Selected 2014 Inflammatory Breast Cancer published research.
Through the courtesy of the US National Library of Medicine and the PubMed Database, we are pleased to offer this easy pre-formatted search link to peer-reviewed research of inflammatory breast cancer from 1/1/2014 to the present. Click here to view the search results.
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Li, XJ., et al. (2014). Lack of prognostic value of human epidermal growth factor-like receptor 2 status in inflammatory breast cancer (IBC): a meta-analysis. Asian Pacific Journal of Cancer Prevention, 15(22), 9615-9. Free full text available at link in title.
Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/ neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.
Maltseva, D., et al. (2014). miRNome of inflammatory breast cancer. BMC Research Notes, 7(1), 871. doi: 10.1186/1756-0500-7-871. Free full text available at link in title.
Inflammatory breast cancer (IBC) is an extremely malignant form of breast cancer which can be easily misdiagnosed. Conclusive prognostic IBC molecular biomarkers which are also providing the perspectives for targeted therapy are lacking so far. The aim of this study was to reveal the IBC-specific miRNA expression profile and to evaluate its association with clinicopathological parameters.
miRNA expression profiles of 13 IBC and 17 non-IBC patients were characterized using comprehensive Affymetrix GeneChip miRNA 3.0 microarray platform. Bioinformatic analysis was used to reveal IBC-specific miRNAs, deregulated pathways and potential miRNA targets.
31 differentially expressed miRNAs characterize IBC and mRNAs regulated by them and their associated pathways can functionally be attributed to IBC progression. In addition, a minimal predictive set of 4 miRNAs characteristic for the IBC phenotype and associated with the TP53 mutational status in breast cancer patients was identified.
We have characterized the complete miRNome of inflammatory breast cancer and found differentially expressed miRNAs which reliably classify the patients to IBC and non-IBC groups. We found that the mRNAs and pathways likely regulated by these miRNAs are highly relevant to cancer progression. Furthermore a minimal IBC-related predictive set of 4 miRNAs associated with the TP53 mutational status and survival for breast cancer patients was identified.
Agollah, G., et al. (2014). In vivo lymphatic imaging of a human inflammatory breast cancer model. Journal of Cancer, 5(9), 774-83. doi: 10.7150/jca.9835. Free full text available at link in title.
Inflammatory breast cancer (IBC) remains the most aggressive type of breast cancer with the greatest potential for metastasis and as a result, the highest mortality rate. IBC cells invade and metastasize through dermal lymphatic vessels; however, it is unknown how lymphatic drainage patterns change during IBC growth and metastasis. Herein, we non-invasively and longitudinally imaged lymphatics in an animal model of IBC using near-infrared fluorescence (NIRF) imaging.
MATERIALS AND METHODS:
Mice were imaged in vivo prior to, and up to 11 weeks after subcutaneous or orthotopic inoculation of human IBC SUM149 cells, which were stably transfected with infrared fluorescence protein (iRFP) gene reporter (SUM149-iRFP), following intradermal (i.d.) injection of indocyanine green (ICG).
Fluorescence images showed well-defined lymphatic vessels prior to SUM149-iRFP inoculation. However, altered lymphatic drainage patterns including rerouting of lymphatic drainage were detected in mice with SUM149-iRFP, due to lymphatic obstruction of normal lymphatic drainages caused by tumor growth. In addition, we observed tortuous lymphatic vessels and extravasation of ICG-laden lymph in mice with SUM149-iRFP. We also observed increased and dilated fluorescent lymphatic vessels in the tumor periphery, which was confirmed by ex vivo immunohistochemical staining of lymphatic vessels.
Our pre-clinical studies demonstrate that non-invasive NIRF imaging can provide a method to assess changes in lymphatic drainage patterns during IBC growth and metastasis.
Matro, J., et al. (2014). Inflammatory breast cancer management in the National Comprehensive Cancer Network: the disease, recurrence pattern, and outcome. Clinical Breast Cancer, doi: 10.1016/j.clbc.2014.05.005. Abstract below, free full text not available.
Inflammatory breast cancer (IBC) is an uncommon clinicopathologic entity characterized by rapid progression and aggressive behavior. We used the National Comprehensive Cancer Network (NCCN) Outcomes Database to characterize recurrence patterns and outcomes.
