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PURPOSE Patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer eventually develop resistance to dual-antibody therapy with trastuzumab plus pertuzumab. Mechanisms of resistance have not been well elucidated. We evaluated the safety, tolerability, and efficacy of ado-trastuzumab emtansine (T-DM1) plus neratinib in patients who progressed on trastuzumab plus pertuzumab. PATIENTS AND METHODS In this 3 + 3 dose-escalation study, patients with metastatic breast cancer who progressed on trastuzumab, pertuzumab, and a taxane were treated with T-DM1 at 3.6 mg/kg intravenously every 3 weeks and dose-escalating neratinib at 120, 160, 200, or 240 mg/d orally. RESULTS Twenty-seven patients were treated across four dose-levels of neratinib. Dose-limiting toxicity in cycle 1 was grade 3 diarrhea in six patients and grade 3 nausea in one; no patient experienced grade 4 diarrhea, and there were no grade 5 toxicities. Other grade 3 to 4 toxicities included nausea (11%), dehydration (11%), electrolyte abnormality (19%), thrombocytopenia (15%), elevated transaminase levels (7%), and fatigue (7%). Twelve (63%) of 19 evaluable patients had an objective response. Responses occurred at all neratinib doses. Plasma cell–free DNA at baseline showed ERBB2 (HER2) amplification in 10 of 27 patients. Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification. Two complete responders had high expression of total HER2 and p95HER2 in baseline tissue. CONCLUSION We report the recommended phase II dose of T-DM1 3.6 mg/kg and neratinib 160 mg/d for this combination. Possible resistance mechanisms to HER2 antibodies may be loss of the HER2 receptor and high expression of p95HER2. These data provide the basis for an ongoing phase II study to better define the activity of this regimen.

Patients with breast cancer receiving antiestrogen therapy, specifically aromatase inhibitors, often suffer from vaginal dryness, itching, irritation, dyspareunia, and dysuria, collectively known as genitourinary syndrome of menopause (GSM). GSM can decrease quality of life and is undertreated by oncologists because of fear of cancer recurrence, specifically when considering treatment with vaginal estrogen therapy because of unknown levels of systemic absorption of estradiol. In this article, we review the available literature for treatment of GSM in patients with breast cancer and survivors, including nonhormonal, vaginal hormonal, and systemic hormonal therapy options. First-line treatment includes nonhormonal therapy with vaginal moisturizers, lubricants, and gels. Although initial studies showed significant improvement in symptoms, the US Food and Drug Administration recently issued a warning against CO2 laser therapy for treatment of GSM until additional studies are conducted. In severe or refractory GSM, after discussing risks and benefits of vaginal hormonal therapy, the low-dose 10-μg estradiol-releasing intravaginal tablet or lower-dose 4 μg estrogen vaginal insert and intravaginal dehydroepiandrosterone (prasterone) are options for treatment, because studies show minimal elevation in serum estradiol levels and significant improvement in symptoms. The decision to offer vaginal estrogen therapy must be individualized and made jointly with the patient and her oncologist.

TPS1125 Background: Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis and is the subtype most often associated with germline mutations of BRCA1 and certain other genes. Alpha-lactalbumin (aLA) is a milk protein that is expressed in lactating breasts but not at other times or in other normal tissues. Expression of aLA is found in approximately 70% of TNBC (Cancers PMID: 27322324) so is an attractive immunologic target for TNBC based on the “retired protein hypothesis” (Semin Immunol PMID: 31926646). Pre-clinical studies have shown that vaccination with aLA provides treatment of established and, more potently, protection from development of autochthonous tumors in transgenic murine models of breast cancer and against 4T1 transplantable breast cancer in BALB/c mice (Nat Med PMID: 20512124). We are conducting a Phase I trial in patients with early stage TNBC to demonstrate the safety of this approach and to document the ability to produce a meaningful immunologic response to aLA. Methods: Patients with ER-negative, PR-negative, HER2-negative breast cancer of pathologic stage I-III or who had residual disease after standard pre-operative systemic therapy are being entered into a Phase I trial of alpha-lactalbumin with a GMP-grade zymosan adjuvant in Montanide ISA 51 VG vehicle. Participants must be within 3 years of initiation of treatment and have no evidence of recurrence. Patients receive a total of 3 vaccinations administered once every 2 weeks with doses escalated using a 3+3 trial design. Toxic events of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater are considered dose-limiting. Dose levels being tested are alpha-lactalbumin/zymosan 0.01 mg/0.01 mg, 0.1 mg/0.1 mg, and 1 mg/1 mg. Patients are being monitored for toxicity until 84 days after the first vaccination or resolution of toxicity, whichever is later. Blood is being drawn prior to therapy and 14, 28, and 56 days after the first vaccination to assess cellular response using enzyme-linked immunosorbent spot (ELISpot) assays of interferon-gamma and interleukin-17 production in response to aLA. Humoral response to aLA vaccination is being assessed by enzyme-linked immunosorbent assay (ELISA). After identification of the Maximum Tolerated Dose we will expand the dose levels associated with effective tumor immunity and enroll a cohort of patients without cancer planning to undergo prophylactic bilateral mastectomy. Funding Source: Department of Defense (W81XWH-17-1-0592 and W81XWH-17-1-0593). Clinical trial information: NCT04674306.

Purpose Precision oncology is widely discussed, but cohort studies are limited. We previously reported our prospective experience of precision oncology in solid tumors, and here we report our longitudinal experience, focusing on therapeutic impact. Patients and Methods We conducted a retrospective review of 600 consecutive patients seen at Cleveland Clinic from 2013 to 2016 for treatment of incurable solid tumor malignancies for whom tumor genomic profiling was ordered using FoundationOne (Cambridge, MA). Results were discussed at our multidisciplinary genomics tumor board. Data analyzed included subsequent therapy and overall survival (OS). Results Median age was 59 years (range, 18 to 94 years), 308 (51.3%) were female, and 533 (88.8%) were white. Targeted therapy was recommended in 310 patients (51.7%). After results, 313 patients (52.2%) started any subsequent therapy; of these, 95 (30%; 15.8% overall) received genomics-driven therapy (G), and 218 (70%) received non–genomics-driven treatment (NG). For the G versus NG group, the on-label, off-label, and clinical trial therapy breakdowns were 23% versus 88%, 47% versus 3%, and 30% versus 9%, respectively. Median OS for patients receiving no therapy after tumor genomic profiling was 5.5 months; for the G and NG groups, it was 18 ( P < .001) and 14.4 ( P < .001) months, respectively ( P = NS for G v NG). The use of G increased from 10% in the first 250-patient cohort (reported earlier) to 20% in the subsequent 350-patient cohort. Conclusion Tumor genomic profiling influenced treatment in 15.8% of patients. More patients received treatment via clinical trials in the G cohort, and although not statistically significant, there was a trend toward increased OS in the G ( v NG) group. These data can further guide real-world applications of precision oncology.

