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Background: Several studies have recently highlighted important roles for adipose tissue in cancer. However, few have examined adipose tissue cholesterol, and no study has been performed in breast adipose tissue associated with breast tumors.Objectives: The present work was designed to determine if breast adipose tissue cholesterol from the tumor-surrounding area is associated with breast cancer aggressiveness.Methods: Between 2009 and 2011, 215 breast adipose tissue samples were collected at the Tours University Hospital (France) during surgery of women (aged 28-89 y) with invasive breast cancer. Associations of free cholesterol (FC), esterified cholesterol (EC), and total cholesterol (TC) amounts with clinical variables (age, BMI, and treated or untreated hypercholesterolemia) and tumor aggressiveness parameters [phenotype, grade, presence of inflammatory breast cancer (IBC), and multifocality] were tested using Student's t test and after ANOVA.Results: The predominant form of cholesterol in adipose tissue was FC, and 50% of patients had no detectable EC. The adipose tissue FC content (μg/mg total lipid) was 18% greater in patients >70 y old than in those 40-49 y old (P < 0.05) and the TC content tended to be 12% greater in untreated hypercholesterolemic patients than in normocholesterolemic patients (P = 0.06). Breast adipose cholesterol concentrations were increased in tissues obtained from patients with human-epidermal-growth-factor-receptor-2 (HER2) phenotype (+13% FC; P < 0.05 compared with luminal A), IBC (+15% FC; P = 0.06 compared with noninflammatory tumors), as well as with multifocal triple-negative tumors (+34% FC, P < 0.05; +30% TC, P < 0.05, compared with unifocal triple-negative tumors). Among patients with triple-negative tumors, hypercholesterolemia was significantly more common (P < 0.05) in patients with multifocal tumors (64%) than in patients with unifocal tumors (25%).Conclusions: This study is the first of this magnitude that analyzes cholesterol concentrations in adipose tissue from female breast cancer patients. An increase in breast adipose tissue cholesterol content may contribute to breast cancer aggressiveness (HER2 phenotype, multifocality of triple-negative tumors, and IBC). [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a rare type of breast cancer that is associated with poor outcomes compared with non-IBC. Overexpression of HER2 is enriched in IBC, and those with HER2-positive disease have a relatively favorable prognosis, with improved survival over the last two decades driven by the advent of novel targeted therapies. Here, we present two patients who have survived for over 10 years after being diagnosed with de novo metastatic HER2-positive IBC. We review the data for the treatments available for metastatic HER2-positive IBC and the evolving treatment recommendations for this disease. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) has a highly invasive and metastatic phenotype. However, little is known about its genetic drivers. To address this, we report the largest cohort of whole-genome sequencing (WGS) of IBC cases. Methods: We performed WGS of 20 IBC samples and paired normal blood DNA to identify genomic alterations. For comparison, we used 23 matched non-IBC samples from the Cancer Genome Atlas Program (TCGA). We also validated our findings using WGS data from the International Cancer Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We examined a wide selection of genomic features to search for differences between IBC and conventional breast cancer. These include (i) somatic and germline single-nucleotide variants (SNVs), in both coding and non-coding regions; (ii) the mutational signature and the clonal architecture derived from these SNVs; (iii) copy number and structural variants (CNVs and SVs); and (iv) non-human sequence in the tumors (i.e., exogenous sequences of bacterial origin). Results: Overall, IBC has similar genomic characteristics to non-IBC, including specific alterations, overall mutational load and signature, and tumor heterogeneity. In particular, we observed similar mutation frequencies between IBC and non-IBC, for each gene and most cancer-related pathways. Moreover, we found no exogenous sequences of infectious agents specific to IBC samples. Even though we could not find any strongly statistically distinguishing genomic features between the two groups, we did find some suggestive differences in IBC: (i) The MAST2 gene was more frequently mutated (20% IBC vs. 0% non-IBC). (ii) The TGF β pathway was more frequently disrupted by germline SNVs (50% vs. 13%). (iii) Different copy number profiles were observed in several genomic regions harboring cancer genes. (iv) Complex SVs were more frequent. (v) The clonal architecture was simpler, suggesting more homogenous tumor-evolutionary lineages. Conclusions: Whole-genome sequencing of IBC manifests a similar genomic architecture to non-IBC. We found no unique genomic alterations shared in just IBCs; however, subtle genomic differences were observed including germline alterations in TGFβ pathway genes and somatic mutations in the MAST2 kinase that could represent potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) as a rare and highly aggressive type of breast cancer displays phenotypic characteristics. To date, the IBC-associated molecular mechanisms are entirely unknown. In addition, there is an urgent need to identify the new biomarkers involved in the diagnosis and therapeutic purposes of IBC. MicroRNAs, a category of short noncoding RNAs, are capable of controlling the post-transcriptional expression of genes and thus can act as diagnostic predictive tools. In this review, we addressed the status of oncogenic and tumor suppressor miRNA-mediated IBC in current studies. Furthermore, based on their targets, their involvement in cancer progression, angiogenesis, metastasis, and apoptosis were determined. [ABSTRACT FROM AUTHOR]

[Display omitted] Inflammatory breast cancer (IBC) is a rare and aggressive disease, accounting for 2–4% of new cases of breast cancer. Owing to its aggressive nature, IBC represent approximately 8–10% of breast cancer deaths. Management of IBC requires a multidisciplinary team for decision-making involving a composite of systemic treatment, surgery, and radiation, or "Trimodality Treatment." Because of the rarity of the disease, systemic therapy of IBC traditionally has been extrapolated from non-IBC clinical trials. The purpose of this review is to provide an overview of the development of systemic treatment of IBC from the past to the present by focusing on IBC clinical trials, including chemotherapy and targeted therapies. We discuss their effects on pathologic complete response (pCR) and survival outcomes, the predictive markers, and the adverse events of these therapies. Further, we summarized the current standard treatment stratified by molecular subtypes based on clinical data. Finally, we discuss the future trend of systemic therapy, including immunotherapy and ongoing IBC clinical trials. [ABSTRACT FROM AUTHOR]

