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Inflammatory Breast Cancer: Diagnostic, Molecular and Therapeutic Considerations

  • Grace X. Li
  • Justin W. Tiulim
  • Julie E. Lang
  • Irene KangEmail author
Hot Topics in Breast Cancer (K Hunt, Section Editor)
  • 15 Downloads
Part of the following topical collections:
  1. Topical Collection on Hot Topics in Breast Cancer

Abstract

Purpose of Review

Inflammatory breast cancer (IBC) is an aggressive type of breast cancer with poor prognosis. Treatment for non-metastatic disease is neoadjuvant chemotherapy followed by mastectomy and radiation. IBC diagnosis is primarily a clinical diagnosis, which can lead to misdiagnosis and delayed management. In addition, there are no molecular criteria for diagnosis or therapeutic regimens developed specifically for IBC. We aimed to discuss recent developments in IBC, including diagnosis, molecular mechanisms, and treatment.

Recent Findings

Recently, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) breast cancer staging system has defined the diagnostic features of IBC. Current molecular characterization of IBC has not revealed a unique signature or marker for diagnosis; however, this work sheds light on the pathophysiology of IBC and provides potential therapeutic targets.

Summary

The prognosis of IBC remains poor, although the survival is improved significantly with trimodal management. To date, a consensus on diagnosis and prospective trials specifically designed for IBC therapy are lacking. Standardized criteria incorporating clinical, pathologic, and molecular criteria remains an unmet need. Recent consensus recommendations regarding diagnosis and management are reviewed with a view towards evolving molecular characterization, potential targets, and current clinical trials.

Keywords

Inflammatory breast cancer Neoadjuvant therapy Modified radical mastectomy Radiation therapy Targeted therapy 

Notes

Funding Information

The project described was supported in part by award number P30CA014089 from the National Cancer Institute.

Compliance with Ethical Standards

Conflict of Interest

Irene Kang reports personal fees from Puma Biotechnology and from Pfizer outside the submitted work. Julie Lang reports grants from ANGLE Parsortix and personal fees from Genomic Health outside the submitted work. Grace Li and Justin Tiulim declare no conflicts of interest relevant to this manuscript.

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.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