Patients with newly diagnosed IBC treated between 1999 and 2009 at 12 NCCN institutions were identified, and baseline characteristics were obtained. Patients had multimodality therapy if they received 2 of 3 treatments: surgery, perioperative (neoadjuvant or adjuvant) chemotherapy, or perioperative radiation. The first site of recurrence/metastatic diagnosis was identified. Overall survival was calculated on the basis of stage at diagnosis and receipt of multimodality therapy.
We identified 673 patients, of whom 195 (29%) had metastatic disease at presentation. Median follow-up was 29 months. Of patients in stage III, 82% received > 1 treatment modality. Among 203 patients in stage III with recurrence, the most frequent sites of first recurrence were bone (28%), central nervous system (CNS), lung, and liver (all 21%). Human epidermal growth factor receptor 2 positive and triple negative subtypes had higher rates of CNS recurrence (P = .001). Median survival was 66 months (95% confidence interval [CI], 54-107) for stage III and 26 months (95% CI, 22-33) for stage IV. Among 82% of patients in stage III receiving multimodality therapy, the median survival was 107 months (95% CI, 71 to not reached).
This large, retrospective, multi-institutional study confirms the aggressive clinical features, unique recurrence patterns, and adverse prognosis of IBC. The high rate of CNS recurrence among high-risk subtypes, despite the inflammatory nature of the breast cancer, suggests that new strategies are needed for earlier detection or prevention of brain metastases to improve long-term prognosis.
Mohamed, H., et al. (2014). Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis. Frontiers in Oncology, 4:246, doi: 10.3389/fonc.2014.00246. Abstract below, free full text available by clicking article title link.
Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCMV genotypes within IBC. Thus, in the present study, we established the incidence and types of HCMV genotypes present in carcinoma tissues of infected non-IBC versus IBC patients. We also assessed the correlation between detection of mixed genotypes of HCMV and disease progression. Genotyping of HCMV in carcinoma tissues revealed that glycoprotein B (gB)-1 and glycoprotein N (gN)-1 were the most prevalent HCMV genotypes in both non-IBC and IBC patients with no significant difference between patients groups. IBC carcinoma tissues, however, showed statistically significant higher incidence of detection of the gN-3b genotype compared to non-IBC patients. The incidence of detection of mixed genotypes of gB showed that gB-1+gB-3 was statistically significantly higher in IBC than non-IBC patients. Similarly, the incidence of detection of mixed genotypes of gN showed that gN-1+gN-3b and gN-3+gN-4b/c were statistically significant higher in the carcinoma tissues of IBC than non-IBC. Mixed presence of different HCMV genotypes was found to be significantly correlated with the number of metastatic lymph nodes in non-IBC but not in IBC patients. In IBC, detection of mixed HCMV different genotypes significantly correlates with lymphovascular invasion and formation of dermal lymphatic emboli, which was not found in non-IBC patients.
Bertucci, F., et al. (2014). Genomic profiling of inflammatory breast cancer: A review. Breast, 23(5), 538-45. doi: 10.1016/j.breast.2014.06.00. Abstract below, free full text not available.
Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite efforts in the past decade to delineate the molecular biology of IBC by applying high-throughput molecular profiling technologies to clinical samples, IBC remains insufficiently characterized. The reasons for that include limited sizes of the study population, heterogeneity with respect to the composition of the IBC and non-IBC control groups and technological differences across studies. In 2008, the World IBC Consortium was founded to foster collaboration between research groups focusing on IBC. One of the initial projects was to redefine the molecular profile of IBC using an unprecedented number of samples and search for gene signatures associated with survival and response to neo-adjuvant chemotherapy. Here, we provide an overview of all the molecular profiling studies that have been performed on IBC clinical samples to date.
Dawood, S., et al. (2014). Survival of women with inflammatory breast cancer: a large population-based study. Annals of Oncology: the official scientific journal of ESMO, 25(6), doi: 10.1093/annonc/mdu121. Abstract below, free full text not available.
