Axillary nodal staging in breast cancer: what have we learned?

Axillary management in patients with breast cancer is in a constant state of evolution. To provide appropriate treatment recommendations, we must understand the historical implications and the current indications for nodal staging as well as the clinical implications of nodal metastases. As we move away from maximal axillary surgical intervention that was previously the mainstay of breast cancer management, future research efforts will focus on targeted therapies based on tumor biology and identifying oncologically safe methods to de-escalate our management strategies.

Oxidized Lipoproteins Promote Resistance to Cancer Immunotherapy Independent of Patient Obesity.

Antitumor immunity is impaired in obese mice. Mechanistic insight into this observation remains sparse and whether it is recapitulated in patients with cancer is unclear because clinical studies have produced conflicting and controversial findings. We addressed this by analyzing data from patients with a diverse array of cancer types. We found that survival after immunotherapy was not accurately predicted by body mass index or serum leptin concentrations. However, oxidized low-density lipoprotein (ox-LDL) in serum was identified as a suppressor of T-cell function and a driver of tumor cytoprotection mediated by heme oxygenase-1 (HO-1). Analysis of a human melanoma gene expression database showed a clear association between higher HMOX1 (HO-1) expression and reduced progression-free survival. Our in vivo experiments using mouse models of both melanoma and breast cancer revealed HO-1 as a mechanism of resistance to anti-PD1 immunotherapy but also exposed HO-1 as a vulnerability that could be exploited therapeutically using a small-molecule inhibitor. In conclusion, our clinical data have implicated serum ox-LDL as a mediator of therapeutic resistance in patients with cancer, operating as a double-edged sword that both suppressed T-cell immunity and simultaneously induced HO-1-mediated tumor cell protection. Our studies also highlight the therapeutic potential of targeting HO-1 during immunotherapy, encouraging further translational development of this combination approach.See article by Kuehm et al., p. 227.

Screening for Breast Cancer: What You Need to Know.

Significant controversy surrounds current recommendations for breast cancer screening. This has resulted in wide variation among national organizations in breast cancer screening guidelines. With the expanding field of breast imaging techniques, risk assessment and genetic testing, it has become clear that the recommendations for breast cancer screening need to be individualized in order to maximize the benefit and minimize harms of screening.

Prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma.

BACKGROUND: Gene expression profiling (GEP) has been integrated into cancer treatment decision-making in multiple neoplasms. We prospectively evaluated the prognostic utility of the 31-GEP test (DecisionDx-Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB). METHODS: One hundred fifty-nine patients (age 26-88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing. GEP results were reported as low-risk Class 1 (subclasses 1A and 1B) or high-risk Class 2 (subclasses 2A and 2B). Statistical analyses were performed with chi-square analysis, t tests, log-rank tests, and Cox proportional hazard models. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were estimated using Kaplan-Meier method. RESULTS: Median follow-up was 44.9 months for event-free cases. Median Breslow thickness was 1.4 mm (0.2-15.0 mm). There were 117 Class 1 and 42 Class 2 patients. Gender, age, Breslow thickness, ulceration, SNB positivity, and AJCC stage were significantly associated with GEP classification (P < 0.05 for all). Recurrence and distant metastasis rates were 5% and 1% for Class 1 patients compared with 55% and 36% for Class 2 patients. Sensitivities of Class 2 and SNB for recurrence were 79% and 34%, respectively. Of 10 SNB-positive/Class 2 patients, 9 recurred. By multivariate analysis, only SNB result and GEP class were statistically associated with both RFS (P = 0.008 and 0.0001) and DMFS (P = 0.019 and 0.001). CONCLUSIONS: Gene expression profiling Class 2 result and SNB positivity were independently associated with recurrence and distant metastasis in primary CM patients. GEP testing may have additive prognostic utility in initial staging work-up of these patients.

Frequency and Significance of Abnormal Pancreatic Imaging in Patients with BRCA1 and BRCA2 Genetic Mutations.

Objective. Pancreatic adenocarcinoma is typically diagnosed in advanced stages resulting in a significant reduction in the number of patients who are candidates for surgical resection. Although the majority of cases are believed to occur sporadically, about 10% show familial clustering and studies have identified an increased frequency of BRCA germline mutations. The role of screening for pancreatic adenocarcinoma in these populations is unclear. Our study aims to identify the abnormal pancreatic imaging findings in BRCA1 and BRCA2 mutation carriers. Methods. A retrospective review of patient medical records with known BRCA1 and BRCA2 mutations was conducted. Data was collected and all available abdominal imaging studies were reviewed. Results. A total of 66 patients were identified, 36 with BRCA1 and 30 with BRCA2 mutations. Only 20/66 (30%) had abdominal imaging (14 BRCA1 and 6 BRCA2 patients). Of those patients with abdominal imaging, abnormal pancreatic imaging findings were detected in 7/20 (35%) cases. Conclusion. Our study shows a high incidence of abnormal pancreatic imaging findings in patients with BRCA genetic mutations (35%). Larger studies are needed to further define the role of pancreatic cancer screening and the significance of abnormal imaging findings in BRCA1 and BRCA2 mutation carriers.

