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INTRODUCTION Neoadjuvant chemotherapy is standard treatment for locally advanced (LABC) or inflammatory breast cancer (IBC). We hypothesized adding sunitinib, a tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2 negative LABC or IBC. PATIENTS AND METHODS We conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2 negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m2 IV weekly x12 followed by doxorubicin 24 mg/m2 IV weekly + cyclophosphamide 60 mg/m2 PO daily with G-CSF support. Response was evaluated using pCR in the breast and the Clinical-pathologic scoring + estrogen receptor (ER) and grade (CPS+EG) score. RESULTS Seventy patients enrolled and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER+ disease and 8 had triple negative disease). When defining response as pCR and/or CPS+EG score ≤ 2, 47% were responders. In ER+ patients, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue. CONCLUSIONS Neoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR. However, 47% were responders using pCR and/or CPS+EG score ≤2. ER+ patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for ER+ patients.

Accumulation of amyloid in breast cancer is a well‐known phenomenon, but only immunoglobulin light‐chain amyloidosis (AL) or transthyretin (TTR) amyloid had been detected in human breast tumor samples previously. We recently reported that another amyloidogenic peptide, amyloid beta (Aβ), is present in an aggregated form in animal and human high‐grade gliomas and suggested that it originates systemically from the blood, possibly generated by platelets. To study whether breast cancers are also associated with these Aβ peptides and in what form, we used a nude mouse model inoculated with triple‐negative inflammatory breast cancer cell (SUM‐149) xenografts, which develop noticeable tumors. Immunostaining with two types of specific antibodies for Aβ identified the clear presence of Aβ peptides associated with (a) carcinoma cells and (b) extracellular aggregated amyloid (also revealed by Congo red and thioflavin S staining). Aβ peptides, in both cells and in aggregated amyloid, were distributed in clear gradients, with maximum levels near blood vessels. We detected significant presence of amyloid precursor protein (APP) in the walls of blood vessels of tumor samples, as well as in carcinoma cells. Finally, we used ELISA to confirm the presence of elevated levels of mouse‐generated Aβ40 in tumors. We conclude that Aβ in inflammatory breast cancer tumors, at least in a mouse model, is always present and is concentrated near blood vessels. We also discuss here the possible pathways of Aβ accumulation in tumors and whether this phenomenon could represent the specific signature of high‐grade cancers., Aβ (amyloid beta) and it's precursor APP can be observed in tumors formed by mouse xenograft model of human inflammatory breast cancer (IBC). Aβ is present in and around carcinoma cells and is concentrated near blood vessels. We suggest that systemic Aβ from mouse blood and/or vessels (containing amyloid precursor APP) may be, jointly with other amyloidogenic peptides, forming aggregated amyloid in these tumors.

BACKGROUND The Current National Comprehensive Cancer Network guidelines recommend modified radical mastectomy (MRM) as the surgical treatment of choice for nonmetastatic inflammatory breast cancer (IBC). Limited studies have looked into the outcomes of breast conserving surgery (BCS) vs. MRM for IBC. METHODS National Cancer Database (NCDB) data from 2004 to 2014 were retrospectively analyzed. Patients' demographics, tumor characteristics, and overall survival (OS) trends were compared for BCS and MRM cases of nonmetastatic IBC. Univariate and multivariate analyses were performed. RESULTS A total of 413 (3.89%) BCS and 10,197 (96.11%) MRM cases were identified. Median follow-up was 58.45 months. Compared to MRM, BCS patients were more likely to be older, be African American, have Medicare/Medicaid or be uninsured, live in lower education ZIP codes, and live in a metropolitan area (all p

Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC‐specific targeted therapies exist. In this study, we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC vs non‐IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non‐IBC cell lines. High expression was associated with poor‐prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced colony formation, migration, and cancer stem cell populations in vitro and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2‐silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC., In this study, the authors demonstrate that lipocalin 2 (LCN2) is highly upregulated in inflammatory breast cancer (IBC), a rare, rapidly‐progressing and aggressive variant of primary breast cancer. Depletion of LCN2 in IBC cell lines reduced colony formation, migration, and cancer stem cell populations in vitro and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC.