Our group has previously reported that women with inflammatory breast cancer (IBC) continue to have worse outcome compared with those with non-IBC. We undertook this population-based study to see if there have been improvements in survival among women with stage III IBC, over time.
PATIENT AND METHODS:
We searched the Surveillance, Epidemiology and End Results Registry to identify female patients diagnosed with stage III IBC between 1990 and 2010. Patients were divided into four groups according to year of diagnosis: 1990-1995, 1996-2000, 2001-2005, and 2006-2010. Breast cancer-specific survival (BCSS) was estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox models were then fit to determine the association of year of diagnosis and BCSS after adjusting for patient and tumor characteristics.
A total of 7679 patients with IBC were identified of whom 1084 patients (14.1%) were diagnosed between 1990 and 1995, 1614 patients (21.0%) between 1996 and 2000, 2683 patients (34.9%) between 2001 and 2005, and 2298 patients (29.9%) between 2006 and 2010. The 2-year BCSS for the whole cohort was 71%. Two-year BCSS were 62%, 67%, 72%, and 76% for patients diagnosed between 1990-1995, 1996-2000, 2001-2005, and 2006-2010, respectively (P < 0.0001). In the multivariable analysis, increasing year of diagnosis (modeled as a continuous variable) was associated with decreasing risks of death from breast cancer (HR = 0.98, 95% confidence interval 0.97-0.99, P < 0.0001).
There has been a significant improvement in survival of patients diagnosed with IBC over a two-decade time span in this large population-based study. This suggests that therapeutic strategies researched and evolved in the context of non-IBC have also had a positive impact in women with IBC.
Rueth, N., et al. (2014). Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database. Journal of Clinical Oncology, 32(19), 2018-24. doi: 10.1200/JCO.2014.55.1978. Abstract below, free full text not available.
To analyze factors that predict the use of trimodality treatment (chemotherapy, surgery, and radiation therapy [RT]) and evaluate the impact that trimodality treatment use has on survival for patients with inflammatory breast cancer (IBC).
Using the National Cancer Data Base, patients who underwent surgical treatment of nonmetastatic IBC from 1998 to 2010 were identified. We collected demographic, tumor, and treatment data and analyzed treatment and survival trends over time. Logistic regression and Cox proportional hazard models were used to examine factors predicting treatment and survival.
We identified 10,197 patients who fulfilled study criteria. The use of trimodality therapy fluctuated annually (58.4% to 73.4%). Patients who were older, diagnosed earlier in the study period, lived in regions of the country outside of the Midwest, had lower incomes or public insurance, and had a higher comorbid score were significantly less likely to receive trimodality therapy (all P < .05). Five- and 10-year survival rates were highest among patients receiving trimodality treatment (55.4% and 37.3%, respectively) compared with patients who received the combination of surgery plus chemotherapy, surgery plus RT, or surgery alone. After adjusting for potential confounding variables, use of trimodality therapy remained a significant independent predictor of survival.
Underutilization of trimodality therapy negatively impacted survival for patients with IBC. The use of trimodality therapy increased marginally with time, but there remain significant factors associated with differences in use of trimodality treatment. We have identified specific barriers to care that may be targeted to improve treatment delivery and potentially improve patient outcomes.
Schinkel, J., et al. (2014). Racial/ethnic differences in breast cancer survival by inflammatory status and hormonal receptor status: an analysis of the surveillance, epidemiology, and end results data. Cancer Causes & Control:CCC, 25(8), 959-68. doi: 10.1007/s10552-014-0395-1. Abstract below, free full text not available.
Compared to non-inflammatory breast cancer (non-IBC), inflammatory breast cancer (IBC) has less favorable survival and is more likely to be estrogen receptor (ER) and progesterone receptor (PR) negative. ER-/PR- tumors, regardless of histology, have less favorable survival. While black women are more likely to have IBC and ER-/PR- tumors than white women, it is unclear whether the racial disparity in survival is explained by these factors. The objective of this study was to assess racial/ethnic differences in breast cancer survival by inflammatory status and hormone receptor status.
This study examined breast cancer mortality among non-Hispanic white (NHW), Hispanic white, black, and Asian/Pacific Islander (API) women diagnosed between 1990 and 2004 using the National Cancer Institute’s Surveillance, Epidemiology, and End Results data. Kaplan-Meier survival curves and Cox proportional hazard ratios (HRs) assessed the relationship between race/ethnicity and survival.
