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The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. In this report, we review cases of secondary IBC and others where localized trauma was followed by the appearance of IBC at the traumatized site that have been identified by our IBC Registry (IBCR) and hypothesize that angiogenesis appearing as part of the healing process could act as an accelerant to an otherwise latent breast malignancy. It is therefore possible that secondary IBC can be used as a model to support local angiogenesis as an important contributor to the development of an aggressive cancer.

Background: The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis. It is fast growing, highly angiogenic and angioinvasive, features that are present from its inception. The idea of a dormant cancer cell and awakening of metastatic disease following a surgical/traumatic event may well be exemplified by secondary IBC, a term used to describe the IBC appearing following surgery for a noninflammatory primary breast carcinoma. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. It is therefore possible that secondary IBC can be used as a model to support local angiogenesis as an important contributor to the development of an aggressive cancer. Materials and Methods: Cases of secondary IBC were identified in a review of patients referred to the IBC Registry (IBCR). In this report we document the histories of three patients with secondary IBC as well as two additional patients whose disease presentation also supports the possible occurrence of IBC secondary to breast trauma. Secondary IBC cases were defined as women who had surgery for non-inflammatory breast cancer with recurrence at the previous mastectomy site manifest as skin erythema shown to be associated with pathologically confirmed tumor emboli in the dermal lymphatics. Results: Two of the patients with secondary IBC developed pathologically confirmed dermal lymphatic invasion two and 42 months after partial mastectomy for non-inflammatory breast cancer. The third had been apparently free of recurrence for seven years when she had reconstructive surgery, which was followed by IBC seven months later. Two additional cases are presented, one in which IBC manifested one month following ductogram procedure and had a contralateral breast IBC recurrence 2 years later. The other patient was diagnosed with IBC one year following nipple piercing and ring removal. Discussion: Recent publications have focused on the role of surgery in the subsequent development of metastatic breast cancer, many of them focusing on a hormonal mechanism triggered by removal of the primary tumor. We propose local angiogenesis as another possible mechanism for post-surgical dissemination of cancer. In view of the hypothesis that trauma can stimulate angiogenesis which can accelerate tumor growth, the documentation of IBC appearing at the site of a traumatic event merits consideration. Our experience with IBC, noted in the case reports above suggest that local trauma probably mediated in large part by angiogenesis can be an important trigger of IBC. We would therefore suggest that secondary IBC be considered for investigation of one possible mechanism for post-surgical tumor dissemination. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-05-09.

The case definition for inflammatory breast cancer (IBC) is controversial. The American Joint Committee on Cancer defines IBC as redness, warmth and edema involving at least half the breast. The SEER program relies on a pathologic finding of dermal lymphatic invasion and recently added those with clinical involvement of more than 3/4 of the breast. We established a registry to collect information and specimens from IBC patients to clarify the epidemiology and biology of these tumors. The goals of this report are to suggest improvements regarding case definitions and provide data on the variety of presentations relevant to early diagnosis.

A previous symptom-based survey of veterans of the 1990-1991 Persian Gulf War suggested a neurological syndrome (blurred vision, loss of balance/dizziness, tremors/shaking, and speech difficulty). The authors conducted the present study to determine whether specific findings could indicate an organic basis for this possible syndrome. They completed an extensive clinical and laboratory evaluation on Gulf War veterans with all 4 symptoms, using 3 comparison groups. A single clinically based neurological syndrome could not be identified. No deployment-related exposure appeared to explain the pattern of symptoms, but this evaluation suggested comorbidities and possibly multiple vaccines as important contributors. Many of the neurological symptoms reported by the studied veterans appear to have an organic basis, but comorbidities must be excluded before researchers can conclude that a definitive syndrome exists.

Optical coherence tomography (OCT) is a new modality that allows noninvasive examination of the internal structure of biological tissue in vivo with a spatial resolution of 10 to 15 microm. This study evaluated the clinical application of OCT to determine epithelial and subepithelial anatomic structure and invasiveness of bladder epithelial lesions.The OCT examination was performed with a 980-nm 10 mW superluminescent diode using a 2.7-mm-diameter optical fiber positioned cystoscopically. A total of 261 scans of 1.5 seconds' duration, which generated 200 x 200-pixel images, were performed on 87 areas in 24 patients at high risk of having transitional-cell carcinoma (TCC). Lesions, visually suspect, and normal areas were photographed, scanned, and biopsied. The scans were evaluated independently before comparison with histopathology findings.Of the 87 areas, 29 of 36 visually suspect areas and 35 of 35 normal areas, were correctly diagnosed with OCT. Of the 16 areas with papillary TCC, all 16 were diagnosed correctly as tumor, and 9 of 10 were diagnosed correctly as invasive, including 6 with lamina propria invasion only. Papillary and flat tumors, carcinoma in situ, inflammation, chronic cystitis, and von Brunn's nests were scanned. Overall, OCT had a sensitivity of 100%, overall specificity of 89%, positive predictive value of 75%, and negative predictive value of 100%. The accuracy was 92%. The positive predictive value for invasion was 90%.Optical coherence tomography is a simple, portable, promising modality for evaluation of bladder lesions and depth of tumor penetration. Further refinement of this technology may lead to the development of an optical surrogate for biopsy.

