bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-08-19: Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype
Authors: Tsukioki T , Taira N , Sakamaki K , Suzuki Y , Kajiwara Y , Hatono M , Takahashi Y , Kawata K , Kochi M , Iwamoto T , Ikeda H , Shien T , Doihara H 
Published: May 2019

Abstract
Background: Overall survival (OS) is the established endpoint to evaluate the effects of drug treatment in comparative clinical trials of metastatic breast cancer. But assessing OS requires long follow-up periods and large sample size, which raise costs and create long delays in the drug approval process. Progression-free survival (PFS) or time to progression (TTP) is considered as a surrogate for OS and is often used as an alternative to OS. In some cancers the two endpoints are highly correlated, but in others they are not. Furthermore, the effect of breast cancer (BC) subtypes on the surrogacy of PFS/TTP for OS has not been completely defined.
Method: A systematic literature review of randomized control trials was conducted to identify studies that reported both the hazard ratio (HR) of PFS/TTP and OS for BC subtypes {i.e. estrogen receptor (ER) positive, HER2 positive, and triple negative (TN)}. The correlation between the HR of PFS/TTP and OS was evaluated using weighted Spearman's rank correlation.
Results: A total of 49 trials (34 phase III trials and 15 phase II trials) were selected for analysis. Among these trials, there were 8 comparison trials between one chemotherapy and another chemotherapy regimen, 18 comparison trials between chemotherapy and chemotherapy plus molecularly-targeted therapy, 9 comparison trials between one endocrine therapy and another endocrine therapy, and 5 comparison trials between endocrine therapy and endocrine therapy plus molecularly-targeted therapy. There were 17 trials reporting the HR of PFS/TTP and OS for ER positive, 16 trials for HER2 positive, and 9 trials for TN BC. Weighted Spearman's rank correlation revealed that coefficient between the HR of PFS/TTP and OS was 0.721(p&lt;.0001) for all trials, 0.873(p&lt; .0001) for ER positive, 0.642(p=0.0055) for HER2 positive, and 0.615(p=0.078)for TN BC.
Conclusion: There was a strong correlation between the HR of PFS/TTP and OS for ER positive BC, and a weak correlation between the HR of PFS/TTP and OS for HER2 positive and TN BC. The validity of using PFS/TTP as an OS surrogate marker was shown for metastatic BC, especially for ER positive BC.
Citation Format: Tsukioki T, Taira N, Sakamaki K, Suzuki Y, Kajiwara Y, Hatono M, Takahashi Y, Kawata K, Kochi M, Iwamoto T, Ikeda H, Shien T, Doihara H. Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-19.
Abstract P4-08-26: Validation of different prognostic scores in breast cancer patients with brain metastases of the BMBC registry (GBG-79)
Authors: Witzel ID , Riecke K , Laakmann E , Weide R , Neunhoeffer T , Park-Simon T-W , Schmidt M , Fasching PA , Hesse T , Polasik A , Mohrmann S , Würschmidt F , Schem C , Bechtner C , Würstlein R , Fehm T , Möbus V , Burchardi N , Loibl S , Müller V 
Published: May 2019

Abstract
Background
The incidence of brain metastases from breast cancer is increasing and treatment is a major challenge. Different scores were developed to estimate the prognosis of patients with brain metastases by objective criteria. Sperduto et al. established the disease-specific breast-graded prognostic assessment (GPA) score in 400 breast cancer patients which includes age, performance status and tumor subtype. It has been described that the Breast- GPA best identifies patients with bad prognosis (Laakmann et al. 2016). Aim of this analysis was to validate the Breast-GPA in a large cohort of breast cancer patients with brain metastases.
Materials and methods
Data of 613 breast cancer patients from the Brain Metastases in Breast Cancer (BMBC) registry treated in 80 different clinical German institutions between 2000 and 2016 was analyzed.
Results
135 patients (22%) had a triple-negative, 199 (32%) a luminal-like und 279 (46%) a HER2-positive primary breast cancer. At diagnosis of brain metastases most patients had a good Karnofsky performance status (100%: 14.4%, 80-90%: 44.7%, 60-70%: 28.9%, 40-50%: 9.0%, 10-30%: 3.1%). Median age of patients was 56 years (22-90 years).