Chemotherapy-induced alopecia is a common and distressing adverse effect of many types of chemotherapy. Scalp cooling has been used since the 1970s for prevention of chemotherapy-induced alopecia; however, most data regarding this treatment modality are retrospective in nature, and use in the United States has been limited by safety concerns, specifically the potential for scalp metastases. Two prospective studies of scalp-cooling systems performed in the United States were published within the last year and add evidence supporting the efficacy and safety of scalp cooling in preventing chemotherapy-induced alopecia in patients receiving chemotherapy for solid tumor malignancies. Available data suggest that this technology is most effective for taxane-based chemotherapy regimens compared with anthracycline-based chemotherapy regimens. Two scalp-cooling devices have been cleared by the US Food and Drug Administration, and multiple cold caps are available for patient rental. The adverse effect profile of scalp cooling includes scalp pain, headache, and chills but is tolerable for most patients included in recent clinical trials. Retrospective data suggest that the incidence of scalp metastases related to scalp cooling is low and should not limit use of this technology. Logistic issues related to use of scalp cooling include availability of devices, inconsistent insurance coverage, and incorporation of use into typical infusion center workflow.

10503 Background: Genetic factors that contribute to endogenous estrogen synthesis and postmenopausal breast cancer risk are unknown. We set out to test the hypothesis that homozygous inheritance of the common 1245A→C missense-encoding polymorphism in HSD3B1, which is common (8-10%) in White populations, functionally adrenal permissive and increases synthesis of the aromatase substrate, androstenedione, is associated with postmenopausal estrogen receptor-positive breast cancer. Methods: A prospective single institution study of postmenopausal estrogen receptor-driven breast cancer for determination of HSD3B1 genotype, circulating steroid concentrations, and adrenal-permissive genotype frequency compared with the genotype frequency in the general population and in estrogen receptor-negative breast cancer. Validation was performed in 2 breast cancer genomic studies with estrogen receptor documentation. The primary outcome is the adrenal-permissive genotype frequency in postmenopausal estrogen receptor-positive breast cancer and the general population. Genotype comparisons were also done with postmenopausal estrogen receptor-negative breast cancer and the association with circulating adrenal androgen concentrations determined. Results: The prospective and validation studies had 199 and 1628 women, respectively. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 9.6% (429/4451) in the general population [p = 0.0077]. The adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using the Cambridge and TCGA genomic datasets together: 14.4% (56/389) compared with 6.0% (9/149) for estrogen receptor-negative breast cancer (p = 0.007) and the general population (p = 0.005). Circulating androstenedione concentration was significantly higher for women with the adrenal-permissive genotype compared with the other genotypes (p = 0.03). Conclusions: The adrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer and have broad implications for risk stratification, prevention, potential biomarkers for hormonal therapy response and possibly other clinical outcomes related to estrogen physiology in postmenopausal women.

e13041 Background: The addition of CDK 4/6 inhibitors (CDK) to endocrine therapy (ET) is the standard of care for HR+ MBC. Currently, no robust predictive markers for CDK inhibitors exist. We hypothesized that baseline imaging features on pre-treatment CT scans using machine learning could correctly identify responders to CDK. Methods: From a retrospective pt registry, 46 pts with HR+ MBC who received palbociclib (palbo) plus ET and had liver metastases were identified, and divided at random into equally sized training and testing cohorts. Patients with objective response/stable disease per RECIST v1.1 were defined as ‘responders’ (65%), and those with progressive disease within 6 months were ‘non-responders’ (35%). The median age at diagnosis was 62. All pts were ER+ and 4% were HER2+. 65% pts received palbo as 1st or 2nd line tx. 503 radiomic texture features measuring subtle differences in lesion heterogeneity on a pixel level were extracted on pre-treatment CT within the first lesion measured for RECIST assessment. An elastic net Cox proportional hazards model was constructed within the training set to derive a Radiomics Risk Score (RRS), which was evaluated for association with prognosis and response within the testing set. A risk score threshold was chosen in the training set for stratifying patients into high and low risk groups. Results: The RRS consisted of 4 radiomic features indicating intratumoral heterogeneity to be associated with poor outcome. In the independent testing set (n = 23), RRS was continuously associated with survival (p = .0027) on multivariate analysis, along with age and RECIST response (Table). Categorical risk groups were similarly associated with survival in the testing set (p = .00491, HR = 4.03, CI = 0.6772). Median survival time in low and high risk groups were 2.33 and 0.673 years, respectively. When compared against RECIST response in the testing set, RRS was found to also be predictive of response with an ROC curve of 0.675. Conclusions: Radiomics analysis was able to predict response and survival in HR+ MBC pts prior to initiation of treatment with CDK. [Table: see text]

TPS1104 Background: LIV-1 is a highly prevalent transmembrane protein in breast cancer cells. Ladiratuzumab vedotin (LV), SGN-LIV1A, is an investigational antibody-drug conjugate (ADC) that targets LIV-1 via a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) by a protease-cleavable linker. LV is internalized when it binds LIV-1 on cell surfaces and MMAE is released, which binds tubulin and induces apoptosis. LV has been shown to be active and tolerable in metastatic breast cancer (mBC) at a recommended dose of 2.5 mg/kg every 21 days (Modi 2017). More frequent, fractionated dosing has improved the activity and/or safety of other ADCs. Thus, this study is actively accruing subjects with metastatic triple negative breast cancer (mTNBC; estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) receptor-negative) and endocrine-resistant ER+ or PR+ (hormone receptor [HR+])/HER2-negative mBC to test weekly dosing of LV (Days 1, 8, and 15 of every 3-week cycle). Methods: This study is enrolling up to 82 subjects (42 HR+/HER2-negative and 40 mTNBC) into dose escalation and dose expansion cohorts (NCT01969643). Eligible subjects are females ≥18 years old with pathologically and radiologically confirmed metastatic HR+/HER2-negative or mTNBC with at least 1 measurable lesion per RECIST v1.1. Subjects with HR+/HER2-negative disease must have received no more than 1 prior line of cytotoxic chemotherapy in the locally advanced (LA)/mBC setting, either as single agent or combination therapy. Subjects with mTNBC must have received 1 prior line of cytotoxic chemotherapy in the LA/mBC setting. Progression within 6 months of completion of neoadjuvant or adjuvant therapy is considered an LA/mBC regimen. Subjects must have adequate organ function, ECOG status of ≤1, and no ≥ Grade 2 peripheral neuropathy. Subjects with brain lesions must have received definitive treatment of the lesions. Prior therapy with MMAE-containing agents is not allowed. Dose escalation follows the modified toxicity probability interval method (Ji 2010). Dose expansion cohorts will provide data about activity and tolerability. Tumor assessments will be conducted every 2 cycles per RECIST v1.1 and all subjects will be followed for safety. Pharmacokinetics and markers of pharmacodynamics will be assessed. Primary safety endpoint is the incidence of adverse events and dose-limiting toxicities. Key efficacy endpoints include confirmed overall response rate, duration of response, and progression-free survival. Clinical trial information: NCT01969643 .