References

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

  1. 1.
    van Golen KL, Cristofanilli M. The Third International Inflammatory Breast Cancer onference. Breast Cancer Res. 2013;15(6):318.  https://doi.org/10.1186/bcr3571.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    •• Woodward WA, Cristofanilli M, Merajver SD, Van Laere S, Pusztai L, Bertucci F, et al. Scientific summary from the Morgan Welch MD Anderson Cancer Center Inflammatory Breast Cancer (IBC) Program 10. J Cancer. 2017;8(17):3607–14.  https://doi.org/10.7150/jca.21200This is an expert summary of recent scientific work in IBC.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Matro JM, Li T, Cristofanilli M, Hughes ME, Ottesen RA, Weeks JC, et al. Inflammatory breast cancer management in the national comprehensive cancer network: the disease, recurrence pattern, and outcome. Clin Breast Cancer. 2015;15(1):1–7.  https://doi.org/10.1016/j.clbc.2014.05.005.CrossRefPubMedGoogle Scholar
  4. 4.
    Wecsler JS, Tereffe W, Pedersen RC, Sieffert MR, Mack WJ, Cui H, et al. Lymph node status in inflammatory breast cancer. Breast Cancer Res Treat. 2015;151(1):113–20.  https://doi.org/10.1007/s10549-015-3367-6.CrossRefPubMedGoogle Scholar
  5. 5.
    Kleer CG, van Golen KL, Merajver SD. Molecular biology of breast cancer metastasis. Inflammatory breast cancer: clinical syndrome and molecular determinants. Breast Cancer Res. 2000;2(6):423–9.  https://doi.org/10.1186/bcr89.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Walshe JM, Swain SM. Clinical aspects of inflammatory breast cancer. Breast Dis. 2005;22:35–44.CrossRefGoogle Scholar
  7. 7.
    Jaiyesimi IA, Buzdar AU, Hortobagyi G. Inflammatory breast cancer: a review. J Clin Oncol. 1992;10(6):1014–24.  https://doi.org/10.1200/JCO.1992.10.6.1014.CrossRefPubMedGoogle Scholar
  8. 8.
    Anderson WF, Schairer C, Chen BE, Hance KW, Levine PH. Epidemiology of inflammatory breast cancer (IBC). Breast Dis. 2005;22:9–23.CrossRefGoogle Scholar
  9. 9.
    •• Li J, Xia Y, Wu Q, Zhu S, Chen C, Yang W, et al. Outcomes of patients with inflammatory breast cancer by hormone receptor- and HER2-defined molecular subtypes: a population-based study from the SEER program. Oncotarget. 2017;8(30):49370–9.  https://doi.org/10.18632/oncotarget.17217This study provided epidemiologic data on IBC outcomes by molecular subtypes. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    •• 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.  https://doi.org/10.7150/jca.23969The most recent consensus guidelines on IBC clinical management. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    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.  https://doi.org/10.1093/jnci/dji172.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Eiró N, González L, González LO, Fernandez-Garcia B, Lamelas ML, Marín L, et al. Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development. PLoS One. 2012;7(11):e49047.  https://doi.org/10.1371/journal.pone.0049047.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Costa R, Santa-Maria CA, Rossi G, Carneiro BA, Chae YK, Gradishar WJ, et al. Developmental therapeutics for inflammatory breast cancer: biology and translational directions. Oncotarget. 2017;8(7):12417–32.  https://doi.org/10.18632/oncotarget.13778.CrossRefPubMedGoogle Scholar
  14. 14.
    Yamauchi H, Woodward WA, Valero V, Alvarez RH, Lucci A, Buchholz TA, et al. Inflammatory breast cancer: what we know and what we need to learn. Oncologist. 2012;17(7):891–9.  https://doi.org/10.1634/theoncologist.2012-0039.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    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.  https://doi.org/10.1093/annonc/mdq345.CrossRefPubMedGoogle Scholar
  16. 16.
    Amparo RS, Angel CD, Ana LH, Antonio LC, Vicente MS, Carlos FM, et al. Inflammatory breast carcinoma: pathological or clinical entity? Breast Cancer Res Treat. 2000;64(3):269–73.CrossRefGoogle Scholar
  17. 17.