Background Inflammatory breast cancer (IBC) is a rare breast malignancy with poor outcomes compared with non-IBC. Age-related differences in tumor biology, treatment, and clinical outcomes have been described in non-IBC. This study evaluated age-related differences in IBC. Methods From an institutional prospective database, patients with an IBC diagnosed from 2010 to 2019 were identified. Age was categorized as 40 years or younger, 41 to 64 years, and 65 years or older. Demographics, clinicopathologic features, and treatment received were compared. Recurrence and survival outcomes were analyzed using the log-rank test and the Cox proportional hazards model. Results Of 523 IBC patients, 113 (21.6%) were age 40 years or younger, and 72 (13.8%) were age 65 years or older. The groups did not differ statistically by race/ethnicity, N stage, clinical stage, or tumor subtype. The younger patients included a higher proportion of Hispanic and Asian patients, triple-negative breast cancer (TNBC), and clinical N2/N3. Trimodality therapy was received by 92% of the stage 3 patients, with no difference in pathologic complete response (pCR) by age (23.3% vs 28.6%; p = 0.46). During a median follow-up period of 40 months, 17% of the patients experienced locoregional recurrence and 42.8% had distant metastasis. No difference in 3-year recurrence-free survival (57.9% vs 42.6% vs 54%; p = 0.42, log rank) or overall survival (OS) (75.6% vs 77.1% vs 64.4%; p = 0.31, log rank) by age was observed, and no difference in OS by age in de novo stage 4 disease was observed. In the multivariate analysis, worse OS was associated with TNBC (hazard ratio [HR], 1.99, 95% confidence interval [CI], 1.31-3.05) and no pCR (HR, 4.45; 95% CI, 2.16-9.18). Conclusion No significant differences were observed in demographics, treatment patterns, or clinical outcomes for IBC patients age 40 years or younger compared with those age 65 years or older treated by a specialized multidisciplinary team. These findings do not support age-related treatment de-escalation in IBC.

National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan–Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P 0.05). Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

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.

Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines. Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004–6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared. Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p > 0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70–2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66–2.85, p < 0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59–4.16, p < 0.001) had higher risk of death (reference: stage III disease). CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

Axillary lymphadenopathy on breast imaging after recent coronavirus disease 2019 (COVID-19) vaccination has been reported in the literature as immunization has become more widespread. While muscle edema at the injection site has been observed on MRI secondary to an immune response, ipsilateral breast imaging observations of edema have not been reported to be seen with the COVID-19 vaccinations to date. Mammographic findings such as trabecular and skin thickening, along with increased echogenicity on ultrasound, can be seen with edema secondary to capillary leak or poor lymphatic drainage, and should be considered as a possible etiology for the observed breast edema following a recent COVID-19 vaccine. Inflammatory changes observed in the breast and axillary tail post vaccination described in this case series are transient, but clinically relevant for patients who experience swelling following injection. Similar to evaluations for suspected mastitis, a short interval imaging follow up to confirm resolution may be appropriate for patients with ipsilateral vaccination histories, and could potentially reduce the number of false positive examinations in this clinical scenario. However, inflammatory breast cancer can mimic inflammation and infection, therefore close follow up to resolution is critical as to not miss cancer.

Introduction: Breast cancer is one of the most common neoplasm occurs in women. Neoadjuvant Chemotherapy (NACT) is widely used in Locally Advanced Breast Cancer (LABC) and Inflammatory Breast Cancer (IBC), to reduce tumor size (down-sizing), and further allowing breast-conserving surgery to be performed. Accurate markers are needed to prevent impractical chemotherapy that allows patients to receive definitive surgery in a timely manner. Previous study showed neutrophil/lymphocyte ratio (NLR) was superior in predicting long-term outcomes over PLR. This study aims to evaluate the relationship between the NLR value and neoadjuvant chemotherapy response in patients with locally advanced breast cancer at Dr. Mohammad Hoesin General Hospital Palembang. Methods: This study is a prognostic test of the NLR accuracy to predict the response of neoadjuvant chemotherapy in patients with locally advanced breast cancer. The study included 113 patients as study subjects. Results: The obtained NLR cut off point value was ≤ 2.92 with an area under the ROC curve (AUC) of 92.2%. The diagnostic measures of the NLR prognostic test had sensitivity of 93%, specificity of 93%, Positive Predictive Value of 97%, Negative Predictive Value of 82%, and accuracy of 93%. There is a significant relationship between NLR and chemotherapy response in patients with locally advanced breast cancer (p = 0.000). Conclusion: There is a significant relationship between NLTR and chemotherapy response. NLR can be used as a predictor of neoadjuvant chemotherapy response with a good degree of accuracy.

