Successful use of biweekly gemcitabine plus nab-paclitaxel in two male patients with stage iv breast cancer: case reports and review of the literature.

Male breast cancer is a rare disease. As a consequence, male breast cancer is often recognized later, and most patients present at an advanced clinical stage. We report the cases of two men with stage IV hormone receptor positive breast cancer who had both received at different times both systemic endocrine therapy with an aromatase inhibitor and gemcitabine as well as nab-paclitaxel-based combination chemotherapy. Although the aromatase inhibitors such as anastrozole, exemestane, and letrozole are very active in postmenopausal women with hormone receptor positive breast cancer, their efficacy in male breast cancer has not been demonstrated in phase II or III trials. Moreover, Gemcitabine and nab-paclitaxel every 14 days, with or without bevacizumab, are an active combination in male metastatic breast cancer and should be considered as an option in patients with extensive visceral metastases or hormone refractory disease.

Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes fails to predict breast cancer recurrence: a final analysis of a prospective multi-institutional cohort study.

BACKGROUND: To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. MATERIALS AND METHODS: Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. RESULTS: Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4-97.2%). No single gene or combination of study genes was predictive of recurrence. CONCLUSIONS: The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.

Improving participation and quality of clinical research in a university-based general surgery residency program.

At a university-based general surgery training program, post-graduate year (PGY) to 5 categorical general surgery residents had been required to complete an annual clinical research project and a year of laboratory research. Since the 80-hour work week, the laboratory experience was made optional, with a resultant decline in laboratory and clinical participation by 50 per cent and 75 per cent, respectively. Our goal was to review the effect of a simple programmatic intervention on the research compliance rate and quality. The Department was informed about the clinical research requirement via e-mail, memo, and announcements. Faculty submitted lists of novel or on-going projects. This was compiled and e-mailed to the Department with a list of project milestones. This included identification of a research mentor and project, Human Subjects Course certification, institutional review board submission dates, a midyear progress report, and final submission date. Rates of compliance and nature of research were recorded the year before and the 2 years after the intervention. Before the intervention, 2 of 16 residents were compliant. Faculty submitted 76 projects for resident review. One hundred per cent compliance with all aspects of the program was seen at the end of both year 1 and 2. Case reports rate fell from 65, to 30, to 25 per cent by the end of year 2. Publications increased from three preintervention to 13 by year 2. Presentations increased from five preintervention to 13 by end of year 2. This study demonstrates that small inexpensive interventions can have a dramatic effect on research participation.

Molecular Programming of Tumor-Infiltrating CD8+ T Cells and IL15 Resistance.

Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration. Probing of this poor responsiveness revealed that IL15cx only weakly activated intratumoral CD8(+) T cells, even though cells in the lung and spleen were activated and dramatically expanded. Tumor-infiltrating CD8(+) T cells exhibited cell-extrinsic and cell-intrinsic resistance to IL15. Our data showed that in the case of persistent viral or tumor antigen, single-agent systemic IL15cx treatment primarily expanded antigen-irrelevant or extratumoral CD8(+) T cells. We identified exhaustion, tissue-resident memory, and tumor-specific molecules expressed in tumor-infiltrating CD8(+) T cells, which may allow therapeutic targeting or programming of specific subsets to evade loss of function and cytokine resistance, and, in turn, increase the efficacy of IL2/15 adjuvant cytokine therapy. Cancer Immunol Res; 4(9); 799-811. ©2016 AACR.

Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology.

PURPOSE: The goal of this study was to develop a molecular diagnostic assay to detect circulating breast cancer cells in the peripheral blood for the purpose of staging breast cancer. Our aim was to make available an assay that was not limited by the low concentration of circulating breast cancer cells and the background gene expression that is typically found in peripheral blood. EXPERIMENTAL DESIGN: In this study, we investigated the ability of two new technologies to significantly enhance the quantification of gene expression in the peripheral blood: enrichment by a novel porous barrier density gradient centrifugation technology; and multimarker real-time reverse transcription-PCR (RT-PCR). RESULTS: Using fluorescence-labeled breast cancer cells and flow cytometry, we show that processing peripheral blood by porous barrier density gradient centrifugation results in a 300-fold enrichment of breast cancer cells. Real-time RT-PCR analysis confirmed a concomitant reduction in background expression of the CK19 and MUC1 genes after enrichment. In a pilot study, porous barrier density gradient centrifugation and multimarker real-time RT-PCR enabled our laboratory to detect breast cancer-associated gene overexpression in 13 of 20 (65%) stage IV breast cancer patients. Nine of these 14 patients overexpressed three or more markers. CONCLUSIONS: These results confirm the promise of such a molecular diagnostic assay and suggest that additional studies are needed to precisely define the clinical relevance.

Primary sarcoid of the breast with incidental malignancy.

Breast sarcoidosis is rare and usually presents in patients with known sarcoid involving other organ systems. In the breast, sarcoidosis may mimic malignancy which must be excluded by core biopsy. We report a very unusual case of primary breast sarcoidosis with incidentally discovered breast carcinoma. The roles of mammography, ultrasound, and MRI in the diagnosis as well as other potential differential diagnosis are discussed.

Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups.

PURPOSE: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups. METHODS: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) ≤ 3 cm, and ≤ 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF). RESULTS: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06). CONCLUSIONS: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.

Six-year experience: long-term disease control outcomes for partial breast irradiation using MammoSite balloon brachytherapy.

BACKGROUND: This report describes estimated 4-year tumor bed and ipsilateral breast recurrence-free intervals, event-free survival, disease-specific survival, and overall survival in a cohort of MammoSite brachytherapy (MBT) patients with mature follow-up treated at a single institution over a 6-year period. METHODS AND MATERIALS: An analysis of MBT cases was performed by using a prospectively collected quality-assurance database, departmental chart review, and electronic medical records. Patient-, tumor-, treatment-, and outcome-specific data were extracted and recorded into a research database. Patients were eligible for inclusion in this analysis if they were at least 6 months post-MBT. RESULTS: From May 2002 through March 2008, 111 MBT patients have been treated and were eligible for the present analysis. With a median follow-up of 46 months, the estimated 4-year outcomes for the entire cohort were tumor bed control 99%, ipsilateral breast control 95%, event-free survival 88%, disease-specific survival 97%, and overall survival 92%. CONCLUSIONS: The present study shows low rates of local and ipsilateral breast disease failure in a well-defined cohort of MBT patients with mature follow-up.

Surgical treatment of obesity.

Once an obese patient has failed attempts at diet modification, physical activity, pharmacologic treatment, and possibly even complementary and alternative therapies, the next step is to consider surgical management. Treatment plans must be customized for individual patients and should involve evaluation by the primary care provider, a dietician, psychologist, and surgeon. Then depending on the individual's needs, comorbidities, and candidacy, a specific surgical intervention may be necessary. These procedures are restrictive, malabsorptive, and a combination of both. Each procedure has its own short-term and long-term complications and must be monitored for the rest of the individual's life.