Median survival in the overall cohort was 7.1 months (95% CI 6.2-7.8 months).
Distribution of GPA scores was: 0-1: 11.9% (n=73), 1,5-2: 22.3% (n=137), 2,5-3: 47.8% (n=293), 3,5-4: 18% (n=110).
Median overall survival within the GPA-subgroups varied between 2.4 (CI95% 2.0 - 3.4); 4.8 (3.6 - 6.9); 9.2 (7.2 - 11.3) and 12.3 (8.9 - 18.0) months and, thus, was significantly shorter compared with the times published by Sperduto et al. (3.4; 7.7; 15.1 und 25.3 months).
Conclusions
The breast-GPA is easy to calculate in clinical routine, allows to assess patients` prognosis objectively and can facilitate making therapeutic decisions. However, absolute survival may differ from the originally published cohort in other settings.
Citation Format: Witzel ID, Riecke K, Laakmann E, Weide R, Neunhoeffer T, Park-Simon T-W, Schmidt M, Fasching PA, Hesse T, Polasik A, Mohrmann S, Würschmidt F, Schem C, Bechtner C, Würstlein R, Fehm T, Möbus V, Burchardi N, Loibl S, Müller V. Validation of different prognostic scores in breast cancer patients with brain metastases of the BMBC registry (GBG-79) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-26.
Abstract P4-08-35: Young age at diagnosis is associated with worse prognosis in the luminal A breast cancer subtype. A retrospective institutional cohort study
Authors: Liu Z , Sahli Z , Wang Y , Wolff AC , Cope L , Umbricht CB 
Published: May 2019

Abstract
Background: Breast cancer (BCA) presents with distinct molecular subtypes, each associated with different patterns of relapse, drug sensitivity, and prognosis. Although age at diagnosis is a recognized independent prognostic risk factor, its relative importance among molecular subtypes is not well documented. The aim of this study was to evaluate the prognostic role of age at diagnosis among BCA patients of different immunohistochemical subtypes (LuminalA, LuminalB, Her2, Triple-negative).
Methods: We conducted a retrospective study of women with invasive BCA undergoing surgery at the Johns Hopkins Hospital from January 2000 - December 2016, excluding patients presenting with stage IV breast cancer. Patients were stratified into three age groups: ≤ 40, 41-60, and &gt; 60 years, and multivariable analysis was performed using Cox regression. To explore age-related differences in gene expression, we identified differentially expressed genes (DEG) between age groups among BCA subtypes in the TCGA dataset. Finally, we identified key driver genes within DEG using a weighted gene co-expression network analysis.
Results: Our cohort included 3,524 patients with a median follow-up of 85.1 months. LuminalA breast cancer patients had significantly lower 5-year Disease Free Survival (DFS) and Distant Metastasis-Free Survival (DMFS) in the ≤ 40 year age group compared to the 40-60 year age group (HR=2.69, 95%CI: 1.72 - 4.23 and HR=2.95, 95%CI: 1.78 - 4.90, respectively), while the other molecular subtypes showed no significant association of DFS or DMFS with age. Age was a stronger predictor of 5- year DFS and 5-year DMFS than tumor grade or proliferative index (Ki67) in LuminalA BCA patients, but not other subtypes.
Gene expression data were obtained from 1097 BCA TCGA patients, divided into two groups (≤40y, n=36; &gt;40y, n=455). We identified 374 DEG between ≤40y and &gt;40y LuminalA BCA subsets. The DEG were enriched in 7 pathways, and the WGCNA analysis identified two modules of co-expressed genes. No age group-specific DEG were identified in non-LuminalA subtypes.
Conclusion: Age at diagnosis may be an important prognostic factor in LuminalA BCA and may improve risk stratification and personalized therapy. Prospective studies are needed to further evaluate the prognostic value of age in this subset of BCA patients.
Citation Format: Liu Z, Sahli Z, Wang Y, Wolff AC, Cope L, Umbricht CB. Young age at diagnosis is associated with worse prognosis in the luminal A breast cancer subtype. A retrospective institutional cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-35.
