Duke Consortium for IBC
Program Overview
The Duke Consortium for Inflammatory Breast Cancer is a multidisciplinary center of research innovation and clinical excellence that is focused on understanding, preventing, and treating inflammatory breast cancer through collaboration with our local, national and international partners.
Support from Duke School of Medicine Interdisciplinary Colloquia funds led to the first meeting on December 3, 2014, which included investigators with diverse research and clinical interests from Duke, NCCU and UNC, research administrators, and patient advocates. In this meeting, the group conducted a detailed analysis of the strengths, weaknesses, challenges and opportunities available at Duke University and at our local university partners and identified the critical need for a cohesive effort in North Carolina for this understudied cancer.
The goals of the Duke Consortium for Inflammatory Breast Cancer are to:
- Identify the molecular determinants underlying the distinct biological features and aggressive progression observed in patients with inflammatory breast cancer
- Develop innovative preclinical models and methods that will improve diagnosis, imaging, and development of therapeutic approaches specifically for treatment of inflammatory breast cancer
- Evaluate the effectiveness of treatment for inflammatory breast cancer patients.
- Provide educational tools to our research and clinical trainees in aspects of translational research, health disparity and clinical outcomes.
- Collaborate with patients, advocates and local community health care providers to increase awareness of inflammatory breast cancer
To learn more, please contact Sarah Weaver, MPH, Research Program Manager.
What is IBC?
Inflammatory breast cancer (IBC) is a distinct and highly aggressive form of breast cancer with a poor prognosis. The five-year survival rate is only 35 to 40 percent. Although categorized as a rare disease, it disproportionately accounts for 10 percent of all breast cancer deaths.
The disease has a unique presentation in which clusters of cancer cells block the lymph vessels in the skin of the breast. Typical symptoms include rapid breast swelling associated with increase in breast size, skin changes including redness/peau d'orange, nipple retraction, and persistent itching. IBC often resembles an infection or mastitis and the absence of a solid tumor mass or one that is undetectable by mammography leads to patients being frequently misdiagnosed, which can lead to delay in life saving treatment.
Treatment
Currently there are no therapeutic regimens developed specifically for inflammatory breast cancer and it is critical to recognize that all aspects of treating inflammatory breast cancer – including staging, diagnosis, and therapy – are vastly different than other breast cancers.
Health Disparity
Inflammatory breast cancer is also designated as a cancer health disparity. Compared with other types of breast cancer, inflammatory breast cancer tends to be diagnosed at younger ages. In the United States, African Americans appear to have higher risk of not only developing inflammatory breast cancer but the disease is particularly aggressive in African American patients, irrespective of hormonal status or molecular subtype. Reports in the last two decades has also shown high incidence of this cancer in the Mediterranean area in North Africa. No risk factors have currently been defined but epidemiological studies reveal an increase in global incidence of inflammatory breast cancer.
Useful Resources
National Institutes of Health information on Inflammatory Breast Cancer
National Cancer Institute Inflammatory Breast Cancer Fact Sheet
Duke Surgery's Duke Multidisciplinary Education and Research in Translational Science (MERITS)
Research Focus Areas
IBC Tumor Biology and Drug Discovery Platforms
Area Leaders: Greg Palmer, PhD; David Hsu, MD, PhD
Clinically, IBC is characterized by redness and swelling of the breast and spreads rapidly and diffusely within the breast instead of developing a solid mass/lump making imaging and diagnosis difficult. Contrary to its inflammatory namesake, the classic skin symptoms are also secondary to tumor cell invasion into the dermal lymphatic channels. Given this unique method of cancer spread, our multidisciplinary investigators are working together and collaborating with external collaborators in developing innovative and multi-scale in vitro and in vivo patient-derived models that reflect the clinic-pathological features of IBC, with the potential to accelerate drug discovery.
Determinants of Population Health, Environmental Factors that impact clinical outcomes
Area Leaders: Rachel Greenup, MD; Trish Moorman, PhD, MSPH
Inflammatory breast cancer (IBC) is particularly devastating in minority women who have both a higher incidence of IBC and worse cancer survival. Disparities in IBC incidence, progression, and outcomes are likely multifactorial, including socioeconomic factors, treatment related disparities, and biological differences. We are focused on addressing each of these individual factors and their impact on IBC outcomes.
Clinical Management
Area Leaders: Lola Fayanju, MD, MA, MPHS; Jeremy Force, DO; and Gita Suneja, MD
A new focused Inflammatory Breast Cancer clinic is being developed at the Duke Cancer Center in order to promote multidisciplinary care and support women being treated for this rare cancer.
