title: Triple negative breast cancer: looking for the missing link between biology and treatments.
abstract: The so called "Triple Negative Breast Cancer" (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Despite this unambiguous definition, TNBCs are an heterogeneous group of tumours with just one common clinical feature: a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared with other subtypes of breast cancer. Because of the absence of well-defined molecular targets, cytotoxic chemotherapy is currently the only treatment option for TNBC. In the last decades, the use of more aggressive chemotherapy has produced a clear improvement of the prognosis in women with TNBC, but this approach results in an unacceptable deterioration in the quality of life, also if some support therapies try to relieve patients from distress. In addition, there is the general belief that it is impossible to further improve the prognosis of TNBC patients with chemotherapy alone. In view of that, there is a feverish search for new "clever drugs" able both to rescue chemo-resistant, and to reduce the burden of chemotherapy in chemo-responsive TNBC patients. A major obstacle to identifying actionable targets in TNBC is the vast disease heterogeneity both inter-tumour and intra-tumour and years of study have failed to demonstrate a single unifying alteration that is targetable in TNBC. TNBC is considered the subtype that best benefits from the neoadjuvant model, since the strong correlation between pathological Complete Response and long-term Disease-Free-Survival in these patients. In this review, we discuss the recent discoveries that have furthered our understanding of TNBC, with a focus on the subtyping of TNBC. We also explore the implications of these discoveries for future treatments and highlight the need for a completely different type of clinical trials.
authors.affiliation: S.S.D. "Sperimentazione Animale", National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.affiliation: Division of Breast Surgery, Department of Breast Disease, National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Frasci
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA.|Department of Psychology of Developmental and Socialisation Processes, "La Sapienza" University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chirico
authors.affiliation: Division of Breast Surgery, Department of Breast Disease, National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Division of Breast Surgery, Department of Breast Disease, National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Siani
authors.affiliation: Department of Pharmacy and Biomedical Science, University of Salerno, Fisciano SA, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: S.S.D. "Sperimentazione Animale", National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.affiliation: National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA.|Department of Medicine, Surgery and Neuroscience, "University of Siena", Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Division of Breast Surgery, Department of Breast Disease, National Cancer Institute, IRCCS, "Fondazione Pascale", Naples, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: D'Aiuto
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D049109:Cell Proliferation; D004260:DNA Repair; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic; D010641:Phenotype; D011379:Prognosis; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D011944:Receptors, Androgen / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen
keywords: biology; breast cancer; oncology; treatments; triple negative