Advertisement

Current Oncology Reports

, 21:86 | Cite as

Inflammatory Breast Cancer: a Separate Entity

  • Jennifer M. Rosenbluth
  • Beth A. OvermoyerEmail author
Breast Cancer (B Overmoyer, Section Editor)
  • 52 Downloads
Part of the following topical collections:
  1. Topical Collection on Breast Cancer

Abstract

Purpose of Review

Inflammatory breast cancer (IBC) is an uncommon but highly aggressive subtype of breast cancer that contributes significantly to breast cancer–related mortality. In this review, we provide an overview of the clinical and molecular characteristics of IBC, and highlight some areas of need for ongoing research.

Recent Findings

The disease is characterized by florid tumor emboli that obstruct dermal lymphatics, leading to swelling and inflammation of the affected breast. Recent studies have focused on tumor cell intrinsic features, such as signaling through pathways involved in growth and stem-like behavior, as well as extrinsic features, such as the immune system, that can be leveraged to develop new potential therapies.

Summary

Key efforts have led to an increase in awareness of the disease as well as new insights into IBC pathogenesis. However, there is a strong need for new therapies designed specifically for IBC, and many unanswered questions remain.

Keywords

Inflammatory breast cancer Locally advanced breast cancer Tumor emboli Dermal lymphatic invasion Clinical trials 

Notes

Compliance with Ethical Standards

Conflict of Interest

Jennifer M. Rosenbluth declares that she has no conflict of interest.

