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Purpose. The purpose of this study was to determine the feasibility and preliminary efficacy of a cardiac rehabilitation (CR) intervention in the breast cancer population. Methods. This single-arm feasibility study evaluated a 14-week CR intervention program in breast cancer survivors. Feasibility was defined as completion of at least 30/36 sessions of the program without serious adverse events (SAE) in 80% of patients. Secondary endpoints included the change in VO2 max, cardiovascular disease (CVD) risk factors, Duke Activity Secondary Index (DASI), Brief Fatigue Inventory (BFI), and QLQ-C30. All outcomes were reported as mean change and compared using paired t-tests. Results. A total of 25 patients were enrolled in the study. 18 patients of the 25 enrolled (72%) completed the 14 weeks program without SAE. The overall adherence to the study protocol was 60%. Of the 18 participants who did not withdraw from the program, 15 (83%) adhered to the study protocol and completed 30 or more sessions. There was a nonsignificant improvement in VO2 max (mean Δ0.5, p = 0.6 ). The scores for DASI, BFI, and QLQ-C30 improved from baseline to posttreatment. Conclusion. A CR intervention in breast cancer survivors had high adherence in those who were able to complete the 14-week program. The program significantly improved patient reported physical activity, fatigue, and quality of life (QoL), without significant improvement in CVD risk factors. Implications for cancer patients are that early implementation of a CR program should be considered by practitioners as it improves QoL and exercise tolerance in breast cancer survivors.

Objective The primary objective of this study was to delineate differences in management, overall and distant disease-free survival in males diagnosed with breast cancer and treated at The Ohio State University Comprehensive Cancer Center as compared to comprehensively matched female subjects. Secondary objectives included assessment of clinical and histopathologic features and recurrence score, as measured by Oncotype DX and the modified Magee equation #2. Materials and methods This single institution retrospective study compared male and comprehensively matched female patients (1:2) with stage I-III breast cancer between 1994 and 2014. Recurrence risk was estimated using a modified Magee equation. Overall survival and distant disease-free survival were estimated and compared using Kaplan-Meier and Log-rank methods. Results Forty-five male breast cancer patients were included (stage I: 26.7%; stage II: 53.3%; stage III: 20.0%; hormone receptor positive: 97.8%; human epidermal growth factor receptor 2 negative: 84.4%) with a median age of 63.8 (43.0-79.4) years at diagnosis. Intermediate and low recurrence scores were most common in male and female patients respectively; mean score was similar between groups (20.3 vs. 19.8). The proportion of male breast cancer patients treated with adjuvant chemotherapy and post-mastectomy radiation was lower compared to female patients (42.2% vs. 65.3%, p=0.013; 22.7% vs. 44.4%, p=0.030, respectively). Overall survival and distant disease-free survival between male and female patients were similar. Conclusion Male breast cancer patient outcomes were similar compared to well-matched female patients suggesting that breast cancer specific factors are more prognostic than gender.

The goal of chemotherapy for metastatic breast cancer (MBC) is palliation of symptoms while minimizing treatment-related toxicities. It remains unclear whether use of granulocyte colony-stimulating factor (G-CSF) to maintain relative dose intensity of chemotherapy for MBC is associated with improved clinical outcomes. The medical records of MBC patients treated with chemotherapy in 1st–3rd-line settings between May 2010 and April 2014 were reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were compared between patients who received G-CSF and those who did not. Antibiotic use, total clinic visits, and pre- and post-treatment Eastern Cooperative Oncology Group (ECOG) performance status were also compared between the groups. Of the 169 patients included, 55 (32.5%) received > 1 G-CSF dose and 114 (67.5%) did not receive any G-CSF. The median TTP was similar between the two groups (5.0 months (95% CI 3.4–7.1) vs. 5.2 months (95% CI 4.8–6.2) respectively; p = 0.998). The median PFS (p = 0.955; 5.0 months (95% CI 3.4–5.9) vs. 5.2 months (95% CI 4.7–6.0), respectively) and OS (14.6 (95% CI 9.0–26.6) vs. 18.5 months (95% CI 15.2–22.0) in G-CSF and non-G-CSF groups, respectively; p = 0.628) were also similar between groups. No significant between-group differences were noted in rate of decline in ECOG performance status, antibiotic use, and number of clinic visits and hospitalizations. This retrospective analysis did not find any evidence that the use of G-CSF to maintain chemotherapy dose intensity for the treatment of MBC improves TTP, PFS, and OS or results in improved ECOG performance status compared with lack of G-CSF use in patients with MBC treated in 1st to 3rd-line settings.

Introduction: Adults age ≥65y constitute the majority of patients (pts) diagnosed with cancer. There is a gap in knowledge about the safest and most effect cancer treatments for older pts. At The Ohio State University, we have a longitudinal multidisciplinary geriatric clinic for adults ≥ 65 years of age diagnosed with breast cancer (BC). The clinic team consists of a physician, nurse practitioner, dietician, physical therapist, social worker nurse, and pharmacist. We evaluate the unique needs of older pts with breast cancer by completing a comprehensive geriatric assessment (CGA). Eligible patients are enrolled into OSU-16153 which is a is prospective cohort study of pts ≥65y with new diagnosis of BC to better understand complex health issues of this population, and to collect data to support future studies. Methods: Forty eight pts have completed the baseline questionnaires including demographics, lifestyle and health history and CGA. Summary statistics were used to describe the baseline characteristics. Results: The median age of patients enrolled in the study was 77 years (range 67-94), the mean BMI was 28, 50% (24/48) were Caucasian and 6% (3/48) were African American. Mobility was assessed mobility with the time get up and go (TGUG), mean 9.8 (SD=6.2) and grip strength, mean of 31. Cognitive limitations were screened with the blessed orientation memory concentration test, mean 3.9 (SD=5.0) and mini-cog, mean 3.6 (SD=1), malnutrition, mean 12.3 (SD=12.2) and depression, mean 1.6 (SD=2.4). Functional limitations were measured with Katz, mean 5.9 (SD=0.2), and Lawson, mean 7.8 (SD=0.8). Disease characteristics included 18% (9/48) Tis, 54% (26/48) T1, 21% (10/48) T2, 2%(1/48) T3, and 4% (2/48) T4 tumors, 65% (31/48) lymph node negative and 81% (39/48) estrogen positive (ER+),17% (8/48) ER negative and 4% (2/48) HER2 positive. Oncotype score was 25 in 4% (2/48). Twelve percent (6/48) received adjuvant chemotherapy for triple negative or ER+ breast cancer with high oncotype with docetaxel/cytoxan and 4% received trastuzumab based therapy and they were able to complete all planned cycles. Two pts received chemotherapy based on results of CGA. Forty-two pts were eligible to receive endocrine therapy (ET); 3 pts with ductal carcinoma in-situ (DCIS) and 2 pts with invasive BC declined, 1 did not follow up after her initial visit. Five pts switched ET due to side effects. The 7 patients with invasive BC who declined or switched ET due to side effects all had an abnormal TGUG, 43% (3/7) had an impaired min-cog and 57% (4/7) had impaired hand grip. Conclusions: The majority of older adults have no functional deficits in ADL/IADL, have adequate mobility and grip strength and did not screen positive for cognitive limitations, depression or, malnutrition. Our data shows that the mobility and cognitive assessment of a CGA may serve as a predictor of toxicity from ET therapy and identify patients who are at risk for side effects and who may benefit from additional interventions. The majority of pts who received adjuvant chemotherapy and ET tolerated well. Our pilot data shows a CGA is feasible and that a CGA helped direct appropriate therapy. Citation Format: Nicole Williams, Julie Stephens, Elizabeth Kress, Erin Frey, Susan Fugett, Paige Erdeljac, Stephanie Yager, Erin Holley, Cari Utendorf, Nikki Ford, Caitln Ubbing, Jeanie Overcash, Bhuvaneswari Ramaswamy, Anne Noonan. Feasibility of comprehensive geriatric assessment in an academic breast oncology clinic [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-16-01.