Background. Anti-PD1/PDL1 immune checkpoint inhibitors (ICIs) showed promising results in breast cancer, and exploration of additional actionable immune checkpoints is ongoing. Inflammatory breast cancer (IBC) is an aggressive form of disease, the immune tumor microenvironment (TME) of which is poorly known. We aimed at providing the first comprehensive immune portrait of IBCs. Methods. From the gene expression profiles of 137 IBC and 252 non-IBC clinical samples, we measured the fractions of 22 immune cell types, expression of signatures associated with tertiary lymphoid structures (TLS) and with the response to ICIs (T cell-inflamed signature: TIS) and of 18 genes coding for major actionable immune checkpoints. The IBC/non-IBC comparison was adjusted upon the clinicopathological variables. Results. The immune profiles of IBCs were heterogeneous. CIBERSORT analysis showed profiles rich in macrophages, CD8+ and CD4 + T-cells, with remarkable similarity with melanoma TME. The comparison with non-IBCs showed significant enrichment in M1 macrophages, γδ T-cells, and memory B-cells. IBCs showed higher expression of TLS and TIS signatures. The TIS signature displayed values in IBCs close to those observed in other cancers sensitive to ICIs. Two-thirds of actionable immune genes (HAVCR2/TIM3, CD27, CD70, CTLA4, ICOS, IDO1, LAG3, PDCD1, TNFRSF9, PVRIG, CD274/PDL1, and TIGIT) were overexpressed in IBCs as compared to normal breast and two-thirds were overexpressed in IBCs versus non-IBCs, with very frequent co-overexpression. For most of them, the overexpression was associated with better pathological response to chemotherapy. Conclusion. Our results suggest the potential higher vulnerability of IBC to ICIs. Clinical trials.

Inflammatory Breast Cancer (IBC) is the most aggressive form of breast carcinoma characterized by rapid onset of inflammatory signs and its molecular fingerprint has not yet been elucidated. The objective of this study was to detect both gene expression levels and alternate RNA splice variants specific for IBC. W e performed splice-sensitive array profiling using Affymetrix Exon Array and quantitative RT-PCR analyses in 177 IBC compared to 183 non-IBC. We also assessed the prognostic value of the identified candidate genes and splice variants. A 5-splice signature (HSPA8 , RPL10 , RPL4 , DIDO1 and EVL) was able to distinguish IBC from non-IBC tumors (p<10-7). This splice signature was associated with poor metastasis-free survival in hormone receptor-negative non-IBC (p=0.02), but had no prognostic value in IBC. PAM analysis of dysregulated genes in IBC compared to non-IBC identified a 10-gene signature highly predictive of IBC phenotype and conferring a poor prognosis in non-IBC. The genes most commonly upregulated in IBC were 3 hemoglobin genes able to reliably discriminate IBC from non-IBC (p<10-4). Hb protein expression in epithelial breast tumor cells was confirmed by immunohistochemistry. IBC has a specific spliced transcript profile and is characterized by hemoglobin gene overexpression that should be investigated in further functional studies. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a clinically distinct and highly aggressive form of breast cancer with rapid onset and a strong propensity to metastasize. The molecular mechanisms underlying the aggressiveness and metastatic propensity of IBC are largely unknown. Herein, we report that decorin (DCN), a small leucine-rich extracellular matrix proteoglycan, is downregulated in tumors from patients with IBC. Overexpression of DCN in IBC cells markedly decreased migration, invasion, and cancer stem cells in vitro and inhibited tumor growth and metastasis in IBC xenograft mouse models. Mechanistically, DCN functioned as a suppressor of invasion and tumor growth in IBC by destabilizing E-cadherin and inhibiting EGFR/ERK signaling. DCN physically binds E-cadherin in IBC cells and accelerates its degradation through an autophagy-linked lysosomal pathway. We established that DCN inhibits tumorigenesis and metastasis in IBC cells by negatively regulating the E-cadherin/EGFR/ERK axis. Our findings offer a potential therapeutic strategy for IBC, and provide a novel mechanism for IBC pathobiology. Xiaoding Hu et al. find that expression of the proteoglycan decorin is decreased in patients with inflammatory breast cancer compared to normal breast tissue and some other types of breast cancer. They demonstrate that decorin acts as a tumor suppressor in cancer cells and human xenograft mouse models by destabilizing the E-cadherin-EGFR signaling axis, and their findings suggest potential therapeutic strategies for this aggressive breast cancer. [ABSTRACT FROM AUTHOR]

Background. Anti-PD1/PDL1 immune checkpoint inhibitors (ICIs) showed promising results in breast cancer, and exploration of additional actionable immune checkpoints is ongoing. Inflammatory breast cancer (IBC) is an aggressive form of disease, the immune tumor microenvironment (TME) of which is poorly known. We aimed at providing the first comprehensive immune portrait of IBCs. Methods. From the gene expression profiles of 137 IBC and 252 non-IBC clinical samples, we measured the fractions of 22 immune cell types, expression of signatures associated with tertiary lymphoid structures (TLS) and with the response to ICIs (T cell-inflamed signature: TIS) and of 18 genes coding for major actionable immune checkpoints. The IBC/non-IBC comparison was adjusted upon the clinicopathological variables. Results. The immune profiles of IBCs were heterogeneous. CIBERSORT analysis showed profiles rich in macrophages, CD8+ and CD4 + T-cells, with remarkable similarity with melanoma TME. The comparison with non-IBCs showed significant enrichment in Ml macrophages, γδ T-cells, and memory B-cells. IBCs showed higher expression of TLS and TIS signatures. The TIS signature displayed values in IBCs close to those observed in other cancers sensitive to ICIs. Two-thirds of actionable immune genes (HAVCR2/TIM3, CD27, CD70, CTLA4, ICOS, IDO1, LAG3, PDCD1, TNFRSF9, PVRIG, CD274/PDL1, and TIGIT) were overexpressed in IBCs as compared to normal breast and two-thirds were overexpressed in IBCs versus non-IBCs, with very frequent co-overexpression. For most of them, the overexpression was associated with better pathological response to chemotherapy. Conclusion. Our results suggest the potential higher vulnerability of IBC to ICIs. Clinical trials. [ABSTRACT FROM AUTHOR]

