bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT1 against breast cancer through downregulating Bcl-2 protein.
Authors: Chen Dar-Ren
Published: February 2017

34

Background: SIRT1, a member of the class III histone deacetylase (HDAC) family, is the mammalian orthologue of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival due to its ability to deacetylate both histone and numerous non-histone substrates. The deacetylase function of SIRT1 has been suggested as playing a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective down- and up-regulation in various cancers. The aim of the present study was to simultaneously evaluate the expression levels of SIRT1 and Ki67, the index of cellular proliferation, in normal and tumor tissues of the breast from 27 breast cancer patients and to determine the role of SIRT1 in breast tumorigenesis. Methods: A total of 27 breast cancer patients were included. Tumor tissues and matched normal breast tissues were immediately frozen after collection between 2007 and 2008. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied for analyses of patients’ specimens. Cell proliferation assay, cell cycle analysis and Western blotting were used to investigate the effects of sirtinol on the human breast cancer lines MCF-7 and MDA-MB-231 cells. Results: Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. In addition, our results showed that inhibition of SIRT1 induces anti-cell growth in both MCF-7 (ER-positive, non-invasive) and MDA-MB-231 (ER-negative, invasive) breast cancer cell lines, especially in MDA-MB-231 cells. The levels of pro-survival protein Bcl-2 were dramatically decreased in both breast cell lines following sirtinol treatment. Conclusions: Our present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.
Staging evaluation with bone scan, liver ultrasound, and chest radiograph in patients with primary breast cancer: A systematic review.
Authors: Staley Stuart-Allison Moffat
Published: February 2017

4

Background: Routinely, radiological investigation with bone scan, chest radiograph, and liver ultrasound are employed as baseline staging tests. The aim of this review was to examine indications for this costly routine screening, and, thus, we posed the following question: Among women with newly diagnosed breast cancer who are otherwise asymptomatic, does evaluation with bone scanning, liver ultrasound, and chest radiograph help to determine the extent of metastatic disease? Methods: We searched PubMed and EMBASE databases for relevant articles to find articles using detection rate, defined as the number of patients with an abnormal test result divided by the total number of patients tested, as the primary outcome of interest. In addition to detection rate, false-positive and false-negative rates are reported if provided in the study reports reviewed. In order to obtain overall estimates of detection rates in each test, the results from the studies were pooled and summed according to pathological stage. A 95% confidence interval was calculated for each of the pooled rates. Results: Eight articles out of 232 reviewed were included in the final analysis. The following pooled detection rates for bone scan were calculated according to stage: Stage I 7 of 544 (1.29%), Stage II 29 of 938 (3.09%), Stage I and II 36 of 1,482 (2.43%), and Stage III 39 of 312 (12.5%). For liver ultrasound: Stage I 1 of 213 (0.47%), Stage II 4 of 400 (1.00%), Stage I and II 5 of 613 (0.82%), and Stage III 6 of 143 (4.20%). And, for chest radiograph: Stage I 0 of 223, Stage II 2 of 473 (0.42%), Stage I and II 9 of 1,782 (0.51%), and Stage III 8 of 175 (4.57%). Conclusions: The routine use of bone scan, liver ultrasound, and chest radiograph in the staging evaluation of primary breast cancer patients is of little value in detecting metastatic disease in women with clinical stage I and stage II cancer, and therefore, should not be performed.
Statin use and the development of bone metastasis in breast cancer patients.
Authors: King Gentry Teng , Yun Jeong H. , Chae Young K. , Valsecchi Matias E. , Morginstin Mark S.
Published: February 2017

40

Background: The Mevalonic Acid Pathway has been implicated in the promotion of a microenvironment suitable for establishment of bony metastasis from breast cancer. The statins, which act on this pathway, have been shown to have in vitro antineoplastic activity against breast cancer. This study was designed to evaluate the association of statin use and development of bony metastasis in breast cancer patients. Methods: Medical records of patients treated for stage II-III breast cancer from 1999 to 2010 were retrospectively reviewed. Statin use was defined as medication use for at least 3 months in patients with no evidence of disease after initial diagnosis and treatment. The primary outcome was development of metastasis to bone. Secondary outcomes were overall survival, disease free survival and other sites of distant metastasis. Results: A total of 841 patients were included in the study of which 223 used statins. Both unadjusted and multivariate analysis adjusted for age, race, grade, stage, BRCA status, showed that patients on statins had a significantly lower incidence of metastasis to bone (OR 0.49, 95% CI 0.25-0.96, p=0.04). Adjusted analysis for other sites showed a trend towards decreased incidence of metastasis for statin users, but was not statistically significant (95% CI 0.39-1.08, p=0.10). Overall survival was increased in statin users with mean survival of 66.45 +/- 2.48 months versus non-users 58.78 +/ - 1.41 months (p=0.05). Statin users had significantly longer disease free survival with a mean of 63.65 +/- 2.49 months versus 53.96 +/- 1.42 months in non statin users (p=0.00). Conclusions: The use of statin drugs in patients with breast cancer was significantly associated with decreased incidence of metastasis to bone, but not to other distant sites. The role of statins in chemoprevention of bone metastasis should be further explored.
Risk-reducing surgery by skin-sparing mastectomy (SSM) and immediate implant-based reconstruction with and without titanized meshes and quality of life.
Authors: Rezai Mahdi , Scherag Andre , Kessel Stefanie , Kimmig Rainer , Kern Peter
Published: February 2017