Patient navigation improves outcomes in various clinical contexts, but has not been evaluated in secondary fracture prevention. We retrospectively reviewed charts of patients, age 50 + from April to October, 2016 hospitalized with fragility fracture contacted by a patient navigator. Patients were identified using an electronic tool extracting data from electronic medical records which alerted the patient navigator to contact patients by phone post-discharge to schedule appointments to “High-Risk Osteoporosis Clinic” (HiROC) and Dual-energy X-ray Absorptiometry (DXA) scan. Primary outcome was transition from hospital to HiROC. We also compared completion of DXA, five osteoporosis-associated in-hospital laboratory tests (calcium, 25-hydroxy vitamin D, complete blood count, renal, and liver function), osteoporosis medication prescription and adherence, and other patient characteristics to historical controls (2014–2015) without patient navigation. Comparisons were made using Chi-square, Fisher’s Exact, two-sample t test or Wilcoxon Rank Sum test, as appropriate. The proportion of patients transitioning to HiROC with and without patient navigation was not different (53% vs. 48%, p = 0.483), but DXA scan completion was higher (90% vs. 67%, p = 0.006). No difference in medication initiation within 3 months post discharge (73% vs. 65%, p = 0.387) or adherence at 6 months (68% vs. 71%, p = 0.777) was found. Patients attending HiROC lived closer (11 vs. 43 miles, p

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1–14 on 21-day cycle) to biweekly dosing (Arm B: days 1–7 and 15–21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm’s correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–7 and 15–21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.

Objectives National data reveal that 60% of the 4.5 million annual emergency department (ED) visits by patients with cancer result in admission. Many of these visits are due to a febrile illness. Current literature provides limited guidance on how to treat non‐neutropenic febrile ED patients. This study characterizes clinical outcomes of non‐neutropenic febrile patients with cancer presenting to an academic, Comprehensive Cancer Center affiliated ED. Methods Retrospective chart review of 101 randomly selected adult patients with active cancer presenting with a chief complaint of fever or a documented fever in the ED and an absolute neutrophil count above 1000 between October 2015 and September 2016. Descriptive statistics were calculated. Results The primary malignancies represented were hematologic (24%), gastrointestinal (13%), head and neck (13%), and genitourinary (8%). Sixty‐two percent were on chemotherapy, 15% on radiation therapy, and 12% were on targeted therapy. Severe illness outcomes occurred in 39% and 83% were admitted with a median length of stay of 4 days. Among admitted patients, 24% experienced a length of stay ≤2 days. A return visit to the ED or an in‐system hospitalization within 7 days of the index visit occurred in 10% and death occurred within 7 days of the index visit in 4%. Conclusion A majority of patients presenting to the ED with non‐neutropenic fever are admitted (83%), of whom nearly a quarter experience a length of stay of ≤2 days with infrequent serious illness outcomes. Future efforts should focus on the development of risk stratification tools in this population to avoid potentially unnecessary hospitalizations.

PURPOSE: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa. METHODS: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes. RESULTS: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa. CONCLUSION: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship.

PurposeLeptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS). MethodsWe performed a single-institution retrospective study of 153 patients diagnosed with LMC treated at The Ohio State University between January 1, 2010 and December 31, 2015. ResultsMedian age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status ≤1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months). ConclusionDespite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC.

Background: Invasive lobular carcinoma (ILC) accounts for 5%–15% of all invasive breast cancer cases. ILC has the propensity for distant late recurrence with widespread metastatic disease. To our knowledge, there is limited data on the clinical outcomes and treatment strategies of metastatic ILC. This retrospective study evaluates the overall survival (OS) and progression-free survival (PFS) in the metastatic ILC population at a single institution, focusing on first line treatment received in the metastatic setting. Methods: A retrospective chart review was performed on patients (Pts) diagnosed with metastatic ILC diagnosed at The Ohio State University Comprehensive Cancer Center between January 1, 2004 and December 31, 2014 using an IRB approved protocol. Patient demographics, clinical characteristics, and treatment modalities were summarized with descriptive statistics. OS (time from metastasis to death or last known follow-up) and PFS (time from diagnosis of metastasis to progression) were compared between types of first-line treatment: endocrine therapy (ET), chemotherapy (chemo), chemo followed by ET, ET plus CDK 4/6 inhibitor, or other treatments. OS and PFS estimates were generated using Kaplan Meier methods and compared using Log-rank tests. Results: 60 female pts were included in this study. The median age was 59 years (24–78). 45 (75%) pts were postmenopausal, 44 (73%) ER+/PR+, 14 (23%) ER+/PR-, and 2 (3%) ER-PR-, 28 (47%) with only bone metastases, 19 (32%) with visceral and bone metastases, and 13 (22%) with liver metastases. Twenty-eight (47%) pts received first line ET therapy, 12 (20%) received ET + CDK 4/6 inhibitor, 7 (12%) received chemo alone, 4 (7%) received chemo followed by ET, and 9 (15%) received other types of first line therapy. The median OS was 3.0 years, and the median PFS was 1.4 years. No difference in the Kaplan-Meier curves was found between first-line treatment groups in OS or PFS (OS: P=.247; PFS: P=.436). Discussion: ILC is a histologically distinct disease from invasive ductal cancer. It has been previously shown that invasive lobular cancer may not be as sensitive to adjuvant chemotherapy. We showed that in the metastatic setting there was no difference in PFS and OS among first line treatment groups. ET remains preferred treatment option; however, based on our data, chemotherapy can be considered in patient with metastatic ILC in the appropriate clinical context such as visceral crisis.

Background:Invasive lobular carcinoma (ILC) accounts for up to 15% of all breast cancers and is clinically and biologically distinct from invasive ductal carcinoma (IDC). Despite that, women with early stage ILC are often treated similarly to IDC. However, several retrospective studies suggest that patients (pts) with ILC may not derive survival benefit from the addition of chemotherapy to endocrine therapy relative to pts with IDC. The purpose of our study was to compare outcomes of pts with ILC treated with chemotherapy with those who received endocrine monotherapy. Methods: A retrospective review of pts with ILC or pleomorphic lobular carcinoma treated at the Ohio State University James Cancer Center from 2004-2014 was performed. Clinico-pathologic characteristics, treatment summary and clinical outcomes were collected. Distant disease-free survival (DDFS) was defined as time from diagnosis to the first distant metastases or death and overall survival (OS) was the time from diagnosis to death or last known follow up. DDFS and OS curves were created using Kaplan-Meier methods and compared using log-rank tests. Cox proportional hazard models were used to calculate univariate and multi variable hazard ratios (HR) for OS and DDFS. Results: We identified 379 pts with early stage ILC (stage I: 43% (162/379), stage II: 34% (127/379), stage III: 22% (84/379), unknown: 1% (6/379)). The majority of pts were post-menopausal (79%), Caucasian (92%) and ER+/PR+ (87%) and HER2 negative (96%). One hundred seventy six pts (46%) received chemotherapy and 189 (50%) pts received endocrine therapy alone. Pts who received chemotherapy had stage II or III disease, positive lymph nodes and grade 2 or 3 tumors; while pts who received endocrine monotherapy had stage I disease, negative lymph nodes and grade 1 or 2 tumors. We found a 51% decrease in chemotherapy (from 63% to 31%) and an increase in endocrine monotherapy use (from 34% to 65%) between 2004-2010 and 2011-2014. One hundred thirty two pts were evaluated with Oncotype DX, of which 76% (100/132) were node negative with the majority having a low recurrence score (low: 64%; intermediate: 33%; high: 3%). The use of Oncotype DX increased from 21.1% in 2004-2010 to 47.9% in 2011-2014. We found that 112 of 149 pts with at least 5 years follow up (75.2%) successfully completed five or more years of endocrine therapy. Univariate cox models showed worse DDFS HRs for type of therapy and node status (HR: 2.36, p=0.005, HR: 4.16, p Conclusion: We found no difference in DDFS between endocrine monotherapy and chemotherapy after adjusting for age, grade, and nodal involvement in pts with early stage ILC. This supports the hypothesis that ILC may not derive a significant benefit from the addition of chemotherapy. We need more prospective clinical trials considering histology to better understand how best to treat ILC. Citation Format: Williams N, Liu J, Stephens J, Palettas M, Boutrid H, Sardesai S, Reinbolt R, Stover D, VanDeusen J, Noonan A, Wesolowski R, Lustberg M, Ramaswamy B. Outcomes in hormone receptor positive, invasive lobular cancer in the era of endocrine monotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-12.

