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How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment
  1. Diana P Saraiva1,
  2. M Guadalupe Cabral1,
  3. António Jacinto1,
  4. Sofia Braga1,2
  1. 1 CEDOC, Nova Medical School, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisbon, Portugal
  2. 2 Instituto CUF de Oncologia, Lisbon, Portugal
  1. Correspondence to Dr Sofia Braga; sofia.braga{at}


Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2). Since there are no positive markers to reliably classify TNBC, these tumours are not yet treated with targeted therapies. Perhaps for this reason they are the most aggressive form of breast carcinomas. However, the clinical observation that these patients do not carry a uniformly dismal prognosis, coupled with data coming from pathology and epidemiology, suggests that this negative definition is not capturing a single clinical entity, but several. We critically evaluate this evidence in this paper, reviewing clinical and epidemiological data and new studies that aim to subclassify TNBC. Moreover, evidence on the role of tumour infiltrating lymphocytes (TILs) on TNBC progression, response to chemotherapy and patient outcome have been published. The heterogeneity, observed even at TILs level, highlights the idea that TNBC is much more than a single disease with a unique treatment. The exploration of the immune environment present at the tumour site could indeed help in answering the question ‘How many diseases is TNBC’ and will help to define prognosis and eventually develop new therapies, by stimulating the immune effector cells or by inhibiting immunological repressor molecules.

In this review, we focus on the prospect of the patient’s diverse immune signatures within the tumour as potential biomarkers and how they could be modulated to fight the disease.

  • Triple negative breast cancer
  • heterogeneity
  • gene expression profile
  • tumour infiltrating lymphocytes

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  • Contributors DPS, MGC and SB reviewed the literature, wrote the manuscript and AJ revised the text.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Hospital Prof Doutor Fernando da Fonseca.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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