bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-07-15: Breast cancer estrogen receptor scoring in tissue microarrays: Specialist breast pathologist versus automation
Authors: Jordan LB , Akbar S , Purdie CA , Thompson AM , McKenna SJ 
Published: May 2016

Abstract
Rationale: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analyzing protein expression in large numbers of patient samples efficient with conservation of tissue. However, manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. Computerized ER scoring relies on tumor localization.
Aim: The objective of this study was to compare the effectiveness of a locally developed automated invasive tumor location system with the skills of specialist breast pathologists.
Methods: In this study, tumor localization for estrogen receptor (ER) scoring was evaluated comparing computer- generated segmentation masks with those of two specialist breast pathologists. Automated tumor localization was achieved using a novel image analysis algorithm, which labeled compact groups of pixels called superpixels. Machine learning techniques were adopted to model color, shape and textural properties of superpixels in a rotation invariant manner, suitable for histopathology images. The resulting automatically and manually-obtained segmentation masks were used to obtain IHC scores for thirty-two ER stained invasive breast cancer TMA samples using FDA-approved IHC scoring software.
Results: Pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ = 0.84) than between pathologists' masks (κ = 0.91). However, this had little impact on computed IHC scores (Allred method; κ = 0.91, Quickscore method; κ = 0.92).
Conclusion: The automated system provides sufficiently consistent measurements for standardized IHC analysis of nuclear staining in TMAs from large clinical trials.
Citation Format: Jordan LB, Akbar S, Purdie CA, Thompson AM, McKenna SJ. Breast cancer estrogen receptor scoring in tissue microarrays: Specialist breast pathologist versus automation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-07-15.
Abstract P5-08-16: Local immunologic environment related with tumor infiltrating lymphocytes (TIL) and PD-1/PD-L1 expression in early stage breast cancer
Authors: Okabe M , Toh U , Iwakuma N , Mishima M , Kawahara A , Kage M , Itoh K , Akagi Y 
Published: May 2016

Abstract
Purpose:
Recent studies have shown that local immune environment revealed with programmed death 1(PD-1)/programmed death ligand 1(PD-L1) and tumor infiltrating lymphocytes(TIL) affects the tumor-growth and prognosis. In this study, we evaluated the tumor local immune environments using immunohistological staining for analysis of PD-1/PD-L1 expression and TIL of tumor local in operable early-stage breast cancer.
Method:
A total of 100 surgical specimens of stageI-III invasive breast carcinoma paraffinembedded between 1995 and 2005 were analyzed. Immunohistological staining for PD-1, PD-L1, PTEN, CD3, CD8, and CD163 were performed by the conventional PAP method. In addition, intratumoral and intrastromal TILs and macrophages were simultaneously stained by anti-CD3, CD8, CD163 antibodies and measured by 'Win ROOF' computer software (version 5.7, Mitani Corporation, Japan).
Results:
Intratumoral PD-1 expressed significantly higher in triple negative breast cancer (TNBC) compared to other subtype BC (p=0.0094), intratumoral and intrastromal CD3+ lymphocytes and CD163+ macrophages were also significantly higher in TNBC, respectively (CD3: p=0.0002; 0.0139 and CD163: p=0.0043; 0.0270). PTEN loss was also more frequently observed in TNBC (p=0.0475). In addition, after a median 5-year follow-up, patients of luminal A subtype with lower PD-L1 and PTEN expression showed better disease free survival (DFS) with a significant difference (p=0.0148, p=0.0475).
Conclusion:
Local expression of PD-1/PD-L1 antigens on tumor cells, CD3+ lymphocytes, CD163+ macrophages infiltration singnificantly increased in early-stage TNBC. PTEN expression on tumor local might be associated with DFS in patients with early-stage BC.
Citation Format: Okabe M, Toh U, Iwakuma N, Mishima M, Kawahara A, Kage M, Itoh K, Akagi Y. Local immunologic environment related with tumor infiltrating lymphocytes (TIL) and PD-1/PD-L1 expression in early stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-16.
Abstract P5-08-26: CYP1A2– A novel genetic marker for aromatase inhibitor response in the treatment of breast cancer patients
Authors: Simonsson M , Veerla S , Markkula A , Rose C , Ingvar C , Jernström H 
Published: May 2016