Through the example Of Anne of Austria's disease (1601-1666), we will see how the physio-pathological and therapeutic concepts of breast cancer evolved in this pivotal period that was the second half of the 17th century in France. We will also be interested in the political meaning ofcancerous disease, and the food therapy that meets the belief of cancer-animal. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory breast cancer (IBC) is an aggressive variant characterized by erythema, edema, and "peau d'orange" of the skin progressing within 6 months. We assessed the incidence and survival of IBC in the US over four decades. Methods: Using SEER*Stat, a case list of IBC patients diagnosed between 1973 and 2015 (n = 29,718) was extracted from SEER 18 registries by using a combination of morphology, stage, and extent of disease criteria. M1 and M0 patients were included. Age-adjusted incidence rates, relative survival rates, and mean survival time were calculated. Significance was determined as non-overlapping 95% confidence intervals. Results: The overall incidence of IBC from 1973 to 2015 is 2.76 (2.73, 2.79) cases per 100,000 people, with white patients having an incidence rate of 2.63 (2.60, 2.67), black patients 4.52 (4.39, 4.65), and patients of other race 1.84 (1.76, 1.93). The overall IBC relative 5-year survival rate is 40.5% (39.0%, 42.0%), 42.5% (40.7%, 44.3%), and 29.9% (26.6%, 33.3%) for white patients and black patients, respectively. Patients diagnosed in 1978–1982 have a mean survival time of 62.3 (52.0, 72.6) months, while those diagnosed in 2008–2012 have mean survival time of 99.4 (96.4, 102.4) months. There is no significant difference in survival time between T4D patients and patients with other T staging and extent of disease coding consistent with clinical IBC presentation. Conclusions: IBC survival has increased over four decades. Despite the improvement in survival for all racial groups, a persistent survival disparity that has not narrowed over two decades remains between white and black patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Inflammatory breast cancer (IBC) is a biologically aggressive subtype with a high risk for rapid local progression and early distant metastasis. We review the updated data for optimal locoregional management of IBC, including areas of active controversy. Recent Findings: Advancements in tri-modality therapies have improved survival among IBC patients in recent years; however, the risk of locoregional and distant recurrence remains high, particularly in triple-negative IBC. Data to support de-escalation of surgery or radiotherapy is limited, and the recommended treatment approach for non-metastatic IBC remains preoperative systemic therapy (PST), modified radical mastectomy (MRM), and adjuvant radiotherapy in all patients. For patients with de novo metastatic disease, locoregional intervention may be appropriate. Summary: Optimal locoregional management of IBC remains PST followed by MRM and adjuvant radiotherapy. With increasingly effective systemic therapies, research to identify a subset of patients who may benefit from de-escalation of locoregional therapies is warranted. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is a highly aggressive entity with a poor outcome and relative resistance to treatment. Despite progresses achieved during the last decades, the survival remains significantly lower than non-IBC. Recent clinical trials assessing PD-1/PD-L1 inhibitors showed promising results in non-IBC. Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of different cancers. Several recent studies suggested a potential interest of targeting the immune system in IBC by revealing a more frequent PD-L1 expression and an enriched immune microenvironment when compared with non-IBC. Here, we describe the rationale and design of PELICAN-IPC 2015-016/Oncodistinct-003 trial, an open-label, randomized, non-comparative, phase II study assessing efficacy, and safety of pembrolizumab in combination with anthracycline-containing neoadjuvant chemotherapy in HER2-negative IBC. The trial is ongoing. The primary endpoint is the pCR rate (ypT0/Tis, ypN0) in overall population and the co-primary endpoint is safety profile during a run-in phase. Key secondary objectives include tolerability, invasive disease-free, event-free and overall survivals, as well as collection of tumor and blood samples for translational research.Clinical Trial Registrationhttps://clinicaltrials.gov/ (NCT03515798).

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

Background: Inflammatory breast cancer is a very aggressive type of breast cancer which invades skin lymphatics. The standard treatment includes neoadjuvant chemotherapy followed by modified radical mastectomy and postsurgical radiation. Preserving the skin or nipple are not considered reasonable due to the involvement of the dermal lymphatics and therefore skin sparing or nipplesparing mastectomy are not usually carried out for this type of breast cancer. Case presentation: In this article, we present a case of inflammatory breast cancer in a very young woman who was positive for BRCA2 genes. Question: The possibility to perform nipple sparing or skin sparing mastectomy and immediate breast reconstruction, and the indication for prophylactic contralateral mastectomy as discussed in the tumor board are presented in this article. Conclusion: Neither of the more conservative techniques of mastectomy was appropriate for this case. Also, the prognosis of the patient mostly depends on the course of the ipsilateral tumor and prophylactic mastectomy would be wise only if the subsequent course of the disease is favourable.

Inflammatory breast cancer (IBC) is the most aggressive and lethal form of breast cancer, characterized by a high infiltration of tumor-associated macrophages and poor prognosis. To identify new biomarkers and to elucidate the molecular mechanisms underlying IBC pathogenesis, we investigated the expression pattern of heparanase (HPSE) and its activator cathepsin L (CTSL). First, we quantitated the HPSE and CTSL mRNA levels in a cohort of breast cancer patients after curative surgery (20 IBC and 20-non-IBC). We discovered that both HPSE and CTSL mRNA levels were significantly induced in IBC tissue vis-à-vis non-IBC patients (p

Objectives The survival benefit of postmastectomy radiotherapy (PMRT) has not been fully proven in inflammatory breast cancer (IBC). Thus, in the present research, we aimed at elucidating the effects of PMRT on the survival of IBC patients. Methods Eligible patients were collected from the Surveillance, Epidemiology, and End Results (SEER) dataset between 2010 and 2013. The Kaplan-Meier method along with the log-rank test was utilized for the comparison of both the overall survival (OS) andthe cancer-specific survival (CSS) in patients undergoing PMRT or not. Additionally, multivariate survival analysis of CSS and OS were performed using the Cox proportional hazard model. Results In total, 293 eligible cases were identified, with the median follow-up time of 27 months (range: 5–59 months). After propensity score matching (PSM), 188 patients (94 for each) were classified intothe No-PMRT and the PMRT group. Consequently, significantly higher OS rates were detected in the PMRT group compared with the No-PMRT group prior to PSM (P = 0.034), and significantly higher CSS (P = 0.013) and OS (P = 0.0063) rates were observed following PSM. Furthermore, multivariate analysis revealed thatPMRT [CSS (HR: 0.519, 95% CI [0.287–0.939], P = 0.030); OS (HR: 0.480, 95% CI [0.269–0.859], P = 0.013)], as well as Her2+/HR+ subtype, was independent favorable prognostic factors.Besides, black ethnicity, AJCC stage IV and triple-negative subtype were independent unfavorable prognostic factors. Further subgroup analysis revealed that most of the study population could benefit from PMRT, no matter OS or CSS. Conclusions Our findings support that PMRT could improve the survival of IBC patients.