Abstract P4-09-02: Validation of iPrevent using the prospective family study cohort (ProF-SC)
Authors: Phillips K-A , Liao Y , Collins IM , Buchsbaum R , Weideman P , Bickerstaffe A , MacInnis RJ ,   kConFab Investigators, Cuzick J , Antoniou A , Andrulis IL , John EM , Daly MB , Buys SS , Hopper JL , Terry MB 
Published: May 2019

Abstract
Background: iPrevent (https://www.petermac.org/iprevent) provides women with highly-tailored risk management information after first estimating their breast cancer (BC) risk using the established risk prediction models, IBIS and BOADICEA. iPrevent has an internal switching algorithm that governs which model is used for each woman, depending on her risk factor data (i.e. LCIS/atypical hyperplasia status, BRCA status, and cancer family history). This study assessed the calibration and discriminatory accuracy of the 10-year BC risk estimates provided by iPrevent. Methods: Subjects were 16,574 women in the ProF-SC, aged 18-70 years and without BC or bilateral mastectomy at recruitment. After 10 years follow-up, 655 women (4%) were diagnosed with invasive BC. A “batch mode” for iPrevent is not available, so the iPrevent-assigned cumulative 10-year invasive BC risks were calculated by entering self-reported risk factors at cohort entry into either the IBIS (10,169 women) or BOADICEA (6,405 women) software packages (according to the iPrevent switching algorithm). To assess calibration, the mean iPrevent-assigned risk was compared with the mean 10-year observed invasive BC incidence, using a chi-squared goodness-of-fit statistic for the whole cohort, and by quartiles of risk. To evaluate discriminatory accuracy, the overall area under the receiver operating characteristic curve (AUC) for the development of invasive BC within 10 years was computed. Data were censored at date of invasive or in situ BC diagnosis, bilateral mastectomy, death, loss to follow-up, or at 10 years of follow-up. Results: For the whole cohort, iPrevent assigned risk was well-calibrated – 690 expected BCs (E) 655 observed (O) (E/O=1.05, 95% CI: 0.98-1.14), although for women in the highest risk quartile, i.e. &gt;6% 10-year risk, E/O=1.19, 95% CI: 1.07-1.32. The AUC was 0.70, 95% CI: 0.68-0.72. Conclusions: iPrevent is well calibrated overall and has good discriminatory accuracy for predicting 10-year BC risk, thus justifying its clinical use.
Citation Format: Phillips K-A, Liao Y, Collins IM, Buchsbaum R, Weideman P, Bickerstaffe A, MacInnis RJ, kConFab Investigators, Cuzick J, Antoniou A, Andrulis IL, John EM, Daly MB, Buys SS, Hopper JL, Terry MB. Validation of iPrevent using the prospective family study cohort (ProF-SC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-02.
Abstract P4-10-15: Obesity influences the character of the breast cancer in postmenopausal women in Japan
Authors: Suzuki M , Takei H 
Published: May 2019

Abstract
Background: We know Estrogen Receptor (ER) positive and/or Progesterone Receptor (PgR) positive tumors tend to develop more frequently in obese individuals in postmenopausal women. However, the average body size of a Japanese woman is relatively smaller than that of a Caucasian woman. There are few reports about the influence of the obesity to the character of the Japanese breast cancer women and the tendency is not clear. The aim of this study is to clarify whether the tendency is the same even in Japanese breast cancer women. Furthermore, we investigate whether HER2 expression (HER2) and Ki-67 index (Ki-67) have some relations with the height (HT), the weight (WT) and the body mass index (BMI) in Japanese breast cancer women.
Methods: HT and WT of 279 Japanese women with breast cancer in Kitamurayama hospital were evaluated. The mean HT and WT of them are 153.6cm and 54.9kg. Subsequently, the women's BMI (WT/(HT)2) was calculated. The mean BMI was 23.3. The ER and PgR were stained for immunohistochemical (IHC) analysis. Regardless of the intensity, stained cases were defined as positive. HER2 was divided into HER2 negative (IHC score 0, +1 and/or FISH negative) or positive (IHC score +3 and/or FISH positive). Ki-67 was determined by staining with MIB-1 antibody, and the cutoff value was decided on 20%, and divided into two groups of more than 20% (Higher) and less than 20% (Lower). Then, we examined the relationship of HT, WT and BMI with ER, PgR, HER2 and Ki-67 in postmenopausal and premenopausal women.