Black women had significantly poorer survival than NHW women regardless of inflammatory status and hormone receptor status. Compared to NHWs, the HRs for black women were 1.32 (95 % confidence interval (CI) 1.21-1.44), 1.43 (95 % CI 1.20-1.69), and 1.30 (95 % CI 1.16-1.47) for IBC, IBC with ER+/PR+, and with ER-/PR-, respectively. Similar HRs were found for non-IBC, non-IBC with ER+/PR-, and non-IBC with ER-/PR-. API women had significantly better survival than NHW women regardless of inflammatory status and hormone receptor status.
Compared to NHW women, black women had poorer survival regardless of inflammatory status and hormone receptor status and API women had better survival. These results suggest that factors other than inflammatory status and hormone receptor status may play a role in racial/ethnic disparities in breast cancer survival.
Takiar, V. et al. (2014). Predictors of durable no evidence of disease status in de novo metastatic inflammatory breast cancer patients treated with neoadjuvant chemotherapy and post-mastectomy radiation. SpringerPlus, 3, 166-166. Abstract below, free full text by clicking title link.
Definitive locoregional therapy including surgery and post-mastectomy radiation therapy (PMRT) has been offered to select IBC patients with de novo metastatic disease. Herein we examined predictive factors for progression-free survival after comprehensive PMRT radiation +/- locoregional treatment of metastatic sites.
Charts of T4d, any N, M1 (de novo) patients who completed PMRT to ≥ 50 Gy from 2006-2011 were reviewed. Patients who received doses RESULTS:
Median age at diagnosis was 54 (range 33-70). Median follow up from primary irradiation completion was 31 months. Sixteen patients were Stage IV NED at last follow-up (IR 37-60 mo). Fifteen patients died of disease. Five patients experienced an in-field recurrence, three of which resulted from local recurrence at the medial edge of the field. Actuarial 5 year locoregional control (LRC) was 86%. Median PFSx was 20 months. All sites of gross disease were treated with radiation in 21/36 patients. Location of metastatic disease had no correlation with PFSx. Estrogen receptor (ER)- patients had shorter 5-yr actuarial PFSx (28% vs. 66%, P = 0.03) and 5 year actuarial OSx (37% vs 71%, P = 0.02). Nine patients (25%) developed a pathological complete response (pCR) after chemotherapy and with a median follow-up of 59 months, 7 remained without evidence of disease.
Despite the poor prognosis associated with metastatic IBC, our data suggest that select patients may be appropriate candidates for locoregional therapy. Patients who achieve a pCR or those with ER + disease have a favorable PFSx. It remains unclear whether all gross disease needs to be addressed with locoregional therapy to provide benefit.
Hirko, K., et al. (2014). A comparison of criteria to identify inflammatory breast cancer cases from medical records and the Surveillance, Epidemiology and End Results data base, 2007-2009. The Breast Journal, 20(2), 185-91. doi:10.1111/tbj.12234. Abstract below, free full text not available.
Inflammatory breast cancer (IBC) is a relatively rare and extremely aggressive form of breast cancer that is diagnosed clinically. Standardization of clinical diagnoses is challenging, both nationally and internationally; moreover, IBC coding definitions used by registries have changed over time. This study aimed to compare diagnostic factors of IBC reported in a U.S. Surveillance, Epidemiology, and End Results (SEER) registry to clinical criteria found in the medical records of all invasive breast cancer cases at a single institution. We conducted a medical record review of all female invasive breast cancers (n = 915) seen at an NCI-designated comprehensive cancer center in Detroit from 2007 to 2009. IBC cases were identified based on the presence of the main clinical characteristics of the disease (erythema, edema, peau d’orange). We compared the proportion of IBC out of all breast cancers, using these clinical criteria and the standard SEER IBC codes. In the reviewed cases, the clinical criteria identified significantly more IBC cases (n = 74, 8.1%) than the standard IBC SEER definition (n = 19, 2.1%; p < 0.0001). No IBC cases were identified in the cancer center records using the SEER pathologic coding, which requires the diagnosis of inflammatory carcinoma on the pathology report, a notation that is rarely made. Emphasis must be placed on the documentation of clinical and pathologic characteristics of IBC in the medical record, so that analysis of putative IBC subtypes will be possible. Our results indicate the need for a consensus on the definition of IBC to be utilized in future research.
