bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifactorial CNS relapse susceptibility in HER2-positive breast cancer patients: First results from a population-based registry study
Authors: Musolino A. , Ciccolallo L. , Panebianco M. , Fontana E. , Zanoni D. , De Lisi V. , Sgargi P. , Ceci G. , Ardizzoni A. 
Published: August 2020

1117 Background: A series of retrospective studies have reported a higher incidence of central nervous system (CNS) metastases in HER-2-positive (HER-2+) metastatic breast cancer. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk. Methods: The aim of this study was to evaluate incidence, survival, and risk factors of CNS metastases in the incident breast cancer population systematically collected by the Tumor Registry of Parma Province over the 4-year period, 2004–2007. Study endpoints were: any distant metastasis as first event; CNS metastasis as first event; CNS metastasis at any time. Associations between CNS metastases and HER-2 status in the entire population and between trastuzumab and CNS metastases in HER-2+ patients (pts) were estimated. A multivariate analysis was performed to test the effect of covariates. Results: We evaluated the total resident population (n = 1500) of breast cancer pts diagnosed during the period 2004–2007 in Parma Province. Two-hundred and twenty-five pts (15%) were HER-2+ (IHC 3+/FISH amplified). Of these, 100 pts were treated with adjuvant trastuzumab-based therapy. At a median follow-up of 36 months from the diagnosis, the incidence of CNS relapse was 3% (1.3% as first recurrence). The median time to death from the diagnosis of CNS metastases was 25 months. Among the HER-2+ pts, there was a significant association between trastuzumab and subsequent CNS metastases (p = 0.02). However, in multivariate analysis, HER-2 status regardless of trastuzumab therapy was found to be the only independent predictive factor for CNS metastases (either as first or as subsequent recurrences; p < 0.01). Conclusions: This is the first population-based registry study analyzing CNS metastases in breast cancer in relation to tumor biological features, systemic treatment, and clinical outcome. Based on our results, HER-2 status independently distinguishes pts with a higher risk of CNS metastases. It is however presumable that, in some cases, improvements in systemic control and overall survival associated with trastuzumab-based therapy lead to an “unmasking” of CNS relapse that would otherwise have remained clinically silent prior to a patient's death. No significant financial relationships to disclose.
Assessment of uterus, bone, serum lipids, and hormones in postmenopausal breast cancer patients treated with TAS-108, a novel steroidal antiestrogen: Results of a randomized phase II study
Authors: Nakayama T. , Inaji H. , Iwata H. , Yamamoto N. , Sato Y. , Tokuda Y. , Aogi K. , Saji S. , Ikeda T. , Noguchi S. 
Published: August 2020

1120 Background: TAS-108, a novel steroidal antiestrogen, has demonstrated a favorable safety profile, including lower agonistic activity on uterus than tamoxifen and supportive effect on bone in preclinical studies. The potential tissue-specific effect of TAS-108 was investigated in postmenopausal breast cancer patients included in a randomized phase II study. (The clinical efficacy and safety results were presented at the 31st San Antonio Breast Cancer Symposium). Methods: Postmenopausal women aged 20–80 years with hormone receptor-positive metastatic breast cancer were eligible for this study and treated with oral TAS-108 (40, 80, or 120 mg/day) once a day. Endometrial thickness (ET) was measured by ultrasonography. The change in Bone Mineral Density (BMD) at lumber spine was assessed by dual energy X-ray absorptiometry. Hormone levels, bone metabolism markers, and serum lipid parameters were also measured at regular intervals. Wilcoxon signed-rank test was used to assess the significance of changes or percentage changes from baseline. Results: Ninety one patients with a median age of 62 years (range 44–80) were included in the analysis population. TAS-108 did not cause significant endometrial thickening (median baseline ET 3.3 mm, last point ET 3.6 mm; n = 36). In particular, after at least 1 year of treatment in 13 cases, no clinically significant increase in ET was found. No change was observed in median BMD (+0.74%; n = 20). Serum carboxy-terminal telopeptide of type I collagen (I CTP) levels remained unchanged although the decrease in osteocalcin levels was significant (p = 0.019; n = 49) in patients without bone metastasis. Median triglyceride levels significantly decreased from 104.0 to 85.0 mg/dl (p = 0.000) after 4 weeks of treatment, while there were no changes in other lipid parameters. An increase in sex hormone-binding globulin and testosterone levels were observed. Conclusions: TAS-108 may have no harmful effects within these parameters and could be used safely. However, further study in a greater number of cases is needed to identify the effect of the long-term use of TAS-108 on the uterus and bone. [Table: see text]
Bevacizumab combined with taxanes in second-line or more for metastatic breast cancer: Efficacy and predictive factors of response
Authors: Vanneuville A. , Gentil J. , Vautravers-Dewas C. , Guiu S. , Favier L. , Causeret S. , Mayer F. , Coudert B. , Fumoleau P. 
Published: August 2020

