bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer patients with ECOG-PS higher than 1: Who are those who benefit of palliative chemotherapy?
Authors: Caires-Lima Rafael , Protásio Bruno Mendonça , Caires Inacelli Queiroz de Souza , Rocha Lucila Soares Da Silva , De Oliveira Julia Andrade , Guerra Raquel Bezerra , Mak Milena Perez , Hoff Paulo M. , Castro Gilberto
Published: March 2020

9561

Background: Palliative chemotherapy (PC) is a treatment option in pts with metastatic cancer. Although pts with ECOG-PS > 1 are underrepresented in clinical trials, they are often treated with PC in daily practice. We aimed to identify factors associated with poorer survival and lack of benefit of PC in this subset of pts. Methods: We conducted a case-control retrospective analysis of 301 consecutive pts with solid tumors and ECOG-PS > 1 when initiated PC, selected from 2514 pts who died between Aug/2011 and Jul/2012 in a tertiary cancer care institution or its hospice. Cases were defined as those pts who survived < 90d after the first cycle of first line PC, and controls were those who had a longer survival. Frequencies were compared by chi-square test or Fisher exact test. Risks were estimated by odds ratios (OR) and logistic regression analysis. Overall survival (OS) was calculated by Kaplan-Meier method and curves was compared using log-rank test. Results: 142 cases/159 controls were included: median age 58/63 y.o. (p=0.09; t-test) and 49%/50% female (p=0.941; chi-square). Gastrointestinal and lung cancers were the most frequent primaries (31 and 17%, respectively). Factors associated with poorer OS were age > 60 y.o. (OR 1.7; 95%CI 1.0–2.6), ECOG-PS > 2 (1.9; 1.2–3.1), weight loss > 10% (1.8; 1.1-2.8), hemoglobin < 10 g/dL (2.6; 1.6-4.2), albumin < 3 g/dL (2.7; 1.5-5.1), serum creatinine (sCr) > 1 mg/dL (2.8; 1.6-5.0), C-reactive protein ≥ 5 mg/L (8.6; 1.0-72.9), altered mental status (4.2; 1.4-13.2) and in-hospital PC (3.2; 1.9-5.2). Cases were more likely to experience grade ≥ 3 toxicity (43 vs. 28%; p=0.005), die of toxicity (16 vs. 6%; p = 0.0007) and not be offered palliative care only (47 vs. 71%; p<0.0001). mOS was 204 and 34d among controls and cases, respectively (HR 0.177; 95%CI 0.015-0.033, p<0.0001). Median time to death was 39.5d (0-1103). Logistic regression analysis identified ECOG-PS > 2 (OR 2.3, p=0.044) and sCr > 1 mg/dL (OR 11.2, p=0.0002) as independent predictors of 3-mo fatality. Conclusions: ECOG-PS > 2 and elevated sCr were identified as independent predictors of poor OS in these pts. PC needs to be prescribed with caution in ECOG-PS > 1 pts, since it seems to offer no benefit in OS and could lead to abbreviation of life.
Safety and quality assurance of MR-guided focused ultrasound (MRgFUS) in palliation of painful bone metastases.
Authors: Meyer Joshua E. , Chen Lili , Ghanouni Pejman , LeBlang Suzanne , Hurwitz Mark
Published: March 2020

9565

Background: Palliation of bone metastases is typically performed with radiation therapy (RT). However, a significant minority of patients cannot obtain durable relief from RT. MRgFUS combines non-invasive focused ultrasound with MR guidance. Preliminary phase III results comparing MRgFUS to sham treatment have demonstrated efficacy. This study examines the safety of this procedure in a large prospective, multi-center study. Methods: Patients with a painful bone metastasis were randomized (3:1) to either MRgFUS or sham treatment for the single most painful lesion. Sham patients were given the opportunity to cross over after 2 weeks. Each adverse event (AE) was recorded prospectively and scored for severity and relation to treatment. Results: Thirty-seven patients were enrolled to receive sham treatment and 115 to receive MRgFUS. Sites of treatment were: 102 pelvis, 28 thorax, 7 lower extremity and 2 upper extremity. Seventy-seven target lesions were osteolytic, 29 were osteoblastic and 33 were mixed. Treatment was discontinued prior to completion in 8 treatments. Of these, 7 were pelvic targets and 6 lesions were osteolytic. The most common reasons for discontinuation were pain (4) and patient movement (2). Forty-seven percent of treatment patients and 2.7% of sham patients reported at least one AE. Of 76 AEs, 67 were considered non-significant and anticipated, 57 being intra-procedure pain. Four significant events included 2 possibly related fractures at treated lytic lesion sites, 1 grade 3 skin burn and 1 patient with neuropathy. Four patients experienced events unrelated to study treatment and 1 patient experienced temporary apnea from anesthesia described as incidental. Conclusions: MRgFUS is a safe treatment for palliation of painful bone metastases. Ninety-three percent of MRgFUS treatments were carried out to completion. Three percent of patients experienced significant AEs, including 2 fractures of treated lytic tumors. These safety data reinforce and confirm previous experience with this technology and encourage its use for patients not suitable for RT. Clinical trial information: NCT00656305.
The Minneapolis-Manchester Quality of Life Instrument (MMQL): Reliability and validity of the Adult Form (AF).
Authors: Bosworth Alysia , Goodman Elizabeth L. , Wu Eric , Francisco Liton , Robison Leslie L. , Bhatia Smita
Published: March 2020