Beth A. Overmoyer has received clinical trial support from Incyte, Eisai, and Genentech.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors. If this does pertain to clinical trials for IBC, Dr. Overmoyer has designed these studies which are mentioned in the aticle.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Lucas FV, Perez-Mesa C. Inflammatory carcinoma of the breast. Cancer. 1978;41(4):1595–605.PubMedGoogle Scholar
  2. 2.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. France: Springer; 2010.Google Scholar
  3. 3.
    Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al. AJCC cancer staging manual, 8th ed. Springer International Publishing: American Joint Commission on Cancer; 2017.Google Scholar
  4. 4.
    Rea D, Francis A, Hanby AM, Speirs V, Rakha E, Shaaban A, et al. Inflammatory breast cancer: time to standardise diagnosis assessment and management, and for the joining of forces to facilitate effective research. Br J Cancer. 2015;112(9):1613–5.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Hirko KA, Soliman AS, Banerjee M, Ruterbusch J, Harford JB, Merajver SD, et al. A comparison of criteria to identify inflammatory breast cancer cases from medical records and the Surveillance, Epidemiology and End Results data base, 2007-2009. Breast J. 2014;20(2):185–91.PubMedGoogle Scholar
  6. 6.
    Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA, et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol. 2011;22(3):515–23.PubMedGoogle Scholar
  7. 7.
    Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97(13):966–75.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Cakar B, Surmeli Z, Oner PG, Yelim ES, Karabulut B, Uslu R. The impact of subtype distribution in inflammatory breast cancer outcome. Eur J Breast Health. 2018;14(4):211–7.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Kertmen N, Babacan T, Keskin O, Solak M, Sarici F, Akin S, et al. Molecular subtypes in patients with inflammatory breast cancer; a single center experience. J BUON. 2015;20(1):35–9.PubMedGoogle Scholar
  10. 10.
    Parton M, Dowsett M, Ashley S, Hills M, Lowe F, Smith IE. High incidence of HER-2 positivity in inflammatory breast cancer. Breast. 2004;13(2):97–103.PubMedGoogle Scholar
  11. 11.
    Biswas T, Efird JT, Prasad S, James SE, Walker PR, Zagar TM. Inflammatory TNBC breast cancer: demography and clinical outcome in a large cohort of patients with TNBC. Clin Breast Cancer. 2016;16(3):212–6.PubMedGoogle Scholar
  12. 12.
    Dawood S, Gong Y, Broglio K, Buchholz TA, Woodward W, Lucci A, et al. Trastuzumab in primary inflammatory breast cancer (IBC): high pathological response rates and improved outcome. Breast J. 2010;16(5):529–32.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Masuda H, Brewer TM, Liu DD, Iwamoto T, Shen Y, Hsu L, et al. Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes. Ann Oncol. 2014;25(2):384–91.PubMedGoogle Scholar
  14. 14.
    Li J, Gonzalez-Angulo AM, Allen PK, Yu TK, Woodward WA, Ueno NT, et al. Triple-negative subtype predicts poor overall survival and high locoregional relapse in inflammatory breast cancer. Oncologist. 2011;16(12):1675–83.PubMedPubMedCentralGoogle Scholar
  15. 15.
    •• Ueno NT, Espinosa Fernandez JR, Cristofanilli M, Overmoyer B, Rea D, Berdichevski F, et al. International consensus on the clinical management of inflammatory breast cancer from the Morgan Welch Inflammatory Breast Cancer Research Program 10th Anniversary Conference. J Cancer. 2018;9(8):1437–47. This paper discusses guidelines for the diagnosis and management of IBC developed by a panel of experts from high-volume centers who treat IBC. Areas of controversy were also highlighted. PubMedPubMedCentralGoogle Scholar
  16. 16.
    Groheux D, Giacchetti S, Delord M, Hindie E, Vercellino L, Cuvier C, et al. 18F-FDG PET/CT in staging patients with locally advanced or inflammatory breast cancer: comparison to conventional staging. J Nucl Med. 2013;54(1):5–11.PubMedGoogle Scholar
  17. 17.
    Jacene HA, Youn T, DiPiro PJ, Hu J, Cheng SC, Franchetti Y, et al. Metabolic characterization of inflammatory breast cancer with baseline FDG-PET/CT: relationship with pathologic response after neoadjuvant chemotherapy, receptor status, and tumor grade. Clin Breast Cancer. 2019;19(2):146–55.PubMedGoogle Scholar
  18. 18.
    Mohamed MM, Al-Raawi D, Sabet SF, El-Shinawi M. Inflammatory breast cancer: new factors contribute to disease etiology: a review. J Adv Res. 2014;5(5):525–36.PubMedGoogle Scholar
  19. 19.
    Morrow RJ, Etemadi N, Yeo B, Ernst M. Challenging a misnomer? The role of inflammatory pathways in inflammatory breast cancer. Mediat Inflamm. 2017;2017:4754827.Google Scholar
  20. 20.
    Walker GV, Niikura N, Yang W, Rohren E, Valero V, Woodward WA, et al. Pretreatment staging positron emission tomography/computed tomography in patients with inflammatory breast cancer influences radiation treatment field designs. Int J Radiat Oncol Biol Phys. 2012;83(5):1381–6.PubMedGoogle Scholar
  21. 21.
