Background Statins are established as first line therapy in patients with hypercholesterolemia and are thought to have pleiotropic effects including inhibition of signaling pathways known to drive cell proliferation and survival responses. Numerous preclinical and observational studies have demonstrated activity and improved outcomes in breast cancer patients who received statins, particularly lipophilic statins, as part of their adjuvant therapy. In the Life After Cancer Epidemiology (LACE) Study, 1,945 early-stage breast cancer survivors were shown to have a 33% decreased risk of breast cancer recurrence with post-diagnosis statin use, an effect that was magnified with increasing duration of statin use. We hypothesized that statin use concurrent with trastuzumab based chemotherapy in patients treated for non-metastatic HER2 positive breast cancer would be associated with improved outcomes. Methods We performed a retrospective review of all patients (n = 300) with HER2+ breast cancer who received trastuzumab from 2006-2012 at UM/SCCC. We identified two groups of patients for comparison - those who received statins (ST) during adjuvant chemotherapy (n = 45) or no statins during chemotherapy (NST) during adjuvant chemotherapy (n = 200). Patients with unclear documentation of concurrent statin use, men, patients with de-novo-metastatic breast cancer or prior primary cancer, bilateral breast cancers, and patients without follow-up were excluded. 5-year disease free (DFS) and overall survival (OS) were calculated. A univariate analysis was performed. Multivariate analysis for time-to-event data, using the Cox and extended Cox regression model will be performed and reported. Results The median age at diagnosis was 58 and 48, in the ST and NST groups, respectively. The most commonly used statin was lipophilic simvastatin (34.1%). The average baseline and post chemotherapy total cholesterol level in the ST group was 200.8 and 218.1mg/dL, respectively. Descriptive characteristics of the ST and NST groups respectively are as follows: postmenopausal (77.8% vs. 43.5%) tumor size <2cm (48.9% vs. 41.0%), node-negative disease (40.0% vs. 40.0%), HR+ status (64.4% vs. 60.5%), diabetes mellitus (26.7% vs. 9.0%), baseline BMI >30 (40.0% vs. 27.0%), and concomitant metformin (28.9% vs. 11.5%). The NST group was more likely to have a reduction of greater than 10% in their EF (9.0% vs. 6.7%). At a median follow-up of 32 and 26 months, the estimated 5-year DFS was significantly improved in the ST group (81.8% vs. 51.5%, p = 0.046). Meanwhile, the estimated 5-year OS was not significantly different between both groups (93.4% vs. 91.6%, p = 0.121). Metformin was not associated with a significant improvement in DFS or OS. Conclusion Our study demonstrated that statin use concurrent with trastuzumab-based chemotherapy for non-metastatic HER2 breast cancer was associated with improved estimated 5-year DFS, but not OS. The retrospective nature of our study does not allow for a definitive answer but further research needs to be done to define the role of statins in HER2+ breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-03.