    Yang WT, Le-Petross HT, Macapinlac H, Carkaci S, Gonzalez-Angulo AM, Dawood S, et al. Inflammatory breast cancer: PET/CT, MRI, mammography, and sonography findings. Breast Cancer Res Treat. 2008;109(3):417–26.  https://doi.org/10.1007/s10549-007-9671-z.CrossRefPubMedGoogle Scholar
  18. 18.
    Groheux D, Giacchetti S, Delord M, Hindié 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.  https://doi.org/10.2967/jnumed.112.106864.CrossRefPubMedGoogle Scholar
  19. 19.
    Carkaci S, Sherman CT, Ozkan E, Adrada BE, Wei W, Rohren EM, et al. (18)F-FDG PET/CT predicts survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2013;40(12):1809–16.  https://doi.org/10.1007/s00259-013-2506-8.CrossRefPubMedGoogle Scholar
  20. 20.
    Bertucci F, Finetti P, Birnbaum D, Viens P. Gene expression profiling of inflammatory breast cancer. Cancer. 2010;116(11 Suppl):2783–93.  https://doi.org/10.1002/cncr.25165.CrossRefPubMedGoogle Scholar
  21. 21.
    Van Laere S, Van der Auwera I, Van den Eynden GG, Fox SB, Bianchi F, Harris AL, et al. Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis. Breast Cancer Res Treat. 2005;93(3):237–46.  https://doi.org/10.1007/s10549-005-5157-z.CrossRefPubMedGoogle Scholar
  22. 22.
    Bertucci F, Finetti P, Rougemont J, Charafe-Jauffret E, Nasser V, Loriod B, et al. Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy. Cancer Res. 2004;64(23):8558–65.  https://doi.org/10.1158/0008-5472.CAN-04-2696.CrossRefPubMedGoogle Scholar
  23. 23.
    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.  https://doi.org/10.1158/1078-0432.Ccr-12-2549.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Carneiro BA, Costa R, Taxter T, Chandra S, Chae YK, Cristofanilli M, et al. Is personalized medicine here? Oncology (Williston Park). 2016;30(4):293–303 7.Google Scholar
  25. 25.
    Van den Eynden GG, Van der Auwera I, Van Laere S, Colpaert CG, van Dam P, Merajver S, et al. Validation of a tissue microarray to study differential protein expression in inflammatory and non-inflammatory breast cancer. Breast Cancer Res Treat. 2004;85(1):13–22.  https://doi.org/10.1023/B:BREA.0000021028.33926.a8.CrossRefPubMedGoogle Scholar
  26. 26.
    Van der Auwera I, Bovie C, Svensson C, Limame R, Trinh XB, van Dam P, et al. Quantitative assessment of DNA hypermethylation in the inflammatory and non-inflammatory breast cancer phenotypes. Cancer Biol Ther. 2009;8(23):2252–9.  https://doi.org/10.4161/cbt.8.23.10133.CrossRefPubMedGoogle Scholar
  27. 27.
    Van der Auwera I, Van Laere SJ, Van den Bosch SM, Van den Eynden GG, Trinh BX, van Dam PA, et al. Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype. Br J Cancer. 2008;99(10):1735–42.  https://doi.org/10.1038/sj.bjc.6604705.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Hamm CA, Moran D, Rao K, Trusk PB, Pry K, Sausen M, et al. Genomic and immunological tumor profiling identifies targetable pathways and extensive CD8+/PDL1+ immune infiltration in inflammatory breast Cancer tumors. Mol Cancer Ther. 2016;15(7):1746–56.  https://doi.org/10.1158/1535-7163.MCT-15-0353.CrossRefPubMedGoogle Scholar
  29. 29.
    Qi Y, Wang X, Kong X, Zhai J, Fang Y, Guan X, et al. Expression signatures and roles of microRNAs in inflammatory breast cancer. Cancer Cell Int. 2019;19(1):23.  https://doi.org/10.1186/s12935-018-0709-6.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Paradiso A, Tommasi S, Brandi M, Marzullo F, Simone G, Lorusso V, et al. Cell kinetics and hormonal receptor status in inflammatory breast carcinoma. Comparison with locally advanced disease. Cancer. 1989;64(9):1922–7.  https://doi.org/10.1002/1097-0142(19891101)64:9<1922::aid-cncr2820640927>3.0.co;2-i.CrossRefPubMedGoogle Scholar
  31. 31.