48

Background: The impact of risk-reducing surgery with skin sparing mastectomy and immediate reconstruction on quality of life using new textured implants and titanized meshes (Tiloop bra) has not beed evaluated by standardized quality of life questionnaires (EORTC) with regards to surgery-related morbidity and patients' satisfaction. Methods: This large case cohort trial (n=197) evaluates safety, aesthetic outcome and patient's satisfaction with immediate reconstruction with and without the use of titanized a mesh versus a corial flap after SSM. Results: This large retrospective case cohort trial analysed 197 skin sparing mastectomies (SSM) in 161 patients (45 bilateral cases) and immediate breast reconstruction (IBR). We used a double-plane technique covering the implant by the submuscular pouch in its cranial half and a corial-fat-flap or titanized mesh (Tiloop bra) for covering its lower pole or a de-epithelized corial flap in breasts with macromastia following an inferior-pedicled reduction mammaplasty pattern according to Ribeiro in the modification of Rezai. Conclusions: 163 women, with a median age of 41 years, with a total of 197 SSMs were evaluated. The majority did not experience pain and expressed satisfaction with volume, symmetry, aesthesis and quality of life in general. Partner interaction after breast reconstruction was normal. The use of titanized meshes was perceived as favourable with regards to better fitting of the breast in the bra and clothing and yielded low complication rates. The rating of patients in terms of self-perception after the reconstruction was good. Immediate reconstruction has a significant positive impact and gives the patient a considerable physical and psychological support.The oncological safety of the method is high with 2 recurrences only in this cohort of 163 women (1.2% ) and a follow-up of up to 6 years.
Presentation of contralateral axillary involvement from breast cancer.
Authors: Prowler Vanessa Leilani , Kiluk John , Lee Marie Catherine , Khakpour Nazanin , Laronga Christine , Cox Charles E.
Published: February 2017

49

Background: Metastatic breast cancer to the contralateral axilla is defined as stage IV disease. We postulate that metastatic disease to the contralateral axilla is secondary to extension of aggressive, local regional disease rather than distant metastatic disease and may have a better outcome. Methods: An IRB-approved retrospective review of breast cancer cases presenting to a single institution between January 2005 and December 2011 was performed to identify cases with contralateral axillary disease. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented metastasis to the contralateral axilla without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Results: Thirteen pts were identified that fulfilled eligibility criteria. The average age was 53 years (range 26.3-72.2) with 12/13 (92%) pts presenting with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at presentation or local recurrence. Contralateral metastatic disease occurred synchronously with the initial primary tumor (3pts, 23%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor in (3pts, 23%), and metachronously with a local recurrence in (2pts, 15%). Resection of involved contralateral nodes was performed in 10/13 (77%) pts; 5/13 (38%) patients received contralateral axillary radiation; all 13 (100%) received systemic therapy. 9/13 pts (69%) developed distant metastatic disease with a mean follow up of 2.6 years (range 0.3-6.8 years). 3/13 pts (23%) have no evidence of disease at a mean follow up of 4.7 years (range 1.5-6.8). Conclusions: Contralateral axillary spread of breast cancer carries a poor prognosis but may have different prognostic implications than metastatic disease. Contralateral axillary metastatic disease may occur through dermal lymphatic spread and requires multidisciplinary management. Further study is warranted on the prognosis and management of these challenging and rare cases.
Racial disparities in clinical presentation, treatment, and outcome of women with breast cancer: Analysis of national inpatient sample database.
Authors: Dehal Ahmed , Abbas Ali , Johna Samir
Published: February 2017

66

Background: Despite the established consensus, guidelines, and treatment protocols, there is wide variability in practice patterns among women treated for breast cancer, leading to variable results, with less favorable outcomes among minorities. The objective of this study was to examine racial/ethnic disparities in stage of disease and comorbidities (pre-treatment factors), surgical treatment allocation (breast conserving surgery [BCS] versus mastectomy [MAS]), and postoperative complication and mortality (post-treatment outcomes). Methods: National inpatient sample is a nationwide clinical and administrative database compiled from 44 states representing 95% of all hospital discharges in the Unites States. Patient discharges with primary diagnosis code of breast cancer and coincident procedure code for breast surgery (BCS or MAS) from 2005 to 2009 were identified using International Disease Codes 9th edition. Information about demographics, hospital characteristics, comorbidities, stage, surgical treatment, post-operative complications, and in-patient death was obtained. Multivariate logistic regression analyses were used to examine risk adjusted association between race and the aforementioned outcomes. Results: We identified 75,100 patient discharges with a mean age of 61 years. Overall, 58.3% of women were white, 8.6% black, 5.7% Hispanic, 2.6% Asian, and 24.8% others. Compared to whites, blacks were more likely to present with regional or metastatic disease (1.17, p <0.001) and more likely to present with comorbidities (1.58, p 0.003). Compared to whites, blacks (1.30, p <0.001) and Hispanics (1.20, p <0.001) were more likely to receive BCS whereas Asians were less likely to undergo BCS (0.80, p 0.01). Compared to whites, blacks were more likely to develop postoperative complications (1.35, p<0.001) and in-hospital mortality (1.87, p 0.13). Conclusions: After controlling for potential confounders, we found some racial/ethnic disparities in clinical presentation, treatment, and outcomes. Future researches should examine the underlying factors of these disparities.
Improving cancer care by linking community cancer center physicians to breast cancer disease site-specific experts.
Authors: Hardenbergh Patricia H.
Published: February 2017

