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Pathology & Oncology Research

, Volume 24, Issue 4, pp 701–716 | Cite as

Therapeutic Implications of the Molecular and Immune Landscape of Triple-Negative Breast Cancer

  • Ana C. Gregório
  • Manuela Lacerda
  • Paulo Figueiredo
  • Sérgio Simões
  • Sérgio Dias
  • João Nuno Moreira
Review Paper

Abstract

Treatment and management of breast cancer imposes a heavy burden on public health care, and incidence rates continue to increase. Breast cancer is the most common female neoplasia and primary cause of death among women worldwide. The recognition of breast cancer as a complex and heterogeneous disease, comprising different molecular entities, was a landmark in our understanding of this malignancy. Valuing the impact of the molecular characteristics on tumor behavior enabled a better assessment of a patient’s prognosis and increased the predictive power to therapeutic response and clinical outcome. Molecular heterogeneity is also prominent in the triple-negative breast cancer subtype, and is reflected by the distinct prognostic and patient’s sensitivity to treatment, being chemotherapy the only systemic treatment currently available. From a therapeutic perspective, gene expression profiling of triple-negative tumors has notably contributed to the exploration of new druggable targets and brought to light the need to align these patients to the various therapies according to their triple-negative subtype. Additionally, the higher amount of tumor infiltrating lymphocytes, and the prevalence of an increased expression of PD-1 receptor and its ligand, PD-L1, in triple-negative tumors, created a new treatment opportunity with immune checkpoint inhibitors. This manuscript addresses the current knowledge on the molecular and immune profiles of breast cancer, and its impact on the development of targeted therapies, with a particular emphasis on the triple-negative subtype.

Keywords

Breast cancer Triple-negative breast cancer Intrinsic subtype Gene expression profiling Targeted therapies Immune checkpoint inhibitors 

Abbreviations

BL1

basal-like 1

BL2

basal-like 2

CTLA-4

cytotoxic T-lymphocyte antigen 4

ER

estrogen receptor

FDA

food and drug administration

HER2

human epidermal growth factor receptor 2

IM

immunomodulatory

LAR

luminal androgen receptor

LHRH

luteinizing hormone-releasing hormone

M

mesenchymal

MSL

mesenchymal stem-like

PARP

poly (adenosine diphosphate-ribose) polymerase

pCR

pathologic complete response

PD-1

programmed death-1 receptor

PD-L1

programmed death-ligand 1

PR

progesterone receptor

TNBC

triple-negative breast cancer

Notes

Acknowledgements

Ana Cristina Leal Gregório is student of the international PhD program in Experimental Biology and Biomedicine (PDBEB) from the Institute for Interdisciplinary Research, University of Coimbra and recipient of the fellowship SFRH/BD/51190/2010 from the Portuguese Foundation for Science and Technology (FCT). The work was supported by the grants PTDC/SAU-BMA/121028/2010 and POCI-01-0145-FEDER-007440 (FEDER/COMPETE 2020/FCT).

Compliance with Ethical Standards

Conflict of Interest

Authors declare no competing financial interests.

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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  1. 1.CNC - Center for Neuroscience and Cell Biology, Faculty of Medicine (Pólo I)University of CoimbraCoimbraPortugal
  2. 2.IIIUC – Institute for Interdisciplinary ResearchUniversity of CoimbraCoimbraPortugal
  3. 3.IPATIMUP – Institute of Molecular Pathology and ImmunologyUniversity of PortoPortoPortugal
  4. 4.IPOFG-EPE – Portuguese Institute of Oncology Francisco GentilCoimbraPortugal
  5. 5.FFUC - Faculty of Pharmacy, Pólo das Ciências da SaúdeUniversity of CoimbraCoimbraPortugal
  6. 6.IMM – Institute of Molecular Medicine, Faculty of MedicineUniversity of LisbonLisbonPortugal

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