bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of receptor activator of nuclear factor kappa b (RANK) expression in breast cancer (BC) at the time of diagnosis with recurrence-free survival (RFS) and risk of bone-dominant metastases (BDM) in the I-SPY 1 trial (CALGB 150007/150012; ACRIN 6657).
Authors: Li Jiali , Yau Christina , Campbell Michael , Esserman Laura , Park John W. , Rugo Hope S. ,   CALGB 150007/150012; ACRIN 6657
Published: February 2017

2 Background: RANK is a tumor necrosis factor receptor family protein that is critical to bone turnover. The ligand to RANK (RANKL) can induce metastases from RANK-expressing tumor cells, and treatment with a RANKL inhibitor can reduce BC metastases (mets) in pre-clinical models and there is an FDA approved drug that targets RANKL. Osteoprotegerin (OPG) is a RANKL decoy receptor that blocks the interaction of RANK/RANKL. I-SPY 1 was a multicenter neoadjuvant trial with well annotated gene expression data and detailed clinical outcomes; we studied the impact of RANK expression on both RFS and BDM. Methods: OPG/RANK/RANKL pathway expression in core biopsies was evaluated at diagnosis in patients (pts) on I-SPY 1, then correlated with ER, intrinsic subtype, stage, response to chemotherapy, site of mets and RFS using the student t-test. Results: Gene arrays were performed on pretreatment tumor from 221 pts; 149 pts have available data with n being ER+. At a median follow-up of 3.5 yrs, 36 pts developed recurrence; 13 pts had BDM, 15 had non-bone mets (NBDM), and 8 pts were not evaluable. RANK, but not OPG or RANKL, was more highly expressed in ER- vs ER+ tumors (p=0.04) and in basal vs luminal A/B subtypes (p= 0.04), but no difference in expression based on tumor grade, node status or response to chemotherapy. Higher (>50%) RANK and lower (<50%) OPG expression correlated with worse RFS (p=0.03). Pts who developed BDM had higher expression of RANK, but not RANKL or OPG compared those with NBDM (p=0.05). After adjusting for ER and intrinsic subtypes, RANK expression was even more significantly correlated with risk for BDM (p=0.004). Conclusions: Higher RANK and lower OPG expression in primary tumor tissue correlates with poor RFS, and high RANK expression is associated with increased risk for BDM. These data suggests that targeting the OPG/RANK/RANKL pathway could be a promising strategy in preventing BDM in pts with high risk BC.
Breast cancer control in Iran: Specialized breast unit/national screening: Which one is the urgent priority?
Authors: Kalantari Mojgan , Joulaee Azadeh , Kadivar Maryam , Joolaee Soodabeh , Bahrani Naser 
Published: February 2017

29 Background: Rapid correct diagnosis and treatment is the key point in breast cancer control worldwide. Though screening decreases mortality, due to high cost, the need for enough imaging centers and radiologists actually is not affordable for many populated low resource countries. Specialized Breast Unit is a cost-effective program. While increasing the accuracy and quality, the total cost of diagnosis and treatment is significantly decreased. The more there is limitation of budget, the more it is important to go through this program as an urgent act for breast cancer control. In this study we try to show the actual problems of breast cancer in Iran and the efficacy of Specialized Breast Unit to solve them. Methods: All published data about breast cancer in Iran are reviewed since 2001 to 2012 to list the problems. Then the workflow and outcome of our unit between 2003 to 2012 with total 60, 021 visits are analyzed to show how does it help to solve these problems. Results: Younger age, late presentation, delayed diagnosis, and small numbers of nonpalpable lesions are the major features. Diagnosis is based on excisional/incisional biopsy or frozen section. Mastectomy and axillary dissection is the dominant approach. Sentinel node biopsy, reconstruction and screening are offered in few centers. Multidisciplinary approach in specialized breast unit provides rapid assessment of breast symptoms with correct pre-operative imaging and trucut biopsy for diagnosis. This results in tailored surgery (conservative, mastectomy with or without immediate reconstruction) and sentinel node biopsy for all eligible cases. Team work has decreased the number of visits and surgeries. Conclusions: If screening as the standard for early detection in asymptomatic women is considered as an option, Specialized Breast Unit is an obligation for correct diagnosis and treatment of both symptomatic and asymptomatic breast cancers as a life threatening disease. It is cost effective and helps to shift from dominant Halstead concept through international standards even in low resource countries. Without these referral units no attempt can be done for breast awareness programs, training, and further screening.
Impact of the U.S. Preventive Services Task Force update for breast cancer screening on mammography utilization in women age 40 to 49.
Authors: Wang Amy T. , Fan Jiaquan , Van Houten Holly K. , Shah Nilay D. 
Published: February 2017