593 Background: HER2-targeted neoadjuvant chemotherapy (NAC) possesses heterogeneous outcomes and currently lacks clinically-accepted markers of response. A means of predicting which patients will benefit prior to the treatment could reduce toxicity and the delay to effective intervention. Computational analysis of MRI via a deep neural network has shown promise in identifying NAC responders among mixed receptor subtype and treatment regimen cohorts, but faces challenges due to reproducibility across institutions and has not yet been explored in the context of HER2-targeted therapy. Here we present a deep learning approach for predicting response to HER2-targeted NAC from pre-treatment MRI. Methods: 100 HER2+ breast cancer patients who received NAC with docetaxel, carboplatin, trastuzumab, and pertuzumab at Cleveland Clinic (CCF) and had pre-treatment contrast-enhanced MRI’s were included in this analysis. 49 patients achieved pathological complete response (pCR, ypT0/is), while 51 patients retained presence of residual disease following NAC (non-pCR). 85 patients were used to train a convolutional neural network to predict pCR based on pre- and post-contrast MRI images, and the model design was optimized based on performance within a 15 patient internal validation cohort. An external, held-out testing dataset consisting of 28 patients (16 pCR, 12 non-pCR) imaged and treated at University Hospitals (UH) Cleveland Medical Center was used to validate the performance of the model. Performance was assessed by area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. A multivariable model incorporating age, hormone receptor status, stage, and tumor size was developed and similarly evaluated. Results: The neural network was able to predict the response to HER2-targeted NAC in the internal validation cohort (AUC = 0.93) as well as in an independent cohort from a separate institution (AUC = 0.85). This model offered superior performance compared to a multivariate clinical model, which achieved AUC = 0.67 and AUC = 0.52, in internal validation and external held-out testing cohorts, respectively. Conclusions: Deep learning analysis of contrast-enhanced MRI could be used to better target anti-HER2 therapy by pre-treatment prediction of response.[Table: see text]

e12538 Background: CDK inhibitors (CDKi), in combination with aromatase inhibitors (AI), are approved for the treatment of hormone receptor positive (HR+) Her2 negative metastatic breast cancer (MBC). The effectiveness of continuing CDKi beyond first disease progression is not known. This study evaluated real world evidence and assessed the impact of continuation of CDKi beyond first disease progression in combination with endocrine therapy. Methods: This is a retrospective, single institution review of HR+ MBC patients treated with CDKi from 2015-2018 who continued CDKi after initial progression. The primary outcome was progression-free survival (PFS) beyond first disease progression, as assessed by the clinician based on radiological and/or clinical criteria. Overall survival (OS) – defined as date of initial CDKi treatment to date of death or last follow up – was a secondary outcome. Results: 30 women with HR+/HER2- MBC, median age 47.5 years (range: 31 – 81), sequentially continued on CDKi beyond first progression were identified from a database of patients treated with Palbociclib. Median and average follow up times on CDKi were 27.18 and 24.53 months, respectively. Initial endocrine/CDKi regimen received included: palbociclib (PA)/letrozole (LTZ) [67%], PA/fulvestrant (FULV) [23%], and PA/other AI [10%]. Prescribed combinations beyond 1st progression were: PA/FULV [56.7%], PA/LTZ [16.7%], and PA/other AI [20%], abemaciclib plus LTZ or FULV [6%]. As of 1/31/2019, 25 patients (83.3%) were still alive, and 19 (63%) had undergone a second progression on CDKi. The estimated median PFS for the entire duration while on CDKi was 23.5 months (95% CI 12.8 – 27.8), of which 11.8 months (95% CI 5.34 – 13.13) was the median PFS beyond first progression. The estimated median OS was 45.4 months. Conclusions: Among a small cohort of HR+ MBC patients, in a non-clinical trial setting, continuation of palbociclib plus endocrine therapy beyond first progression was associated with a median PFS of approximately 11 months. Formal clinical evaluation of continuation of CDK inhibitor plus endocrine therapy beyond first progression is warranted.

1511Background: The clinical impact of addressing potentially GL alterations (PGA) from somatic next-generation sequencing (NGS) is not well characterized. We hypothesize that the addition of scree...

1027Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab and the maytansinoid antimicrotubule, DM1. T-DM1 was granted FDA approval in 2nd-line MBC after prior trastuzumab (T) and...

e13034Background: Palbociclib (PA), a CDK4/CDK6 inhibitor, has been shown in clinical trials to prolong progression free survival (PFS) in HR+/Her-2 negative MBC when combined with an aromatase inh...

e18710Background: Precision oncology approaches to selecting therapies are increasingly being used, but there are limited data on benefit to patients. We expand on our initial prospective cohort da...

582Background: Many breast cancer patients receiving neo-adjuvant chemotherapy (NAC) will ultimately fail to achieve pathological complete response (pCR). A pre-treatment clinical marker of pCR cou...

Purpose: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Patients and Methods: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. Results: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 ± 6.0 hours, the volume of distribution at steady-state was 798 ± 375 L, and the clearance was 712 ± 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. Conclusion: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting.

10088 Background: Adjuvant chemotherapy decreases the risk of recurrence. However, it has distressing side effects, including alopecia. There are no randomized trials assessing modern scalp cooling to prevent alopecia, and success rates in non-randomized trials have varied. Methods: We conducted a multi-center randomized trial to evaluate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System (OPHLPS) in reducing chemotherapy-induced alopecia. Women with stage I-II breast cancer planned to receive anthracycline- or taxane- based chemotherapy for at least four cycles were eligible and randomized in a 2:1 ratio to scalp-cooling or control. Scalp-cooling was done with the OPHLPS 30 minutes prior to, during and 90 minutes after each chemotherapy. The primary efficacy endpoints were hair preservation and device safety. We planned to enroll 235 subjects to provide 85% power to detect a 20% difference in hair preservation. Secondary endpoints included wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Subjects will be followed for 5 years for recurrence, overall survival, and site of recurrence. One interim analysis was planned to allow the study to stop early for efficacy after 142 subjects were enrolled and evaluable for the primary endpoint. To maintain the overall type 1 error rate, an O’Brien-Fleming spending function was used (interim boundary p = 0.0061). Results: This is the first randomized trial with modern scalp cooling in the world. For the interim analysis, 142 subjects were evaluable. Among them, 48 (50.5%) out of 95 in the cooling group and 0 (0%) out of 47 in the control group had hair preservation. The one-tailed p-value from the Fisher’s exact test is < 0.0001, which crosses the superiority boundary (p = 0.0061). Thus on 9/26/2016 the DSMB stopped the study early. The interim analysis was presented at SABCS 2016. There are 195 subjects enrolled on this clinical trial, and the final subject will be evaluable for the primary outcome February 2017. The final analysis will be presented. Conclusions: Our trial showed that scalp cooling using OPHLPS is highly effective in hair retention. Paxman Coolers has applied for FDA clearance for the OPHLPS based on the results of the interim analysis. Clinical trial information: NCT01986140.

