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Background: To compare suspected areas of cancer involvement based on the findings of CT and FDG-PET/CT in patients with inflammatory breast cancer (IBC) and to determine if discrepancies would modify radiation therapy treatment fields. Methods: This is a retrospective study of 29 consecutive female patients with IBC (median age 49 years, range 28-78) who had both CT and PET/CT scans prior to the initiation of systemic therapy. CT and PET/CT scans were obtained within a median of 3 days (range 0 -64). CT and PET/CT scans were independently reviewed by a board-certified radiologist (PD) and a board-certified nuclear medicine physician (HJ), respectively. Findings were recorded by anatomic site and graded as negative, equivocal or positive for malignancy. Radiation fields were then determined by a breast radiation oncologist (JB) after separately reviewing the CT and PET/CT images. Discrepancies between the two modalities were recorded. The study was approved by the hospital institutional review board. Results: Seven of 29 patients (24%) had discrepant findings that likely would have resulted in a modification of radiation treatment fields and/or radiation dose. In four patients, internal mammary nodal involvement was suspected on PET/CT but not on CT. In two of these four patients, PET/CT also detected additional disease (supraclavicular in one patient and chest wall in the other) that likely would have required a change in radiation field and/or dose. Another patient had subpectoral adenopathy on PET/CT that was not considered abnormal on CT. One patient had equivocal findings in the infraclavicular region on CT which was negative on PET/CT. In one patient, body habitus limited the CT evaluation; more extensive infiltrative soft tissue and nodal disease was seen on PET/CT. In four patients, there were discrepant findings for distant disease that likely would have resulted in a change in management or additional imaging studies. In two of these cases, PET/CT showed a clearly positive finding that was negative or equivocal on CT. In an additional two cases, equivocal PET/CT findings would have resulted in additional testing that would not have been recommended by CT alone. In another 4 cases, metastatic disease was suspected based on CT, but additional sites (all in bone and not seen on CT) were suspected on PET/CT. Conclusions: Inflammatory breast cancer patients have a high probability of presenting with extensive local/regional disease and distant metastases. In our IBC population, PET/CT imaging would have likely resulted in a change of radiation field or dose in 7 of 29 (24%) patients. Additionally, in four instances PET/CT suspected additional metastatic disease (14%). These discrepancies most commonly involved inclusion of an internal mammary nodal radiation field and identification of distant metastases. Pathologic verification of abnormal findings is necessary to verify these results. PET/CT imaging should be considered a standard component of radiographic staging for patients with IBC. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) is a virulent subtype of locally advanced breast cancer that accounts for 1-5% of all breast cancers diagnosed in the United States. Conventional therapy for IBC (preoperative chemotherapy, mastectomy, radiation therapy) results in a median 5 year overall survival of 50%, which supports the need for investigation into the molecular distinctiveness of IBC, with the ultimate goal of developing effective therapeutic agents that target these molecular changes. Some of the distinctive molecular characteristics of IBC include the presence of a substantial proportion of CD44+/CD24- breast cancer cells that express stem cell-like characteristics, over-expression of Ecadherin, and extensive formation of tumor emboli. Examination of breast tumors and preclinical data suggests that the JAK2/STAT3 pathway is active in CD44+/CD24- breast cancer cells, and is stimulated by various mechanisms associated with IBC, such as high IL -6 levels. We investigated the role of JAK2/STAT3 activation in IBC as preclinical evidence to pursue JAK2 targeted therapy for IBC in a clinical setting. Methods: Using de-identified breast tissue specimens from both untreated and treated IBC patients obtained on a protocol approved by our institutional review board; we performed immunohistochemical (IHC) and multicolor immunofluorescence analysis to detect the presence of CD44+/CD24- cells and the fraction of activated phospho-STAT3 (pSTAT3). The number of cells positive for pSTAT3 was assessed pre and post-treatment. We also analyzed the status of CD44+/CD24- cells and pSTAT3 in SUM149 and SUM190 IBC cell lines, and an IBC xenograft model (IDC31) derived from primary tumor obtained from an IBC patient. We tested the efficacy of multiple different JAK2 inhibitors to inhibit the growth and viability of cell cultures and xenografts. Results: All IBCs were highly enriched in CD44+/CD24- cells, with approximately 80% of all cancer cells within tumors displaying this phenotype. About 85% of IBC cases show activation of pSTAT3, and a significant fraction (40%) of CD44+/CD24- cells were pSTAT3 positive. Interestingly, the fraction of pSTAT3+ cells was lower in the CD44+/CD24- cells in post treatment samples from triple negative but not from luminal tumors. JAK2 inhibition significantly decreased the proliferation of pSTAT3+ IBC cells lines in vitro and the growth of pSTAT3+ xenografts including the IBC model ICD31. Discussion: Specific molecular characteristics of IBC result in a unique and virulent disease course. Based upon a predominance of CD44+/CD24- breast cancer stem cells present in IBC, we investigated the JAK2/STAT3 pathway in IBC tissue specimens, cell lines and an IBC xenograft model. Our preclinical data demonstrates a highly active JAK2/STAT3 pathway in IBC which lends itself to exploration of the efficacy of a JAK2 inhibitor in the treatment of this disease. A phase I/II study is underway to evaluate combination ruxolitinib and chemotherapy for the primary treatment of triple negative IBC. [ABSTRACT FROM AUTHOR]