Background Vitamin D (VitD) supplementation decreases the risk of osteoporotic fractures in the elderly; however, its extraskeletal benefits, especially in the prevention and treatment of breast cancer, are less well-established. Many studies have shown an association of low VitD levels with higher cancer incidence, including breast cancer and poorer outcomes, but whether this association merely reflects a selection bias to healthier lifestyles, remains an area of controversy. We hypothesized that women with more aggressive HER2+ breast cancer would have improved clinical outcomes while on VitD supplements. Methods We performed a retrospective review of all patients (n = 300) given trastuzumab chemotherapy between 2006 and 2012 at UM/SCCC. We identified two groups of patients for comparison - those who received VitD supplementation (VD) during adjuvant chemotherapy (n = 130) or none (NVD) during adjuvant chemotherapy (n = 123). Patients who lacked sufficient records to clarify VitD supplement use, men, patients with de-novo-metastatic breast cancer, bilateral breast cancers, and patients without follow-up were excluded. Five-year disease-free survival (DFS) and overall survival (OS) were calculated. Univariate and multivariate analyses were performed using a Cox proportional hazards (CPH) model to evaluate the relationship between VD supplementation and death. Results The median age at diagnosis was 54 and 50 in the VD and NVD groups. In the VD group, the average VitD dose was 10,890 IU/wk, and the baseline and post-25-H VitD serum level was 35 and 41ng/ml, respectively. Descriptive analysis of the VD and NVD groups were as follows: postmenopausal (55.4%, 43.9%), tumor <2cm (42.3%, 36.6%), no lymph node involvement (42.3%, 36.6%), LVI (46.4%, 33.3%), high nuclear grade (60%, 61.5%), HR+ (66.2%, 54.5%), African American race (4.6%, 9.8%), and BMI>30 at end of chemotherapy (26.2%, 31.7%). At a median follow-up of 31 and 23 months, the estimated five-year DFS (69.4% vs. 44.7%, p = 0.009) and OS (97.5% vs. 85.6%, p = <0.0001) were significantly superior in the VD group versus the NVD group. These differences remained significant after adjustment for age, ethnicity, menopausal state, tumor size, node positivity, LVI, high-grade tumor, HR+, and BMI>30. Analysis showed an interaction between OS and ethnicity (African American = 0.008) and node positivity (p = 0.02) and near-significance for LVI (p = 0.07). Despite those confounding variables, VitD use remained significantly associated with improved OS (p = 0.003) and had a HR or 0.10 with a 95% CI of 0.02-0.45. Conclusion Our study suggests that Vitamin D supplementation in non-metastatic HER2 breast cancer patients is associated with improved DFS and OS, and the relationship remains significant after adjusting for potential confounding factors. It is unclear whether vitamin D supplementation might have pre-selected for HER2+ breast cancers with more favorable prognosis or synergized with anti-HER2 therapy. To our knowledge, this is the first study reporting improved outcomes associated with relatively high dose Vitamin D supplementation in the HER2+ breast cancer population. Further research is warranted to define the role of Vitamin D in breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-02.

Background. mTNBC has an aggressive course with limited effective therapy options and a median progression-free survival (PFS) of 2-4 months (mos) with standard therapy. Sacituzumab govitecan (IMMU-132) is an ADC targeting Trop-2, an antigen present in many epithelial cancers, including TNBC, and delivering SN-38, a topoisomerase I inhibitor as its therapeutic moiety. IMMU-132 was awarded Breakthrough Therapy designation by FDA based on its previously reported activity in relapsed/refractory mTNBC patients. Here we present updated results from the mTNBC cohort of an ongoing phase I/II study (ClinicalTrials.gov, NCT01631552). Methods. mTNBC patients (pts) received IMMU-132 10 mg/kg on days 1 and 8 every 21 days. Trop-2 expression was not required for enrollment, but available tumor specimens underwent immunohistological (IHC) testing. Efficacy was assessed locally by RECIST 1.1; ORR, PFS and overall survival (OS) were determined for all pts. Pharmacokinetic parameters were estimated in select pts with adequate blood sampling. Immunogenicity to IMMU-132 was examined in all pts. Results. We previously reported preliminary efficacy results in 51 mTNBC patients. Here we present data on 69 patients with data cutoff June 5, 2016. Median age was 56 years (31-81) and a median of 5 prior therapies (range 1-12), with 66 evaluable for response; ORR was 29% (19/66) 2 confirmed complete (CR) and 17 confirmed partial responses (PR). The median intention-to-treat PFS is 5.6 mos (95% CI, 3.6-7.1 mos) and median OS is 14.3 mos (95% CI, 10.5-18.8 mos). PRs included 2 pts whose tumors did not