6557 Background: Increase in time to treatment initiation (TTI) for new cancer diagnoses causes patient distress and may adversely affect outcomes. We investigated trends in TTI for common solid tumors treated with curative intent, determinants of delayed TTI and impact on overall survival. Methods: We utilized population-based, prospective data from the National Cancer Database for newly diagnosed US patients with early-stage breast, prostate, lung, colorectal, renal and pancreas cancers from 2004-13. TTI was defined as days between diagnosis of cancer and first treatment (surgery, systemic or radiation therapy). Negative binomial regression and Cox proportional hazard models were used for analysis. Results: The study population of 3,672,561 patients included breast (N = 1,368,024), prostate (N = 944,246), colorectal (N = 662,094), non-small cell lung (NSCLC)(N = 363,863), renal(N = 262,915) and pancreas (N = 71,419) cancers. Median TTI increased from 21 days in 2004 to 29 days in 2013 (P < 0.0001). Aside from year, determinants of delays included care at academic centers and change in treating facility. Increased TTI was associated with worsened overall survival (OS) for stages I and II breast, lung, renal, and pancreas cancers, and stage II colorectal cancers, with hazard ratios per week of delay ranging from1.005 (1.002-1.008) to 1.030 (1.025-1.035), adjusting for comorbidities and other variables. Prolonged TTI ( > 6 wks) was associated with substantially worsened OS e.g., 5-yr OS for stage I NSCLC was 56% (±0.2) for TTI ≤ 6wks v 43% (±0.2) for TTI > 6 wks and for stage I pancreas was 38% (±0.6) v 29% (±1) respectively (P < 0.0001 for both). Conclusions: TTI has lengthened significantly over recent years, associated with multiple factors. Increase in TTI is associated with substantial increase in mortality ranging from 0.5-3.2% per week of delay in curative settings such as early-stage breast, lung and pancreas cancers. Simplifying access and navigation of complex health systems is essential to diminish this apparently iatrogenic impact on outcomes.

e18118 Background: Precision oncology – use of tumor genomic profiling to guide therapies – is widely discussed but with limited real-world data. We have previously reported our prospective study on feasibility and clinical utility of routine somatic genomic testing of solid tumors [ J Natl Cancer Inst. 2015; 108(3)], and here we report our longitudinal experience, focusing on therapeutic impact. Methods: Records were reviewed for consecutive adult patients seen at Cleveland Clinic for a solid tumor malignancy without known curative options where tumor genomic profiling was ordered using FoundationOne™ (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board, and therapeutic recommendations were conveyed to the primary oncologist. Data for this cohort study approved by the Cleveland Clinic IRB included subsequent therapies and clinical outcomes. Results: From 2013 to 2016, 330 patients had tumor genomic testing ordered. Median age was 61 years (range, 24-94); 170 (51.5%) were female; 289 (87.6%) were Caucasian. Colorectal (21.5%), breast (17%), lung (16.1%), and pancreatobiliary (11.5%) cancers were the most common diagnoses. In 300 resulted cases, a median of 4 (0-20) alterations per specimen were noted; the most commonly altered genes were TP53 (n = 174), KRAS (n = 75), APC (n = 65), CDKN2A/B (n = 49), and PIK3CA/ PIK3R (n = 46). A specific therapy targeting an actionable alteration was recommended in 51% (153/300) of patients, and 11.7% (n = 35) received such therapy: 14 on clinical trials, 5 on-label, and 16 off-label. Most common targets for therapy were PIK3CA/PIK3R/PTEN (n = 7), HER2 (6), BRAF (3), EGFR (3), and ALK, FLT3, NTRK1 and RET (2 each). At last follow-up, of 35 patients receiving targeted therapy, best responses were: complete response (n = 1, 2.9%), partial response (n = 5, 14.3%), stable disease (n = 14, 40%), progressive disease (n = 11, 31.4%); data not available for 4 patients. Non-availability of clinical trials was a common reason for non-receipt of targeted therapy. Conclusions: Tumor genomic profiling influenced treatment in 11.7% of patients in this cohort, and 57% of those receiving targeted therapy experienced clinical benefit. These data can help guide real-world discussions of precision oncology.

e18324 Background: Understanding clinic-based resource utilization among breast cancer (BC) patients is critical for the development of bundled payment models, and redesigning efficient value based systems of care delivery. BC outpatient visits (OVs) are costly from a time and human resource perspective and warrant investigation. Methods: This observational study included patients who were diagnosed with BC (Stages 0 to 3) in 2012 and were followed within our health network. Frequencies of OVs were compared between years 1, 2 and 3 of follow-up across subgroups, using one-sample Kolmogorov-Smirnov test; p < 0.05 was considered significant. Results: Of 643 patients identified, 83% were Caucasian and 99.5 % were females. 99.4% had breast surgery, 60% received radiation, and 42% received chemotherapy. 66% of patients who had mastectomy had reconstruction (73% implants, 27% tissue flap). The average duration of follow-up was 3.2 yrs. The frequency of OVs was highest in the 1st year after diagnosis across all groups in the Table (all p < 0.001). Breast reconstruction was associated with high clinic resource utilization; tissue flap procedures were associated with significantly more OVs than implant procedures during the 3 years (median of 16 vs.14 visits, p < 0.001). Conclusions: Outpatient visits represent a significant resource requirement associated with breast cancer care. These data are an important baseline as we design improved models of care and bundled payment models, and can be used to set expectations among breast cancer patients and care teams. [Table: see text]

e21586 Background: With significant advances in breast cancer (BC) treatment and improvements in long-term survival, high-quality, coordinated survivorship care is important. Methods: In this retrospective study of patients who were diagnosed with BC (Stages 0 to 3) in 2012 and had > 1 year of follow-up within our network (mean follow-up 3.2 yrs), we analyzed BMI trends and compliance with age appropriate health measures. One-sample t-test was used to compare average BMI at diagnosis and year 3. p < 0.05 was considered as statistically significant. Results: Of 643 patients studied, 99.5% were female, 83% were Caucasian, and 27% were ≤ 50 years of age at diagnosis (mean age 59 yrs). 17% had DCIS and 83% had invasive cancer (Stage I – 40%, II – 33%, III- 10%). 40% had a BMI > 30 Kg/m2. BC Surveillance: 89.4% of patients with residual breast tissue or tissue flaps had surveillance mammograms during 3 years of follow-up (Year 1 - 90.0%, 2 - 89.8%, 3 - 88.3%), in compliance with current guidelines. Weight management: There was a statistically significant increase in BMI from diagnosis to year-3. This trend was consistent across different age, race, and baseline BMI groups (See Table). Colon cancer screening: 49% of eligible patients had completed age appropriate screening colonoscopies either prior to diagnosis or during the course of follow-up. Bone health: Among patients who were on aromatase inhibitors, 76% had a documented DEXA scan. Vaccination: Vaccine coverage for eligible patients was low – 63% for pneumococcal, 38% for herpes zoster, and 30% for annual influenza vaccines. Conclusions: While compliance with BC surveillance is high among patients following treatment for BC, adherence to many other important health maintenance practices is low. Renewed focus on these measures, such as weight management, bone health, vaccination and screening for other cancers, represents an important opportunity to improve not only cancer-related outcomes but also the overall health and well-being of BC survivors. [Table: see text]