70

Background: The goal of this project is to improve the quality of cancer care across the U.S. by connecting community cancer center radiation oncologists with highly specialized, disease site-specific radiation oncologists. Methods: We have developed a website named chartrounds.com that allows community radiation oncologist members to interact online in a peer review forum with disease site-specific specialists on a scheduled basis. At the conclusion of each session, participants are asked to complete a questionnaire which requests feedback on the quality and relevance of the session and the manner in which it might result in changes to their practice. Results: To date, 575 community radiation oncology physician members from 50 states have enrolled online. In the initial 18-month period, nine disease site-specific specialists have led 81 breast-specific chart rounds sessions with an average attendance ratio, during the past six months, of eight community physician members to one breast cancer disease site-specific specialist. From 309 initial responses, on a five-point Likert scale with five representing the greatest impact possible, the mean response to feedback questions is as follows: session quality; 4.7, time used effectively; 4.6, discussions relevant to daily practice; 4.7, session is likely to result in a change in practice; 4.0. More specifically, 139 members reported that they would make the following changes in their practice: change in clinical management of the radiation patient: 37%, change in the selection of patients for radiation: 22%, change in the technical delivery of radiation including target, field and dose adjustments: 20%. Conclusions: The chartrounds.com website appears to be making an impact on individual radiation oncology practices resulting in changes in management and the delivery of treatment to patients in community cancer centers. Future directions of this project are aimed at demonstrating how these changes may result in significant improvements in survival of breast cancer patients across the U.S. This work is funded by the Improving Cancer Care Grant of the ASCO Conquer Cancer Foundation supported by Susan G. Komen for the Cure.
Rural and urban disparities in the evolution of sentinel lymph node utilization in breast cancer.
Authors: Arrington Amanda Kathleen , Kruper Laura , Vito Courtney , Yim John H. , Chen Steven L.
Published: February 2017

71

Background: Sentinel lymph node biopsy (SLNB) has become the preferred method for axillary nodal staging. We examined SLNB utilization in urban versus rural settings as this procedure was adopted. We hypothesized that SLNB rates in urban centers quickly increased prior to 2000, while the technology shift and acceptance of SLNB was slower in rural centers. Methods: The SEER registry was used to identify patients with invasive ductal or lobular breast cancer from 1998-2008. Exclusion criteria included evidence of distant metastatic disease, T4 tumors, no curative-intent operation performed, or incomplete staging data. Residential setting was divided into three groups based on population density: rural, intermediate population, and urban. Results: The overall rate of SLNB increased with time (9.5% in 1998 to 72.7% in 2008). The adoption of SLNB was slower in rural settings than in urban populations (p<0.001). By 2003, only urban areas were utilizing SLNB in over 50% of cases. When stratified by population density, there was a significant difference in SLNB rates according to type of surgery performed (lumpectomy vs mastectomy) as well as by T-stage, with lower T-stage positively correlating with the likelihood of SLNB usage in all categories. Overall, there was a two-year lag in the adoption of between the increases in SLNB utilization rates in these groups. Conclusions: Since 1998, the use of SLNB for breast cancer has slowly increased throughout the United States. Though widely accepted as the preferred staging method, the overall rate of SLNB remained near 50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1-T2 had increased to over 50% in all population categories. There was an overall 2-year lag in adoption of SLNB in less populated areas. While this may represent a more conservative approach as noted by the higher utilization in small tumors, the difference may be attributable to a shortage of experienced surgeons, lack of training, or lack of technological support at smaller institutions. The provision of continued training in emerging technologies for rural surgeons, such as SLNB, should remain a priority in continuing surgical education.
Health care utilization and costs associated with skeletal-related events (SREs) in patients with breast cancer (BC) and bone metastases (BMets).
Authors: Hagiwara May , Chung Karen , Delea Thomas E.
Published: February 2017