Community Outreach and Education
We will work with our Community Advisory Board to help guide community engagement through outreach and education with a focus on cancer prevention and control. In addition, NIH- and Duke School of Medicine-supported educational activities in the form of didactic courses, workshops and seminars are ongoing — training the next generation of researchers and physician scientists.
Scientific Highlights
The Duke Consortium for Inflammatory Breast Cancer has received grants and awards to further its research and its findings have been widely published.
DOD Awards 12 Million to Study Breast Cancer Metastasis
NCI Funds $2 Million Grant For Duke-NCCU Disparities Research Partnership
Study Shows that BPA May Affect Inflammatory Breast Cancer
Gayathri Devi, PhD, Presents At Inflammatory Breast Cancer Conference
Duke Surgery Presents Clarence Gardner, MD, Award to Three Collaborative Research Teams
Targeted Strategy to Overcome Resistance to Immunotherapy: An Era of Hope 2011 Investigator Vignette
Publications
Lane WO, Thomas SM, Blitzblau RC, Plichta JK, Rosenberger LH, Fayanju OM, Hyslop T, Hwang ES, Greenup RA. Surgical Resection of the Primary Tumor in Women With De Novo Stage IV Breast Cancer: Contemporary Practice Patterns and Survival Analysis. Ann Surg. 2017 Dec 7. doi: 10.1097/SLA.0000000000002621. [Epub ahead of print]
Fayanju OM, Hall CS, Bauldry JB, Karhade M, Valad LM, Kuerer HM, DeSnyder SM, Barcenas CH, Lucci A. Body mass index mediates the prognostic significance of circulating tumor cells in inflammatory breast cancer. Am J Surg. 2017 Oct;214(4):666-671. doi: 10.1016/j.amjsurg.2017.06.005. Epub 2017 Jun 23. PMID: 28720217
Crawford BM, Shammas RL, Fales AM, Brown DA, Hollenbeck ST, Vo-Dinh T, Devi GR. Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars. Int J Nanomedicine. 2017 Aug 26;12:6259-6272. doi: 10.2147/IJN.S141164. eCollection 2017. PMID: 28894365
Goh G, Schmid R, Guiver K, Arpornwirat W, Chitapanarux I, Ganju V, Im SA, Kim SB, Dechaphunkul A, Maneechavakajorn J, Spector N, Yau T, Afrit M, Ahmed SB, Johnston SR, Gibson N, Uttenreuther-Fischer M, Herrero J, Swanton C. Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory BreastCancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine. PLoS Med. 2016 Dec 6;13(12):e1002136. doi: 10.1371/journal.pmed.1002136. eCollection 2016 Dec.
Plichta JK, Campbell BM, Mittendorf EA, Hwang ES. Anatomy and Breast Cancer Staging: Is It Still Relevant? Surg Oncol Clin N Am. 2018 Jan;27(1):51-67. doi: 10.1016/j.soc.2017.07.010. Review. PMID: 29132565
Freel SA, Smith PC, Burns EN, Downer JB, Brown AJ, Dewhirst MW. Multidisciplinary Mentoring Programs to Enhance Junior Faculty Research Grant Success. Acad Med. 2017 Oct;92(10):1410-1415. doi: 10.1097/ACM.0000000000001620. PMID: 28272113
Spector NL, Robertson FC, Bacus S, Blackwell K, Smith DA, Glenn K, Cartee L, Harris J, Kimbrough CL, Gittelman M, Avisar E, Beitsch P, Koch KM. Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor. PLoS One. 2015 Nov 16;10(11):e0142845. doi: 10.1371/journal.pone.0142845. eCollection 2015. PMID: 26571496
Kurokawa M, Kim J, Geradts J, Matsuura K, Liu L, Ran X, Xia W, Ribar TJ, Henao R, Dewhirst MW, Kim WJ, Lucas JE, Wang S, Spector NL, Kornbluth S.A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53. Sci Signal. 2013 May 7;6(274):ra32. doi: 10.1126/scisignal.2003741.