9570

Background: Cancer survivors are at risk for deficits in health-related quality of life (HRQL). Youth (8-12y) and adolescent (13-20y) versions of the MMQL have been developed to address survivor-specific issues and are currently in use; the MMQL-AF has now been developed to assess HRQL in cancer survivors aged 21-55y, enabling cross-sectional and longitudinal assessment of childhood cancer survivors as they age. Methods: The MMQL-AF was administered to 499 adults: 65 patients undergoing cancer therapy, 107 off therapy, 327 healthy controls (matched on sex, age, education). Factor analysis was performed; items with factor loadings ≥0.40 were retained. The following psychometric properties were evaluated: internal consistency reliability (Cronbach’s alpha), construct validity (concurrent administration of SF-36), known-groups validity (score comparisons across the 3 groups), and stability (intraclass correlations from patients completing MMQL-AF twice, 2 weeks apart). Results: Among patients, 46% had hematological malignancies, 33% were males, 64% were non-Hispanic whites; median age was 40y. Factor analysis resulted in retention of 44 items across 6 scales: social functioning (n=9), physical functioning (n=12), cognitive functioning (n=7), outlook on life (n=4), body image (n=5), and psychological functioning (n=7).Internal consistency was 0.8-0.9 for scales and 0.95 overall.The MMQL-AF distinguished between known groups; healthy controls scored significantly higher (better HRQL) than patients on 4 of 6 scales. Off-therapy patients scored higher than on-therapy patients on physical functioning.The MMQL-AF scales correlated highly with SF-36 scales hypothesized to tap similar domains (all P values <0.001), demonstrating construct validity.Intraclass correlations were 0.82-0.95 for scales and 0.98 overall (all P values <0.001), indicating high stability. Conclusions: MMQL-AF is a reliable and valid self-report instrument for measuring multi-dimensional HRQL in cancer survivors aged 21-55y. Development of this instrument ensures availability of a tool that can assess HRQL from 8-55y, thus addressing needs of childhood cancer survivors as they age.
Differences in psychosocial factors among diverse women enrolled in a phase III cooperative group metastatic breast cancer trial (CALGB 40502/Alliance).
Authors: Polite Blase N. , Allred Jacob B , Rugo Hope S. , Cipriano Toni Marie , Cirrincione Constance , Gehlert Sarah J. , Paskett Electra D. , Hudis Clifford , Winer Eric P.
Published: March 2020

9581

Background: Previous metastatic breast cancer trials have shown lower overall survival among African American (AA) women. Studies have also shown links between higher comorbidities and lower levels of social support and survival. Whether these factors differ by race and ethnicity is not known. Methods: Breast cancer patients enrolling in a phase III cooperative group metastatic breast cancer trial completed a self-administered survey measuring psychosocial and socio-demographic factors and comorbidities. Results were analyzed by self-identified race/ethnicity and evaluated by other measured variables. Results: 703 out of 799 patients completed the survey (88%). Questions were answered by greater than 95% of participants. The table shows differences broken down by Race/Ethnicity. AA and Hispanic (H) patients were more likely to have trouble paying for medications and have incomes less than 15K per year. AA were less likely to be married, and had lower levels of social support. Differences in income did not mediate these social support differences. Marital status did not mediate lower social support for AA (p=0.79) but did so for whites (p<0.001) Conclusions: Compliance with the questionnaire was quite high. Differences in social support by race were apparent and were mediated by different factors according to race. Future efforts will analyze the impact of these factors on survival and as mediators for potential racial and ethnic differences in survival. [Table: see text]
Depression and self-reported memory problems in adult-onset cancer survivors.
Authors: Jean-Pierre Pascal , Winters Paul
Published: March 2020

9586

Background: Memory impairments are debilitating adverse effects of cancer and its treatments. Depression may predispose or exacerbate memory problems. We examined the relationship between depression and memory problems in adult-onset cancer survivors. Methods: We included data from individuals who completed the National Health and Nutrition Examination Survey, a nationally representative, stratified, multistage probability sample of the civilian, non-institutionalized population of the United States from 2005 to 2010. We excluded individuals with a history of brain cancer or stroke since these conditions are expected to cause cognitive problems because of direct brain insults. We determined the prevalence of depression and its relationship to memory problems in cancer survivors by weighting our results proportionally. We controlled for demographic predictors of memory problems. Results: The sample included 14249 adults (6875 men and 7274 women) age 20 years and older. There were 6959 Whites, 2792 Blacks, 3903 Hispanics, and 589 other race/multiracial. Overall, individuals in the United States with a history of depression were 8.4 times more likely to report memory problems (Odds Ratio (OR), 8.406; 95%CI, 6.73 to 10.64). We further explored the depression-memory relationship in a subsample of cancer survivors. Adjusting for age, sex, race-ethnicity, education, income, and general health, cancer survivors with a history of depression were approximately 5 times more likely to report memory problems (N=1283; OR, 4.921; 95%CI, 2.141 to 11.313) than those without a history of depression. Other predictors of memory problems were age (≥ 60 years old, OR = 4.756, 95%CI, 1.957 to 11.560) and lower income (OR, 3.721; 95%CI, 1.951 to 7.098). Conclusions: The likelihood of memory problems is higher in cancer survivors with a history of depression. Future studies are needed to systematically delineate the depression-memory problems relationship, and to inform the development of interventions to treat these conditions for cancer survivors.
Nonalcoholic fatty liver disease after adjuvant therapy in nonmetastatic breast cancer.
Authors: Duman Berna Bozkurt , Gunaldi Meral , Tasdogan Burcak Evren , Usul Afsar Cigdem , Paydas Semra , Gumurdulu Yuksel
Published: March 2020