5 Background: The 11/2009 USPSTF breast cancer screening update recommended against routine screening mammography for women age 40-49, created confusion and prompted organizations to release opposing statements. We aimed to determine if the USPSTF update for breast cancer screening impacted screening mammography utilization in women age 40-49. Methods: We conducted a time-series analysis utilizing administrative claims data from over 100 health plans. Women ages 40-64 with at least one month of enrollment from 01/2006-12/2010 were included. Medicare claims are not included and thus women ≥65 were excluded. The start date of 01/2006 was chosen to account for possible effects of the recent recession. We developed claims-based algorithms to identify the number of monthly screening mammograms. Time series models were fit using SAS PROC AUTOREG; strong seasonal fluctuations were adjusted by including an autoregressive error of order 12. Results: Over 7.9 million women were included. Prior to the intervention, the baseline monthly mammography rate was 40.9/1,000 women for the 40-49 group and 47.4/1,000 women for the 50-64 group. Based on projections from pre-intervention trends, the update was associated with a 5.72% (1.27,10.18) and 4.97% (1.11,8.84) decrease in mammography rate at 3 and 10 months post-intervention, respectively in the 40-49 group. The intervention had no effect on mammography rates in the 50-64 group. This translates to 53,969 fewer mammograms performed in the year following the update for women ages 40-49 in this dataset. Conclusions: We present the first estimates of the impact of the USPSTF breast cancer screening update using a large nationally representative database. The update was associated with a small but significant decrease in mammography rates for women ages 40-49, while no change was seen for women ages 50-64, which is consistent with the context of the guideline change. A modest effect is also in line with public backlash and the release of numerous conflicting guidelines. These findings underscore the need for further research on benefits and risks of screening mammography as it is difficult to act on numerous sources of contradictory information.
ACE inhibitors/ARB and the risk of breast cancer recurrence after surgery in Japanese population: A pilot study.
Authors: Fujii Takeo , Takahashi Osamu , Yamauchi Teruo 
Published: February 2017

52 Background: Angiotensin II can work as a growth promoter via angiotensin II type1 receptor (AT1R). In an in vivo study, Angiotensin Converting Enzyme Inhibitor (ACEI)/Angiotensin Receptor Blocker (ARB) down regulates vascular endothelial growth factor and activates apoptosis pathway through AT1R. In some clinical studies, the efficacy of ACEI/ARB to cancer patients has been investigated; however, the results are various. This has not been examined in Asian population. We investigated breast cancer patients in a single institution if the recurrence rate is related to ACEI/ARB use. Methods: This retrospective study will evaluate disease-free survival (DFS) for Japanese patients who were diagnosed with invasive breast cancer and had curative surgery between January 2004 and December 2006 at St Luke’s International Hospital. We will compare DFS of two groups with and without ACEI/ARB use. DFS is defined as the interval between curative surgery and the recurrence of breast cancer. Recurrence of disease was confirmed by radiographically or pathologically. Patients who took ACEI/ARB are defined as those who had taken them for at least 6 months after initial diagnosis. The following patient data will be extracted from their medical records; age, stage, body mass index, menopausal status, biomarker status (ER, PgR, and HER2), usage of bisphosphonate, usage of statin, diabetes, surgical procedure. Results: A total of 1,163 patients were analyzed. 76 were ACEI/ARB user and 1,087 were non-user. The recurrence rate of ACEI/ARB users was 17.1% (13/76). In comparison, that of non-users was 12.2% (133/1,087). The odds ratio (OR) was 1.480 (95 % CI: 0.793-2.762 p=0.218). Kaplan-Meier analysis did not show a significant difference between them (log-rank test p=0.194). Conclusions: Our study is the first one to evaluate the efficacy of ACEI/ARB in breast cancer recurrence among Asian population. Recurrence rate did not differ in the two groups although molecular biology suggested antitumor effect of ACEI/ARB. We will further explore if any confounding factors lie between the two groups, and plan to conduct a prospective study if ACEI/ARB exhibits antiproliferative effect in postoperative cancer patients.
Does atypical ductal hyperplasia require 6 months of postoperative surveillance?
Authors: Plichta Jennifer Kay , Rumas Natalia , Godellas Constantine V. , Perez Claudia Beth 
Published: February 2017