112 Background: PCa incidence and mortality in African Americans (AA) is higher than in Caucasians. Health-education programs and culturally appropriate outreach to high-risk groups in accordance with American Cancer Society IDM guidelines can reduce disparities. Data show that it is hard to provide comprehensive unbiased education about screening to patients (pts). This study aims to examine whether IDM guidelines in a large high risk group setting can improve knowledge on PCa and screening decision, and whether such education program is overall beneficial to pts. Methods: Pts were included in one-day outreach event and were given a 15-question pre and post- test focused on standard informative educational PowerPoint and then were offered screening (PSA + DRE). Components of IDM were reviewed during this educational intervention. Demographics and family history was collected and UCSF 10-year mortality index was assessed to help IDM. Pre- and post- test number of correct answers were compared (Wilcoxon signed rank); pts were surveyed on their opinion on the program. The decision regarding screening after the intervention was tracked as well as the % of PCa diagnosed. Pts were tracked via an established navigation system to ensure follow up care. Results: 106 pts were included in the current analysis. Median number of correct answers at pre and post test was 8 and 11 (p < 0.001). Overall, 86% responded that they wanted screening. Of those, 92% were AA and 21% had family history of PCa; 21 pts had PSA only, 60 had PSA + DRE. 13 pts (16%) had abnormal PSA per NCCN guidelines, 5 (8%) had abnormal DRE. 5 PCa were biopsy-diagnosed, 4 had abnormal DRE + PSA; 1 had only abnormal DRE. Overall, 82% pts favored IDM before screening, 18% would prefer screening without IDM. 75% of all pts found the information “very helpful” in decision-making (within a 5-point Likert scale). Conclusions: Our education-based IDM led to significant improvement in knowledge about PCa screening. Most pts preferred education prior to screening. Our approach paired with the use of navigation program is feasible and was positively received by a large high risk group. Project is ongoing with more pts and follow up, and further validation is pending. Clinical trial information: NCT02419846.

594Background: HER-2 overexpression confers a more aggressive tumor phenotype in breast cancer, even in stage 1 disease. The large adjuvant trastuzumab trials excluded patients with node-negative tumors smaller than 1 cm. Subset analysis of one trial suggested patients with tumors 1–2 cm in size derived at least as much clinical benefit from adjuvant trastuzumab as did the overall cohort.It is currently unknown whether patients with T1a-T1bN0 HER-2+ tumors should routinely receive adjuvant chemotherapy and trastuzumab. Our goal was to examine clinical outcomes in patients with small HER2+ tumors treated at Cleveland Clinic (CC) to help guide treatment decisions. Methods: Cancer data registry was utilized to identify patients with stage I HER2+ cancer treated with or without trastuzumab and chemotherapy at CC after 2006. Patient charts were reviewed for recurrence and survival information. Disease-free survival (DFS) was defined as time from date of diagnosis to relapse, second primary cancer or death, whi...

e18217Background: Use of staging imaging (SI), including CT, PET and bone scans, is not routinely recommended in stage I-IIA breast cancer patients (ESBCP) in the absence of signs or symptoms of me...

123 Background: The Cleveland Clinic is utilizing disease specific teams to craft care paths for value based disease management. The report by Groheux (JNCI 2012; 104:1879-1887), reported 18 FDG-PET-CT detected distant metastasis in 10.7, 17.5 and 36.5% of stage IIB- IIIB breast cancer patients. Based on this report, the breast team incorporated 18 FDG-PET- CT imaging for initial staging of IIB-IIIB patients. Methods: Treatment algorithms were developed by a multi-disciplinary breast cancer team. The content was reviewed by stakeholders throughout the health system, and feedback was incorporated into the care paths as appropriate. Content was communicated using physician meetings, electronic communication, tumor boards, and operational pilots. The treatment algorithm, along with the supporting narrative, was placed on the cancer center intranet, accessible to all practicing physicians. Additional intranet analysis was performed using Google Analytics, which identifies the site location and frequency of document downloads. We retrospectively examined the impact of this posting after one year (7/2014-7/2015). Manual chart review identified new patient consults for Stage IIB-IIIB breast cancer at our main campus and highest volume regional sites. Results: PET scans were ordered in 36 stage IIB, 19 stage IIIA, and 3 stage IIIB patients. Of the 36 IIB patients scanned, occult metastatic disease was noted in 1, and 2 patients migrated to IIIA without a change in treatment. 19 IIIA patients had no change in stage, although an asymptomatic second primary lung cancer was discovered in 1 .Three stage IIIB patients were without staging change. Conclusions: PET/CT imaging did not contribute to patient management for stage IIB-IIIB breast cancer patients at our institution, unlike the results reported elsewhere. Analysis of care path metrics allows us to expediently review and adjust recommendations to affiliated physicians.

589 Background: Brain metastasis (BM) is a serious complication of HER2+ breast cancer (BC). We evaluated prognostic factors for overall survival (OS) in a contemporary cohort of patients (pts) wit...

6585 Background: Advances in tumor genomic profiling offer the promise of precision oncology but a systematic prospective evaluation is lacking. We conducted a prospective cohort study of tumor gen...

e11506 Background: Genomic assays are routinely used for risk assessment and for prediction of response to adjuvant chemotherapy for ER-positive breast cancer. While the Mammostrat assay (Clarient, Aliso Viejo, CA ) provides prognostic information, its performance in predicting response to chemotherapy is unknown. We sought to evaluate predictors of response to neoadjuvant chemotherapy for ER-positive breast cancer. Methods: We identified a cohort of patients with ER-positive operable breast cancer treated with neoadjuvant chemotherapy at the Cleveland Clinic who had both core biopsy and surgical pathology specimens available. Mammostrat testing was performed on core biopsy specimens for a subset of these patients. Patient and tumor characteristics as well as treatment information was collected. Residual Cancer Burden (RCB) was evaluated in post-treatment surgical specimens. Pathologic complete response (pCR) rates and RCB values were compared amongst categories of age, race, menopausal status, HER2 statu...

531 Background: Pertuzumab is FDA approved for use in combination with trastuzumab and chemotherapy as neoadjuvant therapy in women with non-metastatic HER2+ breast cancer. The TRYPHAENA trial repo...

1523 Background: Approximately 5-10% of all cancers are due to hereditary causes. Panel testing for somatic alterations to identify therapeutic targets has gained widespread use. Germline (heritabl...