72

Background: Patients with BMets secondary to BC are predisposed to SREs, defined as spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiation therapy to bone (RT). Information on health care utilization and costs to treat SRE episodes in BC patients are limited. The objective of this study was to document current patterns of healthcare utilization and costs of SRE in patients with BC and BMets. Methods: This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for BC (ICD-9-CM 174.xx) and for BMets (ICD-9-CM 170.xx or 198.5x), and ≥1 claim(s) for SRE. Key inclusion criteria included no other primary cancer and continuous enrollment ≥6 mos prior to BMets diagnosis. Unique SRE episodes were identified based on a gap of ≥90 days without an SRE claim, and classified by treatment setting (inpatient [IP, hospitalized for SRE during episode] or outpatient [OP]) and SRE type (SCC; PF [and no SCC]; SB [and no SCC or PF]; RT [and no SCC, PF, or SB]). Results: Of 22,709 BC patients with BMets, 11,941 had ≥1 SRE. Among 5,809 patients who met all other criteria, there were 7,617 SRE episodes over a mean (SD) follow-up of 17.2 (15.2) mos. The percent of SRE episodes that required IP treatment ranged from 11% (RT) - 76% (SB) (23% overall). On average, IP SCC episodes were most costly; while OP PF episodes were least costly. Of the total SRE costs (mean [SD] $21,072 [$36,462]/episode), 36% were for OP RT and 31% were for IP PF. Conclusions: In patients with BC and BMets, SREs are frequent and associated with high costs and hospitalizations. OP RT and IP PF account for a large share of SRE costs. Treatments that prevent SREs in these patients may reduce these costs. [Table: see text]
Psycho-oncological screening in patients with newly diagnosed or relapsing breast cancer.
Authors: Karthaus Meinolf , Schuth I. C.
Published: February 2017

80

Background: Breaking news in breast cancer (BC) pts often has to be supported by psychological help. It remains unclear which and how many BC pts need supportive psycho-oncological care, since pts may react in different ways. Some pts show high risk profiles for anxious reactions or depressions after breaking bad news and should be detected for interventions. Need for pychological intervention was screened with a simple 14-point item test (HADS). A scoring of <15 points was assumed to be at low risk for anxiousness and depression, a scoring of 15-21 points was considered medium risk while a score of >21 was assumed to describe high-risk pts. Pts considered to be at low risk, did not receive further intervention. Pts detected to be at medium or high risk received further psychological intervention. The aim was to evaluate efficacy of psychological support in pts with newly diagnosed BC or relapse of cancer >1 yr after a curative approach. Methods: Psycho-oncological screenings and interventions were analyzed in a tertiary cancer within a two-year period. Results: Out of a total of 611 cancer pts, 202 pts had BC. 63 pts had a newly diagnosis of cancer or a relapse of >1 year since primary diagnosis or therapy and signed informed consent. Pts assumed to be at low risk had a mean score of 6,97 (SD 3.71) prior and 7,03 (SD4.97) after the end of cancer therapy. In this group of low risk pts there was no further psychological intervention. In pts detected with a medium risk (15-21) mean HADS score prior therapy was 16.63 (SD 1.38) and fell down during cancer treatment and supportive psychotherapeutically intervention to 13.58 post therapy (SD 6.16). Pts with the highest risk at diagnosis had a mean of 28.25 (SD 4.41) and decreased to a mean HADS of 16.83 (SD 4.84) at the end of cancer therapy while being under supportive psychotherapeutically care. Mean number of psychotherapeutic sessions was 3.86/patient with a mean duration of intervention time of 1.38 h. Conclusions: BC pts with a HADS <15 should not be considered to be candidates for routine psychotherapeutically supportive care. Pts being at high-risk gained most benefit. A simplified scoring system for anxiousness and depression is recommended to detect pts with a need for further therapeutic treatment.
Comorbidity and outcomes after surgery among women with breast cancer: Analysis of national in-patient sample database.
Authors: Dehal Ahmed , Abbas Ali , Johna Samir
Published: February 2017

83

Background: Evidence is scarce about the influence of comorbidity on short-term outcomes of patients with breast cancer after surgery. The objective of this study was to examine the effect of comorbidity on risk of postoperative complications, prolonged hospitalization (defined as above median length of stay), and in-patient death among women with breast cancer. Methods: National inpatient sample is a nationwide clinical and administrative database. Patient discharges with primary diagnosis code of breast cancer and coincident procedure code for breast surgery from 2005 to 2009 were identified using International Disease Codes 9th edition (ICD-9). Information about demographics, hospital characteristics, comorbidities, stage, surgical treatment, postoperative complications, length of hospital stay, and in-patient deaths was obtained. Comorbidities were identified using ICD-9 codes and used to calculate modified Charlson comorbidity index (CCI) score. We divided patients based on these scores into 4 groups: 0, 1, 2, and 3 or more. Multivariate logistic regression analyses were used to examine risk adjusted association between CCI score and the aforementioned outcomes. Results: We identified 75,100 patient discharges with a mean age of 61 years. Compared to patients with a CCI score of 0, as a reference group, CCI scores of 1, 2, and 3 or more increased the risk of post-operative complications by 1.7 fold, 2.6 fold, and 4.6 fold, respectively (p <0.001). Compared to patients with a CCI score of 0, CCI scores of 1, 2, and 3 or more increased the risk of prolonged hospitalization by 1.2 fold, 1.6 fold, and 2.3 fold, respectively (p <0.001). Similarly, Compared to patients with a CCI score of 0, CCI scores of 1, 2, and 3 or more increased the risk of in-patient death by 3.1 fold, 5.4 fold, and 15.8 fold, respectively (p <0.001). Conclusions: After controlling for potential confounders, we found a strong and statistically significant association between comorbidity and outcomes of patients with breast cancer after surgery. Effective control of comorbidity in breast cancer patients may reduce post-operative morbidity and mortality.
Uptake and experiences of breast cancer patients referred for fertility preservation.
Authors: Lewis Jaime D , Silva Celso , Quinn Gwendolyn P. , Lee Marie Catherine
Published: February 2017