Introduction Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs). Patients and Methods Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; ‘treated IDC'; and untreated IDC [n = 27; ‘untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed. Results Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomarker levels were observed in all groups but were generally greatest in untreated IDC and least in IBC, except for JAK2 . Conclusion IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, which suggests a potential mechanism of resistance after NAC. Biomarker levels in surrounding nontumor tissue suggested that the stroma might be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of pS6 and pJAK2 in IBC might support dual targeting of the mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combined targeted therapies in IBC.

To determine whether chemotherapy response and diagnostic delay affect overall survival (OS) of classic inflammatory breast cancer (IBC) cases receiving chemotherapy as initial treatment and to determine whether OS differs between classic and "atypical" IBC cases.This is a prospective cohort study of 155 patients enrolled in the IBC Registry. "Classic" IBC cases met AJCC or SEER case definitions. "Atypical" IBC cases exhibited classic features but involved1/2 breast without documented dermal lymphatic invasion. Variables included OS (years from initial chemotherapy treatment until death or last contact), chemotherapy response (complete, partial, or none), diagnostic delay (days from first medical contact for signs/symptoms of abnormal breast to definitive pathologic IBC diagnosis), age at diagnosis (y), and triple-negative status (yes or no). OS curves stratified by individual predictors were estimated and compared using Kaplan-Meier methods and log-rank tests. Associations between OS and predictors were examined collectively using Cox proportional hazards regression.Classic IBC cases with complete, partial, or no response had respective median (95% confidence interval [CI]) OS times of 10.30 (6.78, +), 6.27 (4.42, +), and 2.86 (1.11, 11.42) years (P=0.0072). Chemotherapy response was significantly associated with OS after controlling for covariates (P=0.003). Women not responding to chemotherapy had a significantly higher hazard of death compared with women with complete (hazard ratio [HR]=5.76; 95% CI, 2.09-15.84) or partial (HR=3.40; 95% CI, 1.27-9.10) response. Diagnostic delay was not significantly associated with OS (HR=1.003; 95% CI, 0.999-1.007). OS did not differ significantly between classic and "atypical" IBC cases (P=0.60).Response to standard IBC chemotherapy is a dominant prognostic factor in determining patient outcomes. In our study, with limited statistical power, delay in diagnosis defined as60 days from the time of first physician contact did not seem to affect patient outcomes. Data support similarities between classic and "atypical" IBC.

Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In most cancers, expression of E-cadherin, an epithelial marker, is indicative of low metastatic potential. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. E-cadherin, a surface component of adherens junctions, is anchored by interaction with p120 catenin (p120). We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. These findings provide a new understanding of translational control in the development of advanced breast cancer.

Background: Inflammatory breast cancer (IBC) is recognized as an aggressive form of breast cancer requiring neoadjuvant chemotherapy. Although IBC affects only a small percentage of breast cancer patients, the estimated 4,810 new cases for 2009 exceeds the number of women diagnosed with other cancers, such as acute lymphocytic leukemia and chronic myelocytic leukemia (as reported by the American Cancer Society). Research on IBC is hampered by the absence of an agreed upon case definition. While the American Joint Committee on Cancer (AJCC) relies on clinical features (more than half of the breast being involved with redness, warmth and edema), the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program focuses on pathologic confirmation. This study was undertaken to determine whether the outcome of IBC differs among patients who meet IBC criteria by AJCC, SEER, and private practitioners to try to improve the case definition for research purposes. Methods: This is a retrospective study of 121 patients in The George Washington University Medical Center IBC Registry who were classified as an IBC case by AJCC, SEER or private practitioners. We grouped these IBC cases into four epidemiological categories: (1) clinical-pathologic presentation of disease involving more than half of the breast, (2) clinical-only presentation of disease involving more than half of the breast, (3) clinical-pathologic presentation of disease involving less than half of the breast, and (4) clinical-only presentation of disease involving less than half of the breast. Note that Categories 1 and 2 meet AJCC criteria, while Categories 1 and 3 meet SEER criteria for IBC. We used an unadjusted Cox proportional hazards model to test the homogeneity of the progression-free survival (PFS) curves among these four epidemiological categories. Results: Of the 121 IBC cases, 33.1% (n=40) were classified as Category 1, 16.5% (n=20) were Category 2, 25.6% (n=31) were Category 3, and 24.8% (n=30) were Category 4. Using Category 4 as the reference group, the Cox proportional hazards model yielded insignificant hazard ratios (95% CI) of 1.69 (0.82, 3.51), 0.80 (0.28, 2.28), and 1.98 (0.95, 4.12) for Categories 1, 2, and 3, respectively. Applying the Score test, we found no significant difference in the PFS curves among the four epidemiological categories (χ2=5.87, p=0.12). Conclusions: The case definitions of IBC as proposed by the AJCC and SEER are inadequate. This study suggests that IBC as identified by private practitioners not meeting these criteria have the same poor prognosis as those meeting the case definitions of these national organizations. Preliminary laboratory studies support the conclusion that women with clinical evidence of IBC not involving half of the breast and with no documentation of involvement of the dermal lymphatics have the same disease as those meeting AJCC and SEER diagnostic criteria. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 889.