    Zell JA, Tsang WY, Taylor TH, Mehta RS, Anton-Culver H. Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry. Breast Cancer Res. 2009;11(1):R9.  https://doi.org/10.1186/bcr2225.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Dawood S, Broglio K, Gong Y, Yang WT, Cristofanilli M, Kau SW, et al. Prognostic significance of HER-2 status in women with inflammatory breast cancer. Cancer. 2008;112(9):1905–11.  https://doi.org/10.1002/cncr.23350.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chaher N, Arias-Pulido H, Terki N, Qualls C, Bouzid K, Verschraegen C, et al. Molecular and epidemiological characteristics of inflammatory breast cancer in Algerian patients. Breast Cancer Res Treat. 2012;131(2):437–44.  https://doi.org/10.1007/s10549-011-1422-5.CrossRefPubMedGoogle Scholar
  34. 34.
    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
  35. 35.
    • Biswas T, Jindal C, Fitzgerald TL, Efird JT. Pathologic complete response (pCR) and survival of women with inflammatory breast cancer (IBC): an analysis based on biologic subtypes and demographic characteristics. Int J Environ Res Public Health. 2019;16(1).  https://doi.org/10.3390/ijerph16010124This retrospective study analyzed the relationship of pCR and survival in IBC based on biologic subtypes, demographic characteristics and treatment characteristics. CrossRefGoogle Scholar
  36. 36.
    Singh JAS, Nock W, Zhang Y, Adams E, Damicis A, Parsons HA, et al. Aggressive subgroups of metastatic triple-negative breast cancer: Inflammatory breast cancer and young patients in the Dana-Farber cell-free DNA cohort. San Antonio Breast Cancer Symposium; 2018 December 7, 2018.Google Scholar
  37. 37.
    Van Laere SJ, Van den Eynden GG, Van der Auwera I, Vandenberghe M, van Dam P, Van Marck EA, et al. Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling. Breast Cancer Res Treat. 2006;95(3):243–55.  https://doi.org/10.1007/s10549-005-9015-9.CrossRefPubMedGoogle Scholar
  38. 38.
    Mueller KL, Yang ZQ, Haddad R, Ethier SP, Boerner JL. EGFR/Met association regulates EGFR TKI resistance in breast cancer. J Mol Signal. 2010;5:8.  https://doi.org/10.1186/1750-2187-5-8.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Cabioglu N, Gong Y, Islam R, Broglio KR, Sneige N, Sahin A, et al. Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer. Ann Oncol. 2007;18(6):1021–9.  https://doi.org/10.1093/annonc/mdm060.CrossRefPubMedGoogle Scholar
  40. 40.
    Charafe-Jauffret E, Tarpin C, Bardou VJ, Bertucci F, Ginestier C, Braud AC, et al. Immunophenotypic analysis of inflammatory breast cancers: identification of an ‘inflammatory signature’. J Pathol. 2004;202(3):265–73.  https://doi.org/10.1002/path.1515.CrossRefPubMedGoogle Scholar
  41. 41.
    Lee CH, Wu YT, Hsieh HC, Yu Y, Yu AL, Chang WW. Epidermal growth factor/heat shock protein 27 pathway regulates vasculogenic mimicry activity of breast cancer stem/progenitor cells. Biochimie. 2014;104:117–26.  https://doi.org/10.1016/j.biochi.2014.06.011.CrossRefPubMedGoogle Scholar
  42. 42.
    Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN, Ueno NT. Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res Treat. 2012;136(2):331–45.  https://doi.org/10.1007/s10549-012-2289-9.CrossRefPubMedGoogle Scholar
  43. 43.
    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.  https://doi.org/10.1158/1078-0432.CCR-09-0951.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kaushal N, Tiruchinapally G, Durmaz YY, Bao L, Gilani R, Merajver SD, et al. Synergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on “smart” particles. J Control Release. 2018;289:79–93.  https://doi.org/10.1016/j.jconrel.2018.07.042.CrossRefPubMedGoogle Scholar
  45. 45.
    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.  https://doi.org/10.1001/jamaoncol.2018.1436.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Cristofanilli M, Gonzalez-Angulo AM, Buzdar AU, Kau SW, Frye DK, Hortobagyi GN. Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson cancer center experience. Clin Breast Cancer. 2004;4(6):415–9.CrossRefGoogle Scholar
  47. 47.
    van Golen KL, Wu ZF, Qiao XT, Bao LW, Merajver SD. RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Res. 2000;60(20):5832–8.PubMedGoogle Scholar
  48. 48.
