Monoamine oxidase A (MAOA) activity is altered in mood disorders and lower activity associated with aggressive behavior. The gene has a functional polymorphism with a variable number tandem repeat (VNTR) in the upstream regulatory region (MAOA-uVNTR). In this study, we examined possible associations between the MAOA-uVNTR polymorphism and mood disorders, suicidal behavior, aggression/impulsivity, and effects of reported childhood abuse. In total, 663 unrelated subjects with a psychiatric disorder and 104 healthy volunteers were genotyped for the 30 base pair functional VNTR. A novel repeat variation was identified. No statistically significant associations were found between this functional MAOA-uVNTR polymorphism and mood disorders or suicide attempts. However, the lower expression allele was associated with a history of abuse before 15 years of age in male subjects and with higher impulsivity in males but not females. Our results suggest that the lower expression of the MAOA-uVNTR polymorphism is related to a history of early abuse and may sensitize males, but not females, to the effects of early abuse experiences on impulsive traits in adulthood. The polymorphism may be a marker for impulsivity that in turn may contribute to the risk for abuse. This trait could then be further aggravated by abuse.

Purpose:To determine the antileukemic activity of weekly oral aminopterin in patients with refractory acute leukemia; to describe the pharmacodynamic properties of aminopterin; and to contrast the intracellular metabolism of aminopterin and methotrexate by patients' blasts in vitro. Experimental Design: Forty-six patients were enrolled in three strata: children with acute lymphoblastic leukemia (ALL), adults with ALL, and patients with acute myeloid leukemia (AML). Aminopterin was given weekly, in two doses of 2 mg/m 2 ,12 hours apart. Limited sampling pharmacokinetic analysis was done during the first week of therapy. Accumulation of [ No relationship between aminopterin pharmacokinetics and response was seen. In vitro, aminopterin showed more consistent metabolism by leukemic blasts to polyglutamates than methotrexate. Lineage-specific differences in the pattern of intracellular antifolylpolyglutamates were observed. Conclusions: Weekly oral aminopterin has significant activity among children with refractory ALL.With greater cellular accumulation and metabolism, more reliable bioavailability than methotrexate, and tolerable toxicity at this dose and schedule, aminopterin deserves further study as a potent alternative to methotrexate.

148 Background: Adequate margin width remains a subject of much controversy in breast conserving surgery. The Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) presented a consensus statement on margins in December 2014. This guideline stated that re-excision is recommended only in cases where tumor is present on inked margin. In this study, we sought to determine the consensus statement’s impact on re-excision practices at our institution. We examined re-excision rates eleven months before the release and 17 months after the release of the statement. Methods: Patients included in this IRB approved study had a diagnosis of invasive breast carcinoma, underwent breast conserving surgery, and were treated with adjuvant radiotherapy. Patients with pure DCIS were excluded. Results: One hundred and two women treated from January to November 2013 were included in the pre-consensus group. One hundred and three women were treated from December 2013 to May 2015 in the post-consensus group. The women treated prior to the consensus statement (n = 102) and those women treated after the statement (n = 103) were equally matched in terms of patient age, hormone positivity, and tumor size. A close margin at our institution is defined as < 2mm from the tumor edge. There were 16/102 women prior to the consensus who had close margins and 32/103 women in the post-consensus group. Of these, 68.8% (11/16) underwent re-excision for close margins in the pre-consensus group compared to 3.1% (1/32) after the consensus statement was released (p value < 0.01). Conclusions: The rapid adoption of the SSO/ASTRO margin consensus statement at our institution, although not statistically significant, led to a decrease in the number of patients who underwent a re-excision for close margins. Women with a close surgical margin were less likely to undergo additional surgery for re-excision after the guidelines were released. In our institution, using a standard criterion for re-excision, the re-excision rate for close margins decreased from 68.8% to 3.1%. Further studies are needed to examine the impact of the consensus statement on re-excision practices in a larger group of patients.