A 79-year-old woman was treated at our department for a neoplasm of the left breast. It was discovered following the spontaneous appearance of a localized ecchymotic lesion of the breast. The only clinical sign was this purpura, with no notion of trauma. The lesion was homogeneous, oval, and measuring 4 × 5 cm, and it was stable for 2 months. The patient had no history of thrombocytopenia and no known allergy. The physical examination was not very helpful and did not find any palpable breast lesion besides a 1-cm left axillary lymphadenopathy. Breast screening revealed a solid, poorly delineated structure of 11 mm. Biopsies were taken and revealed a NOS grade II invasive carcinoma, triple negative, with a Ki-67 proliferation index of 15%. The axillary cytology was positive. Faced with this atypical presentation, a skin biopsy was performed on the bruise in order to exclude skin invasion. Histology showed the presence of carcinomatous lymphatic dermal emboli which could correspond to a mammary origin as well as extravasation of blood in the dermis explaining this ecchymotic aspect. Bone scintigraphy found discrete uptake in the rib cage, spine, and pelvis, suspicious in this context, but a benign origin could not be ruled out. Neoadjuvant chemotherapy was initiated before mastectomy and left axillary node dissection. It was an atypical and rare clinical presentation of advanced breast cancer with no similar case found in the literature. Usually, the presence of emboli with carcinomatous cells obstructing the lymphatic vessels is related to inflammatory breast cancer or carcinomatous mastitis. The authors nevertheless point out that although the presence of tumor emboli in the dermal lymphatic vessels is favorable to the diagnosis, it is not required. In addition, dermal lymphatic invasion without a typical clinical presentation is not sufficient to confirm the diagnosis of carcinomatous mastitis. An important diagnostic criterion is the rapidity of aggravation of the symptoms, which, even if it was not obvious in our case, was present with progressive evolution of the skin lesion over several weeks. The skin lesion of our patient could also make us suspect a primary breast angiosarcoma. This possibility was quickly eliminated in the absence of vascular tumor proliferation on the various biopsies. Any acute purpura is a serious disease to be diagnosed urgently, and a skin biopsy is indicated.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor–positive, HER2-negative breast cancer.

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

Patients may present to the emergency department with breast complaints due to traumatic or nontraumatic changes in the breast. Benign and malignant breast pathologies may mimic each other both in clinical presentation and imaging appearance. A complex cystic and solid mass seen on ultrasound in a patient with a palpable mass can represent breast cancer, abscess, or hematoma. A unilateral swollen breast may result from inflammatory breast cancer, mastitis, or other benign etiologies; correlation with clinical history, physical exam, and close follow-up are required to ensure complete resolution of symptoms. Uncommon breast entities such as granulomatous mastitis and breast implant–associated anaplastic large-cell lymphoma may cause changes in the appearance of the breast that prompt a patient to seek initial evaluation in the emergency department. Imaging evaluation of the breast in the emergency department is limited, and it is important that patients with a breast complaint be referred to a dedicated breast center for complete evaluation at an appropriate time interval after their discharge from the emergency department.

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.

Graphical abstract, Background 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. Aim of Review 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. Key Scientific Concepts of Review 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.

Prophylactic cranial irradiation (PCI) can reduce the incidence of brain metastasis and improve overall survival in some patients with acute lymphoblastic leukemia or small-cell lung cancer. We examined the potential effects of PCI in a mouse model of breast cancer brain metastasis. The HER2+ inflammatory breast cancer cell line MDA-IBC3 was labeled with green fluorescent protein and injected via tail-vein into female SCID/Beige mice. Mice were then given 0 Gy or 4 Gy of whole-brain irradiation 2 days before tumor-cell injection or 5 days, 3 weeks, or 6 weeks after tumor-cell injection. Mice were sacrificed 4-weeks or 8-weeks after injection and brain tissues were examined for metastasis by fluorescent stereomicroscopy. In the unirradiated control group, brain metastases were present in 77% of mice at 4 weeks and in 90% of mice at 8 weeks; by comparison, rates for the group given PCI at 5 days after tumor-cell injection were 20% at 4 weeks (p=0.01) and 30% at 8 weeks (p=0.02). The PCI group also had fewer brain metastases per mouse at 4 weeks (p=0.03) and 8 weeks (p=0.006) versus the unirradiated control as well as a lower metastatic burden (p=0.01). Irradiation given either before tumor-cell injection or 3-6 weeks afterward had no significant effect on brain metastases compared to the unirradiated control. These results underscore the importance of timing for irradiating subclinical disease. Clinical whole brain strategies to target subclinical brain disease as safely as possible may warrant further study.