Objective: Inflammatory breast cancer (IBC) has an unfavourable prognosis despite the advances made in the treatment of breast cancer. Our study aimed to define immunohistochemistry-based surrogate subtype distribution to determine whether the breast cancer subtype accompanied survival outcome differences in IBC.Materials and Methods: Medical records of female breast cancer patients with non-metastatic inflammatory breast cancer admitted to our clinic between March 2000 and December 2015 were retrospectively reviewed. Patient demographics, clinical and pathological feature of the primary tumour, adjuvant treatment options and survival data were analysed. Intrinsic breast cancer subtypes were defined according to ER, PR, HER-2 and ki-67 status.Results: We identified 129 non-metastatic inflammatory breast cancer patients. Median follow-up was 73 months. 10 (7.7%) were luminal A-like, 67 (51.9%) were luminal B-like, 37 (28.6%) were HER-2 positive, and 15 (11.6%) were triple negative (TNBC) by immunohistochemistry. There were no statistically significant differences between subtypes in terms of histological type, grade, tumour size and lymph node status. Median diseasefree survival was 47 months (95% confidence interval [CI] 29.2-82.6) and median overall survival was 75 months (95% CI 64.7-90.8). Triple negative breast cancer showed poorer outcome than other subgroups. Presence of TNBC disease was associated with poorer outcome compared to luminal A (HR: 0.19, 95% CI 0.04-0.92, p: 0.039), luminal B (HR: 0.34, 95% CI 0.15-0.74, p: 0.007) and HER-2 positive subgroups (HR: 0.40, 95% CI 0.17-0.94, p:0.037). Luminal A patients had a trend to have a better overall survival which did not reach to a statistical significant difference.Conclusion: Our study put forth that IBC have a poor prognosis irrespective of breast cancer surrogate subtype distribution. Luminal A, the most frequent subtype of breast cancer was the least common in our IBC patient group. TNBC had the worst outcome when compared to other breast cancer subtypes.

Abstract Background Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Using a custom-made breast cancer gene sequencing panel, we investigated somatic mutations in IBC to better understand the genomic differences compared with non-IBC and to consider new targeted therapy in IBC patients. Methods Targeted next-generation sequencing (NGS) of 91 candidate breast cancer-associated genes was performed on 156 fresh-frozen breast tumor tissues from IBC patients. Mutational profiles from 197 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as non-IBC controls for comparison analysis. The mutational landscape of IBC was correlated with clinicopathological data and outcomes. Results After genotype calling and algorithmic annotations, we identified 392 deleterious variants in IBC and 320 variants in non-IBC cohorts, respectively. IBC tumors harbored more mutations than non-IBC (2.5 per sample vs. 1.6 per sample, p

Abstract Background Usually misdiagnosed, Inflammatory Breast Cancer (IBC) is the most aggressive form of non-metastatic breast cancer. This orphan disease is more frequent in North Africa. Despite intensive treatment, the survival rate remains very low. Methods We have retrospectively studied all breast cancer cases diagnosed at the National Oncology Institute (INO), Rabat between 2005 and 2010. We have collected 219 cases of women with metastatic and non-metastatic IBC. Data have been obtained from patients’ personal medical files over a follow-up period of 5 years. We have described IBC’s clinicopathological features and analyzed its clinical outcome using SPSS software. HR (hazard Ratio) was calculated using Cox regression analysis. Results The frequency of IBC cases is 4.05%. The majority of our patients (65.3%) were under 50 years old. The most prevalent molecular subtype was Luminal A (38.7%) followed by Luminal B HER2+ (27.9%) and Triple negative (21.6%). During the follow-up period, 72 patients (32.9%) had recurrence and 40 patients (18.3%) died. The 3-year OS (Overall Survival) and EFS (Event Free Survival) of non-metastatic patients were 70.4 and 46.5% respectively, while in the metastatic disease, the 3-year OS was only 41.9%. In non-metastatic women, we observed a higher rate of EFS associated to Selective estrogen receptor modulation treatment (p = 0.01), and a lower rate EFS in triple negative breast cancer patients (p = 0.02). In univariate analysis, we found that EFS rate is lower in patients presenting Triple Negative tumors when compared to other molecular subtypes (HR: 3.54; 95%CI: 1.13–11.05; p = 0.02). We also found that Selective estrogen receptor modulation treatment is associated with higher EFS rate (HR: 0.48; 95%CI: 0.07–0.59; p = 0.01). Conclusions IBC in Morocco shows similar characteristics to those in North African countries; however, survival rates are still the highest when compared with neighboring countries. Collaborative studies with prospective aspects are warranted to establish the epidemiological profile and understand the high frequencies of IBC in North Africa. More studies on molecular markers are also needed to improve IBC patients’ management and eventually their survival rate.

Inflammatory breast cancer (IBC) is a highly aggressive entity with a poor outcome and relative resistance to treatment. Despite progresses achieved during the last decades, the survival remains significantly lower than non-IBC. Recent clinical trials assessing PD-1/PD-L1 inhibitors showed promising results in non-IBC. Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of different cancers. Several recent studies suggested a potential interest of targeting the immune system in IBC by revealing a more frequent PD-L1 expression and an enriched immune microenvironment when compared with non-IBC. Here, we describe the rationale and design of PELICAN-IPC 2015-016/Oncodistinct-003 trial, an open-label, randomized, non-comparative, phase II study assessing efficacy, and safety of pembrolizumab in combination with anthracycline-containing neoadjuvant chemotherapy in HER2-negative IBC. The trial is ongoing. The primary endpoint is the pCR rate (ypT0/Tis, ypN0) in overall population and the co-primary endpoint is safety profile during a run-in phase. Key secondary objectives include tolerability, invasive disease-free, event-free and overall survivals, as well as collection of tumor and blood samples for translational research. Clinical Trial Registration: https://clinicaltrials.gov/ (NCT03515798). [ABSTRACT FROM AUTHOR]