No abstract

No abstract

519 Background: The NCCN guidelines state that breast RT may be omitted in patients > 70 years of age with ER+, clinically node-negative, T1 breast cancer (BC) who receive adjuvant ET. Available data on older patients notes that local relapses are the most frequent site of failure, and distant relapse rates are low. The side effects of ET are not inconsequential and negatively affect QOL. The objectives of this study are to examine clinical outcomes including overall survival (OS) in women ≥70 years of age treated by lumpectomy(L)+ET and L+RT in the NCDB. Methods: The 2004-2013 NCDB includes 76,431 women ≥70 years with ER+ stage I BC who underwent L, and had a minimum one year follow up. Women who received no adjuvant therapy, both ET+RT, or any chemotherapy were excluded. To limit the analysis to healthy women, we excluded subjects with a Charlson comorbidity index > 0. We identified 24,572 patients who received either adjuvant ET monotherapy or adjuvant RT alone. Among these, 46% (11,313) received ET and 54% (13,259) breast RT. Overall median follow up was 57 months (range: 12-143 months). Analysis of OS between the 2 treatment groups was performed using Kaplan-Meier statistics and Cox proportional hazards regression; propensity weighting was used to balance covariates across the 2 treatment groups. Results: After propensity weighting, demographic covariates including age, race, insurance, and facility type were balanced between the 2 treatment groups. The median OS for ET was 125.9 months (95% CI 120.1-131.8), and 127.2 months for RT (95% CI 124.5-131.7) (p < 0.0001). The weighted hazard of death was 11.7% less in women receiving RT compared to ET (HR 0.883, 95% CI 0.834-0.936, p < 0.0001). Conclusions: To our knowledge, this is the first large study comparing RT and ET monotherapy in healthy older women with stage I, ER+ BC. The OS with RT alone is not inferior to ET alone, and in this study population is noted to be better. While this analysis has various limitations not dissimilar from other NCDB database studies, our observations are encouraging and warrant further research with prospective studies.

were identified as THL (3 typical and 7 atypical). In those treated with chemotherapy (CT) alone, the median number of CT cycles was 6 (range: 1-10), and in patients treated with CT and RT it was 4 (range: 0-8, P<0.001). Median follow-up from treatment completion was 33 months (0.3-204 months). Median RT dose was 36 Gy (20-54 Gy). A total of 40 patients (21%) were known to be dead at last analysis. The receipt of RT was significant on MVA for the TTR with a HR 0.38 (0.20-0.71; P Z 0.002) with a trend for OS on MVA (P Z 0.08). TTR at 36 months was 46% and 83% in patients treated without and with RT (P<0.0001). MVA demonstrated significance for OS in THL vs. DHL with a HR 6.1 (1.6-22.8, P Z 0.01), and THL vs. none with a HR 4.5 (1.4-12.9, P Z 0.02). MVA demonstrated significance for TTR in THL vs. none HR 6.6 (1.4-30.7, P Z 0.05). TTR and OS rates at 36 months were 80%/83%, 47%/ 72%, and 17%/44% in patients without analyzed genetic aberrations, DHL, and THL (P < 0.0001 and P Z 0.0002), respectively. DHL and THL patients treated with R-CHOP benefited significantly from consolidative RT with a 36 month TTR rate of 64% and 11% in patients treated with and without RT, respectively (P Z 0.04). Conclusion: The receipt of RT and DHL/THL status were the only factors that correlated with TTR on MVA. DHL and THL status correlated with worse OS, and consolidative RT may offer a significant benefit to this cohort of patients. Early identification of these patients for more aggressive treatment utilization may lead to improved outcomes.

Introduction In patients with ductal carcinoma in situ (DCIS), the clinical outcomes with hypofractionated (HF) whole-breast radiation (WBRT), as well as the role of lumpectomy boost, continue to be evaluated. In this paper, we report our experience on DCIS patients treated with HF WBRT with concomitant boost (CB). Methods Early-stage (DCIS, stages I and II) breast cancer patients were treated on an IRB-approved prospective single-arm study with HF WBRT and CB. This study includes only the DCIS subset of patients prescribed a dose of 40.5 Gy × 2.7 Gy per fraction to WB with CB of 4.5 Gy × 0.3G y per fraction over 15 fractions. A total of 107 breasts in 104 patients met the study criteria. Results All patients underwent lumpectomy with negative margins. Median age was 59 years. DCIS nuclear grade distribution was 9.3% grade 1, 50.5% grade 2, and 37.4% grade 3. Majority (86%) were ER positive. 41.1% received endocrine therapy. With median follow-up of 74 months (range, 12-158), 5-year actuarial overall survival was 97.2%. At the time of this report, no patient has experienced local relapse. The CTCAE grades 1 and 2 acute skin toxicity was 66.4% and 3.7%, respectively. No patients experienced grade 3 or higher skin toxicity, breast pain, and fatigue. Conclusion The HF schedule with CB in DCIS patients is well tolerated and associated with excellent clinical outcomes. This schedule affords the benefit of delivering higher dose to the lumpectomy site without protracting overall treatment time.