Background: Trastuzumab (T) induced cardiomyopathy remains a significant limitation to adjuvant HER2 directed therapy. Recent studies have aimed to reduce cardiotoxicity through combination with non-anthracycline (non-A) chemotherapy or shorter treatment duration. However there is limited data regarding cardiac outcomes and long-term survival with early discontinuation of adjuvant T. Methods: An IRB-approved single-institution retrospective analysis was performed for 401 consecutive patients with non-metastatic HER2+ breast cancer treated at the Ohio State University Comprehensive Cancer Center from 2005-2015. Medical records were reviewed for clinicopathologic features, systemic treatment and survival information. Disease Free Survival (DFS) was defined as time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary breast cancer or death. Overall survival (OS) was defined as time from diagnosis to death or last known follow up. OS and DFS estimates were generated using Kaplan Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate univariate and multivariate hazard ratios for OS and DFS. Results: A total of 371/401 (92.5%) patients received adjuvant T (n= 401, mean age: 59.4 years; stage 1: 120, 30%; stage II: 194, 48%; stage III: 87, 22%; ER+: 235, 58%); among whom 106/371 (28.6%) patients held adjuvant T for any reason. Median duration of therapy in patients with any interruption with T was 11.3 (0.5-16.9) months and 23/371 (6.9%) received less than 6 months of adjuvant T. Cardiomyopathy (measured as LVEF decline on 2D echocardiogram or MUGA >= 15 points) was the most common reason for withholding T (66/106, 62.3%). The majority of these patients received a cardiology referral (77/ 106, 72.6%) with a 13 day mean time to evaluation in outpatient clinic. Patients receiving non-A chemotherapy and beta blockers or ACE inhibitors during treatment were significantly less likely to experience cardiomyopathy (A vs non-A: 49/190, 25.8% vs. 16/136, 11.8% p=0.002); (Med vs no Med: 7/148, 4.73% vs 59/184, 32.1%; p Table 1- Discontinuation of adjuvant trastuzumab Number of patients (%)Initial treatment371Completed therapy with no interruption265 (71.4)Interruption of therapy for minimum of 2 weeks64 (17.2)Permanently discontinued42 (11.3) Conclusion: Discontinuation of adjuvant trastuzumab, most often from cardiomyopathy, is an independent prognostic marker for worse DFS in non-metastatic HER2 positive breast cancer. Non-anthracycline chemotherapy and use of cardio-protective medication is associated with significantly reduced incidence of cardiotoxicity in this population. Future prospective studies should consider optimizing cardiovascular function to avoid interruption in adjuvant HER 2 directed therapy. Citation Format: Sardesai S, Liu J, Palettas M, Stephens J, Stover D, Williams N, Reinbolt R, VanDeusen J, Wesolowski R, Lustberg M, Ramaswamy B. Cardiovascular outcomes and long term survival with discontinuation of adjuvant trastuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-03.

Introduction: The protective effects of breastfeeding against developing breast cancer are well known; however, it is unknown whether women are aware of this breastfeeding benefit. Researc...

The objective of this pilot study was to evaluate the change in sexual function following treatment with fractional CO2 laser therapy in breast cancer (BC) survivors with genitourinary syndrome of menopause (GSM).A single-arm feasibility study of BC survivors with symptoms of GSM, including dyspareunia and/or vaginal dryness, was conducted. Participants who received three treatments with fractional CO2 laser and 4-week follow-up were contacted for patient-reported outcomes and adverse events at 12 months. Sexual function was measured using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale Revised (FSDS-R). Descriptive statistics were calculated for patient demographics and disease characteristics for the set of participants who agreed to long-term follow-up and those who were lost to follow-up. FSFI and FSDS-R scores were summarized at baseline, 4 weeks and 12 months, as well as the change from baseline, and were compared using a Wilcoxon signed rank test.A total of 67 BC survivors enrolled, 59 completed treatments and 4-week follow-up; 39 participated in the 12 month follow-up. The overall FSFI score improved from baseline to 4-week follow-up (median Δ 8.8 [Q1, Q3] (QS) (2.2, 16.7)], P 0.001). There were improvements at 4 weeks in all domains of the FSFI (P 0.001 for each) including desire (median Δ 1.2; QS [0.6, 1.8]), arousal (median Δ 1.2; QS [0.3, 2.7]), lubrication (median Δ 1.8 (0, 3.3), orgasm (median Δ 1.2; QS [0, 3.6]), satisfaction (median Δ 1.6 (0.4, 3.2)), and pain (median Δ 1.6 (0, 3.6). The FSDS-R score also improved from baseline to 4-week follow-up (median Δ -10.0; QS [-16, -5] P 0.001) indicating less sexually related distress. The scores of the FSFI and FSDS-R remained improved at 12 months and there were no serious adverse events reported.In BC survivors with GSM, the total and individual domain scores of the FSFI and the FSDS-R improved after fractional CO2 laser therapy.Video Summary:http://links.lww.com/MENO/A711.

Objective: To describe age-specific cervical cancer incidence rates based on demographic and clinical characteristics. Methods: Women with cervical cancer in the SEER program were grouped into 3 age categories. Demographics, clinical characteristics, and incidence rates were obtained for each age group. Results: Older women (≥65 years) had higher incidence rates of cervical cancer than women Conclusion: Older black have the highest cervical cancer incidence rates, regardless of SES, suggesting an age and race disparity when compared to younger and white women.

Dyspnea is the second leading cause of US emergency department (ED) visits and an independent predictor of morbidity and mortality1 in older adult patients aged ≥65 years. Unfortunately, the diagnosis of the cause of dyspnea presents diagnostic challenges to emergency physicians2-4 that disproportionately affects older adults.5 One in 5 dyspneic older adults experience missed diagnosis in the ED2 and 21% are treated for ≥1 pneumonia, acute exacerbation of chronic obstructive pulmonary disease [COPD], and acute exacerbation of heart failure [HF].5 Importantly, some may have multiple causes of their dyspnea but accurate diagnosis remains critical.

Background Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation. Methods The primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS. Results A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5–16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p Conclusions Treatment interruption or early discontinuation of trastuzumab therapy in early HER2-positive BC, most often from TIC, is an independent prognostic marker for worse DFS and OS in operable HER2-positive BC. Future prospective studies should consider targeting at-risk populations and optimizing cardiac function to avoid interruption in trastuzumab therapy.