262 Background: Patients receiving chemotherapy are at risk for febrile neutropenia following treatment. The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommend screening patients for risk of febrile neutropenia and risk stratification based on likelihood of febrile neutropenia events. Prophylactic growth factors (G-CSF) should be in patients receiving high-risk regimens or intermediate-risk regimens with individual risk factors. The impact of electronic medical record system (EMR) implementation on compliance with G-CSF support guidelines has not been studied. Methods: At West Virginia University/Mary Babb Randolph Cancer Center we conducted an IRB approved retrospective chart review of cancer patients receiving chemotherapy from January 1, 2007 to August 1, 2008 (pre-EMR) and January 1, 2011 to December 31, 2011 (post-EMR). We reviewed the chemotherapy regimens and patient risk factors for developing febrile neutropenia, and determined if the G-CSF usage was consistent with guideline recommendations. Results: Compliance with prophylactic G-CSF guidelines was 75.6% in the post-EMR arm, compared to 67.5% in the pre-EMR arm (p=0.041, ch-square). The post EMR data of 1,042 new chemotherapy initiations showed: (see Table). The appropriateness of usage in high and low risk patients were the most compliant, as G-CSF orders were built into chemotherapy plans of high risk regimens and omitted from low risk regimens. Conclusions: Appropriate prophylactic G-CSF usage can be improved when orders are integrated into standard chemotherapy order sets in an EMR. An area of further improvement would include automatic identification of individual risk factors by the EMR. [Table: see text]

637 Background: Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) is frequently used for prognosis for BCBM. We evaluated DS-GPA plus other potential prognostic factors for overall survival ...

1058 Background: Eribulin (E) is a non-taxane, tubulin- and microtubule-targeting agent. In the randomized, phase III EMBRACE trial, disease-free survival and overall survival were prolonged in E v...

127 Background: Studies have shown that breast cancer (BC) treatment can increase weight (wt). Wt gain during chemotherapy is usually significant and maybe associated with poor survival. Role of current treatment regimens and wt gain is not reviewed. Methods: We retrospectively analyzed the mean percentage (%) wt change during the 1st year following BC diagnosis in 246 patients (pts) between Sept 2007 and Oct 2010. Kruskal-Wallis test and post-hoc pairwise comparisons were used to assess the influence of various factors including age, histology, stage, ER/PR/HER-2/neu status, menopausal status and types of therapeutic modalities received on the % wt change. Kaplan-Meier method with log-rank test was used to evaluate recurrence free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free pts were censored at last follow-up. Results: Mean wt gain was 0.39% (±0.40) at 1 year from diagnosis of BC. Premenopausal status was the only factor associated with significant wt gain (+1.67% vs. -0.10% for postmenopausal pts; p=0.02). Stage ≥ III was associated with significant wt loss (-1.64% for III/IV vs. +0.85% for 0/I/II; p=0.02) and a lower RFS at 3yrs and 5yrs (p< 0.0001). Higher baseline wt (>90th percentile) did not have any significant impact on RFS at 3 years (0.84 vs. 0.91; p=0.19). There was no significant change in wt relative to other factors as shown in Table. Conclusions: Our study using current treatment regimens did not show any significant change in % wt with chemotherapy during the 1st year of BC diagnosis. Premenopausal status was the only factor associated with significant wt gain while stage ≥ III was associated with significant wt loss and lower RFS. [Table: see text]

56 Background: Breast irradiation may expose a portion of the heart to radiation. Heart irradiation is associated with late risk of ischemic heart disease, proportional to dose. A recent publication of patients treated with 2-D planning prior to 2001 noted average mean heart dose (MHD) of 6.6 Gy for left breast tumors, 2.9 Gy for right breast. Current treatment planning can minimize the MHD, reducing the risk of late heart injury. Methods: We reviewed treatment plans of 78 patients (86 breasts) treated 1/2012-3/2013 to obtain MHD. Treatment plans were CT-based, field-in-field forward planning with heart blocking. Two treatment regimens were used; hypofractionation (HF) (16 x 2.66 Gy, no boost) or standard (SF) (46.8-50.4 Gy +/- 10 Gy boost). Statistics were obtained for MHD based on right (N = 44) or left breast (N = 42); HF (N = 31) vs SF (N = 55), and total dose. Results: Average (av) MHD for left breast was 1.45 Gy (range 0.19-3.12), for right breast 0.70 Gy (0.12-1.54). For HF patients av MHD left was 1.16 Gy (0.19-1.90), MHD right was 0.48 Gy (0.12-0.91). For SF av MHD left was 1.60 Gy (0.80-3.12), MHD right was 0.84 Gy (0.39-1.54). There was a significant difference in MHD between left and right breasts (p = 0.002) and significant correlation between breast dose and MHD (p = 0.026). Conclusions: MHD from breast RT with current treatment planning is much lower than published reports from 2-D planning. MHD correlates with total breast dose and is greater for the left than right side. Techniques to reduce MHD should be utilized, especially for left-sided breast cancer.

19 Background: The Asian Indian/Pakistani population living in the U.S. (USAIP) is a rapidly growing minority group with persistent cancer disparities. According to SEER (Surveillance, Epidemiology, and End-Result) database, BC is the most frequently diagnosed cancer in USAIP women.The customizing therapeutic and preventive approaches are important to improve health quality across different population therefore, we conducted the largest epidemiological and survival disparities of BC in USAIP women. Methods: SEER has been collecting and reporting data on USAIP as a separate ethnic group since 1988. Using 18 SEER registries from 1988-2009 and SEER*Stat 7.0.9, we performed frequency and survival sessions (Kaplan-Meier adjusted for age) on USAIP women with BC and compared with non-Hispanic White (NHW), Hispanics (H),and African American women (AA) with BC. Cox proportional hazards regression analysis was performed to estimate relative risks (RR) on BC mortality after adjusting confounders using SAS v 9.3. Results: A total of 2,750 BC cases reported in USAIP women in SEER database, accounting (38%) of all cancers compare to NHW (30%), H (31%) and AA (32%). The median age at diagnosis in USAIP is significantly less (54 y, p < 0.001) than other ethnicities. Significantly more USAIP (14%, p < 0.001) were diagnosed at age < 40y vs NHW (5%), H (7%) and AA(10%). Compare to NHW, USAIP were more likely to have stages III or IV (22% vs. 18%, p < 0.01); ER/PR+ (84% vs. 75%, p < 0.001); poorly differentiated histology (47% vs. 35%, p < 0.001). 5 yr overall survival is better in USAIP (97%, p 71y), stage III or IV, high grades, ER/PR negative, divorced/widowed, and diagnosis year (1988-1994). Conclusions:This study identifies unique biological features and disparities of BC in US AIP women compared with other US populations. The difference in survival is intriguing, and could be due to differences in tumor biology, access to care, and other epigenetic factors.This study has potential implications for screening and therapeutic recommendations for BC in the US AIP population.