Il'yasova D, Siamakpour-Reihani S, Akushevich I, Akushevich L, Spector N, Schildkraut J. What can we learn from the age- and race/ethnicity- specific rates of inflammatory breast carcinoma? Breast Cancer Res Treat. 2011 Nov;130(2):691-7. doi: 10.1007/s10549-011-1719-4. Epub 2011 Aug 18. PMID: 21850396
Johnston S, Trudeau M, Kaufman B, Boussen H, Blackwell K, LoRusso P, Lombardi DP, Ben Ahmed S, Citrin DL, DeSilvio ML, Harris J, Westlund RE, Salazar V, Zaks TZ, Spector NL.Phase II study of predictive biomarker profiles for response targeting human epidermal growth factor receptor 2 (HER-2) in advanced inflammatory breast cancer with lapatinib monotherapy. J Clin Oncol. 2008 Mar 1;26(7):1066-72. doi: 10.1200/JCO.2007.13.9949. Epub 2008 Jan 22. PMID: 18212337
Burris HA 3rd, Hurwitz HI, Dees EC, Dowlati A, Blackwell KL, O'Neil B, Marcom PK, Ellis MJ, Overmoyer B, Jones SF, Harris JL, Smith DA, Koch KM, Stead A, Mangum S, Spector NL. Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas.J Clin Oncol. 2005 Aug 10;23(23):5305-13. Epub 2005 Jun 13.
Oladapo HO, Tarpley M, Sauer SJ, Addo KA, Ingram SM, Strepay D, Ehe BK, Chdid L, Trinkler M, Roques JR, Darr DB, Fleming JM, Devi GR, Williams KP. Pharmacological targeting of GLI1 inhibits proliferation, tumor emboli formation and in vivo tumor growth of inflammatory breast cancer cells. Cancer Lett. 2017 Sep 28. pii: S0304-3835(17)30586-4. doi: 10.1016/j.canlet.2017.09.033. [Epub ahead of print]
Arora J, Sauer SJ, Tarpley M, Vermeulen P, Rypens C, Van Laere S, Williams KP, Devi GR*, Dewhirst MW*. IBC tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies. Oncotarget. 2017 Apr 18;8(16):25848-25863. doi: 10.18632/oncotarget.15667. PMID: 8460441. PMCID: PMC5432221 (Cover article with editorial).
Sauer SJ, Tarpley M, Shah I, Save AV, Lyerly HK, Patierno SR, Williams KP, Devi GR. 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 Mar 1;38(3):252-260. doi: 10.1093/carcin/bgx003.
Shammas RL, Fales AM, Crawford BM, Wisdom AJ, Devi GR, Brown DA, Vo-Dinh T, Hollenbeck ST. Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation. Plast Reconstr Surg. 2017 Apr;139(4):900e-910e. doi: 10.1097/PRS.0000000000003187. PMID:28350664
Devi GR, Nath S. Delivery of Synthetic mRNA Encoding FOXP3 Antigen into Dendritic Cells for Inflammatory Breast Cancer Immunotherapy. Methods Mol Biol. 2016;1428:231-43. doi: 10.1007/978-1-4939-3625-0_15. PMID: 27236803
Nath S, Devi GR. Three-dimensional culture systems in cancer research: Focus on tumor spheroid model. Pharmacol Ther. 2016 Jul;163:94-108. doi: 10.1016/j.pharmthera.2016.03.013. Epub 2016 Apr 8. Review.PMID:27063403
Evans MK, Sauer SJ, Nath S, Robinson TJ, Morse MA, Devi GR. X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity. Cell Death Dis. 2016 Jan 28;7:e2073. doi: 10.1038/cddis.2015.412.PMID:26821068
Betof AS, Lascola CD, Weitzel D, Landon C, Scarbrough PM, Devi GR, Palmer G, Jones LW, Dewhirst MW. Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise. JNCI. 2015;107(5). doi: 10.1093/jnci/djv040.
Horton JK, Siamakpour-Reihani S, Lee CT, Zhou Y, Chen W, Geradts J, Fels DR, Hoang P, Ashcraft KA, Groth J, Kung HN, Dewhirst MW, Chi JTA. FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target. Radiation Research. 2015;184(5):456-69. doi: 10.1667/rr14089.1. PubMed PMID: 26488758.
Park S, Chang C-Y, Safi R, Liu X, Bladi R, Jasper JS, Anderson GR, Liu T, Rathmell JC, Dewhirst MW, Wood KC, Locasale JW, McDonnel DP. ERRα-Regulated Lactate Metabolism Contributes to Resistance to Targeted Therapies in Breast Cancer. Cell Reports. 2016; 15:323-335. PMID: 27050525.
Siamakpour-Reihani S, Owzar K, Jiang C, Scarbrough PM, Craciunescu OI, Horton JK, Dressman HK, Blackwell KL, Dewhirst MW. Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival. International Journal of Hyperthermia. 2015;31(4):386-95. doi: 10.3109/02656736. 2015.1016557.
