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Background DCIS with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity and, thus, we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB. Methods Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as one focus or ≥2 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed. Results Of 414 patients, 235 (57%) had one focus of microinvasion and 179 (43%) had ≥2 foci. SLNB macrometastases were found in 1.4% and micrometastases were found in 6.3%; neither were significantly different between patients with one focus vs ≥2 foci (p=1.0). Patients with positive SLNB or ≥2 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0-16.2) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9%. Conclusions Even with large numbers, there was no higher risk of nodal involvement with ≥2 foci of microinvasion as compared to 1 focus. Number of microinvasive foci and results of SLNB appear to be used in decision making for systemic therapy. Prognosis is excellent.

Background Appropriate use of MRI in elderly breast cancer (BC) patients remains unclear; we sought to identify the indications and implications of MRI use in our elderly BC population. Methods Women 70 years of age or older at first BC diagnosis with an MRI performed at our institution either perioperatively or in follow-up were included from a prospectively maintained database from 2000-2010. Univariate logistic regression was used to test associations with upgrade (additional ipsilateral, contralateral, new cancer, or recurrence) following perioperative MRI. Results 305 BCs were imaged in 286 patients. 133 were imaged with MRI in the perioperative setting alone, 88 had only follow-up MRIs after BC treatment, and 65 had both. Indications for perioperative MRI include: extent of disease evaluation (155; 78%); abnormal imaging (13; 7%); protocol (13; 7%); occult primary (10; 5%); high-risk screening (5; 3%); and abnormal physical exam (2; 1%). MRI upgrade for occult primary cases was 4/10 (40%; 95% confidence interval [CI], 12.2-73.8%) and 14/181 (7.7%; 95% CI, 4.3-12.6%) for perioperative MRIs performed for extent of disease evaluation. Analysis of imaging and tumor characteristics failed to find significant predictors of upgrade. 369 postoperative follow-up MRIs were performed in 148 patients with a median of 2 MRIs per patient (range, 1-8), and identified 7 upgrades (1.9%; 95% CI, 0.8-3.9%). Conclusion MRI had the greatest benefit in women presenting with an occult primary cancer and minimal additional benefit in elderly patients with breast cancer undergoing MRI imaging for extent of disease evaluation or in follow-up.

5043 Background: MDS is a heterogeneous group of hematologic diseases characterized by ineffective erythropoiesis and an increased risk of AML. MDS-related deaths are commonly due to infection resulting from impaired immunity, including quantitative and functional neutrophil defects. Maitake extract is from the fruit body of Grifola frondosa mushroom and is widely used in Asia as an adjunctive treatment for malignant diseases. This hot water extract is composed of a central beta 1,6-glucan core surrounded by beta 1,3-branches. Maitake extract enhances hematopoiesis by increasing G-CSF production with subsequent stem cell proliferation and differentiation of granulocyte-monocyte colony forming cells. Maitake also activates macrophages through Dectin-1 receptor binding, increases the weight and number of nucleated cells in the spleen and improves innate immune response in animal and human models. Activated macrophages may reduce iron stores. Compared to G-CSF, maitake may have fewer side-effects, is less costly, and may produce a comparable improvement in granulocyte function. Materials and Methods: MDS patients with IPSS Low and Int-1 risk disease and ANC>500, plts >20K were enrolled. Following double baseline measurements, patients received the maitake extract at 3mg/kg PO BID for 12 weeks. Primary endpoints include change in neutrophil counts and alterations in granulocyte function as measured by the respiratory burst test. The respiratory burst test is a highly sensitive and quantitative flow cytometric assay of granulocyte and monocyte function to assess the production of spontaneous reactive oxygen species (ROS) and stimulated response to 3 activators: opsonized E. coli, phorbol ester and the chemotactic peptide N-formylmethiolyl-leucyl-phenylalanine (fMLP). Results were compared to age-matched normal healthy volunteers. Responses were assessed using the modified International Working Group (IWG) MDS response criteria. Secondary endpoints include serial assessment of hemoglobin and platelet levels, reticulocyte count, monocyte function, and GM-CSF and G-CSF levels. Iron studies were assessed throughout treatment to determine whether the maitake indirectly alters iron stores potentially decreasing iron overload. Results: 14 eligible patients (pts) (8M, 6F; median age 69, range 52–83 yrs) received the maitake extract. IPSS risk categories included: Low-risk, n=7; Int-1, n=7. WHO Stage: RA=2; RARS=1; RCMD=6; RCMD-RS=1; RCUD=1; MDS-U=1; CMML-1=2. Two pts received prior 5-azacytidine therapy. Mean fMLP-stimulated granulocyte function in pts at baseline was lower than control values. Monocyte baseline response to E. coli was significantly reduced (p<0.01); ROS production to phorbol ester was also lower than in controls. No patients met criteria for response using the modified IWG response criteria. Preliminary analyses showed that ROS responses to E. coli stimulation increased by weeks 7–9 in pts who were deficient at baseline. Monocyte ROS production increased in 2 pts by 2–6 fold at week 7. There was a 2–15 fold increase in the neutrophil response to fMLP by week 7 and a 2–35 fold increase in monocyte response to fMLP at week 9. Monocyte response to E. coli increased between 3–10 fold in 2 pts with peak values during weeks 7–9. The two pts with the most pronounced response by fMLP and ROS production also had eosinophilia, which resolved following study participation. The most common toxicities were diarrhea (grade 1) in 6 pts, eosinophilia (2–2.8 × normal) in 3 pts, increases in AST (grade 1) and ALT (grade 1) in 4 pts and nausea (grade 1) in 1 patient. Two pts were removed from the study, one for diarrhea possibly related to study medication and one for disease progression. Conclusion: Maitake mushroom extract is well tolerated without evidence of clinically significant adverse hepatic, renal or metabolic abnormalities. No clinical responses were seen. Based on our preliminary data, the maitake extract appears to enhance ROS in both unstimulated and stimulated cells, confirming preclinical data. The improvement in granulocyte and monocyte function in our in vitro studies suggests that maitake may enhance immune responses in MDS pts. Eosinophilia was noted but the significance remains uncertain at this time. The study is ongoing. Updated results will be presented. Disclosures: No relevant conflicts of interest to declare.

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