Background Older adults in the emergency department (ED) are at high risk for functional decline, unrecognized delirium, falls, and medication interactions. Holistic assessment by a multidisciplinary team in the ED decreases these adverse outcomes and decreases admissions, but there are many barriers to incorporating this type of care during the ED visit. Methods This is a hybrid type II effectiveness-implementation study using a pre-/post-cohort design (n = 380) at a tertiary care academic ED with an ED observation unit (Obs Unit). The intervention is a two-step protocol of (step 1) ED nurses screening adult patients ≥ 65 years old for geriatric needs using the Delirium Triage Screen, 4-Stage Balance Test, and the Identifying Seniors at Risk score. Patients who have geriatric needs identified by this screening but who do not meet hospital admission criteria will (step 2) be placed in the Obs Unit for multidisciplinary geriatric assessment by the hospital’s geriatric consultation team, physical therapists, occupational therapists, pharmacists, and/or case managers. Not all patients may require all elements of the multidisciplinary geriatric assessment. The Consolidated Framework for Implementation Research: Care Transitions Framework was used to identify barriers to implementation. Lean Six Sigma processes will be used to overcome these identified barriers with the goal of achieving geriatric screening rates of > 80%. Implementation success and associated factors will be reported. For the effectiveness aim, pre-/post-cohorts of adults ≥ 65 years old cared for in the Obs Unit will be followed for 90 days post-ED visit (n = 150 pre and 230 post). The primary outcome is the prevention of functional decline. Secondary outcomes include health-related quality of life, new geriatric syndromes identified, new services provided, and Obs Unit metrics such as length of stay and admission rates. Discussion A protocol for implementing integrated multidisciplinary geriatric assessment into the ED setting has the potential to improve patient functional status by identifying and addressing geriatric issues and needs prior to discharge from the ED. Using validated frameworks and implementation strategies will increase our understanding of how to improve the quality of ED care for older adults in the acute care setting. Trial registration ClinicalTrials.gov Identifier, NCT04068311, registered 28 August 2019

Evaluating population‐based data of hematologic malignancies (HMs) in older adults provides prognostic information for this growing demographic. Incidence rates and one‐ and five‐year relative survival rates were examined for specific HMs among adults ages ≥75 years using data from the Surveillance, Epidemiology and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma (HL), non‐Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries. Recent average annual (2010–2014) incidence rates and incidence trends from 1973 to 2014 were examined for cases ages ≥75 years. One‐ and five‐year relative cancer survival rates were examined for adults ages ≥75 years diagnosed 2007–2013, with follow‐up into 2014. From 1973 to 2014, incidence rates increased for NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL, and CML among adults ages ≥75 years. The highest one‐ and five‐year relative survival rates were observed among adults with CLL ages 75–84 years (1 year: 91.8% (95% CI = 91.8–90.8)) and 5 years: 76.5% (95% CI = 74.2–78.6)). The lowest one‐ and five‐year survival rates were observed among adults with AML ages 75–84 (1 year: 18.2% (95% CI = 74.2–78.6) and 5 years: 2.7% (95% CI = 2.0–3.6)). Survival for older adults ages ≥75 years with HMs is poor, particularly for acute leukemia. Understanding the heterogeneity in HM outcomes among older patients may help clinicians better address the hematological cancer burden and mortality in the aging population.

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]

Background Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. Methods We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. Results Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1–19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). Conclusions Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

Fractional CO2 laser therapy is an emerging treatment for genitourinary syndrome of menopause (GSM). The objective of this study was to determine the feasibility and preliminary efficacy of fractional CO2 laser therapy in breast cancer survivors. This was a single arm feasibility study of breast cancer survivors with dyspareunia and/or vaginal dryness. Participants received three treatments of fractional CO2 laser therapy at 30-day intervals and returned for a 1-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in 80% of patients. We collected data on the Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Urinary Distress Index (UDI), and SAE. A total of 64 patients participated in the study. The majority of women had Estrogen receptor/Progesterone receptor (ER/PR) positive/Her2neu negative (n = 37; 63%), stage I (n = 32, 54%) or II (n = 19, 32%) breast cancer. Most were receiving endocrine therapy (n = 54, 92%), most commonly aromatase inhibitors (AI; n = 40, 68%). Fifty-nine (88.1%) of those enrolled completed all treatments according to protocol with no reported SAE. No patient withdrew due to SAE. The scores of the VAS (mean Δ − 0.99; 95% CI [− 1.19, − 0.79], p

Background A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. Methods We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. Results Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for

Incorporation of a Patient Navigator into a Secondary Fracture Prevention Program Identifies Barriers to Patient Care Abstract Introduction: Patient navigation has emerged as a valuable component to improve patient outcomes in the outpatient setting. We investigated the effect of patient navigation in transitioning patients hospitalized for acute fracture to an outpatient clinic for secondary fracture prevention, and explored factors associated with successful transition. Methods: This study was a retrospective chart review of patients, age 50+ from April to October, 2016 hospitalized with fragility fracture at our medical center who were contacted by a patient navigator. We created an electronic tool that extracted data from the electronic medical record alerting the patient navigator to contact the patient by phone to schedule an outpatient appointment into an osteoporosis clinic as well as a Dual-energy X-ray Absorptiometry (DXA) scan. Patient outcomes of transition from hospital to outpatient clinic, completion of DXA scan, completion of all five osteoporosis-associated laboratory tests (calcium, 25-hydroxy vitamin D, complete blood count, renal function, liver function), and osteoporosis medication prescription and adherence, as well other patient characteristics were compared to patients from a historical control period (2014-2015). This group consisted of a similar patient population seen without assistance of a patient navigator. Categorical variables were compared using Chi-square or Fisher’s Exact tests and continuous variables were compared with a two-sample t-test or a Wilcoxon Rank Sum test. We also explored potential factors which might predict barriers to successful outpatient clinic transition using a univariate logistic regression. Results: The proportion of patients who successfully transitioned to osteoporosis clinic modestly improved with the use of a patient navigator versus control (53% vs. 48%, p=0.048). DXA scan completion was higher with patient navigation (90% vs. 67%, p=0.006). No difference in osteoporosis medication initiation within 3 months post discharge (73% vs. 65%, p=0.387) or medication adherence at 6 months (68% vs. 71%, p=0.777) was found between the two groups. Patients who followed up in clinic lived closer (11 vs. 43 miles, p

e24047 Background: Surveys suggest up to 87% of patients with cancer use complementary and integrative (CIM) therapies such as herbal medicine, acupuncture, massage and mind-body practices. These therapies may assist with symptoms of pain, nausea and anxiety. However, several studies have demonstrated that many clinicians do not inquire about CIM use, which may be due to lack of education and/or limited evidence-based data. We sought to explore the perspectives of clinicians at an academic comprehensive cancer center on the use of CIM therapies. Methods: Physicians and advanced practice providers (APPs) who practice medical oncology, hematology, radiation oncology, surgical oncology and neuro-oncology in a Midwest tertiary comprehensive cancer center were asked to participate in a 9-question online survey which inquired about their personal knowledge and recommendation for 21 different CIM therapies (not all are offered at the cancer center). Responses were summarized using descriptive statistics. Results: The response rate for this survey was 24.5% (n = 49). Responders were from the following specialties: hematology (n = 17; 35%); solid tumor (n = 18; 37%); both hematology and solid tumor (n = 8; 16%), surgical oncology (n = 3; 6%); gynecologic oncology (n = 2; 4%) and radiation oncology (n = 1; 2%). Sixty-seven percent were attending physicians and hematology/oncology fellows (n = 33), and 33% were APPs (n = 16). Median age range was 30-39 years (range 20-59). The most recommended CIM therapy for cancer treatment-related effects was massage (80%), followed by deep breathing (55%). The least recommended CIM therapies were traditional Chinese medicine (TCM) and Ayurvedic medicine (2%), followed by vitamins/minerals and homeopathy (both 6%). Participants requested more education on CBD/CBD oil (59%) and herbs/botanicals (49%). Up to 14% of respondents already had education on five integrative therapies. Conclusions: Hematology/oncology clinicians do not routinely recommend most CIM therapies, except for massage therapy. Efforts should be made to educate clinicians regarding CIM therapies used by patients with cancer as well resources that appraise the efficacy, safety, and potential drug interactions of these therapies. Education could encourage informed decision-making and improved patient-clinician communication and satisfaction.