Background: While the survival of patients with inflammatory breast cancer (IBC) is dictated by the status of their distant metastases, local/regional control remains an important component of quality of life. We have sought to determine patterns of local/regional recurrence (LRR) in patients presenting with inflammatory breast cancer. Methods: The medical records of 92 patients (pts) diagnosed with IBC from 1997 until 2007 were reviewed. Pt cohorts were stratified by disease burden at presentation (metastatic or local/regional) and their tumor, treatment, and disease course were analyzed. Primary outcomes were time from diagnosis to LRR, time to distant recurrence, and overall survival (OS). Median follow-up (MFU) for the entire cohort was 6 years (yrs) (range 0.1 to 12.7 yrs); for those patients who presented with metastatic disease versus only local/regional disease, MFU is 2 yrs and 6 yrs, respectively. This study was approved by the hospital institutional review board. Results: Median age at diagnosis was 49 yrs (range 24 to 72). 68 (74%) patients were without evidence of metastatic disease on presentation. With 6yr MFU, 40/68 (59%) had disease recurrence at either local or distant sites, and 15/68 (22%) had documented LRR, either as the first or subsequent site of recurrence. Estimated 5yr OS is 64%. 24 (26%) pts presented with metastatic disease (lung, liver, distant lymph nodes, pleura). All of the 24 pts presenting with metastatic disease developed systemic disease progression; 12/24 (50%) also developed LRR, and for 9/12 pts the LRR was first progression or concurrent with distant progression. Eleven of the 24 pts did not receive radiation or surgery; and within this cohort, 7 (64%) pts developed LLR at a median time of 9 months after diagnosis. Six pts received radiation therapy without surgery; 3/6 (50%) developed LRR. One pt had surgery alone; this patient was not known to have LRR, although had limited follow-up. Six pts received radiation therapy and surgery; 1 for palliation and 5 to prevent LRR. Of these 5 pts, 1/5 (20%) developed LRR that extended to the contralateral breast at 1.2y after diagnosis. Among the 24 patients, the cumulative incidence of LRR was 29%, 37%, and 43% at 1yr, 2yr, and 3yr (accounting for competing risk of death). The median OS was 2.9 yrs and estimated 5yr OS was 36%. Conclusions: Pts with inflammatory breast carcinoma presenting with metastatic disease are at high risk for local/regional disease progression. Aggressive local therapy should be considered to prevent symptoms of uncontrolled local disease, despite an uncertain impact upon OS. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients., Methods: Following review of IBC patients' records (1997-2014), we identified 258 stage III IBC patients; 181 received PST followed by MRM and radiotherapy and were subsequently analyzed. Pathologic complete response (pCR) to PST, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, grade, and histology were evaluated as predictors of TTR and OS by Cox model., Results: Overall, 95/181 (52%) patients experienced recurrence; 93/95 (98%) were distant metastases (median TTR 3.2 years). Seventy-three patients (40%) died (median OS 6.9 years). pCR was associated with improved TTR (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09-0.46, p < 0.01, univariate; HR 0.17, 95% CI 0.07-0.41, p < 0.0001, multivariate) and improved OS (HR 0.26, 95% CI 0.11-0.65, p < 0.01, univariate). In patients with pCR, grade III (HR 1.91, 95% CI 1.16-3.13, p = 0.01), and triple-negative phenotype (HR 3.54, 95% CI 1.79-6.98, p = 0.0003) were associated with shorter TTR, while residual ductal carcinoma in situ was not (HR 0.85, 95% CI 0.53-1.35, p = 0.48, multivariate)., Conclusions: In stage III IBC, pCR was associated with prognosis, further influenced by grade, hormone receptor, and HER2 status. Investigating mechanisms that contribute to better response to PST could help improve oncologic outcomes in IBC.