9587

Background: Nonalcholic fatty liver disease (NAFLD) is an important health problem in the general population. Also NAFLD developing after treatment is very important in cases with cancer especially having long term life expectancy like breast cancer. The aim of this this study is to explore the rate and risk factors of NAFLD in cases with breast cancer receiving adjuvant therapy. Methods: In this prospective study, 201 cases with breast cancer treated by chemo and/or anti-hormonal treatment were included between years 2010-2012. Patients who had ductal carcinoma insitu and metastatic disease and also chronic HBV and HCV infections, chronic liver diseases with other reasons and liver cirrhosis were excluded. Body mass index (BMI) was calculated based on the following formula: weight in kilograms divided by height in meters squared. Diabetes mellitus, hypetension and hyperlipidemia, if there is in past medical history, were documented. NAFLD was deteced by abdominal ultrasound imaging and there was no history of alcohol consumption. Biopsy was performed in 2 patients who had refractory high transaminasis. Results: The patients were divided into three groups. Group I: Patients without NAFLD, Group II: Patients with NAFLD before cancer treatment, Group III: Patients with NAFLD after cancer treatment. There was no difference for age and menopousal status between three groups. Diabetes mellitus, hypetension and hyperlipidemiawere not important risk factors for the development of NAFLD after cancer treatment. (p values 0,085, 0,525, 0,207, respectively). BMI was found to be higher in cases with NAFLD and the occurrence of NAFLD was detected more frequently in obese patients (BMI>30 kg/m2) (p=0,001). Tamoxifen, LHRH analougs and aromatase inhibitors were not found to be asociated with NAFLD (p=0,7, 0,8, 0,5, respectively) while the combination of fluorouracil, antharcycline and cyclophospamide was found to be a risk factor in the development of NAFLD (p=0,02). Conclusions: High BMI (both before and after treatment), obesity and fluorouracil, antharcycline and cyclophospamide combinationin were found to be important risk factors for the occurrence of NAFLD.
Psychosocial health in survivors of adult versus childhood cancer.
Authors: Phillips Charles A , Hardcastle Emily , Desjardins Leandra , Ruiz Rachel , Bemis Heather , Arrington Jasmine , Feldman Rachel , Murphy Alexandra , Compas Bruce , Friedman Debra L.
Published: March 2020

9609

Background: The growing population of cancer survivors is characterized by two subgroups, those diagnosed as children and those diagnosed as adults. While psychosocial challenges are recognized in these survivors, little data exists comparing the psychosocial health between these two subgroups. Our objective is to compare adult and childhood cancer survivors for symptoms of depression, anxiety, somatic complaints, and post traumatic stress disorder (PTSD). Methods: At entry to the Vanderbilt Cancer Survivorship program, survivors of childhood and adult onset cancer, ages 15 – 55 years old, completed the Achenbach System of Empirically Based Assessment and the revised Impact of Event Scale. Using normalized T scores, independent sample t tests,and χ2 analyses, responses were compared to normative data for each group and responses of the two survivor groups were compared to one another. Results: There were 172 survivors of childhood cancer (M= 9 years old at diagnosis) and 125 survivors of adult cancer (M= 41 years old at diagnosis). Childhood cancer diagnoses included hematologic cancer (56%), sarcoma (17%), brain tumor (8%), and other (19%). Adult cancer diagnoses included breast cancer (45%), colon cancer (8%), hematologic cancer (14%), sarcoma (4%), and other (29%). After adjusting for age-related population norms, adult survivors were significantly more likely to have symptoms of depression (p=.011), anxiety (p=.029), somatic problems (p=.043), and PTSD (p=.004) compared to their childhood counterparts. Compared to age-expected norms, significantly more adult, but not child, survivors scored in the clinical range for depression (29%, p<.001; vs. 18% n.s) and somatic problems (23%, p=.013; vs. 12%; n.s.). Time elapsed from cancer diagnosis to completion of the questionnaires was not significantly correlated with any of the measures. Conclusions: Survivors of adult onset cancer face a significantly higher amount of psychologic distress, particularly depressive and somatic symptoms, compared to their childhood counterparts and age-expected norms. Analyses are ongoing to evaluate other demographic, disease, and treatment related risk factors that may contribute to this age-related phenomenon in order to develop interventions.
Hypocalcemia in patients with metastatic bone disease receiving denosumab.
Authors: Body Jean-Jacques , Lipton Allan , Henry David H. , Stopeck Alison , Fizazi Karim , Bone Henry G. , Saad Fred , Van Poznak Catherine H. , De Boer Richard H. , Shore Neal D. , Ibrahim Toni , Takano Toshimi , Damião Ronaldo , Wang Huei , Kostenuik Paul J. , Shaywitz Adam , Bracco Oswaldo L. , Braun Ada
Published: March 2020