Goldner, B., et al. (2014). Incidence of inflammatory breast cancer in women, 1992-2009, United States. Annals of Surgical Oncology, 21(4), 1267-70. doi: 10.1245/s10434-013-3439-y. Abstract below, free full text not available.
The annual incidence of inflammatory breast cancer (IBC) in the United States reportedly increased during the last quarter of the twentieth century. We investigated whether that increase has continued into the twenty-first century.
We queried the Surveillance Epidemiology and End Results database for all cases of IBC in women age 20 and older between 1992 and 2009. Cases were breast tumors with at least one of the following codes: extent of disease size 998, extension 70, or ICD-3-O morphology 8530 or 8533. Age-adjusted incidence was also examined.
During 1992-2009, the annual incidence of IBC did not increase over time in any age group, nor did it vary significantly from year to year, except between 2003 and 2004, when there was a jump from 1.6 (95 % confidence interval 1.4-1.8) to 3.1 (2.8-3.4) cases per 100,000 women. Similar changes occurred in all age and racial groups before gradually returning to prejump levels. Overall, the incidence of IBC rose steeply with age until reaching a plateau at age 65. The incidence was greatest among black women (3.0; 2.8-3.2), intermediate among white women (2.1; 2.1-2.2), and lowest among Asian women (1.4; 1.3-1.6).
The incidence of IBC has remained essentially stable for nearly two decades. A transient jump in 2003-2004 occurred in all age and racial groups, suggesting adjustment to coding changes at that time. Often described as a disease of younger women, IBC in fact disproportionately affects older women. Racial/ethnic variation in the incidence of IBC suggests that dietary, lifestyle, or genetic factors contribute to its pathogenesis.
Masuda, H., et al. (2014). Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes. Annals of Oncology: official journal of the European Society for Medical Oncology, 25(2), 384-91. doi: 10.1093/annonc/mdt525. Abstract below, free full text not available.
Subtypes defined by hormonal receptor (HR) and HER2 status have not been well studied in inflammatory breast cancer (IBC). We characterized clinical parameters and long-term outcomes, and compared pathological complete response (pCR) rates by HR/HER2 subtype in a large IBC patient population. We also compared disease-free survival (DFS) and overall survival (OS) between IBC patients who received targeted therapies (anti-hormonal, anti-HER2) and those who did not.
PATIENTS AND METHODS:
We retrospectively reviewed the records of patients diagnosed with IBC and treated at MD Anderson Cancer Center from January 1989 to January 2011. Of those, 527 patients had received neoadjuvant chemotherapy and had available information on estrogen receptor (ER), progesterone receptor (PR), and HER2 status. HR status was considered positive if either ER or PR status was positive. Using the Kaplan-Meier method, we estimated median DFS and OS durations from the time of definitive surgery. Using the Cox proportional hazards regression model, we determined the effect of prognostic factors on DFS and OS. Results were compared by subtype.
The overall pCR rate in stage III IBC was 15.2%, with the HR-positive/HER2-negative subtype showing the lowest rate (7.5%) and the HR-negative/HER2-positive subtype, the highest (30.6%). The HR-negative, HER2-negative subtype (triple-negative breast cancer, TNBC) had the worst survival rate. HR-positive disease, irrespective of HER2 status, had poor prognosis that did not differ from that of the HR-negative/HER2-positive subtype with regard to OS or DFS. Achieving pCR, no evidence of vascular invasion, non-TNBC, adjuvant hormonal therapy, and radiotherapy were associated with longer DFS and OS.
Hormone receptor and HER2 molecular subtypes had limited predictive and prognostic power in our IBC population. All molecular subtypes of IBC had a poor prognosis. HR-positive status did not necessarily confer a good prognosis. For all IBC subtypes, novel, specific treatment strategies are needed in the neoadjuvant and adjuvant settings.