86

Background: The 2006 ASCO guidelines suggest women of childbearing age receive counseling and referrals regarding the impact of treatment on fertility. Less is known about the use and uptake of FP in these women. The objective of this study was to evaluate the experience of patients referred for FP from a multidisciplinary breast cancer program. Methods: After IRB approval, patients diagnosed with a primary breast cancer between January 1, 2006 and June 30, 2011 and referred for FP counseling were identified via queries of institutional databases. Clinicopathologic, treatment, and outcome data were collected. Patients who received a consultation with a reproductive endocrinologist (REI) and did not pursue FP were selected for further contact via telephone survey. Results: Twenty-two patients had a consultation with REI; 10 were nulliparous. Fifteen of these saw an REI prior to any treatment. Thirteen (59%) had embryo or oocyte preservation. The majority (9) underwent consultation with both surgical and medical oncology prior to REI. Nine of the 13 had surgery prior to FP. Of the remaining 9, 7 (78%) responded to a telephone survey. Six (86%) recalled counseling at the initial visit or prior to chemotherapy. Barriers to FP included: cost (3), perceived delay in chemotherapy (2), being overwhelmed by cancer diagnosis (2), uncertainty of FP effects on cancer (1), and ethical concerns (1). Conclusions: Patients counseled by multiple oncology providers in a multidisciplinary setting prior to REI consultation were more likely to pursue FP. Those who did not cited a number of factors in their decision. Consultation with multiple oncology specialists may enhance decision-making regarding FP. [Table: see text]
Risk of skeletal-related events (SREs) in patients with breast cancer (BC) and newly diagnosed metastases to bone.
Authors: Taneja Charu , Lamerato Lois , Glass Andrew , Richert-Boe Kathryn E. , Edelsberg John , Wolff Greg G. , Czapski Natalie , Chung Karen , Richhariya Akshara , Oster Gerry
Published: February 2017

91

Background: Bone is a common site of metastatic involvement in patients (pts) with BC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary BC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 378 pts with primary BC and newly diagnosed bone mets; 87 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 291 pts, mean (SD) age was 58.2 yrs (14.3 yrs), and 99% were women; 48% were African-American and 46% were Caucasian. Median duration of follow-up after diagnosis of bone mets was 16.1 months (mos). At 12 mos, cumulative incidence of SREs was 44.5% (SCC, 5.2%; PF, 21.0%; SCC and/or PF, 23.3%; SB, 7.6%; RT, 34.3%) (Table). Corresponding figures at 24 mos were 53.8% (SCC, 7.5%; PF, 29.3%; SCC and/or PF, 32.5%; SB, 9.4%; RT, 41.7%). Approximately one-half (45.0%) of study subjects received intravenous bisphosphonates prior to SRE. Conclusions: Pts with BC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]
Male breast cancer: Overall survival in a single institution.
Authors: Bergmann Anke , Bello Marcelo Adeodato , Costa Celia Regina Andrade , Bender Paulo Francisco Mascarenhas , Thuler Luiz Claudio Santos
Published: February 2017

93

Background: Male breast cancer is an uncommon disease and the therapy is mainly based on what is know from female breast cancer. Objective: To investigate the clinicopathologic characteristics of male breast cancer and the overall survival in a single institution. Methods: The clinical data and survival status of 75 male breast cancer treated in a Brazilian public cancer hospital from 2000 to 2009 were collected. The association with clinicopathological characteristics and overall survival was analyzed using Kaplan-Meier curves and the Cox proportional hazards regression (enter method) was used to assess survival differences after adjusting for confounders. The study was approved by National Cancer Institute Research and Ethics Committee (number 128/11). Results: The median patient age was 64 years (range 33-86). Estrogen receptor (ER) was positive in 58 (77.3%) patients, while progesterone receptor (PR) were positive in 47 (62.7%). Histology type was ductal infiltrant carcinoma for 57 (76.0%) and 51 (68.0%) patients underwent surgery. The median follow-up period was 43,1 months (range 2.7-147.8). The median survival from the diagnosis of breast cancer was 97.0 months (95%CI 53.6 -140.4) with a 61.7% 5-year overall survival (OS). In the final Cox regression model, independent factors associated with increased risk of death were metastasis at diagnosis (HR = 18.1; 95%CI: 5.9-55.2), ≥ 65 years old (HR = 4.3; 95%CI: 1.7-10.5); tumor stages ≥ IIb (HR = 3.5; 95%CI: 1.3-9.7) and smoking (HR = 1.6; 95%CI: 1.04-2.6). Conclusions: Invasive ductal carcinoma is the main pathologic type. The median survival from the diagnosis of breast cancer was 97.0 months and metastasis at diagnosis, patient age, tumor stage and smoking are independent prognostic factors.
Breast cancer treatment and recurrence in octogenarians.
Authors: Harris Adam , McLaughlin Sarah A. , Adkisson Cameron , Bagaria Sanjay Prakash , Gibson Tammeza , Diehl Nancy N. , Pockaj Barbara A.
Published: February 2017