9628

Background: Patients (pts) with metastatic bone disease (MBD) are at risk of skeletal-related events (SREs). Potent antiresorptives reduce the risk of SREs, by inhibiting cancer-induced bone destruction, which also reduces release of skeletal calcium (Ca) into the bloodstream. Hypocalcemia (hypoCa) may occur if Ca and vit D intake is inadequate while taking antiresorptive agents. A combined analysis of 3 phase III trials in pts with MBD showed denosumab (DMAb) was superior to zoledronic acid (ZA) in preventing SREs. The overall safety profiles were similar; hypoCa was more common with DMAb (9.6%) than ZA (5.0%). Characteristics of hypoCa events in DMAb pts in these clinical trials and from post marketing adverse event (AE) reports are presented. Methods: Pts with solid tumors or multiple myeloma and MBD were randomized (1:1) to DMAb 120 mg SC or ZA 4 mg IV (adjusted for renal function) every 4 weeks (Q4W). Pts were advised to take daily Ca (≥ 500 mg) and vit D (≥ 400 IU); intake was collected by pt report. Albumin-corrected serum Ca was measured Q4W by central lab. HypoCa events were collected as decreases in serum Ca per central lab and investigator-reported AEs. Post marketing data from spontaneous reports of hypoCa to the sponsor's global safety department (AGS) were reviewed. Results: In the 3 trials, 2841 pts received DMAb and 2836 pts received ZA. The median Ca levels for both treatment groups were similar over time. Among DMAb pts, hypoCa was most common within 6 months of starting treatment and was more common in pts who did not report use of Ca and vit D vs those who did (15.8% vs 8.7%). Grade 3 or 4 (< 7 mg/dL; < 1.75 mmol/L) decreases in serum Ca were reported in 3.1% of DMAb pts and 1.3% of ZA pts. No fatal cases of hypoCa were reported in the trials. From May to Nov 2012, 37 cases of severe symptomatic hypoCa (seizures, tetany, prolonged QTc, altered mental state) were reported to AGS; fatal outcomes were reported for 3 other pts with advanced cancers and various comorbidities. Conclusions: HypoCa is a known risk with antiresorptive therapy, including DMAb 120 mg. HypoCa occurred less often in pts who reported taking Ca and vit D. HypoCa should be corrected prior to starting DMAb and Ca monitored during treatment. Pts should take adequate Ca and vit D while receiving DMAb. Clinical trial information: NCT00321464, NCT00321620, and NCT00330759.
Differential protein expression profile in skin biopsies from patients with hand-foot syndrome who have benefited from topical heparin treatment.
Authors: Rodriguez-Garzotto Analia , Ruppen Isabel , Ximenez de Embun M. Pilar , Iglesias Lara , Gravalos Cristina , Agudo-Lopez Alba , Perez Carlos , Diaz Garcia Vanesa , Lopez-Martin Jose A. , Ciruelos Eva , Manso Luis , Mendiola Cesar , Agullo Ortuno M. Teresa , Cortes-Funes Hernan
Published: March 2020

9641

Background: Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine (CAP), leading to significant morbidity in patients receiving this agent. Interruption or dose reduction of CAP is the only effective strategy. The purpose of our study is to define the pathophysiology and risk factors predictors of CAP-induced HFS. Previously, we had conducted a clinical trial in patients who developed HFS secondary to CAP. Topical heparin was administered in palms and soles of patients four times/day for three weeks (w), evidencing clinical improvement in 99% of patients. Methods: Paired-skin biopsies of palms at baseline and after 3w from 21 patients were obtained. An iTRAQ (isobaric tags for relative and absolute quantitation) proteomics approach was performed to identify molecular pathways associated with HFS reversion. Results: Comparative analysis between baseline and post-treatment skin samples identified 1876 proteins with high confidence (> 99%). The involvement of the identified proteins in biological networks served to characterize molecular pathways associated with HFS reversion. Conclusions: Several proteins identified in this study have a close relationship with keratinocyte terminal differentiation and keratinocyte intercellular strength. Also, we describe differential expression among proteins involved in inflammatory processes, skin immunity and cell death. In summary, our study not only served to uncover molecular mechanisms associated with HFS reversion, but also to reveal the biomarker role of several proteins in this syndrome. [Table: see text]
Inherited mutations in breast cancer genes in African American breast cancer patients revealed by targeted genomic capture and next generation sequencing.
Authors: Churpek Jane E. , Walsh Tom , Zheng Yonglan , Casadei Silvia , Thornton Anne M. , Lee Ming K. , Churpek Matthew , Huo Dezheng , Zvosec Cecilia , Liu Fang , Niu Qun , Zhang Jing , Fackenthal James , King Mary-Claire , Olopade Olufunmilayo I.
Published: March 2020

CRA1501

The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Trastuzumab associated cardiotoxicity: Who is at risk?
Authors: Abulkhair Omalkhair A. M. , Gasmelseed Ahmed , Al Otaibi Shabab
Published: March 2020