respond to anti-PD-L1 therapy. The duration of response in the 19 confirmed responders (8 continuing therapy) is 11.5 mos (95% CI = 7.6 to 12.7). The clinical benefit rate (CR+PR+SD>6 mos) for the 66 assessable patients is currently 45.5%. The majority (88%) of archival tumor specimens were moderately (2+) to strongly (3+) positive by IHC for Trop-2, precluding using Trop-2 expression as a selection criterion. Among current adverse events, grade >3 drug-related toxicities included neutropenia (35%), leukopenia (16%), anemia (13%), vomiting (9%), diarrhea (10%), and febrile neutropenia (4%). Clearance kinetics in 8 pts showed IMMU-132 and IgG had a terminal half-life of 15.3 ± 2.7 h and 86.5 ± 40.5 h, respectively, with area under the curve for free SN-38 (unbound) only 3% of the total amount of SN-38 (e.g., IgG bound). Thus, most SN-38 remains bound to the conjugate, and is released at a rate predicted from in vitro serum stability studies. No pt developed anti-IMMU-132 antibodies. Conclusion The Trop-2-targeting ADC, IMMU-132, delivering cytotoxic doses of SN-38, shows high objective and durable tumor responses with manageable toxicity in heavily-pretreated pts with mTNBC in this updated cohort, supporting further development in this population with an unmet medical need. Citation Format: Bardia A, Diamond JR, Mayer IA, Isakoff SJ, Abramson V, Starodub AN, O'Shaughnessy J, Kalinsky K, Moroose R, Shah N, Juric D, Shapiro GI, Guarino M, Ocean AJ, Messersmith WA, Berlin JD, Wegener WA, Sharkey RM, Goldenberg DM, Vahdat LT. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate (ADC) for the treatment of relapsed/refractory, metastatic triple-negative breast cancer (mTNBC): Updated results [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-15.

Introduction: Vascular compromise causes hand pain, and physical examination requires to differentiate vascular causes from isolated ulnar nerve compression. Diagnostic studies visualize vascular abnormalities such as CT scans, MRA scans, and AV fistulograms. Ulnar artery aneurysms are quite rare discoveries, related to repetitive trauma, vasculitis, anatomic abnormalities, or infections. It is essential to repair any aneurysm when flow impediment causes significant symptoms. Blunt injury to the ulnar artery and superficial palmar arch damages the arterial wall and forms an aneurysm. The sensory branch of the ulnar nerve becomes compressed. Treatment here is to resect the thrombotic segment to relieve the compression. It is interesting to note, in this particular case, that a high origin and superficial ulnar artery had coursed along the forearm and entered along the ulnar side of the hand. The presence of such anatomic variations are essential in medical practice. Case presentation: A 73-year-old Haitian female was admitted to the hospital with complaints of numbness and weakness along the right forearm and wrist. According to the patient's daughter, she has experienced these symptoms for at least two years' duration after minimal trauma to her right hand. Upon physical examination of the right wrist, a 3-cm palpable, pulsatile ulnar mass was found. The Allen's test showed no significant abnormalities, but the Tinel's test and pinprick examination were diminished. An AV fistulogram was scheduled the same day and a repair followed soon after. IV contrast dye demonstrated an aneurysm of the ulnar artery, along with an adjacent superficial branch. The decision was made to resect the aneurysm and allow the superficial ulnar artery remain patent for continuous blood supply to the 4th and 5th digits of her right hand. She was discharged the same day and to follow up in the vascular clinic a week later. Conclusion: This particular case describes a couple important disciplines that establishes further insight about the human anatomy, pathophysiology and vascular surgical management. First, hypothenar hammer syndrome has been illustrated in a patient without any history of vasculitis, infections, or congenital anatomic abnormalities. A diagnostic and therapeutic approach is necessary to relieve ulnar nerve entrapment. Second, this particular patient underwent a simple repair but it was found that an aberrant ulnar artery was discovered, which coursed adjacent and superficial to the aneurysm. It is important to establish an early diagnosis prior to any surgical procedures. Intraoperatively, proper identification to isolate and establish a continuous blood flow is essential. Knowledge of such variations allows for improved care in the fields of radiology, angiography, surgery and the medical sciences. very little English, but her daughter translated. As per her daughter, the patient complained of numbness, pain and weakness along the right arm, forearm, and wrist. She had visited her home in Haiti two years ago, and believ...

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