    Rueth NM, Lin HY, Bedrosian I, Shaitelman SF, Ueno NT, Shen Y, et al. Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(19):2018–24.Google Scholar
  22. 22.
    Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–84.PubMedGoogle Scholar
  23. 23.
    Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791–800.PubMedGoogle Scholar
  24. 24.
    Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018;89:27–35.PubMedGoogle Scholar
  25. 25.
    Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25–32.PubMedGoogle Scholar
  26. 26.
    •• Pernas S GS, Harrison BT, Hu J, Johnson N, Regan M, Chichester LA, Nakhlis F, et al. editors. Assessment of the tumor immune environment in inflammatory breast cancer treated with neoadjuvant dual-HER2 blockade. Proceedings of the 2018 San Antonio Breast Cancer Symposium, Philadelphia (PA); 2018. Analysis of data from a neoadjuvant clinical trial for HER2+ IBC that suggests that immune activation after 1 week of pre-operative dual-HER2 blockade predicts pCR in IBC. Provides further support for clinical trials of immunomodulatory agents as therapy for IBC. Google Scholar
  27. 27.
    •• Matsuda N, Wang X, Lim B, Krishnamurthy S, Alvarez RH, Willey JS, et al. Safety and efficacy of panitumumab plus neoadjuvant chemotherapy in patients with primary HER2-negative inflammatory breast cancer. JAMA Oncol. 2018;4(9):1207–13. This study of an EGFR inhibitor in combination with chemotherapy demonstrated a high pCR rate in patients with HER2-negative inflammatory breast cancer. PubMedPubMedCentralGoogle Scholar
  28. 28.
    Stover DG, Gil Del Alcazar CR, Brock J, Guo H, Overmoyer B, Balko J, et al. Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer. NPJ Breast Cancer. 2018;4:10.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Overmoyer B, Polyak K, Brock J, Van Poznak C, King T, Haddad T, et al. Study of combination ruxolitinib (INCB018424) with preoperative chemotherapy for triple negative inflammatory breast cancer: Translational Breast Cancer Research Consortium Trial 039. San Antonio: San Antonio Breast Cancer Symposium; 2017.Google Scholar
  30. 30.
    Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(−) stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011;121(7):2723–35.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Rosso KJ, Tadros AB, Weiss A, Warneke CL, DeSnyder S, Kuerer H, et al. Improved locoregional control in a contemporary cohort of nonmetastatic inflammatory breast cancer patients undergoing surgery. Ann Surg Oncol. 2017;24(10):2981–8.PubMedGoogle Scholar
  32. 32.
    Nakhlis F, Regan MM, Warren LE, Bellon JR, Hirshfield-Bartek J, Duggan MM, et al. The impact of residual disease after preoperative systemic therapy on clinical outcomes in patients with inflammatory breast cancer. Ann Surg Oncol. 2017;24(9):2563–9.PubMedGoogle Scholar
  33. 33.
    Hieken TJ, Murphy BL, Boughey JC, Degnim AC, Glazebrook KN, Hoskin TL. Influence of biologic subtype of inflammatory breast cancer on response to neoadjuvant therapy and cancer outcomes. Clin Breast Cancer. 2018;18(4):e501–e6.PubMedGoogle Scholar
  34. 34.
    Muzaffar M, Johnson HM, Vohra NA, Liles D, Wong JH. The impact of locoregional therapy in nonmetastatic inflammatory breast cancer: a population-based study. Int J Breast Cancer. 2018;2018:6438635.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Bonev V, Evangelista M, Chen JH, Su MY, Lane K, Mehta R, et al. Long-term follow-up of breast-conserving therapy in patients with inflammatory breast cancer treated with neoadjuvant chemotherapy. Am Surg. 2014;80(10):940–3.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Brzezinska M, Williams LJ, Thomas J, Michael DJ. Outcomes of patients with inflammatory breast cancer treated by breast-conserving surgery. Breast Cancer Res Treat. 2016;160(3):387–91.PubMedGoogle Scholar
  37. 37.
    Chen H, Wu K, Wang M, Wang F, Zhang M, Zhang P. A standard mastectomy should not be the only recommended breast surgical treatment for non-metastatic inflammatory breast cancer: a large population-based study in the Surveillance, Epidemiology, and End Results database 18. Breast. 2017;35:48–54.PubMedGoogle Scholar
  38. 38.
    Stearns V, Ewing CA, Slack R, Penannen MF, Hayes DF, Tsangaris TN. Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer. Ann Surg Oncol. 2002;9(3):235–42.PubMedGoogle Scholar
  39. 39.
    DeSnyder SM, Mittendorf EA, Le-Petross C, Krishnamurthy S, Whitman GJ, Ueno NT, et al. Prospective feasibility trial of sentinel lymph node biopsy in the setting of inflammatory breast cancer. Clin Breast Cancer. 2018;18(1):e73–e7.PubMedGoogle Scholar
  40. 40.
    Motwani SB, Strom EA, Schechter NR, Butler CE, Lee GK, Langstein HN, et al. The impact of immediate breast reconstruction on the technical delivery of postmastectomy radiotherapy. Int J Radiat Oncol Biol Phys. 2006;66(1):76–82.PubMedGoogle Scholar
  41. 41.
    Mortenson MM, Schneider PD, Khatri VP, Stevenson TR, Whetzel TP, Sommerhaug EJ, et al. Immediate breast reconstruction after mastectomy increases wound complications: however, initiation of adjuvant chemotherapy is not delayed. Arch Surg. 2004;139(9):988–91.PubMedGoogle Scholar