e11518

Background: Trastuzumab is an important agent in the treatment of both adjuvant and metastatic breast cancer with known cardio toxicity. Cardio toxicity is defined as reduction in left ventricular ejection fraction (LVEF) of > 5% with signs and symptoms of heart failure (HF) or > 10% without such symptoms. Methods: Retrospective review of all breast cancer patients treated in King Abdulaziz Medical City with trastuzumab for adjuvant and metastatic setting from 2003 to 2012. 150 cases were identified, patients with good quality echocardiogram and base line LVEF > 55% were included (104). Patients had base line, then 3 monthly echocardiogram thereafter. Results: Studied patients showed that median age was 49 (43 - 58) years. There was a relevant decline in LVEF in 16 patients (15.38%), after mean exposure duration of 15 months. The study also revealed significant difference in EF decline between diabetic and non diabetic receiving herceptin (31.82% and 10.98% respectively, p-value 0.0213), and in 64.71% with hypercholesrolemia compared to 5.75% in those with normal cholesterol (p-value 0.0001). Conclusions: Given the limitations of this small retrospective review, we have shown that the prevalence of cardio toxicity in our patients is higher than published figures. Also, we have shown a significant correlation between diabetes, hyperlipidimia and cardio toxicity in trastuzumab treated patients. Such patients might need to be closely monitored for cardio toxicity.
Inflammatory markers in metastatic breast cancer.
Authors: Sahin Ugur , Petekkaya Hilbrahim , Gecmez Gizem , Babacan Taner , C. Roach Emir , Sarici Saim Furkan , Arslan Cagatay , Arik Zafer , Aksoy Sercan , Altundag Kadri
Published: March 2020

e11545

Background: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The aim of this study is to find out the importance of serum markers as a prognostic indicator in metastatic breast cancer Methods: Women with metastatic breast cancer at the time of diagnosis were included. The study was conducted in Hacettepe University, Institute of Oncology, Department of Medical Oncology. Patient data were collected between December 2009 and January 2013. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value of < 0.05 was considered statistically significant. Results: Median follow-up time was 26 months. There were 29 mortalities due to disease progression during the follow up. The levels of serum albumin, ESR and LDH were not associated with a significant effect on overall survival. Among patients with a higher serum CRP estimated median survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p = 0.49). Among patients with higher serum ferritin levels estimated median survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p = 0.01). Among patients with higher serum beta-2 microglobulin estimated median survival was 28±8 months, compared to 84±57 months for normal levels (p<0.01). Conclusions: Serum CRP, ferritin and beta-2 microglobulin can be useful prognostic factors for overall survival among metastatic breast cancer patients.
Evaluation of factors related to late recurrence (later than 10 years after the primary treatment) in early breast cancer.
Authors: Nishimura Reiki , Osako Tomofumi , Nishiyama Yasuyuki , Tashima Rumiko , Nakano Masahiro , Fujisue Mamiko , Toyozumi Yasuo , Arima Nobuyuki
Published: March 2020

e11557

Background: Breast cancer is associated with a relatively good prognosis and heterogeneity. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence, later than 10 years after primary treatment, in early breast cancer. Methods: From 1980 to August 2012, 4774 patients who underwent primary treatment, including operation and estrogen and progesterone receptors (ER and PgR) measurement, were enrolled in this study. The patients were divided into two groups, those with a follow-up period within 10 years, and those (1323 patients) without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients within 10 years and occurred in 51 patients from ≥10 years. The items examined were tumor size, lymph node status, and biological markers such as ER, PgR, Ki-67 values, p53 and human epidermal growth factor receptor 2 (HER2) expressions. Results: The overall 10-year cumulative disease-free survival (DFS) rate was 79.5%, and the recurrence rate at ≥10 years was 5.8% (some cases had recurrence 20 years later). A multivariate analysis revealed that the factors related to late recurrence were positive nodes and PgR positive. This result differed from that for early recurrence, where the DFS rate was low in patients with ER/PgR negative, high Ki-67 index values and p53 overexpression. Conclusions: The PgR positivity and lymph node metastasis significantly correlated with late recurrence (later than 10 years after primary treatment) in early breast cancer. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive (ER and/or PgR positive) patients. In addition, how to inform patients about the recurrence rate and recurrence time from the initial treatment, and the Informed Consent regarding the follow-up period and surveillance plan must be examined.
Meta-analysis of 59 gene expression based biomarker candidates predicting survival after tamoxifen treatment in breast cancer.
Authors: Gyorffy Balazs , Kormos Mate , Lanczky Andras , Mihaly Zsuzsanna
Published: March 2020

e11564

Background: To date, three molecular markers (ER, PR and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment by evaluating these in a meta-analysis of available microarray datasets with known treatment and follow-up. Methods: Biomarker candidates were identified in Pubmed 2007-2012 and in the 2010-2012 ASCO and SABCS abstracts. Breast cancer microarray datasets were downloaded from GEO and EGA. Of the biomarker candidates, only those identified or already validated in a clinical cohort were included. In the transcriptomic datasets, only patients with tamoxifen treatment for relapse-free survival and endocrine treatment for overall survival were eligible. The raw microarray data was re-processed and integrated into two databases. Relapse free survival (RFS) up to 5 years was used as endpoint in a ROC analysis in the GEO datasets. In the EGA dataset, Kaplan-Meier analysis was performed for overall survival (OS). Statistical significance was set at p<0.01. Results: The transcriptomic datasets included 667 GEO-based and 1208 EGA-based patient samples. All together 59 biomarker candidates were identified. Of these, the best performing genes were PGR (AUC=0.64, p=2.3E-07), MAPT (AUC=0.62, p=7.8E-05), SLC7A5 (AUC=0.62, p=9.2E-05) and TP53 (AUC=0.60, p=1.2E-03). Further genes significantly correlated to relapse-free survival include BTG2, HOXB7, DRG1, CXCL10, BCL2, TPM4, IGF1R and SMC3. Correlation to overall survival was significant for PGR (HR=0.67, p=1.7E-04), MAPT (HR=0.7, p=7.2E-04) and SLC7A5 (HR=1.6, p=1.6E-05). None of the remaining genes including ESR1 reached statistical significance for relapse-free survival. Conclusions: We validated two genes (MAPT and SLC7A5) as being capable to select those patients most likely benefit from tamoxifen treatment.
Breast cancer patients' risk perceptions and treatment values following surgical consult.
Authors: Kaiser Karen , Cameron Kenzie A. , Stolley Melinda , Bethke Kevin P. , Hansen Nora M. , Jeruss Jacqueline Sara , Clayman Marla L. , Khan Seema Ahsan
Published: March 2020