1122 Background: In metastatic breast cancer (MBC), bevacizumab (BEVA) and taxanes (TAX) (paclitaxel or docetaxel) are very efficient as first line metastatic therapy. However, such combination is questionable in subsequent lines of therapy. Aims: evaluate the efficacy and the factors of response of BEVA and TAX combination in second line or more for MBC. Methods: A retrospective study was done on all the MBC patients treated with BEVA combined with TAX, between July 2007 and November 2008, in the medical oncology department. Statistics were descriptive for the population and the efficacy. Univariate and multivariate analysis were used to determine the predictive factors of response. Results: 31 patients received BEVA combined with paclitaxel in 30 cases (96.7%) or docetaxel in one case (3.3%). Mean age was 55.3 years (IC95% [50.8–59.7]). Median number of previous lines was 4 (range [2–10]). 14 patients had already progressed under TAX therapy. Mean follow up was 7.1 months (IC 95% [5.9–8.4]). Thirteen (41.9%) patients had a clinical response, partial in 12 (38.7%) and complete in 1 (3.2%) patients. Four (12.9%) additional patients were stabilized therefore clinical benefit (CR+PR+SD) was obtained in 17 (60.7%) patients. The mean duration of the clinical benefit, measured as the delay between the first day of BEVA-TAX treatment and the date of progression or last news date, was of 5.8 months (IC95% = [4.4–7.1]). The progression delay, for patients who presented a progression and needed the introduction of a new therapy, was of 2.4 months (IC95% = [1.7–3.1]). Eleven (35.5%) patients had no clinical benefit and readily progressed under therapy. Multivariate analysis showed that age less than 65 (OR = 14.5 IC95% = [1.6–128.7]; p = 0.016) and a number of previous lines less than 6 (OR = 11.0 IC95% = [1.2–102.7]; p = 0.036) were related to the clinical benefit. Previous TAX resistance had no significant influence on the efficacy of the combination. Conclusions: In pretreated MBC patients, the combination of BEVA and TAX can be effective with a mean duration of clinical benefit around 6 months. Age over than 65 and a number of previous lines over 5 could be considered as factors of resistance to such a combination. These results have to be confirmed in larger studies. [Table: see text]
Evaluation of Ki-67 measured in benign breast tissue acquired from premenopausal women treated with a flaxseed derivative
Authors: Fabian C. J. , Khan Q. J. , Sharma P. , Baxa S. , Metheny T. , Zalles C. M. , Kimler B. F. 
Published: August 2020