    van Golen KL, Wu ZF, Qiao XT, Bao L, Merajver SD. RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia. 2000;2(5):418–25.  https://doi.org/10.1038/sj.neo.7900115.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    van Golen KL, Davies S, Wu ZF, Wang Y, Bucana CD, Root H, et al. A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. Clin Cancer Res. 1999;5(9):2511–9.PubMedGoogle Scholar
  50. 50.
    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
  51. 51.
    Brewer TM, Masuda H, Liu DD, Shen Y, Liu P, Iwamoto T, et al. Statin use in primary inflammatory breast cancer: a cohort study. Br J Cancer. 2013;109(2):318–24.  https://doi.org/10.1038/bjc.2013.342.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Sansone P, Bromberg J. Targeting the interleukin-6/Jak/stat pathway in human malignancies. J Clin Oncol. 2012;30(9):1005–14.  https://doi.org/10.1200/JCO.2010.31.8907.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Jhaveri K, Teplinsky E, Silvera D, Valeta-Magara A, Arju R, Giashuddin S, et al. Hyperactivated mTOR and JAK2/STAT3 pathways: molecular drivers and potential therapeutic targets of inflammatory and invasive ductal breast cancers after neoadjuvant chemotherapy. Clin Breast Cancer. 2016;16(2):113–22.e1.  https://doi.org/10.1016/j.clbc.2015.11.006.CrossRefPubMedGoogle Scholar
  54. 54.
    Zoratti GL, Tanabe LM, Hyland TE, Duhaime MJ, Colombo É, Leduc R, et al. Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer. Oncotarget. 2016;7(36):58162–73.  https://doi.org/10.18632/oncotarget.11262.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Kleer CG, van Golen KL, Braun T, Merajver SD. Persistent E-cadherin expression in inflammatory breast cancer. Mod Pathol. 2001;14(5):458–64.  https://doi.org/10.1038/modpathol.3880334.CrossRefPubMedGoogle Scholar
  56. 56.
    Ye Y, Tellez JD, Durazo M, Belcher M, Yearsley K, Barsky SH. E-cadherin accumulation within the lymphovascular embolus of inflammatory breast cancer is due to altered trafficking. Anticancer Res. 2010;30(10):3903–10.PubMedGoogle Scholar
  57. 57.
    Tomlinson JS, Alpaugh ML, Barsky SH. An intact overexpressed E-cadherin/alpha,beta-catenin axis characterizes the lymphovascular emboli of inflammatory breast carcinoma. Cancer Res. 2001;61(13):5231–41.PubMedGoogle Scholar
  58. 58.
    Alpaugh ML, Tomlinson JS, Kasraeian S, Barsky SH. Cooperative role of E-cadherin and sialyl-Lewis X/A-deficient MUC1 in the passive dissemination of tumor emboli in inflammatory breast carcinoma. Oncogene. 2002;21(22):3631–43.  https://doi.org/10.1038/sj.onc.1205389.CrossRefPubMedGoogle Scholar
  59. 59.
    Colpaert CG, Vermeulen PB, Benoy I, Soubry A, van Roy F, van Beest P, et al. Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong E-cadherin expression. Br J Cancer. 2003;88(5):718–25.  https://doi.org/10.1038/sj.bjc.6600807.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Vermeulen PB, van Golen KL, Dirix LY. Angiogenesis, lymphangiogenesis, growth pattern, and tumor emboli in inflammatory breast cancer: a review of the current knowledge. Cancer. 2010;116(11 Suppl):2748–54.  https://doi.org/10.1002/cncr.25169.CrossRefPubMedGoogle Scholar
  61. 61.
    Overmoyer B, Fu P, Hoppel C, Radivoyevitch T, Shenk R, Persons M, et al. Inflammatory breast cancer as a model disease to study tumor angiogenesis: results of a phase IB trial of combination SU5416 and doxorubicin. Clin Cancer Res. 2007;13(19):5862–8.  https://doi.org/10.1158/1078-0432.Ccr-07-0688.CrossRefPubMedGoogle Scholar
  62. 62.
    Wedam SB, Low JA, Yang SX, Chow CK, Choyke P, Danforth D, et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006;24(5):769–77.CrossRefGoogle Scholar
  63. 63.
    • Bertucci F, Fekih M, Autret A, Petit T, Dalenc F, Levy C, et al. Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2016;17(5):600–11.  https://doi.org/10.1016/S1470-2045(16)00011-5The BEVERLY-1 trial failed to identify clinical benefit of the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment of patients with HER2-negative inflammatory breast cancer. CrossRefPubMedGoogle Scholar
  64. 64.