Background: Inflammatory breast cancer (IBC) is a rare and aggressive subtype. This study analyzes the patterns of failure in patients with IBC treated at our institution., Methods: We retrospectively analyzed the records of 227 women with IBC presenting between 1997 and 2011. Survival analysis was used to calculate overall survival (OS) and disease-free survival. Competing risk analysis was used to calculate locoregional recurrence (LRR)., Results: A total of 173 patients had locoregional-only disease at presentation (non-MET). Median follow-up in the surviving patients was 3.3 years. Overall, 132 (76.3 %) patients received trimodality therapy with chemotherapy, surgery, and radiotherapy. Three-year OS was 73.1 % [95 % confidence interval (CI) 64.9-82.4]. Cumulative LRR was 10.1, 16.9, and 21.3 % at 1, 2, and 3 years, respectively. No variable was significantly associated with LRR. Fifty-four patients had metastatic disease at presentation (MET). Median follow-up in the surviving patients was 2.6 years. Three-year OS was 44.3 % (95 % CI 31.4-62.5). Twenty-four (44.4 %) patients received non-palliative local therapy (radiotherapy and/or surgery). For these patients, median OS after local therapy was 2 years. Excluding six patients who received local therapy for symptom palliation, the crude incidence of locoregional progression or recurrence (LRPR) was 17 % (4/24) for those who received local therapy compared with 57 % (13/23) for those who did not., Conclusions: For non-MET patients, LRR remains a problem despite trimodality therapy. More aggressive treatment is warranted. For MET patients, nearly 60 % have LRPR with systemic therapy alone. Local therapy should be considered in the setting of metastatic disease to prevent potential morbidity of progressive local disease.

Brain metastases are associated with significant morbidity. Minimal research has been conducted on the risk factors for and incidence of brain metastases in women with inflammatory breast cancer (IBC). 210 women with Stage III or IV IBC diagnosed from 1997-2011 were identified. Competing risk analysis and competing risks regression were used to calculate the incidence of brain metastases and identify significant risk factors. After a median follow-up in surviving patients of 2.8 years (range 0.6-7.6) and 3.3 years (range 0.2-14.5) in the 47 and 163 patients with (MET) and without (non-MET) metastatic disease at diagnosis, 17 (36 %) and 30 (18 %) developed brain metastases, respectively. The cumulative incidence at 1, 2, and 3 years was 17 % [95 % confidence interval (CI), 8-30], 34 % (95 % CI, 20-48), and 37 % (95 % CI, 22-51) for the MET cohort. The corresponding non-MET values were 4 % (95 % CI, 2-8), 8 % (95 % CI 5-13), and 15 % (95 % CI, 10-22). Once non-MET patients developed extracranial distant metastases, the subsequent 1, 2, and 3 years cumulative incidence of brain metastases was 18 % (95 % CI, 10-28), 25 % (95 % CI, 15-36), and 31 % (95 % CI, 20-43). On multivariate analysis, brain metastases were associated with younger age [hazard ratio (HR), 0.73; 95 % CI, 0.53-1.00; P = 0.05] and distant metastases at diagnosis (HR, 2.33; 95 % CI, 1.11-4.89; P = 0.03). The incidence of brain metastases is high in women with IBC. Particularly for patients with extracranial distant metastases, routine screening with magnetic resonance imaging should be considered.

Few studies have examined care processes within providers' and institutions' control that expedite or delay care. The authors investigated the timeliness of breast cancer care at a comprehensive cancer center, focusing on factors influencing the time from initial consultation to first definitive surgery (FDS). The care of 1,461 women with breast cancer who underwent surgery at Dana-Farber/Brigham and Women's Cancer Center from 2011 to 2013 was studied. The interval between consultation and FDS was calculated to identify variation in timeliness of care based on procedure, provider, and patients' sociodemographic characteristics. Targets of 14 days for lumpectomy and mastectomy and 28 days from mastectomy with immediate reconstruction were set and used to define delay. Mean days between consultation and FDS was 21.6 (range 1-175, sd 15.8) for lumpectomy, 36.7 (5-230, 29.1) for mastectomy, and 37.5 (7-111, 16) for mastectomy with reconstruction. Patients under 40 were less likely to be delayed (OR = 0.56, 95 % CI = 0.33-0.94, p = 0.03). Patients undergoing mastectomy alone (OR = 2.64, 95 % CI = 1.80-3.89, p < 0.0001) and mastectomy with immediate reconstruction (OR = 1.34 95 % CI = 1.00-1.79, p = 0.05) were more likely to be delayed when compared to lumpectomy. Substantial variation in surgical timeliness was identified. This study provides insight into targets for improvement including better coordination with plastic surgery and streamlining pre-operative testing. Cancer centers may consider investing in efforts to measure and improve the timeliness of cancer care.