60 Background: Standard follow-up imaging for women with a history of breast cancer is well defined, but the appropriate screening guidelines for other high risk breast lesions, such as atypical ductal hyperplasia (ADH), remain unclear. Current practices often parallel those of cancer patients and include a 6 month interval mammogram prior to resuming annual screening, which may be unnecessary. As such, it is critical to evaluate the utility of the current standard practice of additional screening beyond a routine annual mammogram. Methods: Our pathology database was queried for the phrase "atypical ductal hyperplasia" from 2008 to 2010, and patients who underwent surgical excision were identified. Those who did not have subsequent follow up at our institution were excluded. Results: There were 44 patients who underwent excisional biopsies that were diagnosed with ADH and proceeded with follow up. In addition to a routine clinical exam, a short-term follow up diagnostic mammogram was performed in 24 patients. The median age was 56.5 years, and the median breast cancer risk assessment scores were 2.8% at 5 years and 13.4% lifetime. Of the 24 interval mammograms, 21 yielded benign findings on initial imaging (BIRADS 2), while 3 patients (12.5%) required additional imaging that ultimately resulted in benign findings. There were only 4 patients with a lifetime risk ≥25%, and all of these patients had benign findings on their initial imaging and resumed routine follow up. To date, 22 patients have received at least one additional mammogram, and all subsequent findings have been benign. No additional biopsies or surgeries have been performed. Conclusions: In sum, a clinical exam is still recommended at 6 months following surgical excision for a diagnosis of ADH. In the post-surgical breast, imaging may be misleading and result in psychological distress for patients and possibly unnecessary procedures. Based on our findings, a 6-month follow up mammogram is not recommended and patients should resume annual surveillance.
Accrual of under-represented minority women to breast cancer clinical trials in Inland Empire, California.
Authors: Yuan Yuan , Uppala Padma Tadi , Lum Sharon S. , Morgan John W. , Garberoglio Carlos 
Published: February 2017

64 Background: Ethnic minority women are currently underrepresented in breast cancer clinical trials. The age-adjusted incidence and mortality rates for breast cancer are higher in Riverside and San Bernardino Counties (Inland Empire), California, than the statewide average. During the 10 years of enrollment at Loma Linda University Cancer Center (LLUCC) between 1999 and 2009, a total of 151 patients were enrolled to breast cancer clinical trials. Among the enrolled patients, only 26.7% were ethnic minority women in contrast with the 59% of ethnic minority women living in Inland Empire. Methods: A countywide breast cancer awareness campaign using billboard, print ads, and newsletters, combined with direct mailing sent to regional physician offices and breast imaging centers was launched. We specifically addressed previously identified barriers to participation in clinical trials, such as lack of medical insurance, time, invitation, awareness of available studies, access to the institution or doctors conducting the trial, and coordination among clinics. In addition, we utilized a culturally sensitive multidisciplinary team to address the breast cancer care for minority women. Results: During the two year period since implementation of the regional culturally sensitive breast cancer awareness campaign, we successfully enrolled 32 patients into breast cancer clinical trials. Minority breast cancer patient accrual increased from a 10-year average of 26.7% to 46.9% in comparison with non-Hispanic white patients (p=0.02). The accrual rate of Hispanic population increased from 10% to 21.9%. The accrual rate of black patients increased from 5.3% to 12.5%. Conclusions: The use of materials specifically targeting known barriers to participation in clinical trials successfully improved accrual of minority women, and has the potential to improve the cure rate, decrease disparities in breast cancer care, and eventually decrease the breast cancer burden particularly in underserved minority groups in Inland Empire, California.
Stratification of 5-year cancer detection rate in an organized breast screening program based on Gail model risk factors.
Authors: Rajapakshe Rasika , Parker Brent , Araujo Cynthia , Ruscheinsky Stephanie , McAvoy Steven , Hoegg Tanja , Coldman Andy , Wilson Christine 
Published: February 2017