94

Background: Octogenarian breast cancer (BrCa) patients accept less aggressive BrCa treatment due to decreased life expectancy, increased comorbidities, and high likelihood of death from other causes. Unfortunately little data exist stratifying octogenarian outcomes by disease risk. We sought to characterize treatment and recurrence patterns in patients >80yo. Methods: Retrospective review identified 432 women >80yo treated surgically for stage 0-3 BrCa between 11/99-8/11. We gathered clinicopathologic data and classified patients by disease risk as DCIS only, low risk (<2cm and ER positive and node negative), or high risk (>2cm or ER negative or node positive). We compared recurrence rates and estimated survival by Kaplan-Meier curves. Results: Among the 432 women, disease was found by mammogram in 86%, treated with BCT in 64%, and predominantly ER-positive (87%). We classified patients as having DCIS only (N=61), low risk (N=205), or high risk (N=166) disease. We identified the following deviations from standard treatment guidelines: 68% DCIS BCT and 38% high risk BCT patients did not have radiation therapy, 25% low risk BCT patients had surgery only, 51% low risk patients did not take adjuvant hormonal therapy, and 40% high risk patients had no adjuvant chemo/hormonal therapy. At 5 and 10 years the overall estimated survival was 63% and 31%, respectively. Overall, 19/432 (5%) patients developed recurrence (table 1). Patients needing mastectomy for high risk disease had significantly higher risk of recurrence than high or low risk BCT patients (p=0.02). Of the 19 recurrence patients, 7/19 (37%; 1 DCIS, 1 low risk, 5 high risk) occurred despite standard multimodality treatment, while12 (63%; 3 low risk, 9 high risk) had the initial tumor treated less aggressively due to patient choice (n=9) or medical co-morbidities (n=3). Conclusions: Significant deviations from treatment guidelines occur in women >80yo. Those with high risk disease should be counseled accordingly and encouraged to receive adjuvant treatment as two thirds of women >80yo will live at least 5 years. [Table: see text]
Outcome of rare types of breast cancer in Hispanic woman.
Authors: Campos Gomez Saul , Cruz Marlid , Perez Alvarez Sandra Ileana , Gamboa Dominguez Armando , Soriano Rodriguez Alejandra , Leon Rodriguez Eucario
Published: February 2017

96

Background: Rarer histological types of breast cancer represent less than 5% of all cases. The identification might be of value in assessing prognosis and predicting response to therapy in a Hispanic population. Methods: A total of 1,400 consecutive woman diagnosed with any type of breast cancer between 1991 and 2010 were identified. Histological types were classified according to World Health Organization criteria and the Armed Forces. Ductal, lobular and mixed ductal/lobular carcinomas and women with missing data were excluded, leaving a total of 60 patients. Tumor grade, vascular invasion, hormonal receptor status, ki-67 labeling index, HER2 overexpression, tumor size and nodal status were recorded and analyzed by histologic type. Survival curves were calculated by histology. Results: A total of 60 patients were classified according histology in order of frequency as mucinous (36.7%), medullary (10%), papillary (8.3%), metaplastic (8.3%), tubulo-lobular (6.7%), tubular (5.0%), metaplastic with epidermoid differentiation (3.3%), signet cell adenocarcinoma (3.3%), apocrine (3.3%), neuroendocrine (3.3%), acinary (1.7%), histiocytoid (1.7%), leiomyosarcome (1.7%), phyllodes (1.7%), high grade sarcoma (1.7%), and mucinous papillary (1.7%). Women with leiomysarcome type had the youngest mean age at diagnosis (27y) followed by mucinous (32y), and high grade sarcoma was the oldest mean age (76yrs). Most of histologists (82%) presented as stage I and II at diagnosis. Only mucinous, medullary and metaplastic presented with advanced disease (4%). With respect to ER/PR status, 36% of mucinous cases and 60% of papillary cases were ER+/PR+, while 50% of medullary cases and 60% of metaplastic cases were ER−/PR−. Only 13% had overexpression of HER2. Compared with OS reported for ductal and lobular carcinoma, median survival was significantly longer 54 months (40.4–67.5) and DFS median 66.1 months (48-82 months). Conclusions: Rare breast carcinomas are a heterogeneous group with more favorable prognosis compared to ductal carcinoma. Though many of these histologic subtypes are quite rare, an accurate and reliable histopathology assessment is crucial in order to determinate treatment, principally to the need for systemic treatment.
A systematic approach to companion diagnostic development: A case study for omacetaxine (OM) for the treatment of chronic myelogenous leukemia (CML).
Authors: Preisig Carol L.
Published: February 2017