Objective: The incidence of esophageal adenocarcinoma, one of the most lethal gastroenterological diseases, has been increasing since the 1960s. Prevention of esophageal adenocarcinoma is important because no early detection screening programs have been shown to reduce mortality. Obesity, gastroesophageal reflux disease, and tobacco smoking are risk factors for esophageal adenocarcinoma. Due to the high prevalence in Ohio of obesity (32.6%) and cigarette smoking (21.0%), this study sought to identify trends and patterns of these risk factors and esophageal adenocarcinoma in Ohio as compared with the United States. Methods: Data from the Ohio Cancer Incidence Surveillance System, Surveillance Epidemiology and End Results Program (SEER), and Behavioral Risk Factor Surveillance System were used. Incidence rates overall, by demographics and by county, as well as trends in incidence of esophageal adenocarcinoma and the percent of esophageal adenocarcinoma among esophageal cancers were examined. Trends in obesity and cigarette smoking in Ohio, and the prevalence of each by county, were reported. Results: There was an increasing trend in esophageal adenocarcinoma incidence in Ohio. Ohio’s average annual esophageal adenocarcinoma incidence rate was higher than the SEER rate overall and for each sex, race, and age group in 2009 to 2013. There was also an increasing prevalence of obesity in Ohio. Although the prevalence of cigarette smoking has been stable, it was high in Ohio compared with the United States. Conclusions: Health care providers and researchers should be aware of the esophageal adenocarcinoma incidence rates and risk factor patterns and tailor interventions for areas and populations at higher risk.

Background Heat shock protein 90 (HSP90) is a molecular chaperone required for proper folding and stabilization of proteins. Client proteins of HSP90 include many oncogenic proteins known to be over-activated in triple negative breast cancer (TNBC) such as AKT, EGFR and members of RAS/MAPK signaling pathway. Over-expression of HSP90 client proteins such as AKT and c-RAF has also been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent non-ansamycin small molecule inhibitor of HSP90. Methods Patients (pts) with inoperable or metastatic, TNBC were treated with onalespib and paclitaxel on days 1, 8, 15 every 28 days. Paclitaxel was given at a dose of 80 mg/m2 while the dose of onalespib was gradually increased from 120 mg/m2 to 260 mg/m2 in dose levels (DL) 1-4 using standard 3 + 3 design. In order to assess the effect of each drug on pharmacokinetics (PK) of the other drug, onalespib was given on day -7 prior to cycle 1 and skipped on day 1 of cycle 1. The primary objective was to determine dose limiting toxicities (DLT) and maximum tolerated dose (MTD). The secondary objectives were PKs of each agent, overall response rate (ORR), response duration and progression-free survival. Results 20 pts were enrolled to dose escalation part (5, 3, 7 and 6 to DL 1-4 respectively). One pt in DL 1 did not start therapy due history of severe paclitaxel hypersensitivity and 2 pts (DL1 and DL 3) had to be replaced due to disease progression in cycle 1. One DLT occurred in 1 pt in DL3 (grade 3 nausea, vomiting and abdominal pain). No DLTs were noted in the highest DL testing onalespib at 260 mg/m2. The most common grade 3 or higher adverse events included diarrhea (55%), fatigue (55%), anemia (14%), leukopenia (24%) and neutropenia (41%). Diarrhea was self limiting, lasting 24-48 hrs post infusion and responded well to loperamide. ORR and clinical benefit rate in 16 evaluable pts was 25% and 62.5% respectively. Preliminary PK analysis showed no evidene of interaction between onalespib and paclitaxel. Conclusions Study regimen demonstrated acceptable safety profile. MTD of onalespib in combination with standard dose and schedule of paclitaxel was determined to be 260 mg/m2. Dose expansion study at MTD is currently ongoing. Clinical trial identification NCI 9876 (NCT02474173). Legal entity responsible for the study Robert Wesolowski, MD. Funding Cancer Therapy Evaluation Program at the National Cancer Institute. Disclosure All authors have declared no conflicts of interest.

BACKGROUND We aimed to: (1) examine relationships between the Functional Oral Intake Scale (FOIS), Eating Assessment Tool-10 (EAT-10), and objective measures of swallowing (Modified Barium Swallow Impairment Profile [MBSImP©] and penetration-aspiration scale [PAS]) in patients with head and neck cancer, (2) compare outcomes between oral intake vs tube-dependent patients, and (3) compare outcomes across time points. METHODS A total of 58 patients with head and neck cancer completed the FOIS, EAT-10, and underwent a standardized videofluoroscopy (VFSS). VFSS were analyzed using the PAS and MBSImP©. Nonparametric analyses were performed. RESULTS A relationship between the FOIS and EAT-10 (r = -0.46; P

Emergency departments (EDs) have seen rising numbers of patients in psychiatric crises, patient boarding, and throughput delays. This study describes and evaluates the impact of a Crisis Assessment Linkage and Management (CALM) service designed to manage behavioral health crises. A year-to-year comparison was performed before (n = 2211 ED visits) and after implementation of CALM (n = 2387). CALM was associated with reductions in median ED and hospital length of stay (LOS) from 9.5 to 7.3 hours and 46.2 to 31.4 hours, respectively. Mean transformed ED LOS decreased by 32.4% ( P < .001). The CALM model improved patient care and throughput metrics by proactively managing behavioral health crises.

There are care gaps in the evaluation and treatment of osteoporosis after a fragility fracture. The Joint Commission is considering adoption of core measures. We compared compliance between two secondary fracture prevention programs in our institution. Incorporating strengths of both may provide the best outcomes for secondary fracture prevention.There are significant care gaps in the evaluation and treatment of osteoporosis after occurrence of fragility fracture. The Joint Commission is considering adoption of a core measure set on osteoporosis-associated fractures, including laboratory assessment, bone density testing, and osteoporosis pharmacologic therapy. We compared compliance to these proposed measures between two secondary fracture prevention programs in patients hospitalized for acute fracture in an open medical system.We conducted a retrospective, single center medical records review of a nurse practitioner-led Fracture Liaison Service (FLS), a physician-led Fracture Prevention Program (FPP), and a historical time without any secondary fracture prevention program (Usual Care) for baseline care. Primary outcomes were the completion of five laboratory tests (calcium, 25-hydroxy vitamin D, renal function, liver function, and complete blood count), order placement and completion of dual x-ray absorptiometry (DXA) scan within 3 months, prescription of osteoporosis medication within 3 months, and medication adherence at 6 months after hospital discharge.Completion of all five laboratory tests was higher in FPP versus FLS (84.7 vs. 36.9%, p 0.001). DXA scan completion was higher in FPP than FLS but not statistically significant (66.7 vs. 54.9%, p = 0.11). Medication prescription at 3 months and adherence at 6 months were significantly higher in FPP versus FLS (65.3 vs. 24.0%, p 0.001 and 70.8 vs. 27.7%, p 0.001, respectively).Incorporating strengths of both FLS (care coordination) and FPP (physician direction) may provide the best outcomes for secondary fracture prevention by ensuring laboratory and DXA testing and initiating osteoporosis medication.

MELF invasion has been associated with non-vaginal recurrences and lymph node (LN) metastases in multi-institutional case control studies, but has not been well examined in large single institution cohorts. Hysterectomy specimens with FIGO 1 endometrioid endometrial carcinoma (EEC) and lymphadenectomies from 2007 to 2012 were identified. Electronic medical records and histologic slides were reviewed. Of 464 identified cases, 163 (35.1%) were noninvasive, 60 (12.9%) had MELF, 222 (47.8%) had a component of the infiltrative invasion pattern without MELF, 13 (2.8%) had pure pushing borders of invasion, 5 (1.1%) had pure adenomyosis-like invasion, and 1 (0.2%) had pure adenoma malignum-like invasion. Sixteen cases had LN metastases. Significantly more MELF cases had positive LNs than non-MELF cases overall (18.3% vs 1.2%, p

e12050 Background: The clinical heterogeneity seen in HER 2 positive breast cancer (BC), mostly related to hormone receptor (HR) expression has been suggested to underlie the variability of response not only to endocrine treatments, but also to anti-HER-2 therapies. Herein, we describe our single institution experience with clinical outcomes by HR expression in early HER 2 positive BC. Methods: An IRB-approved single-institution retrospective analysis was performed for 400 consecutive patients with non-metastatic HER 2 + BC treated at the Ohio State University Comprehensive Cancer Center from 2005-2015. Medical records were reviewed for clinic-pathologic, treatment, and survival information. Disease Free Survival (DFS) was defined as time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as time from diagnosis to death or last known follow up. OS and DFS estimates were generated using Kaplan Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate univariate and multivariate hazard ratios for OS and DFS. Results: a total of 180/400(45%) patients were diagnosed with HR positive disease. The mean age was 54.1y and patients were predominately white (267, 84%), post-menopausal (190, 60%) and presented with invasive ductal cancer (293, 92%). HR negative disease was significantly associated with high tumor grade (72% vs. 52%, p