Background: Advances in HER2-directed therapy have significantly improved survival in HER2+ metastatic breast cancer. Approximately 30% of de novo metastatic inflammatory breast cancer (mIBC) is HER2+, though there has been limited IBC representation in clinical trials evaluating the role of HER2-directed agents as first-line metastatic therapy. Elevated rates of locoregional progression or recurrence (LRPR) with systemic therapy alone also raise the question of whether trimodality therapy (TMT) may improve outcomes in IBC patients (pts) with limited metastatic disease, particularly in the setting of increasingly effective anti-HER2 therapy. Methods: Pts diagnosed with de novo HER2+ mIBC were identified from an IRB-approved IBC registry at Dana-Farber Cancer Institute. Clinical, pathology and treatment data were manually abstracted by chart review. Progression-free survival (PFS) was defined as time from IBC diagnosis to LRPR, distant progression/relapse or death (in the absence of event, censored at date of last follow-up). Overall survival (OS) was defined as time from IBC diagnosis to death from any cause or censored at date last known alive. For pts who underwent surgery of the primary tumor, pathologic complete response (pCR) was defined as no residual invasive carcinoma in the breast and axilla and survival was estimated from date of surgery. Median PFS and OS were estimated by Kaplan-Meier method; cumulative incidence of CNS metastasis and LRPR were estimated with death as competing risk. Results: 78 pts diagnosed between 1998-2019 with de novo HER2+ mIBC (41 hormone receptor (HR)-positive; 37 HR-negative) were identified. Median age at diagnosis was 53 years (yr; range: 24-91). Sites of metastatic disease at presentation included bone only (n=12), lymph node/contralateral chest wall only (n=17), bone and lymph node (n=5), visceral (n=40) and CNS with extracranial disease (n=4). As initial HER2-directed therapy, 37 pts received trastuzumab (H), 40 H plus pertuzumab and 1 T-DM1. At a median follow-up of 2.7 yr in the overall cohort, median PFS was 1.0 yr (IQR: 0.5-2.8 yr; 60 events) and median OS was 4.6 yr (IQR: 2.9-8.7 yr; 39 deaths). 34 pts had CNS metastasis with a cumulative incidence of 20% and 28% at 1 and 2 yr, respectively. LRPR developed in 26 pts, of which 16 occurred within 12 months (mo) of diagnosis. Cumulative incidence of LRPR at 1 and 2 yr was 21% and 29%, respectively. In 41 pts (53%), mastectomy was performed after receipt of systemic therapy. Median time from IBC diagnosis to surgery was 7.5 mo (IQR: 6.0-9.9 mo). Radiation was administered in 33 pts, 3 pre- and 30 post-mastectomy. Median OS from surgery was 5.2 yr (IQR: 3.1-8.4 yr). 9/41 pts (22%) achieved pCR; all pCR pts were alive at 1.3-8.9 yr since surgery. To investigate the value of therapy for locoregional control, a landmark analysis was performed in the subset of pts alive and LRPR free at 12 mo from diagnosis (n=56). 27 had surgery within 12 mo from diagnosis and 29 did not. LRPR occurred in 10/56; 9 were among pts who did not undergo surgery. Cumulative LRPR incidence at 1 and 2 yr since the 12 mo landmark was 21% and 29%, respectively, in pts who did not undergo surgery, and 0% at both time points in pts who had surgery (1 LRPR at 8 yr). Conclusion: Long-term outcomes in de novo HER2+ mIBC are overall similar to those reported in metastatic HER2+ non-IBC. More than half of pts underwent systemic and local therapy with good locoregional control and prolonged survival, suggesting a potential role for aggressive local therapy in this mIBC subset with favorable prognosis and effective systemic therapy. The high incidence of early CNS involvement in de novo HER2+ mIBC prompted us to explore this group in detail (Warren SABCS 2020 abstract). Larger studies are needed to better understand the effectiveness of TMT in HER2+ mIBC, highlighting the importance of collaborative research efforts in this rare subset. Citation Format: Ana C. Garrido-Castro, Samuel M. Niman, Marie Claire Remolano, Jennifer M. Rosenbluth, Caroline Block, Laura E. Warren, Jennifer Bellon, Beth T. Harrison, Faina Nakhlis, Meredith Regan, Beth Overmoyer. Clinical outcomes in de novo metastatic HER2-positive inflammatory breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-34.

Background: Breast cancer is one of the most common types of cancer in United States women, with inflammatory breast cancer (IBC) being among the most aggressive, accounting for only 1-4% of all breast cancer cases yet causing 8-10% of breast cancer related deaths. It is reported that survival outcomes differ significantly between races and that specific races such as African-American tend to have aggressive and advanced disease. Previously, we reported that the proportion of IBC to non-IBC is significantly high in Native Hawaiian (NH) and Pacific Islander (PI) populations. The same study showed that NH and PI have shorter overall survival (OS) than Caucasians in patients with non-IBC but not in those with IBC. However, it is still not well known if poor prognosis in specifc races is due to aggressive disease biology, advanced stage at diagnosis, or socioeconomic status such as insurance status. Our primary objective was to determine the factors that predict OS after adjusting for baseline patient and disease characteristics. One of the novelties in our study is that we analyzed IBC and non-IBC, separately in our unique population in Hawaii. Methods: Patients with newly-diagnosed primary invasive breast cancer were identified from January 1, 2000 through December 31, 2018 using The Queen’s Medical Center Tumor Registry in Honolulu, Hawaii. Patients whose baseline and disease characterics were not available were excluded from the final analysis. Clinical T4d was used to differentiate IBC and non-IBC. OS was defined as the time from diagnosis to death or last follow-up. Patients who were alive at the date of last follow-up were censored. All the variables were summarized using standard descriptive statics. Univariate and multivariate cox proportional hazards models were used to assess the effects of variables of interest on OS. P-values Citation Format: Kyle SY Miyazaki, Jared D Acoba, Takeo Fujii. The impact of insurance status on survival in patients with inflammatory breast cancer (IBC) and non-IBC among a unique population in Hawaii [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-18.