  42. 42.
    Nakhlis F, Regan M, Chun YS, Dominici LS, Jacene HA, Yeh ED, et al. Patterns of breast reconstruction in patients diagnosed with inflammatory breast cancer. San Antonio: San Antonio Breast Cancer Symposium; 2015.Google Scholar
  43. 43.
    Woodward WA. Postmastectomy radiation therapy for inflammatory breast cancer: is more better? Int J Radiat Oncol Biol Phys. 2014;89(5):1004–5.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Bristol IJ, Woodward WA, Strom EA, Cristofanilli M, Domain D, Singletary SE, et al. Locoregional treatment outcomes after multimodality management of inflammatory breast cancer. Int J Radiat Oncol Biol Phys. 2008;72(2):474–84.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Lacerda L, Reddy JP, Liu D, Larson R, Li L, Masuda H, et al. Simvastatin radiosensitizes differentiated and stem-like breast cancer cell lines and is associated with improved local control in inflammatory breast cancer patients treated with postmastectomy radiation. Stem Cells Transl Med. 2014;3(7):849–56.PubMedPubMedCentralGoogle Scholar
  46. 46.
    •• Jagsi R, Griffith KA, Bellon JR, Woodward WA, Horton JK, Ho A, et al. Concurrent veliparib with chest wall and nodal radiotherapy in patients with inflammatory or locoregionally recurrent breast cancer: the TBCRC 024 Phase I Multicenter Study. J Clin Oncol. 2018;36(13):1317–22. This is the report of the Phase I study of a PARP inhibitor given concurrently with radiotherapy, demonstrating the potential of this regimen but also underscoring the importance of long-term monitoring for toxicity. PubMedGoogle Scholar
  47. 47.
    Regan MM, Fleming GF, Walley B, Francis PA, Pagani O. Adjuvant systemic treatment of premenopausal women with hormone receptor-positive early breast cancer: lights and shadows. J Clin Oncol. 2019;37(11):862–6.PubMedGoogle Scholar
  48. 48.
    Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147–59.PubMedGoogle Scholar
  49. 49.
    von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122–31.Google Scholar
  50. 50.
    von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617–28.Google Scholar
  51. 51.
    Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1688–700.PubMedGoogle Scholar
  52. 52.
    Warren LE, Guo H, Regan MM, Nakhlis F, Yeh ED, Jacene HA, et al. Inflammatory breast cancer: patterns of failure and the case for aggressive locoregional management. Ann Surg Oncol. 2015;22(8):2483–91.PubMedGoogle Scholar
  53. 53.
    Akay CL, Ueno NT, Chisholm GB, Hortobagyi GN, Woodward WA, Alvarez RH, et al. Primary tumor resection as a component of multimodality treatment may improve local control and survival in patients with stage IV inflammatory breast cancer. Cancer. 2014;120(9):1319–28.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Warren LE, Guo H, Regan MM, Nakhlis F, Yeh ED, Jacene HA, et al. Inflammatory breast cancer and development of brain metastases: risk factors and outcomes. Breast Cancer Res Treat. 2015;151(1):225–32.PubMedGoogle Scholar
  55. 55.
    Sauer SJ, Tarpley M, Shah I, Save AV, Lyerly HK, Patierno SR, et al. Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells. Carcinogenesis. 2017;38(3):252–60.PubMedGoogle Scholar
  56. 56.
    Williams KP, Allensworth JL, Ingram SM, Smith GR, Aldrich AJ, Sexton JZ, et al. Quantitative high-throughput efficacy profiling of approved oncology drugs in inflammatory breast cancer models of acquired drug resistance and re-sensitization. Cancer Lett. 2013;337(1):77–89.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Jolly MK, Boareto M, Debeb BG, Aceto N, Farach-Carson MC, Woodward WA, et al. Inflammatory breast cancer: a model for investigating cluster-based dissemination. NPJ Breast Cancer. 2017;3:21.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Cheung KJ, Padmanaban V, Silvestri V, Schipper K, Cohen JD, Fairchild AN, et al. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc Natl Acad Sci U S A. 2016;113(7):E854–63.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Rodriguez FJ, Lewis-Tuffin LJ, Anastasiadis PZ. E-Cadherin’s dark side: possible role in tumor progression. Biochim Biophys Acta. 2012;1826(1):23–31.PubMedPubMedCentralGoogle Scholar
  60. 60.
    •• Lacerda L, Debeb BG, Smith D, Larson R, Solley T, Xu W, et al. Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model. Breast Cancer Res. 2015;17:42. This study demonstrates that co-injection with mesenchymal stem cells improves skin invasion and metastasis in a SUM149 IBC xenograft model. These features were generally not found in most prior models of IBC. PubMedPubMedCentralGoogle Scholar
  61. 61.
    Raposo TP, Arias-Pulido H, Chaher N, Fiering SN, Argyle DJ, Prada J, et al. Comparative aspects of canine and human inflammatory breast cancer. Semin Oncol. 2017;44(4):288–300.PubMedGoogle Scholar
  62. 62.