Her2 positivity and race predict higher mastectomy rates: a SEER database analysis.

Given the difference in incidence of biologic subtype of breast cancer between black and white women, and the potential disparity in type of surgery in black and white women presenting with early stage breast cancer, this study aimed to examine the odds of mastectomy compared to lumpectomy by molecular subtype in black and white women with size T1 and T2 invasive breast cancer. Using the SEER database, breast operation choice for women over the age of 15 with T1 or T2 tumors between 2010 and 2012 were examined. Tumors were categorized according to the Breast Subtype variable in the SEER database and data were stratified by tumor size and race. Bivariate comparisons and logistic regression models adjusted for age were used. In women with T1 or T2 tumors, mastectomy rates were higher in women with Her2 positive tumors than in those with Her2 negative tumors. When Her2 results are the same among comparison groups, those women with HR positive tumors were less likely to undergo a mastectomy than those with HR negative tumors. In T1 tumors, the magnitude of the association was larger for white women than women of other races. Results suggest there are differences in surgical decision making based on breast cancer subtype in women with T1 or T2 tumors and that race may play a role for size T1 tumors. The strong association between Her2 positive tumors and higher mastectomy rates warrants further investigation.

Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies.

Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer that tends to have an aggressive clinical presentation as well as a variety of distinct histologic designations. Few systemic treatment options are available for MBC, as it has consistently shown a suboptimal response to standard chemotherapy regimens. These characteristics result in a worse overall prognosis for patients with MBC compared to those with standard invasive breast cancer. Due to its rarity, data focusing on MBC is limited. This review will discuss the clinical presentation, breast imaging findings, histologic and molecular characteristics of MBC as well as potential future research directions.

Accessory spleen masquerading as a pancreatic neoplasm.

A patient with a pancreatic mass noted on a computed tomography scan was suspected of having a nonfunctioning pancreatic neuroendocrine neoplasm. The eventual diagnosis of intrapancreatic accessory spleen was made by noninvasive means, thus avoiding unnecessary surgery.

Amyand's hernia: a case report describing laparoscopic repair in a pediatric patient.

Amyand's hernia is a rare hernia in which an incarcerated or perforated appendix is found in the right inguinal canal. This case report looks at the clinical presentation, the modalities for preoperative evaluation, and finally a combined approach of laparoscopic appendectomy and open repair of the hernia. To our knowledge, this is the first report of this type of management, and we feel that it is a safe and effective option.

Fontan operation: a comparison of lateral tunnel with extracardiac conduit.

BACKGROUND: The purpose of this report is to compare the outcome of the extracardiac (EC) with the lateral tunnel (LT) Fontan. METHODS: From January 1990 to October 2004, the Fontan operation was performed in 162 patients, of which 49 were EC and 113 were LT. Cardiac morphology and ventricular dominance were similar, except EC patients were older and had a greater frequency of heterotaxy syndrome, and LT patients had a higher incidence of hypoplastic left heart syndrome. Preoperative transpulmonary gradient, ventricular end-diastolic pressure, McGoon index, room air saturation, and cardiac rhythm were similar. EC patients underwent superior caval pulmonary connection, and LT patients underwent hemi-Fontan. Cardiopulmonary bypass time was similar, but fewer EC patients needed aortic cross-clamping. Fenestration was more frequent in LT patients (EC, 16% versus LT, 73%; p < 0.01). RESULTS: Overall operative mortality was 1.8% (EC, 1 versus LT, 2; p = NS). Postoperative transpulmonary gradient, readmission for chylous effusion, and change in ejection fraction relative to preoperative level did not differ between cohorts. Resource utilization was higher in the EC group. The loss of sinus rhythm and the frequency of all neurologic events did not differ. There were seven late deaths (EC 4 versus LT 3; p = NS). Actuarial survival at 5 years was not significantly different (EC, 90% versus LT, 95%; p = 0.08). CONCLUSIONS: The EC and LT operation had comparable early and late mortality, readmission for chylous effusion, preservation of sinus rhythm, and frequency of all neurologic events. The more frequently fenestrated LT cohort used fewer resources.