Background: Patients (pts) with inflammatory breast cancer (IBC) have a high risk of central nervous system (CNS) metastasis (mets) with their associated impact on longevity and quality of life. Given evolving CNS-directed treatments, including focal radiation (RT), we compared the proportion of pts diagnosed with asymptomatic CNS mets before and after 2012 as data from Phase III trials in the preceding years (yr) increasingly supported the use of stereotactic radiosurgery (SRS). Specific attention was paid to pts treated with tri-modality therapy (TMT), defined as preoperative systemic therapy, surgery, and RT to determine whether screening for asymptomatic CNS mets would be beneficial. Methods: We retrospectively reviewed the records of pts diagnosed with IBC 1997-2019 and enrolled in an IRB-approved registry at a dedicated IBC center. CNS met-free survival time was defined as the time from IBC diagnosis to date of CNS mets. Alive CNS met-free pts were censored at their latest survival date and death was treated as a competing risk. Cumulative CNS mets incidence was computed. Analyses were stratified based on stage at diagnosis (III vs. de novo IV) and receipt of TMT. For pts completing TMT, the completion date was the starting point for cumulative incidence calculations. Overall survival (OS) was estimated as the time from CNS mets diagnosis to death, with censoring for pts who were still alive. Results: A total of 531 pts were identified; 372 (70%) with stage III; 159 (30%) with de novo Stage IV disease. The median follow-up for pts presenting with stage III and stage IV disease at diagnosis was 5.6 yr and 1.8 yr, respectively. 124 pts had CNS mets; 5 of them at diagnosis. CNS was the first site of mets or progression in 50 pts (9.4%). The cumulative incidence of CNS mets stratified by stage at diagnosis and receipt of TMT is seen in Table 1. Among the 50 de novo Stage IV pts who completed TMT, 4 developed CNS mets prior to surgery. The median overall survival (mOS) after CNS mets was 0.6 yr (IQR: 0.2 - 1.4). Results stratified by tumor subtype were: HER2+ disease (n=51) 1.4 yr (IQR: 0.6 - 3.7); hormone receptor+/HER2- (n=27) 0.6 yr (IQR: 0.2 - 1.2); triple negative (n=40) 0.2 yr (IQR: 0.1 - 0.5). Most pts with CNS mets (87/124, 70%) had neurologic symptoms prompting imaging. There was no difference in the proportion of asymptomatic pts diagnosed with CNS mets prior to or after 2012. Management of CNS mets was as follows: 47 pts (38%) received whole brain RT (WBRT) alone, 22 (18%) SRS alone, 15 WBRT + SRS (12%), 6 resection + WBRT (5%), and 5 resection + SRS (4%). The remaining pts received several of these modalities with or without intrathecal chemotherapy (13, 11%) or CNS treatment was not documented (16, 13%). A total of 258/531 pts have died (49%). Of these pts, 103 (40%) had CNS mets. 67/103 (65%) died due to CNS mets. Conclusions: Among pts with IBC completing TMT, the incidence of CNS mets is as high as 20% both in de novo Stage IV pts at 1 yr and in Stage III pts within 5 yrs, supporting routine surveillance brain MRI among pt with Stage IV disease. The majority of pts continue to receive WBRT with its resultant toxicities. Efforts should be made to identify CNS mets early to facilitate more focal therapy. Future research on systemic therapy with CNS penetrance for IBC patients should be pursued. These data support an ongoing prospective study of screening brain MRI in pts with Stage III IBC to quantify the incidence of CNS mets, utilization of WBRT and impact on neurologic quality of life (NCT04030507). Cumulative Incidence of CNS MetsNo.1 year (95% CI)2 year (95% CI)3 year (95% CI)Stage III (All)3725% (3-7)9% (6-12)18% (14-23)Stage IV (All)15417% (12-24)30% (22-37)42% (32-51)Stage III (TMT)3045% (3-8)11% (8-16)19% (14-24)Stage IV (TMT)4621% (10-34)28% (16-43)35% (20-50) Citation Format: Laura Warren, Samuel M Niman, Marie Claire Remolano, Jean Landry, Faina Nakhlis, Jennifer R Bellon, Meredith M Regan, Beth A Overmoyer. Incidence and management of central nervous system metastases in patients with inflammatory breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-06.