    Pierga JY, Petit T, Delozier T, Ferrero JM, Campone M, Gligorov J, et al. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol. 2012;13(4):375–84.  https://doi.org/10.1016/S1470-2045(12)70049-9.CrossRefPubMedGoogle Scholar
  65. 65.
    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.  https://doi.org/10.1111/j.1524-4741.2010.00953.x.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    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.  https://doi.org/10.1016/j.canlet.2013.05.017.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Cristofanilli M, Johnston SR, Manikhas A, Gomez HL, Gladkov O, Shao Z, et al. A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer. Breast Cancer Res Treat. 2013;137(2):471–82.  https://doi.org/10.1007/s10549-012-2369-x.CrossRefPubMedGoogle Scholar
  68. 68.
    Ueno NT, Buzdar AU, Singletary SE, Ames FC, McNeese MD, Holmes FA, et al. Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer center. Cancer Chemother Pharmacol. 1997;40(4):321–9.  https://doi.org/10.1007/s002800050664.CrossRefPubMedGoogle Scholar
  69. 69.
    Gray R, Bradley R, Braybrooke J, Liu Z, Peto R, Davies L, et al. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37&#x2008;298 women with early breast cancer in 26 randomised trials. Lancet. 2019;393(10179):1440–52.  https://doi.org/10.1016/S0140-6736(18)33137-4.CrossRefGoogle Scholar
  70. 70.
    Untch M, Möbus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I, et al. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 2009;27(18):2938–45.  https://doi.org/10.1200/JCO.2008.20.3133.CrossRefPubMedGoogle Scholar
  71. 71.
    Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13–21.  https://doi.org/10.1200/jco.2014.57.0572.CrossRefPubMedGoogle Scholar
  72. 72.
    von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15(7):747–56.  https://doi.org/10.1016/s1470-2045(14)70160-3.CrossRefGoogle Scholar
  73. 73.
    Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. The Lancet Oncology. 2018;19(4):497–509.  https://doi.org/10.1016/s1470-2045(18)30111-6.CrossRefPubMedGoogle Scholar
  74. 74.
    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.  https://doi.org/10.1056/NEJMoa1612645.CrossRefPubMedGoogle Scholar
  75. 75.
    Francis PA, Regan MM, Fleming GF. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(17):1673.  https://doi.org/10.1056/NEJMc1502618.CrossRefPubMedGoogle Scholar
  76. 76.
    Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–18.  https://doi.org/10.1056/NEJMoa1404037.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    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.  https://doi.org/10.1016/j.breast.2003.08.004.CrossRefPubMedGoogle Scholar
  78. 78.
    Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15(6):640–7.  https://doi.org/10.1016/S1470-2045(14)70080-4.CrossRefPubMedGoogle Scholar
  79. 79.
    Gianni L, Bisagni G, Colleoni M, Del Mastro L, Zamagni C, Mansutti M, et al. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an exploratory, open-label, phase 2 study. Lancet Oncol. 2018;19(2):249–56.  https://doi.org/10.1016/S1470-2045(18)30001-9.CrossRefPubMedGoogle Scholar
  80. 80.
    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.  https://doi.org/10.1056/NEJMoa1814017.CrossRefGoogle Scholar
  81. 81.
    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. The Lancet Oncology. 2017;18(12):1688–700.  https://doi.org/10.1016/s1470-2045(17)30717-9.CrossRefPubMedGoogle Scholar
  82. 82.
    Singletary SE. Surgical management of inflammatory breast cancer. Semin Oncol. 2008;35(1):72–7.  https://doi.org/10.1053/j.seminoncol.2007.11.008.CrossRefPubMedGoogle Scholar
  83. 83.
    Perez CA, Fields JN, Fracasso PM, Philpott G, Soares RL, Taylor ME, et al. Management of locally advanced carcinoma of the breast. II Inflammatory carcinoma. Cancer. 1994;74(1 Suppl):466–76.  https://doi.org/10.1002/cncr.2820741336.CrossRefPubMedGoogle Scholar
  84. 84.
    Panades M, Olivotto IA, Speers CH, Shenkier T, Olivotto TA, Weir L, et al. Evolving treatment strategies for inflammatory breast cancer: a population-based survival analysis. J Clin Oncol. 2005;23(9):1941–50.  https://doi.org/10.1200/JCO.2005.06.233.CrossRefPubMedGoogle Scholar