123 Background: Radiation exposure is associated with an increased risk of secondary cancers. Few studies have examined radiation exposure from DP in BC. Methods: We retrospectively analyzed the cumulative radiation doses (millisievert [mSv]) of routine DP done in 305 pts during the 1st yr following BC diagnosis between Jan 2008-Oct 2010. Data regarding the frequency of DP including mammograms, sentinel lymph node biopsies, X-rays, computed tomographic (CT) and/or positron emission tomographic (PET) scans, MUGA scans and bone scans were collected. Mean radiation doses of DP were obtained from Departments of Nuclear Medicine and Radiation at our institution. Kruskal-Wallis test and post-hoc pairwise comparisons were used to assess the influence of various factors including age, histology, ER/PR (Estrogen/Progesterone) status and stage on the amount of radiation exposure. Results: Mean radiation exposure relative to various factors is shown in the Table. Pts < 40yrs had a significantly higher radiation dose as compared to pts > 60yrs (35.9mSv vs. 19.2mSv; p = 0.009). Pts with DCIS (ductal carcinoma in situ) had a significantly less radiation exposure as compared to IDC (infiltrating ductal carcinoma) and ILC (invasive lobular carcinoma) (8.5mSv vs. 26.7mSv and 22.4mSv respectively; p< 0.0001). Stage ≥ IIB disease was associated with a significantly higher radiation exposure (p< 0.0001). Stage ≥ IIIA was the only factor associated with a higher radiation dose from PET/CTs (p< 0.0001). Conclusions: Radiation exposure from DP is significant in the 1st yr of BC diagnosis, especially for younger and advanced stage pts. Risk is small but relevant, especially in younger pts. [Table: see text]

1603 Background: Asian Indian and Pakistani population living in the US (US-AIP) comprises 1.5% of total US population and is a rapidly growing minority group. Colorectal (CRC) is the third most co...

1131 Background: Triple-negative breast cancers are associated with poor outcomes; however, the patterns of metastatic spread following diagnosis are less defined. Methods: Records for 593 patients with breast cancer at West Virginia University Hospital were reviewed (for tumor receptor status and the occurrence of, and time to, first distant metastasis and overall survival) and compared triple-negative versus other receptor subtypes. Distant metastasis-free survival was defined as the interval between the initial diagnosis and the time at which a metastasis to bone and visceral sites (liver, lung, brain) was detected. If more than one site was involved, it was prioritized in the order: liver, lung, brain, and bone. Results: Ninety-five of 593 patients (95/593,16%), developed metastases to bone (40/95) or visceral sites (55/95). Metastases to liver, lung, and brain occurred within the first five years, a latent period that was shorter than that for bone (p= 0.042). The median time to recurrence was shorte...

e13158 Background: The use of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in cancer patients underwent a rapid increase in the 1990s and early 2000s. At their peak, they were used in nearly half of all U.S. cancer patients to increase hemoglobin concentrations, reduce the need for blood transfusions, and increase quality of life. In the past 3 years however, the publication of data calling the safety of these agents into question has resulted in increased regulation of ESAs. We examine the impact these events have had on the use of ESAs at our institution. Methods: A retrospective review of 3,289 cancer patients treated at West Virginia University (inpatients and outpatients) between 2004 and 2008 was initiated. The data collected was primarily for epogen (epoetin alpha) only as this was the institutional preferred formulary agent. The data extracted was the number of patients per month using epoetin alpha as dispensed by the pharmacy. The number of patients using epoetin alpha pe...

e11611 Background: Fluorine-18-FDG positron emission tomography (FDG-PET) role in the follow up care of non-metastatic breast cancer is not defined. Methods: We retrospectively analyzed 177 patients with stage I-III breast cancer between November 2004 and June 2006. IRB approval was obtained for this study. Patients were divided into two groups. Group A consisted of patients who had one or more FDG-PET scans as part of their clinical follow up (N=68), and Group B consisted of patients who did not (N=109). Clinical, radiological and pathology data were obtained from patients’ records. Results: Median follow-up is 35 months. Mean age 53 years for group A and 57 years for group B. Group A patients were more likely to have had higher stages (29% stage I, 53% stage II, and 18% stage III) compared with group B (64 % stage I, 31% stage II and 4% stage III). The two groups did not differ significantly in ER+ status (69% vs. 78% p=0.21), or Her2neu status (19% vs. 17%; p=0.6). Group A patients had more clinic visits (18 vs. 11; p=0.009), their tumor marker was checked more often (13 vs. 9 times; p=0.0001), had more radiological studies (10 studies vs. 5; p=0.0001), and had more biopsies (0.88 vs. 0.48 biopsy per patient; p=0.05). These differences were significant even after controlling for stage and chemotherapy. 9/68 patients in group A had tumor recurrence compared to 1/109 in group B (p=0.0003). PET scan indications were as follows: 29 (43%) for asymptomatic follow up evaluation [2 recurred]; 18 (26%) concerning symptoms [0 recurred]; 10 (15%) elevated tumor marker [2 recurred]; 7 (10%) other abnormal imaging studies [1 recurred]; 4 (6%) metastatic workup. Conclusions: While FDG-PET might aid in detecting recurrence in some patients with non-metastatic breast cancer, its use was associated with more clinic visits, blood tests, biopsies, and radiological tests. No significant financial relationships to disclose.

20699 Background: Smoking is a known risk factor for cancer, such as lung, head and neck. Studies showed that smoking can adversely affects outcome of different treatment modalities of cancer inclu...

17502 Background: With advancement in research, it is imperative for clinical trials to be accurate and generalizable. This is best achieved through improving patient participation in clinical tria...

11550 Background: Although magnetic resonance imaging (MRI) is superior to conventional imaging techniques in breast cancer, its correlation with actual tumor size has not been shown to be impressive. The purpose of our study is to determine the correlation of MRI with pathological findings of breast cancer in patients treated in West Virginia University Hospitals. Methods: This is a retrospective study analyzing a database of 43 patients with breast cancer who had preoperative MRI. We estimated the correlation between the preoperative largest tumor diameter on MRI and diameter on pathological evaluation after surgery. The size of the surgical specimen is considered the gold standard for tumor measurement. A subset of 15 patients received neoadjuvant chemotherapy, while 28 patients did not. In all patients, MRI diameters were measured preoperatively. All MRI diameters were estimated by only two radiologists in our institution. Results: The mean age of our patient population was 47.4 years (range: 36–70). ...