Background: Inflammatory breast cancer (IBC) is the most aggressive locally advanced breast cancer subtype. It is associated with loco-regional recurrence rates of 12-25%, and neoadjuvant chemotherapy (NAC) followed by modified radical mastectomy and comprehensive chest wall and regional nodal radiotherapy remain the standard of care. As has been demonstrated in non-IBC, achievement of pathologic complete response (pCR) has been shown to be associated with improved loco-regional control, recurrence-free and overall survival. Advances in NAC for IBC have resulted in improved pCR rates in both the breast and the axilla, with overall axillary pCR rates of approximately 30%, reaching as high as 67% in patients with HER2-positive disease receiving HER2-directed therapy. Hypothesis: Sentinel lymph node biopsy (SLNB) may be feasible in IBC patients who experience a good clinical and pathologic response in the axilla to NAC. Primary Objective: To evaluate the sentinel lymph node (SLN) identification rate in stage III IBC patients who experience cN0 status at completion of NAC. Secondary Objective: To assess the incidence of lymphedema following standard local-regional therapy for IBC. Methods and Study procedures: In this feasibility study, 50 patients with cT4dN0-2M0 IBC will be enrolled in order to evaluate 40 patients whose axillary nodal status becomes cN0 upon completion of NAC. All patients will undergo a research breast biopsy and lymphoscintigram pre and post NAC to evaluate lymphatic drainage patterns and patency of breast and axillary lymphatics. Post NAC lymphoscintigraphy will be appropriately timed for pre-operative SLN mapping and all patients will undergo SLNB using dual tracers (Tc99 Sulfur colloid and blue dye) with immediate axillary lymph node dissection (ALND), at the time of mastectomy. The patient-reported Lymphedema Symptom Intensity and Distress Survey (LSIDS-A) will be collected at 6 timepoints. Patients will be followed for 2 years post-surgery for oncologic outcomes. Correlatives: We plan to evaluate genetic and phenotypic heterogeneity in IBC and to assess markers of angiogenesis and lymph-angiogenesis associated with IBC, as well as to explore immunologic aspects of the tumor microenvironment and their association with pCR. Statistics: The identification rate will be calculated as number of patients in whom SLNs were successfully identified over the number of patients with cN0 disease after NAC in whom SLN mapping was attempted. Using a Simon two-stage design (α=.10, β=.10), a SLN identification rate of ≥90% would result in considering this procedure feasible whereas an identification rate of ≤75% (null hypothesis) would lead to the conclusion that it is not feasible. In the first stage, if greater than 18 of 25 patients have SLNs identified, then a total of 40 patients will be enrolled. If fewer than 33 of 40 patients have SLN identified, then the null hypothesis is rejected. Citation Format: Faina Nakhlis, Meredith Regan, Heather Jacene, Beth Harrison, Jennifer Bellon, Jean Landry, Eren Yeh, Elizabeth Mittendorf, Beth Overmoyer, Tari King. Refining loco-regional therapy for inflammatory breast cancer protocol in progress [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-21.

This paper presents a case study of a 78-year-old male patient who presented with exacerbated skin redness and edema on the left chest wall, especially on the left breast, and who had been suffering from associated pruritus for 6 months. The patient also presented with enlarged ipsilateral axillary lymph nodes that were suspected to be carcinomas after a preliminary ultrasound and enhanced computerized tomography (CT) examination were performed. To examine these symptoms, an ultrasound-guided core biopsy and a chronic inflammatory test were also performed. The results of the excision biopsy and the immunohistochemistry test of the left breast and ipsilateral lymph node revealed no signs of cancer in this patient. Finally, combined with his medical history, the laboratory tests and pathology results, the patient was diagnosed with plasma cell mastitis (PCM) after another suspicious lesion (e.g., inflammatory breast cancer, etc.) was excluded. PCM is a kind of benign lesion of the breast with an unclear etiology. It usually affects non-pregnant and non-lactational females, who display clinical symptoms that are often similar to those of inflammatory breast cancer (IBC), the main manifestations were erythema and edema on the chest wall. To date, there is no standardized clinical treatment strategy or management approach for PCM.

Graphical abstract, Introduction 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. Objectives The objective of this study was to detect both gene expression levels and alternate RNA splice variants specific for IBC. Methods 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. Results A 5-splice signature (HSPA8, RPL10, RPL4, DIDO1 and EVL) was able to distinguish IBC from non-IBC tumors (p

The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007–2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local–regional recurrence patterns were described and survival analyses were conducted. All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2−]: 31.1% vs. 44.2%; HR-negative [HR−]/HER2+: 24.4% vs. 15.4%; and HR−/HER2−: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p

Background and Objectives: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer treated up-front with systemic treatment. Both breast-conserving surgery and sentinel lymph node biopsy (SLNB) are controversial issues in the management of IBC. In this study, we aimed to assess the feasibility of SLNB in pathologically proven node-positive IBC patients. Methods: All patients with a histopathological diagnosis of IBC and biopsy-proven metastatic axillary lymph nodes underwent systemic treatment. Patients with a complete clinical response in the axilla who underwent SLNB followed by standard axillary dissection were analyzed. Results: The study consisted of 25 female patients. The identification rate (IR) and the false negativity rate (FNR) were 17/25 and 2/10, respectively. Overall, 9/25 and 7/25 of patients had a complete pathological response (pCR) in the breast and axilla after systemic treatment, respectively. Although the pCR in the axilla was 2/4 in nonluminal HER2-positive patients, the highest IR 4/4 and the lowest FNR 0/2 were determined in these patients. In triple-negative patients, however, the IR was 2/4 and the FNR was found to be 0/2. Conclusions: SLNB may be considered in selected axilla-downstaged IBC patients including patients with a pCR with HER2-positive and triple-negative tumors. Axillary dissection may be, therefore, omitted in those with negative SLNs.