Result: In postmenopausal women, WT and BMI were significantly higher in ER positive (p=0.0230, p=0.0129). WT and BMI were also significantly higher in PgR positive (p=0.0049, p=0.0294,). There was no significant difference between HER2 positive and Her2 negative, and between Ki-67 Higher and Ki-67 Lower either. In premenopausal women, no significant association was observed in all items.
Conclusion: In postmenopausal women, HT did not have the significant difference between ER (and PgR) positive and ER (and PgR) negative. However, ER (and PgR) positive were significantly higher in WT and BMI. It was thought that the obesity influences the character of the breast cancer in postmenopausal women. Compared to less obese postmenopausal Japanese women with breast cancer, more obese postmenopausal Japanese women have a propensity for developing hormone sensitive tumors.
Citation Format: Suzuki M, Takei H. Obesity influences the character of the breast cancer in postmenopausal women in Japan [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-15.
Abstract P4-10-16: Neoadjuvant chemotherapy infusion in the arm ipsilateral to breast cancer increases the risk of lymphedema
Authors: Bergmann A , Bello MA , Thuker LC , Andrade MF , Bevilacqua JI 
Published: May 2019

Abstract
Background: Neoadjuvant chemotherapy (NAC) has been administered to clinically axillary positive breast cancer (BC) patients. Current guidelines still recommend axillary lymphadenectomy (AL) in patients with persistent positive axillary lymph node disease. We aimed to evaluate the association of NAC and/or adjuvant chemotherapy (CT) infusion in the ipsilateral upper limb (IA) with AL and the occurrence of lymphedema (LE) secondary to BC treatment. Methods: A prospective cohort study of 683 women subjected to AL and treated with NAC and/or adjuvant CT for BC. The patients were evaluated before treatment, immediate and every 6 months after surgery. Cumulative incidence and population attributable risks of LE were calculated. Results: 8-year cumulative incidence of LE was 33.1%. NAC and CT infusion and infusion of &gt;2 cycles into the IA respectively increased by 1.68, 1.67 and 1.78 times the risk of LE respectively (all P&lt;0.01). LE could be avoided in 9.4% of cases if the CT infusion had not been administered in the IA. Conclusions: 33.1% of women developed LE. The risk of LE was increased among women who received CT in the IA. Avoidance of NAC or adjuvant CT in the IA could prevent 9% of the LE cases observed in this population.
Citation Format: Bergmann A, Bello MA, Thuker LC, Andrade MF, Bevilacqua JI. Neoadjuvant chemotherapy infusion in the arm ipsilateral to breast cancer increases the risk of lymphedema [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-16.
Abstract P4-11-03: Withdrawn
Authors: Kim EY , Park YL , Park CH , Suh BC 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Kim EY, Park YL, Park CH, Suh BC. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-11-03.
Abstract P4-14-13: Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer
Authors: Kim MK , Shin H-c 
Published: May 2019

Abstract
Introduction
Adjuvant endocrine therapy is an integral compo-nent of care for endocrine-dependent breast cancer.
To date, international consensus statements recommend tamoxifen (20 mg/day) for five years as the standard adjuvant endocrine therapy for premenopausal women. Tamoxifen is a potent inducer of ovarian function and consequent hyper-estrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenone were not clarified.
Methods
Among consecutive patients who were operated under diagnosis of breast cancer from March 2012 to December 2016 in Chung-Ang university hospital, patients who received post-operative tamoxifen therapy for endocrine-dependent breast cancer (stage 0-III) at age under 60 were selected and retrospectively analysed. Serial data on serum estradiol and follicular stimulating hormone(FSH) were collected. When the serum concentration of estradiol was higher than 400 pg/mL, which exceeds the normal estradiol production by a single preovulatory follicle, we classified them as tamoxifen induced ovarian hyperstimulation group. Clinicopathologic factors were analyzed between ovarian hyperstimulation group and non-hyperstimulation group by x2 and student t-test.