Purpose: Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. Methods: Between 2009 and 2015, we conducted a case–control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups. Results: After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types. Conclusions: We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor‐stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three‐dimensional, in vitro, vascularized, microfluidic IBC platform to quantify the spatial and temporal dynamics of tumor‐vasculature and tumor‐ECM interactions specific to IBC. Platforms consisting of collagen type 1 ECM with an endothelialized blood vessel were cultured with IBC cells, MDA‐IBC3 (HER2+) or SUM149 (triple negative), and for comparison to non‐IBC cells, MDA‐MB‐231 (triple negative). Acellular collagen platforms with endothelialized blood vessels served as controls. SUM149 and MDA‐MB‐231 platforms exhibited a significantly (p <.05) higher vessel permeability and decreased endothelial coverage of the vessel lumen compared to the control. Both IBC platforms, MDA‐IBC3 and SUM149, expressed higher levels of vascular endothelial growth factor (p <.05) and increased collagen ECM porosity compared to non‐IBCMDA‐MB‐231 (p <.05) and control (p <.01) platforms. Additionally, unique to the MDA‐IBC3 platform, we observed progressive sprouting of the endothelium over time resulting in viable vessels with lumen. The newly sprouted vessels encircled clusters of MDA‐IBC3 cells replicating a key feature of in vivo IBC. The IBC in vitro vascularized platforms introduced in this study model well‐described in vivo and clinical IBC phenotypes and provide an adaptable, high throughput tool for systematically and quantitatively investigating tumor‐stromal mechanisms and dynamics of tumor progression. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory breast cancer (IBC) is a rare, poorly understood and aggressive tumor. We extended prior findings linking high body mass index (BMI) to substantial increased IBC risk by examining BMI associations before and after adjustment for well-characterized comorbidities using medical record data for diabetes, insulin resistance, and disturbances of cholesterol metabolism in a general community healthcare setting. Methods: We identified 247 incident IBC cases diagnosed at Kaiser Permanente Northern California between 2005 and 2017 and 2470 controls matched 10:1 on birth year and geographic area and with ≥ 13 months of continuous enrollment prior to diagnosis/index date. We assessed exposures from 6 years up to one year prior to the diagnosis/index date, using logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results: Before adjustment for comorbidities, ORs (95% CIs) for BMI of 25–< 30, 30–< 35, and ≥ 35 compared to < 25 kg/m2 were 1.5 (0.9–2.3), 2.0 (1.2–3.1), and 2.5 (1.4–4.4), respectively. After adjustment for pre-diabetes/diabetes, HDL-C and triglyceride levels, and dyslipidemia, corresponding ORs were 1.3 (0.8–2.1), 1.6 (0.9–2.9), and 1.9 (1.0–3.5). The OR for HDL-C levels < 50 mg/dL compared to ≥ 65 mg/dL was 2.0 (1.2–3.3) in the adjusted model. In a separate model the OR for a triglyceride/HDL-C ratio ≥ 2.50 compared to < 1.62 was 1.7 (1.1–2.8) after adjustment for BMI, pre-diabetes/diabetes, and dyslipidemia. Results did not differ significantly by estrogen receptor status. Conclusions: Obesity and measures of insulin resistance independently increased IBC risk as did obesity and low HDL-C levels. These findings, if confirmed, have implications for IBC prevention. [ABSTRACT FROM AUTHOR]