202 Background: Fractional CO2 laser therapy is an emerging treatment for GSM. The objective of this study was to determine the feasibility, tolerability and preliminary efficacy of fractional CO2 laser therapy in BC survivors. Methods: This was a single arm feasibility study of BC survivors with dyspareunia and/or vaginal dryness. Participants received three treatments with office-based fractional CO2 laser on at least 30 day intervals and returned for a one-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in a minimum of 80% of patients. Primary efficacy was evaluated using the mean change (∆) in the score on the Vaginal Assessment Scale (VAS). Secondary efficacy endpoints included mean ∆ in scores on the Female Sexual Function Index (FSFI) and Urogenital Distress Inventory (UDI). Descriptive statistics (means and 95% confidence intervals (CI) for continuous variables and proportions for categorical variables) were used. Results: The study is ongoing with 65 patients enrolled. To date, 37 patients have completed all study treatments and follow-up. Median age for those who have completed treatment was 57 years (range 34-72). Most were ER/PR positive (78%) and Her 2 negative (81%) with stage I (43%) or II (41%) BC. Ninety-five percent were receiving endocrine therapy, most commonly aromatase inhibitors (73%). No SAEs were reported in the 37 patients who have completed study treatments and their outcomes are as follows. Based on the VAS, 78% reported moderate-severe dyspareunia and 89% reported moderate-severe vaginal dryness at baseline. At follow up, 28% reported moderate-severe dyspareunia and 28% reported moderate-severe vaginal dryness. The VAS score improved from baseline to follow up (mean ∆ 4.1; 95% CI [3.1, 5.1]). Similarly, the FSFI score improved (mean ∆ -10.0; 95% CI [-13.2, -6.9]) and the UDI score improved (mean ∆ -5.7; 95% CI [-10.1, -1.3]). Final efficacy analysis will be reported once all patients have completed all time points. Conclusions: Fractional CO2 laser treatment is feasible and tolerable in BC survivors and may reduce symptom burden from GSM. A randomized controlled trial with sham laser is currently in development. Clinical trial information: NCT03307044.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in young children worldwide and an increasingly recognized cause of death in developing countries [1, 2]. Despite that selected groups of infants have increased risk for severe disease and mortality, the majority of children hospitalized with RSV LRTI are previously healthy with no known risk factors for severe disease [3, 4]. Of those hospitalized infants, 10%–20% will develop a disease severe enough to require admission to the pediatric intensive care unit (PICU) [5, 6]. It has been proposed that the combination of both viral factors and the host immune response probably contribute to the severity of RSV disease [7–11]. The importance of the innate immune response in the pathogenesis of severe RSV disease is being increasingly recognized. To date, however, studies addressing the role of innate immunity cytokines on RSV disease severity have been focused on determining concentrations of blood and respiratory cytokines, with inconsistent results [10–13]. Studies in critically ill patients with bacterial sepsis suggest that innate immune hyporesponsiveness, defined by decreased whole blood tumor necrosis factor α (TNF-α) production after ex vivo lipopolysaccharide (LPS) stimulation, is associated with worse clinical outcomes [14, 15]. Whether the functional capacity of the innate immune response is impaired in children with severe RSV disease, and how it correlates with plasma concentrations of innate immunity cytokines has not been characterized. The overall aims of this study were to determine whether patients with severe RSV bronchiolitis admitted to the PICU had decreased whole blood functional innate immune responses and to evaluate the relationships between innate immune dysfunction and disease outcomes.

Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan–Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1–5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.

Background: Obesity is a main risk factor for endometrial carcinoma (EC). Insulin-like growth factor 1 receptor (IGF1R) expression may influence this association. Methods: IGF1R IHC was performed on a tissue microarray with 894 EC and scored according to the percentage and intensity of staining to create immunoreactivity scores, which were dichotomized into low and high IGF1R expression groups. Logistic regression modeling assessed associations with body mass index (BMI), age, histology, pathologic extent of disease (pT), and lymph node metastasis (pN). Overall survival (OS) and disease-free survival (DFS) were compared between IGF1R expression groups using Kaplan–Meier curves and log-rank tests. Results: The proportion of patients with high IGF1R expression increased as BMI ( Conclusions: There is an association between BMI and EC IGF1R expression. Higher IGF1R expression is associated with lower pT and better DFS and OS. Impact: These findings suggest a link between IGF1R EC expression and obesity, as well as IGF1R expression and survival. Cancer Epidemiol Biomarkers Prev; 25(3); 438–45. ©2015 AACR.

Background Cowden syndrome (CS) is associated with benign hamartomatous lesions and risks for thyroid, breast and endometrial cancers. Bannayan–Riley–Ruvalcaba syndrome is an allelic disorder characterised by macrocephaly, intestinal polyps, lipomas, and pigmented penile macules. Diagnostic criteria for CS are based on the presence of a range of clinical features. However, prior data on the component clinical features have been based primarily on compilations of cases reported before development of consensus diagnostic criteria. Objective This study sought to determine the clinical features most predictive of a mutation in the largest single cohort of patients with clinical testing for PTEN mutations reported to date. Methods Molecular and clinical data were reviewed on 802 patients referred for PTEN analysis by a single laboratory. Results Deleterious mutations were found in 172 (21.4%) subjects. Among mutation carriers significant differences from previous reports were found for the frequencies of several clinical features, including macrocephaly, uterine fibroids, benign breast disease, and endometrial cancer. Logistic regression analyses indicated that female mutation carriers were best identified by the presence of macrocephaly, endometrial cancer, trichilemmomas, papillomatous papules, breast cancer, benign thyroid disease, and benign gastrointestinal (GI) lesions. For males, the most discriminating features were macrocephaly, lipomas, papillomatous papules, penile freckling, benign GI lesions, and benign thyroid disease. Age related differences were also identified. Conclusion The mutation frequency in patients meeting CS diagnostic criteria (34%) was significantly lower than previously reported, suggesting a need for reevaluation of these criteria. A mutation prediction model has been developed which can help identify patients appropriate for PTEN testing in clinical practice.