100

Background: In the age of genomically informed medicine, therapeutic development carries with it the imperative to employ genomics in patient selection. Physicians expect genomics-based methods to identify treatments likely to be effective, and identify anomalies likely to cause adverse response for a given patient. Companion diagnostics should support such rule-in and rule-out decisions. We demonstrate a systematic approach to companion diagnostics that leverages new methods in translational bioinformatics and clinical economics. CML therapies have been at the forefront of genomically informed medicine. Early TKI inhibitors targeting the BCR-ABL fusion protein are highly effective. With time, however, they induce resistance-creating mutations in many patients. Omacetixine, a translation inhibitor, was expected to help this CML patient subpopulation which has few therapeutic alternatives. We use this well-characterized drug and publicly available data to demonstrate a prospective approach to companion diagnostics. Methods: We used translational bioinformatics, incorporating pathway, cell line, and patient data to identify biologically plausible biomarkers from which alternative companion diagnostic paths were constructed. These alternatives were analyzed using a modified version of the MIT Stratified Medicine Model to assess the clinical economics of each path. Results: From a systematic look at the biology of the disease, the unique mechanism of action of OM and the clinical need, we identified 3 alternative companion diagnostics for OM. Economic analyses quantified the trade-offs of targeting different subpopulations for the indication, clarifying the impact of biomarker selection based on clinical need or biology. Other analyses have shown that eNPV can be halved or doubled based on strategy choice. Conclusions: Combining applied translational bioinformatics and stratified medicine economics provides an effective approach to companion diagnostic selection. This approach can reduce drug-development cost and clinical risk while providing physicians with better genomics-based methods for clinical decision-making.
Uptake of BRAF and ALK mutation screening versus HER2 overexpression testing.
Authors: Steele Savanna D. , Combest Austin J. , Bonneterre Marie-Edith Anne , Adair Joseph Walt , Barefield Eric , Reitsma Dirk J.
Published: February 2017

101

Background: Genetic mutation testing in cancer has become standard practice with the advent of targeted therapies such as vemurafenib, crizotinib, and trastuzumab and their associated companion diagnostics. We observed a rapid uptake in BRAF mutation screening in melanoma compared to ALK mutation in NSCLC and HER2 overexpression in breast cancer. Hypothesizing this discrepancy may be related to the overall impact the drugs had on standard of care within their respective indications, we evaluated the relationship between mutation screening frequency and hazard ratios (HRs) from pivotal clinical trials (Shaw Lancet Oncol 2011; Gerber Cancer Cell 2010; Slamon NEJM2001). As a historical control, we also assessed HER2 screening trends. Methods: BRAF, ALK, and HER2 screening data were collected via Ipsos’ Tandem Oncology Monitor, a commercial system in which oncologists in US (500) and EU (783) enter de-identified data on actual prescriptions and mutation screening orders by indication for cancer patients from their practice. Results: Our results show an increase in mutation testing from 42 to 83% for BRAF and from 13 to 34% for ALK from Q1 2011 to Q4 2011. HER2 testing has increased from 56%, Q1 2001, to 95%, Q4 2011. Correlation in uptake in testing vs. PFS/TTP HR endpoints in the US was -0.866. This implies a relationship between outcomes and the propensity for mutation testing. Conclusions: While it is likely that the potential for benefit drives mutation testing, clinicians may also be less likely to screen for an uncommon mutation (~5% of NSCLC patients), or may choose to test only those patients with known predisposing factors. Additionally, oncologists may go through a testing algorithm for NSCLC patients where mutations that are more common are screened first (i.e., EGFR – KRAS – ALK). BRAF testing reached nearly 90% in one year compared to nearly 10 years for HER2 and emphasizes the impact vemurafenib has had on standard of care. ALK mutation screening increased, but not to the same extent as BRAF. These results are encouraging, but also demonstrate that mutation testing in all patients is not yet a reality. [Table: see text]
New tissue aquisition tools for molecular biology.
Authors: Janssens Jaak
Published: February 2017