There are scant data identifying epidemiologic characteristics among individuals diagnosed with inflammatory breast cancer (IBC), which is considered the most aggressive subtype of breast cancer. The purpose of this study was to evaluate the epidemiologic features among patients seen at a dedicated IBC program, to elucidate the potential causes of this disease and guide prevention strategies. We reviewed retrospective data from 447 patients enrolled in an IRB‐approved IBC registry through Dana‐Farber Cancer Institute from 1997 to 2016. The data examined included the following: demographics, medical, reproductive and family history, duration of symptoms prior to the diagnosis of IBC, pathologic characteristics, and clinical outcome. JMP statistical software was used to compile the data. Descriptive statistics were used to evaluate the data. The majority of patients (66.0%) were overweight or obese (body mass index [BMI] ≥25) at the time of diagnosis. Fifty patients (11.1%) had "secondary" IBC, defined as developing IBC after a previous history of non‐IBC breast cancer in an ipsilateral breast. Of those patients with secondary IBC, 60% were also overweight or obese at the time of IBC diagnosis. Approximately 58% of IBC patients had a family history of breast or ovarian cancer, including first‐ and second‐degree relatives. This analysis suggested a high frequency of familial breast/ovarian cancer among IBC patients which supports further evaluating genetic risks. This may have implications for screening and prevention strategies as well as insight into additional contributing risk factors. The prevalence of a high BMI among both pre‐ and postmenopausal women with IBC, including those diagnosed with secondary IBC, warrants focusing on strategies targeting the obesity crisis as a potential means of reducing the risk of developing this disease. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) is a rare type of breast cancer with poor prognoses, moreover its pathogenesis is not entirely clear. The aim of this study was to identify key genes of IBC, which might serve as diagnostic biomarkers and/or therapeutic targets. Methods: Two microarray datasets, GSE23720 and GSE45581, were obtained from the Gene Expression Omnibus database, and a differential expression analysis was performed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to understand the potential biological functions of the differentially expressed genes (DEGs). Next, a protein–protein interaction (PPI) network was constructed and visualized by Cytoscape. Functional modules and hub genes were screened using MCODE and cytohubba plug-ins, and the Cancer Genome Atlas survival analysis along with quantitative reverse transcriptional polymerase chain reactions of clinical samples was used to validate the effect that the hub genes have on IBC. Results: A total of 215 DEGs were identified, consisting of 105 upregulated and 110 downregulated genes. GO and KEGG analyses showed that the enriched terms and pathways were mainly associated with cell cycle, proliferation, drug metabolism, and oncogenesis. From the PPI network, we identified six hub genes, including Cell Division Cycle 45 (CDC45), Polo Like Kinase 1 (PLK1), BUB1 Mitotic Checkpoint Serine/Threonine Kinase B (BUB1B), Cell Division Cycle 20 (CDC20), Aurora Kinase A (AURKA), and Mitotic Arrest Deficient 2 Like 1 (MAD2L1). The survival analyses and expression validation studies verified the robustness of these hub genes. Conclusion: This study provides new insights into the understanding of the molecular mechanisms of IBC; in addition, the identified hub genes may serve as potential targets for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory breast cancer (IBC) is a rare type of breast cancer with poor prognosis, and the pathogenesis of this life-threatening disease is yet to be fully elucidated. This study aims to identify key genes of IBC, which could be potential diagnostic or therapeutic targets. Methods: Four datasets GSE5847, GSE22597, GSE23720, and GSE45581 were downloaded from the Gene Expression Omnibus (GEO) and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to understand the potential bio-functions of the differentially expressed genes (DEGs). Protein–protein interaction (PPI) network was constructed for functional modules analysis and hub genes identification, and TCGA survival analysis and qRT-PCR of clinical samples were used to further explore and validate the effect of hub genes on IBC. Results: A total of 114 DEGs were identified from the GEO datasets. GO and KEGG analyses showed that the DEGs were mainly enriched in oncogenesis and cell adhesion. From the PPI network, we screened out five hub genes, including PTPRC, IL6, SELL, CD40, and SPN. Survival analysis and expression validation verified the robustness of the hub genes. Discussion: The present study provides new insight into the understanding of IBC pathogenesis and the identified hub genes may serve as potential targets for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Optimizing treatment strategies for patients with inflammatory breast cancer (IBC) relies on accurate initial staging. This study compared contrast-enhanced computed tomography (ce-CT) and FDG-PET/CT for initial staging of IBC to determine the frequency of discordance between the two imaging modalities and potential impact on management. Methods: 81 patients with IBC underwent FDG-PET/CT and ce-CT prior to starting treatment. FDG-PET/CT and ce-CT scans were independently reviewed for locoregional and distant metastases and findings recorded by anatomic site as negative, equivocal, or positive for breast cancer involvement. Each paired ce-CT and FDG-PET/CT case was classified as concordant or discordant for findings. Discordant findings were subclassified as (a) related to the presence or absence of distant metastases; (b) affecting the locoregional radiation therapy plan; or (c) due to incidental findings not related to IBC. Results: There were 47 discordant findings between ce-CT and FDG-PET/CT in 41 of 81 patients (50.6%). Thirty (63.8%) were related to the presence or absence of distant metastases; most commonly disease detection on FDG-PET/CT but not ce-CT (n = 12). FDG-PET/CT suggested alterations of the locoregional radiation therapy plan designed by CT alone in 15 patients. FDG-PET/CT correctly characterized 5 of 7 findings equivocal for metastatic IBC on ce-CT. Conclusions: This study demonstrates differences between ce-CT and FDG-PET/CT for initial staging of IBC and how these differences potentially affect patient management. Preliminary data suggest that FDG-PET/CT may be the imaging modality of choice for initial staging of IBC. Prospective trials testing initial staging with FDG-PET/CT versus important clinical end-points in IBC are warranted. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the risk factors of inflammatory breast cancer (IBC) compared to non-IBC and according to histological subtype. Methods: Cases of IBC (n = 160) and controls of non-IBC (n = 580) were collected from the cohort of breast cancer patients treated in two oncology centers matched based on age at cohort entry. Data about breast cancer risk factors were collected. We evaluated correlation and ORs using conditional logistic regression analysis for each case group versus the control group. We also evaluated those factors in three further subgroups: luminal (HR+, HER2–), HER2-overexpressing (HER2+, HR–), and triple-negative (TN) patients. Results: Long duration of breastfeeding of ≥12 months (OR = 4.64, 95% CI 2.97–7.26), body mass index ≤25 (OR = 2.48, 95% CI 1.71–3.58), and use of oral contraceptives (OR = 2.48, 95% CI 1.62–3.84) were the most significant risk factors in favor of IBC compared to non-IBC. There was no impact of contraceptives use in the luminal subgroup and no impact of long duration of breastfeeding in the TN subgroup. The role of socioeconomic and educational levels was unclear. Age at menarche, age at first pregnancy, and age at menopause were nonsignificant risk factors of IBC. Conclusion: Reproductive risk factors were distinct in IBC patients reflecting the clinical entity of IBC. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer is a very aggressive type of breast cancer which invades skin lymphatics. The standard treatment includes neoadjuvant chemotherapy followed by modified radical mastectomy and postsurgical radiation. Preserving the skin or nipple are not considered reasonable due to the involvement of the dermal lymphatics and therefore skin sparing or nipplesparing mastectomy are not usually carried out for this type of breast cancer. Case presentation: In this article, we present a case of inflammatory breast cancer in a very young woman who was positive for BRCA2 genes. Question: The possibility to perform nipple sparing or skin sparing mastectomy and immediate breast reconstruction, and the indication for prophylactic contralateral mastectomy as discussed in the tumor board are presented in this article. Conclusion: Neither of the more conservative techniques of mastectomy was appropriate for this case. Also, the prognosis of the patient mostly depends on the course of the ipsilateral tumor and prophylactic mastectomy would be wise only if the subsequent course of the disease is favourable. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with elevated metastatic potential, characterized by tumor emboli in dermal and parenchymal lymph vessels. This study has investigated the hypothesis that TGFβ signaling is implicated in the molecular biology of IBC. Methods: TGFβ1-induced cell motility and gene expression patterns were investigated in three IBC and three non-IBC (nIBC) cell lines. Tissue samples from IBC and nIBC patients were investigated for the expression of nuclear SMAD2, SMAD3, and SMAD4. SMAD protein levels were related to gene expression data. Results: TGFβ1-induced cell motility was strongly abrogated in IBC cells (P = 0.003). Genes differentially expressed between IBC and nIBC cells post TGFβ1 exposure revealed attenuated expression of SMAD3 transcriptional regulators, but overexpression of MYC target genes in IBC. IBC patient samples demonstrated a near absence of SMAD3 and -4 expression in the primary tumor compared to nIBC patient samples (P < 0.001) and a further reduction of staining intensity in tumor emboli. Integration of gene and protein expression data revealed that a substantial fraction of the IBC signature genes correlated with SMAD3 and these genes are indicative of attenuated SMAD3 signaling in IBC. Conclusion: We demonstrate attenuated SMAD3 transcriptional activity and SMAD protein expression in IBC, together with obliterated TGFβ1-induced IBC cell motility. The further reduction of nuclear SMAD expression levels in tumor emboli suggests that the activity of these transcription factors is involved in the metastatic dissemination of IBC cells, possibly by enabling collective invasion after partial EMT. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) exhibits dermal lymphatic involvement at presentation, and thus, the standard surgical approach is a nonskin‐sparing modified radical mastectomy (MRM) without breast reconstruction (BR). In this study, we evaluated immediate and delayed BR receipt and its outcomes in IBC. Using an IRB‐approved database, we retrospectively evaluated stage III IBC patients who received trimodality therapy (preoperative systemic therapy, followed by MRM and postmastectomy chest wall/regional nodal radiation). Patients with an insufficient response to preoperative systemic therapy and/or who required preoperative radiotherapy were excluded. BR receipt, timing, and morbidity were evaluated. Among 240 stage III IBC patients diagnosed between 1997 and 2016, 40 (17%) underwent BR. Thirteen (33%) had immediate, and 27 (67%) had delayed BR. Four patients had complications (1 [8%] immediate BR and 3 [11%] delayed BR); only 1 BR (delayed) was unsuccessful. From the MRM date, the median time to recurrence was 35 months (<1‐212) and median overall survival was 87 months (<1‐212). In this cohort of stage III IBC patients, only 11% pursued delayed BR following trimodality therapy, possibly attributable to the observed high recurrence rates hindering BR. Further studies addressing BR outcomes in IBC are needed for better counseling patients regarding their reconstructive options. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) is the most pro‐metastatic form of breast cancer. Better understanding of its pathophysiology and identification of actionable genetic alterations (AGAs) are crucial to improve systemic treatment. We aimed to define the DNA profiles of IBC vs noninflammatory breast cancer (non‐IBC) clinical samples in terms of copy number alterations (CNAs), mutations, and AGAs. We applied targeted next‐generation sequencing (tNGS) and array‐comparative genomic hybridization (aCGH) to 57 IBC and 50 non‐IBC samples and pooled these data with four public datasets profiled using NGS and aCGH, leading to a total of 101 IBC and 2351 non‐IBC untreated primary tumors. The respective percentages of each molecular subtype [hormone receptor‐positive (HR+)/HER2−, HER2+, and triple‐negative] were 68%, 15%, and 17% in non‐IBC vs 25%, 35%, and 40% in IBC. The comparisons were adjusted for both the molecular subtypes and the American Joint Committee on Cancer (AJCC) stage. The 10 most frequently altered genes in IBCs were TP53 (63%), HER2/ERBB2 (30%), MYC (27%), PIK3CA (21%), BRCA2 (14%), CCND1 (13%), GATA3 (13%), NOTCH1 (12%), FGFR1 (11%), and ARID1A (10%). The tumor mutational burden was higher in IBC than in non‐IBC. We identified 96 genes with an alteration frequency (p < 5% and q < 20%) different between IBC and non‐IBC, independently from the molecular subtypes and AJCC stage; 95 were more frequently altered in IBC, including TP53, genes involved in the DNA repair (BRCA2) and NOTCH pathways, and one (PIK3CA) was more frequently altered in non‐IBC. Ninety‐seven percent of IBCs displayed at least one AGA. This percentage was higher than in non‐IBC (87%), notably for drugs targeting DNA repair, NOTCH signaling, and CDK4/6, whose pathways were more frequently altered (DNA repair) or activated (NOTCH and CDK4/6) in IBC than in non‐IBC. The genomic landscape of IBC is different from that of non‐IBC. Enriched AGAs in IBC may explain its aggressiveness and provide clinically relevant targets. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory breast cancer (IBC) is an aggressive variant for which axillary lymph node (LN) dissection following neoadjuvant chemotherapy (NACT) remains standard of care. But with increasingly effective systemic therapy, it is unclear whether more limited axillary surgery may be appropriate in some IBC patients. We sought to examine whether extent of axillary LN surgery was associated with overall survival (OS) for IBC. Methods: Female breast cancer patients with non-metastatic IBC (cT4d) diagnosed 2010–2014 were identified in the National Cancer Data Base. Cox proportional hazards modeling was used to estimate the association between extent of axillary surgery (≤ 9 vs ≥ 10 LNs removed) and OS after adjusting for covariates, including post-NACT nodal status (ypN0 vs ypN1-3) and radiotherapy receipt (yes/no). Results: 3471 patients were included: 597 (17.2%) had cN0 disease, 1833 (52.8%) had cN1 disease, and 1041 (30%) had cN2-3 disease. 49.9% of cN0 patients were confirmed to be ypN0 on post-NACT surgical pathology. Being ypN0 (vs ypN1-3) was associated with improved adjusted OS for all patients. Radiotherapy was associated with improved adjusted OS for cN1 and cN2-3 patients but not for cN0 patients. Regardless of ypN status, there was a trend towards improved adjusted OS with having ≥ 10 (vs ≤ 9) LNs removed for cN2-3 patients (HR 0.78, 95% CI 0.60–1.01, p = 0.06) but not for cN0 patients (p = 0.83). Conclusions: A majority of IBC patients in our study presented with node-positive disease, and for those presenting with cN2-3 disease, more extensive axillary surgery is potentially associated with improved survival. For cN0 patients, however, more extensive axillary surgery was not associated with a survival benefit, suggesting an opportunity for more personalized care. [ABSTRACT FROM AUTHOR]