Clinically, acute mastitis presents as a red, swollen, and painful breast. Targeted ultrasound can be performed to evaluate the extent of infection and for an underlying abscess. Noncomplicated mastitis or a small fluid collection may respond to oral antibiotics without further intervention, but a larger or more complex abscess may require single or serial percutaneous aspiration. Breast infections, particularly those complicated by an abscess, can have a prolonged clinical course, and close follow-up is required. Since the clinical presentation and imaging features of acute infectious mastitis can overlap with other etiologies, such as inflammatory breast cancer and idiopathic granulomatous mastitis, a percutaneous biopsy may be indicated to accurately diagnose patients.

Purpose To evaluate the survival of patients with inflammatory breast cancer (IBC) and to correlate these survival rates with the histopathological parameters found in the resection specimen of the tumor. Patients and methods This retrospective study was based on 27 patients that had been diagnosed and had undergone surgery in the 2nd General and Oncological Surgery Clinic of the County Emergency Hospital in Timisoara, Romania. Data about the patient group were collected from archived patient files over a period of eight years starting from January 2008. The collected data regarded age, tumor size and histopathological type and immunohistochemistry (IHC), presence or absence of tumor embolus in lymphatic or blood vessels and the presence or absence of distant metastases at the time of diagnosis. We evaluated the impact of tumor characteristics on the patients' outcome. Results The 12-month survival rates postsurgery were significantly increased if tumors were 5 cm (p=0.046), if nodal status was N0 vs N1-2 (p=0.039), as well as in cases where distant metastases were absent, compared to patients with distant metastases (p=0.001, α=0.001) and positive-hormone receptors (p=0.043). Survival was influenced neither by histopathological type (p=0.357) nor by the presence of tumor embolus in the resection specimen (p=0.250) and HER2 status (p=0.763). Survival at 12 months after surgery was equal between those with stage IIIB noninflammatory breast cancer (NIBC) and IBC. At 24 months after surgery, IBC cases presented a significantly lower probability of survival. Conclusion The prognosis of patients with IBC is reserved compared to NIBC, increased tumor size, positive lymph node, hormone receptors negative cases and distant metastases drastically decreasing survival rates.

Metastasis of ovarian cancer to breast (MOCB) is rare, and the diagnosis is difficult due to the varied imaging manifestations. The objective of this paper is to report a special case of MOCB, review the imaging manifestations of MOCB and attempt to determine the characteristic imaging features that might be helpful in making the diagnosis and providing appropriate systemic therapy. A 40-year-old woman presented with a breast lesion six years after a diagnosis of ovarian serous cystadenocarcinoma. Ultrasound (US) and magnetic resonance imaging (MRI) examinations were performed; the final diagnosis was metastasis of ovarian serous cystadenocarcinoma to breast according to the histological examination and immunohistochemical examination after lumpectomy. Herein, we reviewed 41 cases diagnosed with MOCB, which include imaging of the metastatic breast lesion or a detailed description without imaging. In this review, we summarized that MOCB could present with calcifications (especially microcalcifications) on mammography (MM). MOCB presenting as inflammatory breast cancer usually shows swelling and skin thickening on MM and US, and increased fludeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). These manifestations could be helpful in differentiating malignant tumors from benign ones, but it may still be difficult to distinguish between primary and metastatic tumors. The correct diagnosis of MOCB requires a combination of the clinical history of the primary tumor, careful clinical examination, radiology and anatomic pathological evaluation.

Purpose of ReviewInflammatory 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 FindingsAdvancements 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.SummaryOptimal 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.

The objective of this study was to describe the diagnostic value of positron emission tomography/computed tomography (PET/CT) and ultrasound (US) for identifying metastatic axillary disease in primary breast cancer. This is a retrospective review of 240 patients with treatment-naive unilateral primary breast cancer of at least stage T2. Eighty-five patients met our inclusion criteria. Initial whole-body PET/CT and axillary US examinations were reviewed and compared with the criterion standard of fine-needle aspiration cytology. Sensitivity, accuracy, and positive predictive value (PPV) for each modality were computed. Because of all positive US cases, specificity and negative predictive value of US were not determined. Sensitivity and accuracy between modalities were compared using McNemar test. The majority of the patients were White women with clinical inflammatory breast cancer and with histologically invasive ductal carcinoma. The most common tumor and nodal stage was T4N3. The tumors were predominantly estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor 2 negative. The sensitivities of PET/CT and US were 96.2% and 100%, respectively. The accuracies for PET/CT and US were 91.8% and 94.1%, respectively. The PPV for PET/CT was 95.1%, and for US, the PPV was 94.1%. No significant difference in sensitivity or accuracy was shown between PET/CT and US for the diagnosis of metastatic axillary nodal disease. Three of 85 cases showed discordance between negative PET/CT and positive US and fine-needle aspiration cytology.