10533 Background: Both tumor marker CA 27.29 and combined [18-F]-fluorodeoxyglucose-positron emission tomography/computed tomography scan (PET/CT) are used to follow up response to treatment and disease progression in patients with metastatic breast cancer (MBC). Recently, circulating tumor cell testing (CTC) has been used in this context. It is not known if one of the three tests can be a surrogate for the other 2 tests. Methods: We analyzed the database of 35 patients with MBC. There were 173 time points (at least 6 weeks apart), when at least 2 of these tests were done. CA 27.29 test (chemiluminescent immunoassay by Bayer Advia Centaur) was either high or normal (< 38.6 U/ml). Circulating tumor cells cell test (Cell Search by Quest Diagnostics, Nichols Institute, Chantilly, VA) was either high or normal (0 cells detected). Results: PET/CT scan results were compared to CA 27.29 at 163 time points. There was statistically significant correlation between both groups (P value: 0.02), however, sensitivity of CA 27.29 to detect metastatic disease seen in PET/CT scan was 59%. The positive predictive value (PPV) of CA 27.29 was 90%, while the negative predictive value (NPV) was only 24%. PET/CT scan results were compared to CTC at 100 events, where there was statistically significant correlation between both groups (P value: 0.0002), however, sensitivity of CTC to detect metastatic disease shown in PET/CT scan was 55%. The positive predictive value of CTC was 98% while the negative predictive value was only 33%. CTC test was more specific (94% Vs 67%) than CA 27.29 to rule out metastatic disease that is seen in PET/CT scan. CA 27.29 results were also compared to CTC at 93 events, where there was statistically significant correlation between both groups (P value: 0.0002). However, only 64 % of those with high CA 27.29 had abnormal CTC. Conclusion: Our data shows correlation among PET/CT scan, CA 27.29, and CTC. However, both CA 27.29 and CTC had poor sensitivity and negative predictive value to detect metastatic disease seen in PET/CT scan. Normal CA 27.29 test or CTC has to be interpreted cautiously in patients with MBC. No significant financial relationships to disclose.

20112 Background: About 1.5% of the US population is South East Asian in origin and it is one of the rapidly growing groups. Colon cancer is the second most common in male and third most common cancer in females in Asian Indian and Pakistani population living in the USA. This is the first study examining the epidemiologic characteristics of colon cancer in this group. Methods: SEER cancer incidence public use database have reported cancer incidence in 13 SEER registries from 1973 to 2002. Since 1988, Indian/Pakistani populations were reported separately under race and ethnicity. Frequency sessions were performed and descriptive parameters were calculated regarding age, sex, stage, grade, tumor location and diagnostic methods used. Results: A total of 4,229 cases of cancer were reported from 1988 to 2002 in this group and 352 (9%) were colon cancers. The reported incidence of colon cancer in SEER database is increasing (11 in 1988 vs. 53 in 2002). Table shows the comparative studies of different variables of colon cancer between Indian/Pakistani and US White population reported in SEER database. Conclusions: Our study shows that the incidence of colon cancer in Asian Indian and Pakistani population under age 50 is substantially higher than the US White population and the predilection is towards the male sex. Our results suggest that this ethnic group warrants close screening and risk factor stratification for earlier detection of colon cancer as well as awareness and counseling in high-risk families. [Table: see text] No significant financial relationships to disclose.

6553 Background: Allogeneic stem cell transplantation is used to treat different types of hematologic malignancies. The target stem cell dose typically is based on the recipient’s ideal body weight (IBW) with CD34 dose of 2.0–5.0 ×106/Kg. The dose of CD3 in the infusate is typically not taken into account in a stem cell product, except in T-depleted transplantation. The dose of T-cells in peripheral blood stem cell collections has been found to be at least 10-fold more than that in a bone marrow harvest product. Combined CD4+ and CD25+ cells infused have been directly correlated with increased incidence of GVHD. Methods: This is a retrospective study reporting the correlation of the CD34 and CD3 doses of stem cell transplant with incidence of acute GVHD in 67 consecutive patients who were treated between 2003 and 2005. All patients were followed up for at least 100 days following the stem cell transplant. Results: Among the 67 patients, 35 patients developed acute GVHD, while 32 patients had no evidence of acute GVHD. The CD3 and CD34 doses did not correlate. The correlation coefficient was 0.14 (P value: 0.27). Using t-test, there was NO statistical difference between the mean CD34 dose when comparing the group of patients who developed acute GVHD with the group that did not develop acute GVHD (P value: 0.31). Those who developed acute GVHD (n = 35) received a mean CD3 dose of 41.9 × 107/kg IBW (95% CI: 35.9–47.9). Those who did NOT develop acute GVHD (n= 32) received a mean CD3 dose of 33.5 × 107/kg IBW (95% CI: 27.3–39.8). By using the t-test, the P value for the different means was 0.0575. However, using a CD3 dose cutoff value of 30 × 107/kg IBW, the incidence of acute GVHD was statistically significantly less among those who received CD3 dose < 30 × 107/kg IBW. The Chi Square P value was 0.04. Conclusions: In our series, CD3 dose less than 30 × 107/kg IBW was associated with reduced risk of acute GVHD (P value: 0.04). There was no correlation between CD3 and CD34 counts in peripheral stem cell product. In addition, the CD34 dose did not influence the incidence of acute GVHD. These data suggest that, in addition to considering CD34 dose required for engraftment in allogeneic transplant, the CD3 dose will need to be considered to try to minimize the risk of acute GVHD. No significant financial relationships to disclose.

20111 Background: BRCA1 and 2 mutations are rare in general population and women with these mutations confer a significantly increased risk of invasive breast and ovarian cancer (65% to 85%, and 15% to 65% cumulative lifetime risk, respectively). A few of these are variant mutations also known as Variant of unknown significance (VUS). Methods: Observational study of 155 patients who presented to MBRCC, WVU for genetic counseling between November 2001 and March 2005. Patients underwent genetic testing after detailed genetic counseling. Clinical data, such as patient’s age, ethnic origin, follow up period, Myriad risk of mutation, clinical outcome i.e., Mastectomy versus Bilateral Salpingo-oophorectomy versus Surveillance, total numbers of patients screened, tested and reason for not testing, and other data, were available for statistical analysis. Results: In out patient population who underwent genetic counseling, 46% (71 out of 155) underwent genetic testing. A large number of patients (54%; 84 out of 155) who underwent genetic counseling could not undergo the genetic testing. Total number of patients not genetically tested were 84, out of which, 27 were low risk, 35 had insurance denial, 7 were not interested, 14 were awaiting results or insurance approval and 1 was deceased. 27 out of 71 patients (38%) who underwent genetic testing were positive for a mutation. Among these patients (n = 27), 8 had BRCA 1; 3 had BRCA1 VUS; 7 had BRCA 2 and 9 had BRCA2 VUS. The average age for patients who had a genetic mutation was 42 years. The most prevalent genetic mutation in our study population was BRCA2 VUS (33%; 9 out of 27) followed by BRCA 1 mutation (29%; 8 out of 27). 11 out of 27 (40%) who had a mutation underwent mastectomy. 13 out of 27 patients (48%) who had a mutation underwent bilateral salpingo-oophorectomy. 7 out of 27 patients (26%) who had a mutation underwent total abdominal hysterectomy. 4 out of 27 patients (15%) who had a germline mutation were lost to followup. Conclusion: We report the prevalence and the clinical outcomes in patients with BRCA mutations in the state of West Virginia, which is comparable to the national database. High number of patients could not undergo genetic testing because of insurance denial. No significant financial relationships to disclose.