7 Background: The Gail model has been validated in the United States and several European countries, but to our knowledge, it has not been validated in organized breast screening programs in Canada. The Screening Mammography Program of British Columbia (SMPBC) records participant data from a questionnaire based on Gail model parameters (which include family and personal medical history). This study investigates whether the Gail model is a valid tool to predict the breast cancer risk for the population undergoing screening mammography in the province of BC. Methods: Client information of the 223,349 British Columbian women who participated in the year 2000, along with their tumor status from 2000-2004, was extracted from the provincial database. A software program was developed to rapidly calculate the absolute 5-year Gail score from questionnaire data. Participant data was separated into .5% risk intervals and also into quintiles based on increasing Gail scores, and the mean absolute risks were compared to the actual five year rate of cancer as detected by the SMPBC. Results: Overall, goodness of fit between Gail score and SMPBC detection (E/O) across the categories can be rejected (χ2=247.9, df=9, p value < .001). The Gail model significantly underpredicts the cancer detection for risk categories up to 2%, however it provides a sufficient fit for categories 2%-4% as the E/O ratio is not significantly different from 1.0 in these intervals. For the highest risk interval, categorized as greater than 4% risk, the model significantly overpredicts cancer detection. Additionally, when presented in quintiles, the Gail model under-predicts risk in all but the highest quintile (1.77-11.43% risk range). Conclusions: Our results, based on participants of SMPBC, suggest that the Gail model significantly under-predicts cancer detection. Although this model provides a sufficient fit for women with a Gail score between 1.51-4%, it does not predict breast cancer risk accurately for low and high risk women in the Screening Mammography Program of BC.
The effect of a varied exercise program (VEP) on shoulder function and lymphedema (LE) in breast cancer survivors (BCs): A pilot study.
Authors: Hanssens Sophie , Fontaine Christel , Decoster Lore , Schallier Denis C. C. , Luyten Rik , Watthy Christiaan , Van Hemelrijck Roxane , De Greve Jacques 
Published: February 2017

82 Background: A common physical sequel after adjuvant therapy is a decrease in shoulder movement of the upper-limb of the affected side and the development of LE. Resistance exercise is known to be safe and does not increase the risk of LE. The objective of this study is to evaluate the effect of a VEP on shoulder range of motion and upper-limb LE after adjuvant therapy in BCs. Methods: 22 BCs treated with surgery and adjuvant therapy were randomly assigned to the VEP (n=12) or the control (n=10). The VEP aimed at improving aerobic endurance, joint mobility and muscle strength. The frequency of the VEP was 2 times a week, during 3 months, with a total of 30 sessions. Primary endpoints included the range shoulder motion and arm volumes of both arms. The secondary outcome was quality of life (QoL) as measured by the EORTC QLQ-C30. All outcome measures were assessed at baseline and after 3 months. Results: After ending the VEP, in the exercise group, the movements such as abduction (p=0.04), external rotation (p=0.02), extension (p=0.03) and flexion (p=0.01) of the affected arm increased significantly but there was no change for internal rotation (0.27). No significant changes in arm volume (p=0.06) were found after 3 months compared to baseline, whereas the quality of life did improve significantly (p=0.01). After 3 months the range of motion of the shoulder of the affected arm (sum of abduction, external rotation, extension and flexion) in the exercise group tended to be better although this was not significant (p=0.50). The arm volume difference between the two groups was not significant (p=0.10) but it was for the QoL (p=0.02). Conclusions: A VEP lead to significant specific improvements in arm mobility compared to baseline. These BCs also compared favourably to the control cohort, but this was not significant. The study confirms that exercising the ipsilateral arm and shoulder has no detrimental effect on LE and has a positive impact on the QoL. Standard guidelines concerning physical therapy to ameliorate shoulder function and LE are not available. Additional patients will be enrolled to develop standard recommendations for physical therapy to improve shoulder and limb function in BCs.
Evaluation of a breast cancer survivorship clinic that uses a group medical appointment model: Patient program evaluation and financial analysis.
Authors: Trotter Kathy , Schneider Susan M. 
Published: February 2017

