Review Article

Inflammatory breast cancer biology: the tumour microenvironment is key

Published:

Abstract

Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2–4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7–10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.

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Change history

  • Correction 10 May 2018

    The originally published article contained an error in Table 1, in which two neoadjuvant clinical trials (NCT02876107 and NCT03101748) were not included. This omission has been corrected in the online and print versions of the manuscript through the addition of these two trials and their relevant details (agents, cohort details, targeted biology, main targeted pathway or characteristic and phase) to Table 1.

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Acknowledgements

This work was supported by US National Institutes of Health (NIH) grant 1R01CA205043-01A1 (N.T.U.), the Morgan Welch Inflammatory Breast Cancer Research Program, the Breast Cancer Research Foundation (N.T.U.), the State of Texas Rare and Aggressive Breast Cancer Research Program (N.T.U.), the MD Anderson Cancer Center Support Grant from the US National Cancer Institute (CA016672), which supports the Biostatistics Shared Resource, and the US National Cancer Institute grant CA079466. D. Chalaire of the Department of Scientific Publications at MD Anderson Cancer Center provided scientific editing services.

Author information

Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Bora Lim
    • , Xiaoping Wang
    •  & Naoto T. Ueno
  2. Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Bora Lim
    • , Wendy A. Woodward
    • , Xiaoping Wang
    • , James M. Reuben
    •  & Naoto T. Ueno
  3. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Wendy A. Woodward
  4. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • James M. Reuben

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Contributions

B.L. researched data for the article. N.T.U., B.L. and W.A.W. made a substantial contribution to the discussion of content. B.L., W.A.W., X.W. and J.M.R. wrote the article. All authors reviewed and/or edited the article before submission. The order of authorship is B.L., W.A.W., X.W., J.M.R. and N.T.U.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Bora Lim or Naoto T. Ueno.

Glossary

Tumour emboli

Clusters of cancer cells that directly invade dermal–lymphatic vessels or other lymphatic vessels, causing inflammation, breast oedema and lymph node metastasis.

Chemotherapy-resistant dormant units

Units of cells with a 3D composition that mimics the normal gland structure within breast tissue. Formation of an acinar structure in cancer cells has been associated with chemotherapy resistance.

Tumour microenvironment

(TME). The cellular environment in which cancer cells exist, which includes other cell types and components, such as blood vessels, immune cells, fibroblasts, bone marrow-derived stromal cells, signalling molecules and extracellular matrix.

Pathological complete response

(pCR). A category of histopathological post-neoadjuvant therapy response assessment that is often defined as the absence of invasive and/or in situ residual tumours within breast tissue and lymph nodes. Achieving pCR can predict favourable long-term clinical outcomes.

Vascular patency

The degree to which blood vessels are not blocked or obstructed.

Endocrine therapy

Treatment that adds, blocks or removes hormones. Endocrine therapy can be used as single or combination therapy for hormone receptor (HR)-positive breast cancer but has limited activity against HR-positive inflammatory breast cancer.

Synoikis

The activation of survival signals through junctional adhesions between neighbouring cells.

Anoikis

The induction of apoptosis owing to detachment from the extracellular matrix.