Abstract
Background: Endocrine resistance is a major obstacle for optimal endocrine treatment in breast cancer (BC). Several genetic markers for tamoxifen response have been proposed. Although some genetic markers have been proposed for response to aromatase inhibitors (AI), data is insufficient. The aim of this study was 1) to perform an exploratory analysis of genes involved in Absorption, Distribution, Metabolism, and Elimination (ADME) to find new predictive markers in a subset of the cohort and 2) examine these potential markers in relation to risk for events in the extended cohort.
Materials and methods: In Lund, Sweden, 190 AI-treated primary breast cancer patients with estrogen receptor positive tumors, who underwent breast cancer surgery between 2002 and 2008, were followed until December 31st 2012. Clinical data were obtained from medical records and population registries. The impact of single nucleotide polymorphisms (SNPs) on risk for breast cancer events was conducted on a subset of the cohort followed until December 31st 2011 (13 cases, 11 controls) and analyzed with data from a DMET (TM) chip including 1931 SNPs in 225 ADME-related genes. Secondly, four SNPs in CYP19A1 and the significant SNPs from the first analysis were reanalyzed concerning disease-free survival in the extended cohort of 190 patients.
Results: A CYP1A2 SNP was significantly associated with risk for early events among the 24 AI-treated BC patients both in the subset of the cohort, (P=0.0007) and in the extended cohort, adjusted HR 3.83 (95% CI 1.40-10.42). SNPs in CYP19A1 alone were not significantly associated with disease-free survival in any of the analyses. The impact of the CYP1A2 SNP was modified by a SNP in CYP19A1, where patients with both SNPs had increased risk for early events, adjusted HR 5.21 (95% CI 2.05-13.23) compared to other patients.
Conclusion: This study identified a potential and new predictive marker in BC patients: CYP1A2 alone and CYP1A2 in combination with CYP19A1. If confirmed, these results may provide a way to more personalized medicine.
Citation Format: Simonsson M, Veerla S, Markkula A, Rose C, Ingvar C, Jernström H. CYP1A2– A novel genetic marker for aromatase inhibitor response in the treatment of breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-26.
Abstract P5-08-41: Prognostic contribution of mammographic breast density and HER-2 overexpression to the Nottingham prognostic index in patients with invasive breast cancer
Authors: Masarwah A , Sudah M , Sutela A , Päivi A , Ritva V 
Published: May 2016

Abstract
Purpose: To examine the associations between very low mammographic breast density (VLD), HER2, ER and PR status in a more homogenized patient group within matched NPI categories. We also aimed to investigate whether those variables could be added to the NPI to enhance its prognostic and predictive values and better categorize which patients are at higher risk.
Materials and methods: A total of 270 patients with invasive breast cancer were included in the final analysis. Patients with mammographic breast density of &lt;10% were considered as VLD. We compared the performance of NPI with and without ER, PR , VLD and/or HER2. Factors first underwent univariate and then multivariate analysis to assess the factors combined until the best fit was obtained. Cox multivariate analysis, time-dependent receiver operating characteristic curve (tdROC), concordance index (c-index) and prediction error (i.e. 0.632+ bootstrap estimator) were used to derive an updated version of NPI. Patients' survival was assessed by the Kaplan-Meier method using a log rank (Mantel-Cox) test.
Results: The average NPI value was 4.66 (range 2.12-7.40), the percentage of HER2 positive patients progressively increased from the low to the high prognostic groups of NPI (p&lt;0.001). While MBD, ER and PR status showed no such difference in distribution. Patients showed survival differences in the intermediate and high risk groups of NPI according to VLD and HER2 status (p&lt;0.001 and p=0.02, respectively). Outcome analysis showed that the addition of both factors combined provides improved patient outcome stratification superior to the traditional NPI helping to significantly decrease the percentage of patients in the intermediate patient groups.
Conclusion: VLD breasts and HER2 positivity are prognostic factors for breast cancer independent of the NPI. Moreover, their addition to the NPI helps increase its prognostic accuracy and reduces the percentage of patients in the intermediate prognostic group.
Citation Format: Masarwah A, Sudah M, Sutela A, Päivi A, Ritva V. Prognostic contribution of mammographic breast density and HER-2 overexpression to the Nottingham prognostic index in patients with invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-41.
Abstract P5-09-12: The importance of education for adherence to mammographic screening in the Brazilian public health services
Authors: Blanco EC , Ribeiro IM , Nascimento CCP , da Silva CA , Abrah㯀 CF , Borges MM 
Published: May 2016