Background: The approved dosing schedule of capecitabine monotherapy in metastatic breast cancer (MBC) is 1250 mg/m2/dose administered days 1 through 14 of a 21-day cycle, but many patients (pts) have difficulty with this schedule due to side effects. Use of a lower starting dose such as 1000 mg/m2/dose or use of an alternative 28-day administration schedule (7 day on, 7 day off, repeat) allows for greater tolerability. Given limited data regarding efficacy of the alternative 28-day schedule, the primary objective of this study was to compare the efficacy of different schedules of capecitabine in patients with MBC. Methods: A retrospective chart review of pts with metastatic breast cancer who received capecitabine as monotherapy between 2002 and 2014 at the Ohio State University James Cancer Hospital was performed. We excluded any HER2-positive patients who had received concurrent HER2-targeted therapy. Pts who initiated therapy at a dose of 1000 mg/m2/dose were classified by these dosing schedules: Arm A (21 day), B (28 day), and C (changeover from 21 day to 28 day). Time to treatment failure (TTF) and overall survival (OS) were compared between dosing schedules using Kaplan Meier curves and log-rank tests. Results: A total of 181 MBC patients (Arm A: n = 113, Arm B: n = 25, Arm C: n = 43) with the following patient characteristics met eligibility criteria; 86.2% Caucasians, 13.8% non-Caucasians, 64.64% estrogen receptor (ER)-positive, 3.31% ER positive/HER2-positive, 2.22% ER negative/HER2-positive, and 29.83% triple-negative. The HER2-positive patients were excluded as they received concurrent therapy. A significant difference was seen in TTF (Arm A: 2.7 mo, Arm B: 2.8 mo, Arm C: 7.1 mo, p = 0.001) when comparing all dosing schedules as well as in OS (Arm A: 5.7 yrs, Arm B: 9.6 yrs, Arm C: 7.8 yrs, p = 0.006). After an initial dose reduction, patients on Arm B tolerated capecitabine for a longer period of time than patients on Arm A before needing a second dose reduction (Table 1). The median time on capecitabine for Arm A was 11.9 weeks and 12.6 weeks for Arm B, and the mean time of both Arm A and Arm B on capecitabine was 22.2 weeks. Patients with ER-positive breast cancer had improved TTF (4.45 months vs 2.32 months, p < 0.001) and OS (7.26 years vs 3.99 years, p < 0.001) compared to ER-negative breast cancer. Caucasians had improved TTF compared to African Americans (AA) and other races (3.90 mo vs 2.87 mo, p = 0.004); however, there was no significant difference in OS. Median starting dose (mg/m2): Arm A - 1000; Arm B - 1043; Arm C - 1000 Time to 1st dose reduction (weeks): Arm A - 6; Arm B - 6; Arm C - 6.5 Dose after 1st reduction (mg/m2): Arm A - 808; Arm B - 848.5; Arm C - 802 Time to 2nd dose reduction (weeks): Arm A - 6; Arm B - 20; Arm C - 8 Dose after 2nd reduction (mg/m2): Arm A - 599.5; Arm B - 690; Arm C - 697 Time to 3rd dose reduction (weeks): Arm A - 6; Arm B - 0; Arm C - 24 Dose after 3rd reduction (mg/m2): Arm A - 575; Arm B - 0; Arm C - 557 Table 1: Median dose (mg/m2) and median time to reductions (in weeks) Conclusions: Our study shows that patients who received the 28-day cycle initially or who were switched to the 28-day cycle appeared to have improved TTF and OS compared to patients on the 21-day cycle. It also shows that AA women had worse TTF on capecitabine when compared to Caucasians. One hypothesis for the improved TTF and OS is that this could be due to a higher total dose of capecitabine received in Arm B and C as shown in Table 1. We acknowledge that the limitations of our study include the sample size and the retrospective nature, and that further work needs to be done. However, the 28-day dosing schedule for capecitabine could be an alternative for elderly patients or patients with poor performance status who are at higher risk for drug toxicities. Citation Format: Nicole Olivia Williams, Anupama Suresh, Julie Stephens, Marilly Palettas, Michael J. Berger, Akaansha Ganju, Raquel Reinbolt, Robert Wesolowski, Anne M. Noonan, Jeffrey Bryan VanDeusen, Sagar Sardesai, Maryam Lustberg, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. Efficacy of alternative 28-day capecitabine dosing schedule in metastatic breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A69.

Background: Adults over age 65 are the fastes- growing segment of the US population. However, clinicians have less evidence of how to treat older adults, because they are underrepresented in clinical trials, and studies designed specifically for older adults are rare. Therefore, clinicians have to extrapolate from trials conducted in younger, healthier populations when developing treatment plans for older adults. Over 40% of new breast cancer diagnoses in the US occur in women aged over 65 years. In general, breast cancer in the older woman has distinct biologic features, including less aggressive characteristics and greater expression of estrogen receptor and progesterone receptor. Increasing age is associated with higher rates of comorbidity and frailty, which has been shown to potentially reduce the survival advantage of more aggressive breast cancer therapies. We are conducting a prospective cohort study of adults > or = 65 years with a new diagnosis of breast cancer (OSU-16153) in order to better understand the complex health issues faced by this population, and to collect data with which to support future studies designed to improve the management of these patients. Specific Aims: 1) To assess overall and progression-free survival of breast cancer patients ages 65 and older seen in the Breast Medical Oncology clinics at the Stefanie Spielman Comprehensive Breast Center at The Ohio State University; 2) to examine the association of demographic, diagnostic, and treatment data with patient outcomes, such as progression-free and overall survival, within this patient population; 3) to evaluate the unique needs of breast cancer patients ages 65 and older by implementing a Comprehensive Geriatric Assessment (CGA) within the Breast Medical Oncology clinics at The Ohio State University. Methods: The study will enroll patients > or = 65 years with a new diagnosis of breast cancer. Participants will complete a brief baseline questionnaire, including items addressing demographics, lifestyle, and health history. Patients will then be asked to complete a Comprehensive Geriatric Assessment (CGA) at the time of enrollment, and approximately every six months while on follow-up. The CGA contains both performance-based assessments of patients’ function, completed by study staff, as well as the patients’ self-reports of symptoms and quality of life. The CGA contains a multifaceted battery of clinical instruments including the PROMIS Global Short Form, Functional Assessment of Cancer Therapy-Breast (FACT-B), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale, The Pittsburgh Sleep Quality Index, Geriatric Depression Scale, The James Supportive Care Screening Tool, Timed Up & Go Test, Grip Strength, Blessed Orientation-Memory-Concentration Test, Mini-Cog Test, Charlson Comorbidity Index, Mini Nutritional Assessment, Katz Index of Independence in Activities of Daily Living, and Instrumental Activities of Daily Living. Participant medical records will be reviewed every three months to assess survival, disease progression, and treatment changes. All questionnaire data will be completed using iPads, and will be directly recorded into the REDCap database. Electronic medical records will be reviewed by research staff, and relevant data will be manually entered into the REDCap database. The aim is to enroll 1,000 participants, and the recruitment period will be five years from study initiation. Participants will be followed for five years from the time of enrollment, resulting in a total study length of ten years. The study opened to accrual on 18 April 2017. To date 3 patients have been enrolled and have completed baseline assessments. Citation Format: Anne M. Noonan, Janine A. Overcash, Anupama Suresh, Laura K. Flora, Julie Stephens, Geetika Bhatt, Raquel Reinbolt, Nicole O. Williams, Robert Wesolowski, Jeffrey B. VanDeusen, Sagar D. Sardesai, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. A prospective geriatric breast cancer cohort study to define unique features and outcomes in older breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A55.

Background: Increasing evidence suggests that higher parity and lack of breastfeeding associates strongly with the risk of developing the aggressive triple-negative breast cancer (TNBC). There is a 25-50% reduction in risk of developing TNBC in women who have breastfed >4-6 months when compared to parous women who have never breastfed. Higher rates of breastfeeding and lower incidence of BC observed in native African women support this postulate. Observational studies and recent national statistics indicate that the prevalence of breastfeeding is markedly low among African-American women (AAW) (58.9%) compared to Caucasian women (CW) (75.2%). Due to the remarkable health and economic benefit of breastfeeding, we investigated whether patients received information about breast cancer risk reduction as part of breastfeeding counseling and whether this knowledge affected participants' decision to initiate and sustain breastfeeding. Methods: A cross-sectional survey study was conducted from September 2016 to June 2017 at The Ohio State University Comprehensive Cancer Center (OSUCCC) on women aged 18-50 who had at least one live-born child. Participants completed an electronic survey that included demographic information and details of breastfeeding history. Recruitment occurred via primary care secure patient portal electronic messaging (MyChart) and an online national clinical research registry (Research Match). Summary statistics were used to describe responses. Wilcoxon Rank Sum test was used to compare length of breastfeeding. Results: A total of 724 women (496 CW and 152 AAW and 76 unknown) completed the online survey; 503 responses through Research Match, 197 through MyChart, and 24 unknown. 92% of those who responded had breastfed. 56% (60.7% Caucasians and 46.1% AA) of women said they were aware breastfeeding reduced the risk of cancer. Of those who were aware of the risk, 36.4% said that this knowledge affected their decision to breastfeed. Of the 39 who did not breastfeed, 23 (59.0%) said being aware of this risk would have influenced their decision. Only 16.6% of women reported they received this information from health care providers; others were informed through magazines and Internet. The mean length of breastfeeding among women who were aware of this benefit was significantly longer than the women who were not aware (13.2 months vs 9.3 months, respectively, p Conclusions: Our study showed that there are disparities between AAW and CW in the knowledge that breastfeeding reduces the risk of breast cancer and in the duration of breast feeding. In addition, we showed that increased knowledge impacts decision-making regarding breastfeeding. Hence, development of culturally relevant communication strategies, especially in AAW, can impact initiation and maintenance of breastfeeding, and ultimately result in aggressive breast cancer reduction. Citation Format: Akaansha Ganju, Anupama Suresh, Julie Stephens, Marilly Palettas, Diana Burke, Laura Miles, Maryam Lustberg, Seuli Brill, Bhuvaneswari Ramaswamy. Knowledge of breastfeeding to reduce breast cancer risk [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C57.

