Background. Chemicals that store in lipid-rich compartments have the potential for long-term disruption of metabolic and endocrine processes. Given the evidence that persistent organic pollutants (POPs) also alter systemic metabolic, endocrine, and immune system functions, it follows that elevated chemical concentrations in intra-abdominal fat may alter function, through local chemical signaling, of visceral organs. Despite this potential, there has been little study defining POP concentrations in live human intra-abdominal fat. It is at present uncertain whether POPs distribute equally to all fat compartments, including fat in serum. Methods. Seven human subjects scheduled for elective surgery for benign lesions or cancer provided consent for removal of samples of subcutaneous and intra-abdominal fat and/or cancerous tissue. These samples were analyzed for 22 chlorinated pesticides and 10 polychlorinated biphenyl (PCB) congeners by GC/ECD plus GC/MS. Results. In only two subjects were the patterns and relative concentrations of PCBs and pesticides about the same in all fat compartments. In the other subjects, there were major differences in levels in subcutaneous as compared to other compartments, but with some higher and some lower. While the pattern of PCBs in the various compartments matched that of the pesticides in some, it was opposite in others. Interpretation. These results demonstrate a complicated distribution of PCB congeners and pesticides in various lipid compartments. The difference may reflect various Kows, different rates of metabolism, and/or different lengths of exposure. But the results suggest that contaminant levels in serum or even subcutaneous fat do not necessarily indicate concentrations and patterns in other kinds of adipose tissue.

Gene expression profiling assays are frequently used to guide adjuvant chemotherapy decisions in hormone receptor-positive, lymph node-negative breast cancer. We hypothesized that the clinical value of these new tools would be more fully realized when appropriately integrated with high-quality clinicopathologic data. Hence, we developed a model that uses routine pathologic parameters to estimate Oncotype DX recurrence score (ODX RS) and independently tested its ability to predict ODX RS in clinical samples. Patients and MethodsWe retrospectively reviewed ordered ODX RS and pathology reports from five institutions (n = 1,113) between 2006 and 2013. We used locally performed histopathologic markers (estrogen receptor, progesterone receptor, Ki-67, human epidermal growth factor receptor 2, and Elston grade) to develop models that predict RS-based risk categories. Ordering patterns at one site were evaluated under an integrated decision-making model incorporating clinical treatment guidelines, immunohistochemistry markers, and ODX. Final locked models were independently tested (n = 472). Results Distribution of RS ConclusionThe proposed model accurately predicts high-and low-risk RS categories (. 25 or # 25) in a majority of cases. Integrating histopathologic and molecular information into the decision-making process allows refocusing the use of new molecular tools to cases with uncertain risk.

Patients with normal axillary physical exam and ultrasound rarely harbor a large nodal disease burden. Randomized trials of sentinel lymph node biopsy versus no axillary surgery in patients with normal AUS must be powered for subgroup analysis of patients with invasive lobular carcinoma and pT2-pT4 tumors. Preoperative identification of nodal metastasis may decrease the need for second surgeries and identify candidates for neoadjuvant chemotherapy. AUS is a noninvasive means of predicting disease burden preoperatively and as such is a powerful tool to individualize treatment plans.

More than half of patients without palpable adenopathy but with preoperative US-guided biopsy proven axillary LN metastases had N1 disease. For patients with both tumor size ≤2 cm and only 1 abnormal LN on axUS, 73% had N1 disease. This suggests that such patients, if they are otherwise analogous to Z11 patients, may undergo attempt at SLNB.