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. 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. 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. 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.

Inflammatory breast cancer (IBC) is a rare and highly aggressive subtype of advanced breast cancer. The aggressive behavior, resistance to chemotherapy, angiogenesis, and high metastatic potential are key intrinsic characteristics of IBC caused by many specific factors. Pathogenesis and behavior of IBC are closely related to tumor surrounding inflammatory and immune cells, blood vessels, and extracellular matrix, which are all components of the tumor microenvironment (TME). The tumor microenvironment has a crucial role in the local immune r09esponse. The communication between intrinsic and extrinsic components of IBC and the abundance of cytokines and chemokines in the TME strongly contribute to the aggressiveness and high angiogenic potential of this tumor. Critical modes of interaction are cytokine-mediated communication and direct intercellular contact between cancer cells and tumor microenvironment with a variety of pathway crosstalk. This review aimed to summarize current knowledge of predictive and prognostic biomarkers in IBC.

Modified radical mastectomy (MRM), which includes axillary dissection, is the standard of care for inflammatory breast cancer (IBC). While more limited axillary staging after neoadjuvant chemotherapy (NAC) in clinically node-positive non-IBC has been increasingly adopted, the impact of these techniques in IBC is not clear. To inform patient selection for further study of limited axillary surgery, we aimed to describe the frequency and factors associated with pathological node-negativity (ypN0) in IBC. Patients with IBC who received NAC and MRM were identified from a prospective institutional database (2004–2019). Binary logistic regression analyses were conducted to identify factors associated with ypN0. Of 453 patients, 189 (41.7%) had a post-NAC clinical nodal stage (ycN stage) of N0 (ycN1: 150, 33.1%; ycN2: 4, 0.9%; ycN3: 47, 10.4%; unknown: 63, 13.9%); 156 (34%) were ypN0. On multivariable analysis, higher tumor grade was not associated with ypN0 (odds ratio [OR] 1.59, 95% confidence interval [CI] 0.90–2.81, p =0.11). Compared with hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-negative tumors (n =113, 24.9%), HR-positive/HER2-negative tumors (n =169, 37.3%) had a trend toward less ypN0 (OR 0.55, 95% CI 0.29–1.02, p =0.06); HR-positive/HER2-positive tumors (n =79, 17.4%) were similar to HR-negative/HER2-negative tumors (OR 0.72, 95% CI 0.35–1.48, p =0.37); and HR-negative/HER2-positive tumors (n =92, 20.3%) were associated with increased ypN0 (OR 4.82, 95% CI 2.41–9.63, p

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 2005–2017 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

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.

Inflammatory breast cancer (IBC) is an uncommon and highly aggressive form of breast cancer. The disease is characterized by rapid progression with approximately 50% of IBC patients to have human epidermal growth factor receptor 2 (HER2) amplification. HER2-positive IBC is associated with unfavourable prognosis and increased risk of brain metastasis. Ironically, HER2-positive metastatic breast cancer is still prevalent where therapeutic targeting of HER2-receptor is well developed. In addition, the ability to accurately predict the risk of metastatic potential in these cells poses a substantial challenge. Lapatinib (Lap), a dual kinase inhibitor of HER2 and epidermal growth factor receptor is used in the treatment of advanced HER-2 positive breast cancers and is currently being evaluated in the adjuvant setting. In this study, we report the effectiveness of Lap in the suppression of low-dose response to doxorubicin (Dox) in HER2-positive SKBR3 cells. Upon treatment of SKBR3 cells with 0.1 µM of Dox, the cell viability was significantly increased as compared to the human mammary fibroblasts, and triple-negative human breast cancer MDA-MB-231 cells. Interestingly, the effect of 0.1 µM Dox revealed morphological changes consistent with a significant increase in the formation of prominent F-actin filaments and mitochondrial spread compared with the control SKBR3 cells. Furthermore, an enhanced migration was also evident in these cells. However, a combinational dose of 0.1 µM Dox + 5 µM Lap suppressed the observed phenotypic changes in the 0.1 µM Dox treated SKBR3 cells. There was a significant difference in the prominent F-actin filaments and the mitochondrial spread compared with the 0.1 µM Dox versus combination regimen of 0.1 µM Dox + 5 µM Lap. In addition, the combinational therapy showed a decrease in the percentage of wound closure when compared to the control. Hence, the combinational therapy in which Lap suppresses the low-dose effect of Dox in SKBR3 cells may provide an effective intervention strategy for reducing the risk of metastasis in HER2-positive breast cancers.