    Caceres S, Pena L, Silvan G, Illera MJ, Woodward WA, Reuben JM, et al. Steroid tumor environment in male and female mice model of canine and human inflammatory breast cancer. Biomed Res Int. 2016;2016:8909878.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Lehman HL, Dashner EJ, Lucey M, Vermeulen P, Dirix L, Van Laere S, et al. Modeling and characterization of inflammatory breast cancer emboli grown in vitro. Int J Cancer. 2013;132(10):2283–94.PubMedGoogle Scholar
  64. 64.
    Sachs N, de Ligt J, Kopper O, Gogola E, Bounova G, Weeber F, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell. 2018;172(1–2):373–86 e10.PubMedGoogle Scholar
  65. 65.
    Rosenbluth JMZI, Boedicker M, Wagle N, Dillon D, Nakhlis F, Brugge JS, et al., editors. Patient-derived organoid models of inflammatory breast cancer. San Antonio: SABCS; 2018.Google Scholar
  66. 66.
    •• Lim B, Woodward WA, Wang X, Reuben JM, Ueno NT. Inflammatory breast cancer biology: the tumour microenvironment is key. Nat Rev Cancer. 2018;18(8):485–99. This is a comprehensive review of the role of the microenvironment in IBC pathogenesis. PubMedGoogle Scholar
  67. 67.
    Bertucci F, Ueno NT, Finetti P, Vermeulen P, Lucci A, Robertson FM, et al. Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival. Ann Oncol. 2014;25(2):358–65.PubMedGoogle Scholar
  68. 68.
    Van Laere SJ, Ueno NT, Finetti P, Vermeulen P, Lucci A, Robertson FM, et al. Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets. Clin Cancer Res. 2013;19(17):4685–96.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Woodward WA, Krishnamurthy S, Yamauchi H, El-Zein R, Ogura D, Kitadai E, et al. Genomic and expression analysis of microdissected inflammatory breast cancer. Breast Cancer Res Treat. 2013;138(3):761–72.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Woodward WA. Inflammatory breast cancer: unique biological and therapeutic considerations. Lancet Oncol. 2015;16(15):e568–e76.PubMedGoogle Scholar
  71. 71.
    •• Reddy JP, Atkinson RL, Larson R, Burks JK, Smith D, Debeb BG, et al. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer. Res Treat. 2018;171:283–93. In this study, immunostaining of normal breast tissue from IBC patients revealed enrichment of mammary stem cells as well as macrophages. This provides additional evidence for the role of the microenvironment and host factors in IBC. Google Scholar
  72. 72.
    Reddy SM, Reuben A, Barua S, Jiang H, Zhang S, Wang L, et al. Poor response to neoadjuvant chemotherapy correlates with mast cell infiltration in inflammatory breast cancer. Cancer Immunol Res. 2019;7:1025–35.PubMedGoogle Scholar
  73. 73.
    •• Bertucci F, Finetti P, Colpaert C, Mamessier E, Parizel M, Dirix L, et al. PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy. Oncotarget. 2015;6(15):13506–19. This study assessed PDL1 mRNA levels in IBC samples. A high level of PDL1 was predictive of response to chemotherapy in this retrospective study. PubMedPubMedCentralGoogle Scholar
  74. 74.
    Wolfe AR, Trenton NJ, Debeb BG, Larson R, Ruffell B, Chu K, et al. Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models. Oncotarget. 2016;7(50):82482–92.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Mego M, Gao H, Cohen EN, Anfossi S, Giordano A, Tin S, et al. Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer. Oncotarget. 2017;8(22):35656–68.PubMedGoogle Scholar
  76. 76.
    Datta J, Berk E, Xu S, Fitzpatrick E, Rosemblit C, Lowenfeld L, et al. Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer. Breast Cancer Res. 2015;17:71.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Valeta-Magara A, Gadi A, Volta V, Walters B, Arju R, Giashuddin S, et al. Inflammatory breast cancer promotes development of M2 tumor-associated macrophages and cancer mesenchymal cells through a complex cytokine network. Cancer Res. 2019;79:3360–71.PubMedGoogle Scholar
  78. 78.
    Xiao Y, Ye Y, Yearsley K, Jones S, Barsky SH. The lymphovascular embolus of inflammatory breast cancer expresses a stem cell-like phenotype. Am J Pathol. 2008;173(2):561–74.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Levine PH, Portera CC, Hoffman HJ, Yang SX, Takikita M, Duong QN, et al. Evaluation of lymphangiogenic factors, vascular endothelial growth factor D and E-cadherin in distinguishing inflammatory from locally advanced breast cancer. Clin Breast Cancer. 2012;12(4):232–9.PubMedGoogle Scholar
  80. 80.
    Zhang D, LaFortune TA, Krishnamurthy S, Esteva FJ, Cristofanilli M, Liu P, et al. Epidermal growth factor receptor tyrosine kinase inhibitor reverses mesenchymal to epithelial phenotype and inhibits metastasis in inflammatory breast cancer. Clin Cancer Res. 2009;15(21):6639–48.PubMedPubMedCentralGoogle Scholar
  81. 81.
    van Golen KL, Bao L, DiVito MM, Wu Z, Prendergast GC, Merajver SD. Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. Mol Cancer Ther. 2002;1(8):575–83.PubMedGoogle Scholar
  82. 82.
    van Golen KL, Bao LW, Pan Q, Miller FR, Wu ZF, Merajver SD. Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer. Clin Exp Metastasis. 2002;19(4):301–11.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Susan F. Smith Center for Women’s Cancers, Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA

Personalised recommendations