90 Background: Group medical appointments have been shown to improve access, health outcomes and health care utilization rates, as well as self-management skills. A new model of breast cancer survivor care was designed and piloted at Duke Cancer Center. Survivors attended the clinic together in groups of six. An interdisciplinary group visit format in the initial part of the appointment provided surveillance, education and support, as well as formation of an individualized survivorship care plan. The first hour included review of their personal care plan and a 45-minute facilitated discussion. Afterwards, individual visits with the nurse practitioner, and dietitian, physical therapist, or social worker occurred. Methods: A 22-item Likert-type questionnaire sought opinions regarding logistics and the style and function of care delivered. 122 surveys were collected. Descriptive statistics (via SPSS v19) using ANOVA type regression were accomplished. Secondly, a retrospective two-group study of clinic financial data for follow-up patients was done. Revenues from the group medical visit by the NP were compared to those seen traditionally by the MD (N=300). Review of time to third available appointment for each clinician was also recorded. Results: 122 surveys were collected with a 86% response rate. Mean scores for all questions rated at least 4.4 of 5, with the highest score given for the confidence felt in the nurse practitioner (4.93) and the lowest for the acceptability of the wait time in the breast imaging area (4.4). Overall, 98% felt the program provided quality care and 97% were likely to recommend the clinic to other breast cancer survivors. What participants liked most about the program was sharing with other survivors. Cost benefit analysis revealed that revenues and direct costs were nearly equal between delivery models. Time to third available appointment for the primary referring oncologist, dropped from 29.4 to 26.7 days, while the NPs time remained stable at 8.7 days. Conclusions: The group visit model applied to survivor care appears feasible and highly satisfactory to participants.
Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.
Authors: Pegram Mark D. , Blackwell Kimberly , Miles David , Bianchi Giulia Valeria , Krop Ian E. , Welslau Manfred , Baselga José , Oh Do-Youn , Dieras Veronique , Guardino Ellie , Olsen Steven R. , Fang Liang , Lu Michael , Verma Sunil 
Published: February 2017

98 Background: T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic agent DM1; it incorporates the antitumor activities of T and the HER2-targeted delivery of DM1. Methods: EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2+ MBC. Patients (pts) received T-DM1 (3.6 mg/kg IV q3w) or X (1,000 mg/m2PO bid, days 1–14 q3w) + L (1,250 mg PO daily) until progressive disease (PD) or unmanageable toxicity. Pts had confirmed HER2+ MBC (IHC3+ and/or FISH+), and prior therapy with T and a taxane. Primary end points were PFS by independent review, OS and safety. An interim OS analysis was planned at the time of the final PFS analysis. Results: 991 pts were enrolled; 978 received treatment. Median (med) durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months (mo). Baseline demographics, prior therapy and disease characteristics were balanced. There was a significant improvement in PFS favoring T-DM1 (med 9.6 vs 6.4 mo; HR=0.650 [95% CI, 0.549–0.771]; p < .0001). The med T-DM1 OS was not reached vs 23.3 mo (HR=0.621 [95% CI, 0.475–0.813]; p =.0005); the interim efficacy boundary was not crossed (HR= 0.617; p =.0003). T-DM1 was well tolerated with no unexpected safety signals. The most common Grade ≥3 adverse events (AEs) per treatment were for T-DM1: thrombocytopenia (12.9% vs 0.2%), increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs 1.4%); for XL: diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%). The table lists other end points. Conclusions: T-DM1 conferred a significant and clinically meaningful improvement in PFS compared with XL. Other end points support T-DM1 as an active and well-tolerated novel therapy for HER2+ advanced BC. [Table: see text]