To determine whether DNA mismatch repair (MMR) modifies the response to chemotherapy or radiotherapy in patients with endometrial cancer.Immunohistochemistry (IHC) for the DNA MMR proteins MLH1, MSH2, MSH6, and PMS2 was performed on a tissue microarray of specimens of primary endometrial cancer. MMR deficiency was defined as lack of expression of one or more proteins. Expression of all proteins classified a tumor as having an intact MMR system. Recurrence rates were calculated for women treated with platinum-based chemotherapy or pelvic external beam radiation. Comparisons were made using the log-rank test. Multiple comparisons were controlled for by utilizing the Bonferroni correction method.Four hundred seventy-seven cases of endometrial cancer were evaluated on a tissue microarray (TMA). One hundred fifty-eight patients (41%) received chemotherapy. Sixty-six patients (17%) received pelvic teletherapy. Overall and progression-free survival were not different between patients whose tumors had intact MMR and those with defective MMR when stratified by adjuvant treatment with radiation or chemotherapy. Subgroup analyses stratified by histology (non-endometrioid versus endometrioid) and stage did show significant survival differences. There was a significant increase in overall (p=0.003) and progression-free (p=0.004) survival in those with MMR-deficient, non-endometrioid tumors treated with teletherapy compared to those with an intact MMR system. Improved progression-free survival was noted in patients with intact MMR with stage III/IV disease treated with adjuvant chemotherapy (p=0.031).Subgroups of patients with non-endometrioid endometrial cancer and defective MMR may have improved survival after adjuvant radiotherapy. Patients with advanced stage endometrial cancer and defects in mismatch repair may receive less benefit from adjuvant chemotherapy.

Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan–Riley–Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense Pten ∆4–5 and missense Pten C124R and Pten G129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectra with varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for Pten ∆4–5 , hypomorphic function for Pten C124R , and gain of function for Pten G129E . These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specific mutations in PTEN that alter protein function through distinct mechanisms.

An increasing trend in the use of contralateral prophylactic mastectomy (CPM) for the treatment of unilateral breast cancer has been observed nationally. The purpose of this study was to confirm this trend and to identify differences between the groups that chose unilateral mastectomy alone or with CPM. A prospectively maintained breast cancer database was retrospectively reviewed. Age, histologic grade, stage, education, family history, tumor receptor status, and use of immediate reconstruction were evaluated. Statistical analysis was performed by Fisher’s exact test, χ2 test, and Student’s t-test. Between 1998 and 2007, a total of 1639 women who selected UM and 201 who had UM and CPM for unilateral breast cancer were identified. An increasing trend in CPM was observed (6.5% in 1999 vs. 16.1% in 2007). The CPM group was significantly younger (mean age 47.8 vs. 55.1 years, P

International audience; The Rb-E2F axis is an important pathway involved in cell-cycle control that is deregulated in a number of cancers. E2f transcription factors have distinct roles in the control of cell proliferation, cell survival and differentiation in a variety of tissues. We have previously shown that E2fs are important downstream targets of a CSF-1 signaling cascade involved in myeloid development. In cancer, tumor-associated macrophages (TAMs) are recruited to the tumor stroma in response to cytokines secreted by tumor cells, and are believed to facilitate tumor cell invasion and metastasis. Using the MMTV-Polyoma Middle T antigen (PyMT) mouse model of human ductal carcinoma, we show that the specific ablation of E2f3 in TAMs, but not in tumor epithelial cells, attenuates lung metastasis without affecting primary tumor growth. Histological analysis and gene expression profiling suggest that E2f3 does not impact the proliferation or survival of TAMs, but rather controls a novel gene expression signature associated with cytoskeleton rearrangements, cell migration and adhesion. This E2f3 TAM gene expression signature was sufficient to predict cancer recurrence and overall survival of estrogen receptor (ER)-positive breast cancer patients. Interestingly, we find that E2f3b but not E2f3a levels are elevated in TAMs from PyMT mammary glands relative to controls, suggesting a differential role for these isoforms in metastasis. In summary, these findings identify E2f3 as a key transcription factor in TAMs, which influences the tumor microenvironment and tumor cell metastasis.Oncogene advance online publication, 9 November 2015; doi:10.1038/onc.2015.429.

Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. Methods: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. Results: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3–68.0 y). The lifetime risk for CRC was 68.7% (CI, 58.6%–78.9%) for men and 52.2% (CI, 37.6%–66.9%) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0–46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54% (CI, 41.9%–66.1%). Conclusions: A markedly later age of onset for CRC at 61 y than previously reported (∼44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before.

A 4-month-old, intact female schipperke was presented for evaluation and treatment of subcutaneous (SC) emphysema. Radiographs revealed pneumomediastinum and SC emphysema. Sequential radiographs confirmed a worsening of the SC emphysema. Extensive, nonsurgical evaluation failed to reveal the source of the air within the mediastinum. Exploratory thoracotomy revealed an emphysematous right middle lung lobe. Lobectomy of the right middle lung lobe resolved both the pneumomediastinum and SC emphysema. Histopathological evaluation confirmed pulmonary emphysema. A variation of congenital pulmonary emphysema was considered in this case.

Objective The aim of this study is to determine the expression of caspase-14, a key protein in maturation of squamous epithelia, in archival malignant and premalignant vulvar squamous lesions and examine in-vitro effects of a black raspberry extract (BRB-E) on a vulvar squamous cell carcinoma (VSCC) cell line. Methods VSCC cell cultures were exposed to different BRB-E concentrations and used to create cell blocks. Immunohistochemistry for caspase-14 was performed on cell block sections, whole tissue sections, and a tissue microarray consisting of normal vulvar skin, lichen sclerosus (LS), classic and differentiated vulvar intraepithelial neoplasia (cVIN and dVIN respectively), and VSCC. Results LS demonstrated abnormal full thickness (5/11) or absent (1/11) caspase-14 staining. dVIN often showed markedly reduced expression (4/7), and cVIN occasionally demonstrated either absent or reduced caspase-14 (6/22). VSCC predominantly had absent or markedly reduced caspase-14 (26/28). VSCC cell cultures demonstrated a significant increase in caspase-14 ( p =0.013) after BRB-E treatment: 7.3% (±2.0%) of untreated cells showed caspase-14 positivity, while 21.3% (±8.9%), 21.7% (±4.8%), and 22.6% (±5.3%) of cells were positive for caspase-14 after treatment with 200, 400, and 800μg/mL BRB-E, respectively. Pair-wise comparisons between the treatment groups and the control demonstrated significant differences between no treatment with BRB-E and each of these treatment concentrations (Dunnett's adjusted p -values: 0.024, 0.021, and 0.014, respectively). Conclusions Caspase-14 is frequently decreased in premalignant and malignant vulvar squamous lesions, and is upregulated in VSCC cell culture by BRB-E. BRB-E should be further explored and may ultimately be incorporated in topical preparations.