Results
Among 205 patients, 19 patients(9.3%) showed high values of serum estradiol during tamoxifen therapy. They showed 44 times of high estradiol level during follow up period. The serum concentrations of estradiol and FSH were 1047.97638.8pg/mL and 11.57.3 mIu/mL, respectively. The mean duration from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol was 666.4+433.1 days.
Univariate and multivariate analysis between ovarian hyperstimulation and non-hyperstimulation groups showed younger age(&lt;40years) and only endocrine therapy without chemotherapy were related to higher prevalence of ovarian hyperstimulation significantly. (p &lt;0.001, =0.031 each) Pathologic stages and progesterone receptor expressions on breast tumor were not related to manifestation of ovarian hyperstimulation.
Conclusions
The Incidence rate and occurrence time of ovarian hyperstimulation associated with adjuvant tamoxifen treatment in breast cancer patients under age 60 were 9.3% and around 2-year after treatment with tamoxifen. Young age under 40 years old and endocrine treatment without chemotherapy were risk factors predicting occurrence of ovarian hyperstimulation during tamoxifen treatment. It should be noted that tamoxifen is a potent inducer of ovarian function and close monitoring of the endocrine parameters during treatment with tamoxifen would be essential.
Citation Format: Kim MK, Shin H-c. Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-13.
Abstract P5-02-03: Testing machine learning algorithms' performance for non-invasively identifying breast cancer molecular subtypes using BI-RADS evaluations
Authors: Ozcan A , Aksoy Ozcan U , Ekemen S , Ulus S , Oyan B 
Published: May 2019

Abstract
Purpose: Inter- and intra-observer variability adversely affects interpretation of highly advantageous MRI data in breast cancer diagnosis, prognosis and therapeutic decisions. Machine learning (ML) might potentially provide support to the physicians for objective decision strategies. In this work, ML methods using BI-RADS features were tested for non-invasively determining molecular subtypes of breast cancer.
Methods: In this IRB approved study, Out of 126 consecutive patients' retrospective data with written consent, 69 patients (mean±std age 48.24±11.62 and range [27-82]) with full histopathological and MRI data were selected. In surgical histopathological data ER+PR+HER2- was classified as luminal HER2(-), ER+PR+HER+ was classified as luminal HER2(+), ER-PR-HER2+ was classified as HER2(enriched) and ER-PR-HER2- was classified as triple negative. The cohort revealed 51 luminal HER2(-), 11 luminal HER2(+), 7 triple negative cases without any HER2(enriched) occurrence. DCE, DW, T2W MRI data were obtained on a 1.5T Magnetom Espree (Siemens, Erlangen, Germany) scanner which were subsequently interpreted in consensus by 2 radiologists of 15 and 10 years of experience.
Age, mass and non-mass properties, non-enhancing BI-RADS findings, ADC values obtained from radiologist drawn ROIS and kinetic curve properties were fed to 22 standard ML algorithms provided in Matlab® (Mathworks, Natick, MA, USA) as predictors for 3 categories. The algorithms were run by cross validating on 50 folds whereby reported classifier accuracy was obtained from each of the observations when in held-out fold.
Results: Out of 22 ML algorithms tested Support Vector Machine's Fine Gaussian variant, Ensemble Boosted Trees and Fine K-Nearest Neighbor resulted in 76.8%,71.0% and 53.6% accuracy with (100%, 18%, 0%), (92%, 9%, 14%) and (67%, 18%, 14%) true positive rates for predicting each histopathological category respectively. Furthermore, PCA based dimension reduction worsened the outcomes indicating high sensitivity to the feature set.
Conclusion: ML algorithms demonstrated potential as a decision support system increasing assessment objectivity with an added non-invasiveness advantage. However, overall algorithm performance indicates further studies with larger cohorts and broader feature are necessary for refinements and improving ML methodology in breast cancer imaging.
Citation Format: Ozcan A, Aksoy Ozcan U, Ekemen S, Ulus S, Oyan B. Testing machine learning algorithms' performance for non-invasively identifying breast cancer molecular subtypes using BI-RADS evaluations [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-02-03.
Abstract P5-02-04: Not presented
Authors: Sheth D , Pineda F , Karczmar G , Abe H 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Sheth D, Pineda F, Karczmar G, Abe H. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-02-04.