. F.A. received research funding and served as speaker/advisor (compensated to the hospital) for Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis and Lilly. G.C. received honoraria for speaker, consultancy or advisory rule from AstraZeneca, Roche, Pfizer, Novartis, Seattle Genetics, Lilly, Ellipses Pharma, Foundation Medicine, Daiichi Sankyo and Samsung. The remaining authors declare no competing interests.

Figures

**Fig. 1. Next decade research agenda for neo(adjuvant) immunotherapy in TNBC.**
Abbreviations: IO, immunotherapy, TNBC, triple negative breast cancer; TMB, tumor mutational burden; ADC, antibody-drug conjugate; ER, estrogen receptor; CD, cluster of differentiation; TILs, tumor infiltrating lymphocytes; PD-L1, Programmed death-ligand 1; HLA, human leukocyte antigen; PD-1, Programmed cell death protein 1; A, adenosine; T, thymine; C, cytosine; G, guanine; BRCA, BReast CAncer gene; EFS, event-freee survival; RD, residual disease; me1, mono-methylated form; BC, breast cancer. Created with biorender.com.

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Immunotherapy for early triple negative breast cancer: research agenda for the next decade

Affiliations

Immunotherapy for early triple negative breast cancer: research agenda for the next decade

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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