e11572

Background: Contralateral breast cancer (CBC) is the most common second primary cancer in breast cancer patients. The 10-year risk of CBC for patients with locally invasive or intraductal disease is approximately 6%. However, a recent study reported that prior to surgical consult newly diagnosed breast cancer patients without a BRCA mutation estimated their 10-year CBC risk to be 31.4%. We sought to evaluate breast cancer patients’ perceived risk of future cancer and their treatment values following surgical consult. Methods: Women diagnosed with ductal carcinoma in-situ or stage I-III invasive breast cancer were interviewed in the period between surgical consult and surgical treatment. Participants completed the Perceived Risk Questionnaire (PRQ) and the Values Scale. The PRQ contains 5 questions to assess perceived likelihood of future cancer on a 5-point scale (1=not at all likely, 5=very likely). For each question, women also estimate the likelihood of cancer in the next 10 years as a percentage from 0 to 100. The Values Scale measures the importance of 11 treatment-related values (e.g., How important is it to you to keep your breast?) on a 10-point scale (1=not at all important, 10=very important). Results: Interviews were completed with 20 patients (mean age 54.7 years) without a known BRCA mutation. On the Values Scale, women identified minimizing the chance of cancer elsewhere in the body (mean=9.2), in the other breast (mean=9.1), and in the same breast (mean=8.8) as most important. Patients estimated their 10-year risk to be 13.6% for CBC, 14.2% for breast cancer appearing in the same breast, and 19.6% for cancer appearing elsewhere in the body. One-fourth of participants believed they faced at least a 50% chance of encountering breast cancer again in the next 10 years. Conclusions: Women in this study reported lower perceived risk of CBC than in a prior study of perceived risk prior to surgical consult, thus suggesting that the surgical consult may lead to a reduction in perceived risk. Nonetheless, participants’ estimated their 10-year risk of CBC to be twice the actual estimated risk. Our findings indicate a need for additional patient education about CBC risk.
D538G acquired mutation of estrogen receptor (ER) alpha: A novel mechanism of endocrine resistance in metastatic breast cancer.
Authors: Wolf Ido , Merenbakh Keren , Rubinek Tami , Soussan-Gutman Lior , Klein Baruch , Sarid David , Rizel Shulamith , Ben-Baruch Noa
Published: March 2020

e11578

Background: Resistance to endocrine therapy occurs in virtually all patients with ER-positive metastatic breast cancer (MBC) and is attributed to various mechanisms including loss of ER expression, altered activity of coregulators and cross-talk between the ER and growth factor signaling pathways. To our knowledge, acquired mutations of the ER have not been described as mediating endocrine resistance to endocrine treatment. Methods: Deep sequencing of the ER was conducted, as part of a commercially available next-generation sequencing of 182 cancer-related genes, on samples obtained from 10 heavily pre-treated, endocrine resistant patients with ER positive MBC. In one patient, a sample obtained at diagnosis was also available. Mutated ER was cloned and overexpressed in breast cancer cells. Transcriptional activity was tested using estrogen response element (ERE)-Luciferase construct, effects on viability were tested using MTT assays and computerized modeling was used to assess structural effects. Results: A novel mutation resulting in substitution of aspartic acid at position 538 to glycine was identified in 4 of 10 samples. Moreover, in one case in which samples were available prior to and following development of resistance, the D538G mutation was noted only in the latter sample. Structural modeling indicated that the substitution leads to a conformational change in the ligand binding domain which prevents binding of either estrogen or tamoxifen and mimics the conformation of activated receptor. Experiments in cell lines indicated constitutive ligand-independent transcriptional activity of the mutated receptor. Overexpression of the receptor in MCF-7 cells enhanced proliferation and conferred resistance to treatment with tamoxifen and fulvestarnt. Conclusions: We report here a novel mutation D538G of the ER in human breast cancer and demonstrate its role in mediating resistance to endocrine treatment. Our study also indicates, for the first time, acquired mutation of the ER as a novel mechanism of endocrine resistance. Further studies on larger populations and on less selected patients are needed in order to assess the accurate frequency of this novel mutation.
Early stage “T2N0” breast cancer: Does it consist two different “T2” stages?
Authors: Arslan Cagatay , Sahin Ugur , Kizilarslanoglu Cemal , Solak Mustafa , Gullu Ibrahim Halil , Ozisik Yavuz , Altundag Kadri
Published: March 2020