102

Background: Histological and biomolecular examinations are a prerequisite to understand diseases, determine optimal individualized care, and identify targets for potential novel therapies. Despite this key role of tissue-based research the act of biopsy still remains troublesome. New direct and frontal biopsy technologies are emerging with the aim to alleviate the bottleneck of inappropriate minimal invasive interventions. Recent clinical trials evaluated the use of macrobiopsies in providing the necessary tissues for molecular biology. Methods: The new instruments for minimal-invasive procedures were evaluated in different single and multicenter clinical trials to generate data on providing enough high-quality tissue for biomolecular research in comparison to diagnostic surgery for various soft tissues and bone lesions throughout the body. In addition, patient comfort and costs data were taken up in the survey. Results: Direct and frontal type macrobiopsy systems give tissue samples between 150 mg and 300 mg of highly specified parts of the diseased area in a way very similar to open surgery. In addition, biopsy procedures are increasingly more patient friendly with appropriate comfort and safety. The new macrobiopsies are less expensive, making molecular biology at reach for every oncological patient, company, and health care provider. Conclusions: Direct and frontal macrobiopsies open new avenues for future bio-banking, pharmacogenomics, biomolecular research, and personalized medicine. It is anticipated that drug discovery and clinical implementation of targeted therapies will be highly facilitated, and that clinical research time for multicenter trials will be significantly shortened.
Decrease in CA-19-9 after neoadjuvant chemoradiation therapy to predict survival in locally advanced pancreatic cancer.
Authors: Singh Jaswinder , Jafri Syed Faisal , Pabla Maninder , Freilich Bradley L. , Cates Joe , Sheldon John M. , Shaeffer David , Connor Michael , Shah Raj , Cope Reed , Rath Niharika , Burt Michael , Mukherjee Srijita , Parikh Unnati , Feeback Jennifer Wanpen
Published: February 2017

12

Background: Pancreatic adenocarcinoma is among the most lethal of human cancers. Data on overall survival rates of patients treated in the community hospital setting are limited. The purpose of this retrospective data collection study was to assess the CA19-9 change during the neo-adjuvant treatment of locally advanced pancreatic cancer patients and whether this test predicts the overall survival (OS). This study was conducted within a high volume community hospital setting. Methods: Eligibility included cytological or histological evidence of locally advanced, unresectable, and borderline resectable adenocarcinoma of the pancreas, not amenable for surgical resection. Resectability was determined with EUS and CT scan/MRI and was discussed in the multi-disciplinary conference. Patients diagnosed before July 2009 were treated with continuous 5-FU 200mg/m2 for 5 weeks with radiation of 1.8 Gy per daily fraction, for a total dose of 50.4 Gy over 5.5 weeks. Patients diagnosed after July 2009 received gemcitabine 400mg/m2 intravenously (over 60 minutes) beginning on the first day of radiation therapy (before radiation), then weekly thereafter during radiation. Results: Data were abstracted on 64 patients (40 deceased; 24 alive) diagnosed between 6/2005 and 4/2011. The median age was 68 years (range 41-87), and 52% were male. The majority of patients (97%) were diagnosed by endoscopic ultrasound (EUS) with biopsy. At diagnosis, 56 (88%) patients were locally advanced unresectable (without metastasis) or borderline resectable; 49 of these had neoadjuvant treatment, and 13 were later resected. Median OS for all 64 patients was 45.4 weeks (95% CI: 29.6-61.3), with no significant differences in OS by sex of patient (p = 0.210) or smoking history (p = 0.625). Twenty-two patients (34%) had >75% decreases in CA19-9 from baseline; median OS was 89.4 weeks in this group compared to 41.3 weeks in patients with changes in CA19-9 <75% (p = 0.025). Conclusions: This trial demonstrates improved overall survival in patients with locally advanced pancreatic cancer, who had significant decrease in CA19-9 (>75% decreases in CA19-9 from baseline) in response to neo-adjuvant chemotherapy and radiation.
Rapid detection of cancer-related cfc-DNA biomarkers directly from whole blood.
Authors: Heller Michael James , Sonnenberg Avery
Published: February 2017

14

Background: We have developed a “Sample to Answer” dielectrophoretic (DEP) technology for detecting cancer and other disease-related cfc-DNA biomarkers directly from whole blood. Using AC/DC electric field microarray devices specifically designed for the isolation of cfc-DNA, exosomes and cellular nanoparticulates from blood samples, experiments were carried out by adding about 20ul of the patient blood sample to the DEP microarray device. Methods: The DEP field was applied at 10 kHz and 20 Vp-p for 15 minutes to nine microelectrodes. The microarray was then washed three times with 0.5x PBS with the DEP field on, and finally examined by epifluorescent microscopy. Results: For Chronic Lymphocytic Leukemia (CLL) cancer patient blood samples, results clearly show greenish white fluorescent circles around the nine DEP microelectrodes on the array. This is the SYBR Green fluorescent stained cfc-DNA from the CLL cancer patient blood sample now concentrated in the DEP high field regions. Normal blood samples show little or no fluorescence around the DEP high field microelectrodes. More than fifty CLL samples have been analyzed to date. Conclusions: DEP devices are now being used to collect cfc-DNA from other cancer patient whole blood, plasma and serum samples. Blood sample to PCR is now achieved in less than twenty minutes. Newer work has demonstrated that PCR can be carried out in-situ (in the same device). Thus, the new DEP technology and devices set the stage for “seamless sample to answer” diagnostic systems which will allow a variety of important cancer and other disease biomarkers to be rapidly isolated and analyzed directly from whole blood and other clinical samples.