Abstract
Introduction: A third of the registration of new cases of breast cancer in Brazil corresponds to locally advanced or late diagnosed disease. The benefits of screening in this sense become evident and measurable in terms of their temporal extent and adherence of the target population to its recommendations. Unlike the organized mammographic screening where there is call, breast health education, monitoring and enforcement of the intervals between examinations, in the opportunistic model, individuals are subject to the recommendations from the spontaneous demand by health services. Objective: To determine the influence of education in breast cancer for adherence to mammographic screening in brazilian public health services. Methods: This is a cross-sectional, descriptive and comparative study between two groups of women with (group A, n=136) and without (group B, n=128) knowledge about breast cancer, who appeared in the Center of Detection, Diagnosis and Monitoring (CDDM) for organized screening. For this were interviewed 264 women in relation to the realization of previous mammograms in the last three years. The repetition of examinations, respecting the range of 24 months was defined as criteria to classify participants in adherent or not to screening. Results: Both groups of women had a similar mean age (50.2 ± 9.2 and 49.5 ± 9.5 years; p&gt;0.05). Of the respondents, 77.2% (n=204) reported mammographic screening before joining the CDDS, however highest proportion was registered in group A (64.8%). Sixty women denied conducting prior mammography with predominance in the Group B (93.4% vs 6.6%, p&lt;0.05). One hundred forty-four women were adherent to screening, 90.2% (n=130) of these belonged to group A. The remaining variables (education, occupation, family income, distance between place of residence and mammography center and personal / family history of breast cancer) were not associated with adherence to screening (p&gt;0.05). Conclusion: The decrease in the adherence to conducting periodic mammography observed in group B reflects the opportunistic character of the screening in the country, where it loses the chance to sensitize women through education to improve their effective adhesion. Acknowledgements to the Brazilian Ministry of Health for their support to the study.
Citation Format: Blanco EC, Ribeiro IM, Nascimento CCP, da Silva CA, Abrah㯀 CF, Borges MM. The importance of education for adherence to mammographic screening in the Brazilian public health services. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-09-12.
Abstract P5-12-08: Time course of changes in serum FSH, serum estradiol, and menstruation in premenopausal patients with breast cancer taking tamoxifen after completing chemotherapy: A report from the ASTRRA study
Authors: Kim HJ , Ahn SH , Nam SJ , Park SH , Ro JS , Im SA , Jung YS , Noh WC 
Published: May 2016