e11595

Background: Lymph node negative stage IIA early breast cancer (BC) patients (pts) according to TNM classification consists T2N0 tumors reprsenting a wide range of size (>2-5 cm). We aimed to compare clinicopathological features and prognosis of T2N0 stage pts with tumor size larger vs smaller than 4 cm. Methods: Data of 2200 BC pts followed between years 1998 and 2012 at our institute were analysed, retrospectively. pT2N0 stage BC pts (T:2 to 4,9 cm) were divided into 2 subgroups as 2 to 3,9 cm (T2a) and 4 to 4,9 cm (T2b). Clinicopathological features and survival analyses were evaluated. Results: There were 268 (80%) T2a and 65 (20%) T2b pts among T2N0 (n=333) population. All but 2 pts in T2a (99%) and all pts in T2b subgroups were female. Mean age of diagnosis was 50.8±11 and 46.2±10.1 years in T2a and T2b subgroups, respectively (p= 0.003). Number of premenopausal pts were higher in T2b (n=39, 60%) compared to T2a (n=100, 37%) subgroup (p= 0.003). There were no differences in histopathological subtypes, tumor grade, ER, PR, HER-2 status, adjuvant radiotherapy and chemotherapy regimens, -cycle numbers, endocrine, and trastuzumab treatments between T2a and T2b subgroups. Higher number of pts in T2a subgroup was treated with breast conserving surgery [110 (%41.2) vs 11 (%16.9)] and higher number of pts in T2b subgroup were treated with mastectomy [T2a= 158 (%58.8) vs T2b= 54 (%83.1)]. Disease recurrence was seen in 25 pts in T2a and 13 pts in T2b subgroups. Median progression free survival (PFS) could not be reached in T2a subgroup. Median PFS was 96.5 (min – max: 66 – 127) months in T2b subgroup (p= 0.02). There were no differences in PFS and number of events between goups when all pts analysed according to menopausal status and surgical treatment type. Overall survival data could not be analyzed due to small number of events (5 pts in T2a and 1 patient in T2b subgroups were died). Conclusions: T2N0 subgroup of stage IIA BC consists a wide range of tumor size between >2 to 4.9 cm. Pts with T2b (≥4 cm) tumors had shown worse prognosis compared to patients with T2a (<4cm) tumors and might be treated with more agressive adjuvant chemotherapy. This finding might be helpful for treatment decisions but must be evaluated in studies with larger number of pts.
A network meta-analysis assessing the comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer.
Authors: Nagayama Aiko , Hayashida Tetsu , Okabayashi Koji , Jinno Hiromitsu , Takahashi Maiko , Seki Tomoko , Matsumoto Akiko , Murata Takeshi , Kitagawa Yuko
Published: March 2020

e11598

Background: The growing number of anti-HER2 agents suggests the eventual need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. Multiple-treatments meta-analysis synthesizes information from a network of trials and combines direct and indirect evidence on the relative effectiveness. An indirect estimate of the benefit of A over B can be obtained by comparing trials of A v C with trials of B v C. In this study, we assessed the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer by conducting the direct and indirect comparisons from multiple RCTs. Methods: The primary outcome of the study was the number of the patients who achieved pathological complete response (pCR) defined as no invasive residual in breast or node. Secondary objectives were the number of patients who completed the treatment as planned and adverse events including diarrhea, neutropenia, cardiac events and skin disorder. Results: We identified 1047 articles by database search and 10 studies met our criteria. A total of 2247 patients in 7 different treatment arms were assessed; chemotherapy (CT) alone, CT with single or dual anti-HER2 agents and dual anti-HER2 agents without CT. Anti-HER2 agents evaluated were trastuzumab (T-mab), lapatinib, pertuzumab (P-mab). There was no significant difference between dual targeting treatment arms (CT + T-mab + lapatinib v CT + T-mab + P-mab, OR; 1.11, [0.42-2.86], p=0.41), however, lapatinib reduced the treatment completion mainly due to adverse events. Patients in dual targeting arms had significantly higher incidence of pCR than in other treatment arms. (CT + T-mab + P-mab v CT + T-mab, OR; 2.29, [1.02-5.02], p=0.02) Surface under the cumulative ranking probability curve (SUCRA) also indicated that CT + T-mab + P-mab had the highest probability of being the best treatment arm for pCR followed by CT + T-mab + lapatinib and CT + T-mab. Conclusions: This study provides evidence that combining two anti-HER2 agents with chemotherapy are the most effective treatment arms. Considering the cost and limited medical resources, CT + T-mab showed a well-balanced profile for efficacy, completion and safety.
Mesothelin expression and survival outcomes in triple-receptor negative breast cancer.
Authors: Parinyanitikul Napa , Blumenschein George R. , Wu Yun , Lei Xiudong , Chavez-Mac Gregor Mariana , Smart Melody L. , Gonzalez-Angulo Ana M.
Published: March 2020