The authors sought to measure the timeliness of care for patients with breast cancer at Dana-Farber/Brigham and Women's Cancer Center throughout the treatment continuum, and to identify sources of variation that may serve as targets for improving care delivery. This report describes the methods that were developed to measure and analyze baseline performance.

Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the sentinel lymph node (SLN) procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 mL of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of NIR fluorescence for SLN mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using (99)Technetium-colloid in all subjects and patent blue in 27 (28 %) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99 %) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean 1.9, range 1-5) were resected: 100 % NIR fluorescent, 88 % radioactive, and 78 % (of 40 nodes) blue. In 2 of 95 subjects (2.1 %), SLNs-containing macrometastases were found only by NIR fluorescence, and in one patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies.

Inflammatory breast cancer (IBC) is a rare breast cancer with a highly virulent course and low 5-year survival rate. Trimodality treatment that includes preoperative chemotherapy, mastectomy, and radiation therapy is the therapeutic mainstay and has been shown to improve prognosis. Proper diagnosis and staging of IBC is critical to treatment planning and requires a multidisciplinary approach that includes imaging. Patients with IBC typically present with rapid onset of breast erythema, edema, and peau d'orange. Both tissue diagnosis of malignancy and clinical findings of inflammatory disease are required to confirm diagnosis of IBC. Imaging is used to identify a biopsy target; direct biopsy; stage IBC; differentiate curable from incurable (stage IV) disease; and help plan chemotherapy, surgical management, and radiation therapy. Comparison of baseline and posttreatment images helps confirm and quantitate disease response. When imaging is used early in the course of therapy to noninvasively predict treatment response, optimal tailored strategies for management of IBC can be implemented. Imaging is vital to diagnosis and treatment planning for patients with IBC, and radiologists are an integral part of the multidisciplinary patient care team.

Unlabelled: Chinese translation, Background: Rates of contralateral prophylactic mastectomy (CPM) have increased dramatically, particularly among younger women with breast cancer, but little is known about how women approach the decision to have CPM., Objective: To examine preferences, knowledge, decision making, and experiences of young women with breast cancer who choose CPM., Design: Cross-sectional survey., Setting: 8 academic and community medical centers that enrolled 550 women diagnosed with breast cancer at age 40 years or younger between November 2006 and November 2010., Patients: 123 women without known bilateral breast cancer who reported having bilateral mastectomy., Measurements: A 1-time, 23-item survey that included items related to decision making, knowledge, risk perception, and breast cancer worry., Results: Most women indicated that desires to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk., Limitations: The survey, which was administered a median of 2 years after surgery, was not validated, and some questions might have been misinterpreted by respondents or subject to recall bias. Generalizability of the findings might be limited., Conclusion: Despite knowing that CPM does not clearly improve survival, women who have the procedure do so, in part, to extend their lives. Many women overestimate their actual risk for cancer in the unaffected breast. Interventions aimed at improving risk communication in an effort to promote evidence-based decision making are warranted., Primary Funding Source: Susan G. Komen for the Cure.

Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer.

A 1986 audit of 150 randomly selected radiation therapy patient records revealed 147 records containing completed nursing assessment and weekly progress notes. Documentation of care provided was comprehensive, but concern was expressed over the length of time it required--an average of 40 minutes for the patient interview and an additional 20 minutes for documentation. Two strategies were proposed to reduce the amount of time spent in documentation without jeopardizing the detail of information contained in the initial nursing assessment: to pilot a patient self-assessment tool based on our original functional health pattern nursing assessment and to develop a standard flow sheet that contained both frequently used nursing diagnoses and potential interventions. Selected patients completed self-assessment records and discussed them with their primary nurses on the first day of treatment. Based on the pilot data, the forms were modified and revised. In 1987, 50 revised patient self-assessment records were reviewed revealing that both subjective and objective information had improved. Documentation time was reduced and information was more comprehensive.