Abstract
BACKGROUND
Ovarian suppression with tamoxifen after chemotherapy is a promising therapeutic approach, particularly in young, high-risk breast cancer patients. Assessment of restoration of ovarian function is important with respect to the initiation of ovarian suppression.
METHODS
In total, 1289 women who remained or resumed premenopausal status after chemotherapy were randomized to receive 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. Prospectively collected hormone data were available for 24 months after completing chemotherapy for 267 breast cancer patients without ovarian suppression.
RESULTS
At 6 months, a premenopausal status was identified in 56.6%, 36%, and 16.2% of patients using serum FSH, E2, and with menstruation bleeding, respectively, and about 30% more women achieved ovarian restoration using all three parameters during the 24-month follow-up. Ovarian function restoration differed significantly according to age group (log-rank, P&lt;0.001 for all definitions). At 6 months, the distribution of patients according to hormone levels was as follows: group 1 (FSH &lt;30 mIU/ml, E2 &gt;20 pg/ml), 28.0%; group 2 (FSH &lt;30 mIU/ml, E2 ≤20 pg/ml), 28.4%; group 3 (FSH ≥30 mIU/ml, E2 &gt;20 pg/ml), 8.0%; and group 4 (FSH ≥30 mIU/ml, E2 ≤20 pg/ml), 35.6%. During the 24-month follow-up, the prevalence of menstruation restoration was higher in group 1 (71.6%) than in the other three groups. Restoration of serum E2 and menstrual bleeding occurred in 44% and 33% of patients in group 2, respectively; the corresponding percentages in group 4 were 40.6% and 28.7% (P&lt;0.001).
CONCLUSIONS
Ovarian function should be monitored using serum FSH, serum E2, and menstruation history for at least 24 months after completing chemotherapy during tamoxifen treatment to establish eligibility for ovarian suppression.
Citation Format: Kim HJ, Ahn SH, Nam SJ, Park SH, Ro JS, Im SA, Jung YS, Noh WC. Time course of changes in serum FSH, serum estradiol, and menstruation in premenopausal patients with breast cancer taking tamoxifen after completing chemotherapy: A report from the ASTRRA study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-08.
Abstract P5-12-11: Duration of ovarian function suppression for premenopausal women with hormone receptor-positive breast cancer: Retrospective study
Authors: Ozaki Y , Tamura N , Utiyama M , Masuda J , Koganemaru S , Miura Y , Tanabe Y , Ogura T , Kadowaki M , Miura D , Kawabata H , Takano T 
Published: May 2016

Abstract
Background: Although tamoxifen (TAM) plus ovarian function suppression (OFS) is one of standard adjuvant treatments in premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not been clearly established.
Patients and Methods: We retrospectively reviewed data of premenopausal patients with breast cancer, who received TAM and OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and April 2015. The primary analysis was to compare disease-free survival (DFS) between patients who received OFS shorter than 3 years and those who received OFS longer than 3 years. The analyses were performed with Cox proportional hazards models and propensity score matching models.
Results: We analyzed 206 premenopausal patients with hormone receptor-positive breast cancer. Median follow-up time was 56 months. Median age was 42 years (range, 24-52 years). Twenty six per cent of the patients had positive axillary nodes and 30% had received neo-adjuvant or adjuvant chemotherapy. Median duration of OFS was 26 months. Duration of OFS was shorter than three years (OFS &lt; 3y) in 74% patients, and longer than three years (OFS &gt; 3y) in 26% patients. Patients with node-positive disease were more in OFS &gt; 3y group than in OFS &lt; 3y group, and more patients received chemotherapy in OFS &gt; 3y group than in OFS &lt; 3y group. 5-year disease-free survival (DFS) was 96.1%. DFS in patients aged ≤ 40 years and aged &gt; 40 years were 91.8% and 99.0%, respectively (p=0.0223). Propensity score matching model showed that DFS was not significantly different between patients in OFS &lt; 3y group and those in OFS &gt; 3y group (97.4%, 91.6%; p=0.2406). In patients aged ≤ 40 years and/or those who received chemotherapy, 5-year DFS was 96.7% in OFS &lt; 3y group, 90.1% in OFS &gt; 3y group (p=0.3011).
Conclusions: Our data suggest that OFS &lt; 3y is not inferior to OFS &gt; 3y for premenopausal women with hormone receptor-positive breast cancer as adjuvant endocrine therapy. A randomized trial is needed to establish the optimal OFS duration for these patients.
Citation Format: Ozaki Y, Tamura N, Utiyama M, Masuda J, Koganemaru S, Miura Y, Tanabe Y, Ogura T, Kadowaki M, Miura D, Kawabata H, Takano T. Duration of ovarian function suppression for premenopausal women with hormone receptor-positive breast cancer: Retrospective study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-11.
Abstract P5-14-02: Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials
Authors: Niraula S , Pitz M , Gordon V , Grenier D , Amir E , Brandes L 
Published: May 2016