Cancer in the dermis of the breast has a poor prognosis. The breast dermis can become malignantly involved primarily in inflammatory breast cancer, through the direct extension of locally advanced breast cancer, or metastatically from an underlying breast mass or a distant primary malignancy (e.g., gastric adenocarcinoma). Breast dermal metastases have the shortest median survival among them. Breast dermal metastases are classified into eight clinicohistopathologic groups, one of which is carcinoma en cuirasse. We present a case of a 52-year-old female with a history of invasive ductal carcinoma, Stage IIIC (pT2N3a), treated with lumpectomy, axillary node dissection, and chemoradiation therapy that recurred as carcinoma en cuirasse breast dermal metastases. Through18F-fludeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) and clinical images, the case illustrates the rapid progression and devastating consequences of carcinoma en cuirasse breast dermal metastases over a 4-month period despite optimal therapy. Furthermore, the case emphasizes the sensitivity of18F-FDG PET-CT to detect pathology in the breast dermis. Finally, the case highlights the crucial role that nuclear medicine physicians play in helping clinical colleagues differentiate between the various breast dermal malignant manifestations and benign mastitis, a common confounder in postradiation patients. [ABSTRACT FROM AUTHOR]

Renae D Van Wyhe,1,2 Omar M Rahal,1 Wendy A Woodward1 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 2Baylor College of Medicine, Houston, TX, USA Abstract: Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are medications that have been used for decades to lower cholesterol and to prevent or treat cardiovascular diseases. Since their approval by the US Food and Drug Administration in the 1980s, other potential uses for statins have been speculated on and explored. Basic science and clinical research suggest that statins are also effective in the management of breast cancer. Specifically, in various breast cancer cell lines, statins increase apoptosis and radiosensitivity, inhibit proliferation and invasion, and decrease the metastatic dissemination of tumors. Clinical trials in breast cancer patients support these laboratory findings by demonstrating improved local control and a mortality benefit for statin users. A role for statins in the management of aggressive breast cancers with poor outcomes – namely, inflammatory breast cancer and triple-negative breast cancer – is particularly implicated. However, data exist showing that statins may actually promote invasive breast disease after long-term use and thus should be prescribed cautiously. Furthermore, a general consensus on the type of statin that should be administered, for how long, and when in relation to time of diagnosis is lacking. Given their low toxicity profile, affordability, and ease of use, consideration of statins as a therapy for breast cancer patients is imminent. In this review, we summarize current evidence regarding statins and clinical breast cancer outcomes, as well as discuss potential future studies that could shed light on this increasingly relevant topic. Keywords: statins, HMG-CoA reductase inhibitors, breast cancer, inflammatory breast cancer, triple-negative breast cancer, locoregional recurrence

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Tumor microenvironment is involved in the development of Inflammatory breast cancer. • A panel of 12 analytes (Eotaxin-3, Fractalkine, FGF-2, IL-8, IL-16, IL-21, IL-22, MIF, MIP-1α, MIP-1β, and TNFRII) that can be used for early detection of IBC. • A panel of 7 analytes (CD-30, Eotaxin-3, IL-8, IL-16, MIF, MIP-1α, and MIP-1β) that may represent potential biomarkers for high risk of developing metastasis in IBC patients. • A panel of 10 analytes (Eotaxin-3, Fractalkine, IL-1α, IL-8, IL-16, IL-22, MIF, MIP-1α, MIP-1β, and TNFRII) that can help clinicians prevent lymph node invasion in patients with IBC. Inflammatory breast cancer (IBC), accounts for the majority of deaths associated with breast tumors. Because this form is aggressive from its appearance and has a strong metastatic potential. The majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Immune mediators may affect IBC progression and metastasis installation. Analysis of serum proteins to identify a panel of prognostic biomarkers for IBC. Serum levels of 65 analytes were determined in IBC and Non-IBC patients with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. Fifteen analytes: 5 cytokines (IL-8, IL-16, IL-21, IL-22 and MIF), 7 chemokines (Eotaxin, eotaxin-3, Fractalkine, IP-10, MIP-1α, MIP-1β and SDF-1α), One growth factors (FGF-2) and 2 soluble receptors (TNFRII and Tweak); were significantly differentially expressed between the two groups. ROC curves showed that twelve of them (IL-8, IL-16, IL-21, IL-22, MIF, MIP-1α, MIP-1β, SDF-1α, TNFRII, FGF-2, Eotaxin-3, and Fractalkine) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, seven cytokines: IL-8, IL-16, MIF, Eotaxin-3, MIP-1α, MIP-1β, and CD-30 are positively associated with patients who developed distant metastasis. Ten analytes: Eotaxin-3, Fractalkine, IL-16, IL-1α, IL-22, IL-8, MIF, MIP-1α, MIP-1β, and TNFRII are positively associated with patients who had Lymph-Nodes invasion. This study has uncovered a set of 8 analytes (Eotaxin-3, Fractalkine, IL-16, IL-8, IL-22, MIF, MIP-1α, MIP-1β) that can be used as biomarkers of IBC, and can be utilized for early detection of IBC, preventing metastasis and lymph-Nodes invasion. [ABSTRACT FROM AUTHOR]

Inflammatory breast cancer (IBC) poses an ongoing challenge as rates of disease recurrence and mortality remain high compared to stage-matched controls. However, frontline therapy has evolved through the years, including the widespread use of neoadjuvant chemotherapy (NAC) given the prognostic importance of pathologic complete response (pCR). Due to these sweeping changes, we need new data to assess current recurrence and survival outcomes for locally advanced IBC in the context of matched non-inflammatory controls. We conducted a retrospective analysis of institutional IBC data from 2010 to 2016 with the primary objective of comparing overall survival (OS), relapse-free survival (RFS), and distant relapse-free survival (DRFS). We matched IBC patients to non-inflammatory controls based on age, receptor status, tumor grade, clinical stage, and receipt of prior NAC. Secondary objectives included assessing pCR rates and identifying prognostic factors. Among NAC recipients, we observed similar pCR rates (47.6 % vs. 49.4 %, p = 0.88) between IBC (n = 84) and matched non-IBC (n = 81) cohorts. However, we noted a significant worsening of OS (p = 0.0001), RFS (p = 0.0001), and DRFS (p = 0.001) in the IBC group. Specifically, 5-year OS in the IBC cohort was 58.9 % vs. 86.7 % for matched controls (p = 0.0003). Older age was a weak negative predictor for OS (HR 1.03, p = 0.001) and RFS (HR 1.02, p = 0.01). For DRFS, older age was also a weak negative predictor (HR 1.02, p = 0.02), whereas the use of NAC was a positive predictor (HR 0.47, p = 0.02). Despite no clear difference in pCR, survival outcomes remain poor for IBC compared to matched non-inflammatory controls. • Patients with IBC fared significantly worse than controls with non-IBC disease in terms of OS, RFS, and DRFS. • IBC treatment remains a serious challenge despite advancements in cancer therapies. • National registries and the use of genomic data are needed to guide future therapies. [ABSTRACT FROM AUTHOR]