e12002

Background: Mesothelin is an ideal tumor-associated marker for the development of targeted therapy due to its limited expression in normal tissues. Identify the frequency of mesothelin expression in triple negative breast cancer may lead the path to customize the drug development in this lack of effective targeted subgroup. The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes. Methods: Mesothelin expression was completed using immunohistochemistry on formalin fixed paraffin tumor sections, and quantified by H-score. An H-score >10 was considered positive. Patient’s characteristics were compared by mesothelin expression. Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. Results: Median age was 52 years. Of the 109 TNBC, 37 (34%) were positive for mesothelin expression. There were no differences on patient/tumor characteristics by mesothelin expression with the exception of high frequency of lymphovascular space invasion in mesothelin-negative tumors (P=0.03). At a median follow up of 75.8 months 20 (18.3%) had experienced a recurrence and 22 (20.2%) had died. Five-year progression-free survival was 87% and 92% in patients with mesothelin-positive and mesothelin-negative tumors (P=0.43), and 5-year overall survival was 85% and 91% patients with mesothelin-positive and mesothelin-negative tumors (P=0.57), respectively. Mesothelin expression was not independently associated with PFS or OS in TNBC after adjustment for other patient and disease characteristics including grade, pathologic stage, lymphovascular invasion, and adjuvant chemotherapy survival outcomes. Conclusions: There was mesothelin expression in 34% of TNBC. No significant differences in the clinical characteristics by mesothelin expression with the exception of high lymphovascular invasion in mesothelin-negative tumors. Mesothelin expression did not correlate with survival outcomes in TNBC.
Combined use of indocyanine green fluorescence and methylene blue dye versus methylene blue dye alone for sentinel lymph node biopsy in breast cancer patients.
Authors: Wang Shu , Guo Jiajia , Yang Deqi , Cao Yingming , Tong Fuzhong , Zhou Bo , Liu Peng , Liu Hongjun , Cheng Lin , Liu Miao , Yang Houpu , Xie Fei , Wang Siyuan
Published: March 2020

e12006

Background: Methylene blue (MB) dye is widely used in China for sentinel lymph node biopsy (SLNB). Recently indocyanine green (ICG) was reported to be an innovative fluorescent tracer that could be visualized by near-infrared camera. In this study we compared the efficacy of combined use of ICG fluorescence and methylene blue eye versus methylene blue alone for SLNB in breast cancer patients. Methods: Two hundred and sixteen consecutive early breast cancer patients in our hospital underwent SLNB from December 2010 to May 2012, 107 patients received combined use of ICG and MB as the lymphatic mapping tracer and 109 patients received MB alone. In combination group, sentinel lymph nodes were identified by ICG fluorescence using a near-infrared camera and/or blue dye, while in blue dye alone group sentinel lymph nodes were identified as blue nodes along the blue lymphatic vessel. Intra-operative frozen section analysis was performed, followed by conventional histopathologic examination. Results: In combination group, subcutaneous lymphatic channels were successfully visualized in all the patients, 325 sentinel lymph nodes were identified in 105 patients. While in blue dye alone group, 242 SLNs were found in 100 patients. The detection rate was 98.1% vs. 91.7 %(p=0.033), the average number of SLNs was 3.1 versus 2.4(p<0.001). 29 metastatic SLNs were found in 19 patients by combination method vs. 21 metastatic SLNs in 17 patients by MB alone. No axillary recurrence was observed in either group during 16 months of median follow-up. Conclusions: The combined use of ICG fluorescence and MB enables visualized and more sensitive SLN detection than MB alone.
EUFORIA study (Eribulin Use for the Treatment of Advanced Breast Cancer: Observational, Retrospective Analysis): Initial experience with eribulin in daily clinical practice in Spain.
Authors: Ruiz-Borrego Manuel , Garcia Saenz José Ángel , Hornedo Javier , Manso Luis , Calvo Isabel , Lao Juan , González-Martín Antonio , Feijoo Margarita , Florián Gericó Jesús , Morales Serafin , Illarramendi Jose J. , Jimenez Valero Pedro , Sánchez-Jiménez Javier , Rodriguez Cesar Augusto , Sánchez-Rovira Pedro , Ayala Francisco , Alvarez Isabel , Virizuela Juan Antonio , Lopez Rafael , Rodríguez-Villanueva Julio
Published: March 2020

e12015

Background: Spanish MoH authorized eribulin in 04/2011 for use in patients as per license. Pending reimbursement, public hospitals used it through a national compassionate use program. After 1 year, we analyzed the pre-specified patient selection criteria and eribulin efficacy and safety results in a representative sample to confirm whether real world use matched the data from the pivotal phase III study. Methods: An observational, retrospective analysis was proposed to the top 20 hospitals by eribulin use, with at least 3 candidate patients who had/could have received ≥3 cycles of treatment by 03/2012. Patient and disease characteristics, as well as efficacy and safety parameters were obtained. Patient´s data were collected until September 2012. Living patients able to respond at the time of the study signed an informed consent. Study was approved by ethics committees. Results: Out of 112 screened ABC patients in 19 participating hospitals, 104 were enrolled. Median age was 56.6 years and 66% were post-menopausal. Visceral disease occurred in 2/3 of patients. ECOG status was ≤1 in 75,4% of patients. Estrogen receptor expression was found in 64.4% of tumors; 15.4% overexpressed HER2. 49% of patients received 1-5 treatment lines for ABC before eribulin. Mean eribulin treatment duration was 3 months (4,7 cycles). Disease control rate was 48.8% (1.1% CR, 22.1% PR, 25.6% SD). By 09/2012, 64,4% patients were still alive and median PFS was 97 days (95% IC: 81-129). 78.8% of patients reported ≥1 adverse events, being asthenia, neutropenia, anemia, alopecia, nauseas, and mucositis the most frequent ones (≥10%). Grade ≥3 adverse events occurred in ≤5% of patients. Conclusions: The favorable efficacy and safety profile of eribulin observed in this observational study is consistent with the pivotal phase III study (EMBRACE) and confirms its position for the treatment of ABC. Pre reimbursement usage has been restricted to later lines but use per the licensed indication in 3L is expected to yield additional clinical benefit. A confirmatory observational study (EUFORIA-2) is planned.