Abstract
Background: While fulvestrant is approved by the United Stated Food and Drug Administration as an alternate endocrine therapy for treatment of advanced breast cancer, data on its efficacy compared to other endocrine treatments are inconsistent. Clinical markers predictive of greater benefit from fulvestrant compared to the alternate endocrine agents have not been identified.
Methods: We searched the literature from inception to May, 2015 from MEDLINE, EMBASE, and major conference proceedings. We included randomized controlled trials that evaluated Fulvestrant compared to either tamoxifen or an AI. We collected the efficacy data reported as Time to Progression (TTP) or Progression Free Survival (PFS) on 7 distinct subgroup of patients from the RCTs defined by: age, time to cancer reoccurrence from primary diagnosis, presence of visceral metastasis, previous chemotherapy exposure, presence of measurable disease, hormone receptor status and, HER-2 status. Data on rates of occurrences of 9 most frequently reported adverse events were also collected from both arms of the studies. Data on both efficacy and toxicity were then weighted using generic inverse variance approach and pooled in a meta-analysis using RevMan 5.3 software.
Results: We identified 8 RCTs that fulfilled our criteria and involved 4,024 patients (2,032 on fulvestrant and 1,992 on control arms). TTP/PFS was the primary endpoint in 7 out of 8 RCTs and secondary endpoint in one. Compared to an AI or tamoxifen, there was a statistically significant improvement in TTP favoring fulvestrant in patients who had visceral metastasis [Hazards Ratio (HR) 0.86; 95% Confidence Interval (CI) 0.77 to 0.96, p&lt;0.01], measurable disease [HR 0.74; 95% CI 0.58 to 0.93, p=0.01], and HER-2 overexpression [HR 0.43; 95% CI 0.27 to 0.70, p&lt;0.001]. Similar effect sizes were observed in a sensitivity analysis excluding the trials of combinations of fulvestrant and AI in the experimental arm. Rates of occurrences of adverse events were similar between fulvestrant and other endocrine agents.
Conclusion: Patients with advanced breast cancer that have visceral disease, measurable disease, or HER-2 driven disease are likely to derive higher benefits from treatment with fulvestrant compared to tamoxifen or an AI. These results may have implications for selection of patients in the design of future clinical trials and to inform treatment decisions in clinical practice.
Citation Format: Niraula S, Pitz M, Gordon V, Grenier D, Amir E, Brandes L. Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-02.
Abstract P5-15-04: Zoledronic acid combined with adjuvant tamoxifen with or without ovarian function suppression in premenopausal early breast cancer patients
Authors: El-Ibrashi MM , El-Sadda WM , Abdel-Halim II , Elashri MS 
Published: May 2016

Abstract
Background:
Bisphosphonates can delay the onset and reduce the risk of skeletal related events in patients with bone metastatic breast cancer; it can prevent and controlcancer treatment-induced bone loss. Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease free survival. The aim of the study is to evaluate the benefits of ZOL combined with adjuvant therapy in premenopausal early breast cancer patients.
Patients and methods:
Patients were premenopausal females who had undergone primary surgery for stage I, II ER +ve and/or PR +ve breast cancer with &lt; 10 positive lymph nodes. All 300 patients were scheduled for standard tamoxifen 20mg/day for five years plus goserelin 3.6 mg every 28 days and were randomized to ZOL 4mg every 6 months for 3 years (group A) and without ZOL (group B). The primary end points were toxicity and disease-free survival (DFS), while overall survival (OS) was the secondary end point.
Results:
Between April 2005 and March 2012, 300 patients were enrolled, the median follow up duration was 98.4 months (range 14-120 months), adding ZOL to endocrine therapy strongly suggests improved DFS versus endocrine therapy alone (90% versus 85% for an absolute increase of 5%). There were fewer disease recurrences in the ZOL group versus no ZOL group (12% vs. 16%) with the greatest reductions in the loco-regional recurrence (3% vs. 5%), distant metastasis (6% vs. 7%) and bone metastasis (3% vs. 5%).
Conclusion:
ZOL with adjuvant endocrine therapy were generally well tolerated with no reports of renal failure or osteonecrosis of the jaw. So, a twice yearly ZOL enhanced the efficacy of adjuvant endocrine treatment, and this benefit is maintained for long time.
Citation Format: El-Ibrashi MM, El-Sadda WM, Abdel-Halim II, Elashri MS. Zoledronic acid combined with adjuvant tamoxifen with or without ovarian function suppression in premenopausal early breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-04.