  85. 85.
    De Boer RH, Allum WH, Ebbs SR, Gui GP, Johnston SR, Sacks NP, et al. Multimodality therapy in inflammatory breast cancer: is there a place for surgery? Ann Oncol. 2000;11(9):1147–53.  https://doi.org/10.1023/a:1008374931854.CrossRefPubMedGoogle Scholar
  86. 86.
    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.  https://doi.org/10.1007/s10549-016-4017-3.CrossRefPubMedGoogle Scholar
  87. 87.
    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.  https://doi.org/10.1245/s10434-017-5952-x.CrossRefPubMedGoogle Scholar
  88. 88.
    Fleming RY, Asmar L, Buzdar AU, McNeese MD, Ames FC, Ross MI, et al. Effectiveness of mastectomy by response to induction chemotherapy for control in inflammatory breast carcinoma. Ann Surg Oncol. 1997;4(6):452–61.CrossRefGoogle Scholar
  89. 89.
    Hidar S, Bibi M, Gharbi O, Tebra S, Trabelsi A, Korbi S, et al. Sentinel lymph node biopsy after neoadjuvant chemotherapy in inflammatory breast cancer. Int J Surg. 2009;7(3):272–5.  https://doi.org/10.1016/j.ijsu.2009.04.012.CrossRefPubMedGoogle Scholar
  90. 90.
    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.  https://doi.org/10.1016/j.ijrobp.2008.01.039.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Liao Z, Strom EA, Buzdar AU, Singletary SE, Hunt K, Allen PK, et al. Locoregional irradiation for inflammatory breast cancer: effectiveness of dose escalation in decreasing recurrence. Int J Radiat Oncol Biol Phys. 2000;47(5):1191–200.  https://doi.org/10.1016/s0360-3016(00)00561-7.CrossRefPubMedGoogle Scholar
  92. 92.
    Woodward WA, Debeb BG, Xu W, Buchholz TA. Overcoming radiation resistance in inflammatory breast cancer. Cancer. 2010;116(11 Suppl):2840–5.  https://doi.org/10.1002/cncr.25173.CrossRefPubMedGoogle Scholar
  93. 93.
    Greenwalt JC, Mendenhall NP, Kennedy WR, Lightsey J, Morris CG, Bradley JA. Radiation therapy in the treatment of inflammatory breast cancer (IBC): a retrospective review of IBC patients. Int J Radiat Oncol Biol Phys. 2016;96(2):E1–2.  https://doi.org/10.1016/j.ijrobp.2016.06.598.CrossRefGoogle Scholar
  94. 94.
    Robson M, Goessl C, Domchek S. Olaparib for metastatic Germline BRCA-mutated breast cancer. N Engl J Med. 2017;377(18):1792–3.  https://doi.org/10.1056/NEJMc1711644.CrossRefPubMedGoogle Scholar
  95. 95.
    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.  https://doi.org/10.1200/jco.2017.77.2665.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    • Van Berckelaer C, Rypens C, van Dam P, Pouillon L, Parizel M, Schats KA, et al. Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression. Breast Cancer Res. 2019;21(1):28.  https://doi.org/10.1186/s13058-019-1108-1This prospective international study identified PD-L1 expression as predictive of response to neo-adjuvant therapy and that stromal tumour-infiltrating lymphocytes (sTIL) have prognostic significance in IBC.
  97. 97.
    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.  https://doi.org/10.18632/oncotarget.3642.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21.  https://doi.org/10.1056/NEJMoa1809615.CrossRefPubMedGoogle Scholar
  99. 99.
    Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort a of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30(3):397–404.  https://doi.org/10.1093/annonc/mdy517.CrossRefPubMedGoogle Scholar
  100. 100.
    Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30(3):405–11.  https://doi.org/10.1093/annonc/mdy518.CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Grace X. Li
    • 1
    • 2
  • Justin W. Tiulim
    • 1
    • 2
  • Julie E. Lang
    • 2
    • 3
  • Irene Kang
    • 1
    • 2
    Email author
  1. 1.Department of Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Norris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of Surgery, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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