1507 Background: The lignans enterolactone and enterodiol are derived from the action of gut bacteria on ingested secoisolariciresinol diglycoside (SDG) which is commonly found in flaxseed. Enterolactone and enterodiol are thought to impair mammary carcinogenesis via reduction in aromatase activity and the mid-cycle surge of luteinizing hormone. We assessed the modulatory activity of 1 year of SDG on a number of risk biomarkers for breast cancer in a prospective phase II pilot study. We report the effect of SDG on the primary endpoint, proliferation in benign breast tissue as measured by Ki-67 immunocytochemistry, in the first 35 women completing study. Methods: Premenopausal women age 21 to 55 at increased risk for breast cancer underwent a baseline random periareolar fine needle aspiration (RPFNA) between the first and tenth days of their menstrual cycle. Those with RPFNA evidence of hyperplasia and Ki-67 greater than or equal to 2% were invited to participate. Women taking flaxseed or oral contraceptives were ineligible. All women took one Brevail (lignan research) capsule containing 50 mg of SDG daily. Ki-67 staining was performed with DAKO M7240 antibody on hematoxylin counterstained slides and the number of cells staining positive in 500 cells within hyperplastic clusters was counted. Results: Forty-nine women were enrolled on study between February 2006 and June 2008. Of these, four stopped prematurely, 10 women have not completed, and 35 have completed study and undergone follow-up RPFNA. Baseline characteristics of the 35 women completing study are as follows: median age 44 (range 29–50), median baseline 5-year Gail model risk 1.6% (range 0.1%-5.7%), median Ki-67 4.2% (range 2.0%-16.8%). Thirty seven percent had hyperplasia without atypia, and 63% had atypia. At repeat RPFNA, Ki-67 expression was reduced (median value of 2.0%, range 0%-15.2%); with 29 of the 35 women demonstrating a decrease (median relative reduction of 0.70). Conclusions: Based upon reduction in Ki-67 expression in hyperplastic benign breast tissue after 12 months, 50 mg of SDG administered daily as Brevail appears promising as a preventive. Supported in part by grant R21 CA117847 from the National Cancer Institute. No significant financial relationships to disclose.
Telephone disclosure of BRCA1/2 test results? Experience and opinions of genetic counselors and consumers
Authors: Patrick-Miller L. J. , Fetzer D. , Schmidheiser H. , Daly M. , Toppmeyer D. , Olopade O. , Bradbury A. 
Published: August 2020

1510 Background: BRCA1/2 test results have historically been disclosed in person (IPD) by a certified genetic counselor (GC). Greater consumer demand and access to BRCA1/2 testing, and greater prevalence and acceptance of telemedicine, have interested providers in conducting BRCA1/2 testing and disclosing results by telephone (TD) and internet. GC and consumer experiences and opinions about TD have not been well described. Methods: To determine experience, opinions and interest in TD of BRCA1/2 test results we conducted semi-structured interviews with 194 GC recruited via NSGC Cancer Special Interest Group and with 30 consumers (to date) less than 9 months post IPD of BRCA1/2 test results at two cancer centers. Descriptive statistics characterize GC and consumer experiences and opinions. Results: 98% GC had provided TD; 46% rarely. Most frequent reasons for TD: perceived consumer hardship of IPD (n = 190); consumer preference (n = 49) and medical benefit (n = 30). GC comfort with TD varied by test result (true negative [TN] 77%, indeterminate [IND] 49%; mutation carriers [MC] 37%; variant of unknown significance [VUS] 33%). GC cited consumer convenience (n = 132), medical (n = 71) and psychological benefit (n = 42), and greater GC counseling capacity (n = 33) as TD advantages. No nonverbal communication (n = 161), poorer communication/understanding (n = 67), and difficulty explaining complex results (n = 41) were disadvantages GC most frequently reported. 46% post-IPD consumers reported interest in TD; interest varied by test result (VUS 67%; IND, 63%; TN 57%; MC 25%). Consumers’ perceived advantages: convenience (n = 22) and medical benefit (n = 9); and disadvantage to TD; lack of visual and personal connection with GC (n = 18). Conclusions: Results of the ongoing study suggest many consumers of BRCA1/2 testing are interested in, and nearly all GC have conducted, TD. GC and consumers share perceptions of TD convenience, and of challenges of lack of visual cues, however, GC comfort with, and consumer preference for, TD vary differently by test result. Given consumer and provider interest, longitudinal study of TD impact on knowledge, risk perception, communication, and health behaviors, and their mediators will be critical to develop policy and procedures optimizing adaptive responses to TD. No significant financial relationships to disclose.
A short-term biomarker modulation prevention study of anastrazole in women at increased risk for breast cancer
Authors: Arun B. , Valero V. , Brewster A. , Gutierrez A. , Green M. , Esteva F. , Buzdar A. , Hortobagyi G. N. , Sneige N. 
Published: August 2020

1514 Background: Selective estrogen receptor modulators (SERMs) reduce the risk of breast cancer. Acceptance of SERMs is low due to toxicities. Agents with a better toxicity profile and surrogate endpoint biomarkers to evaluate the effect of preventive agents are needed. In addition to reducing the risk of recurrence of breast cancer, the aromatase inhibitors (AI) have been shown to reduce the risk of contralateral breast cancer in large phase III adjuvant studies. Our objective in this prospective short-term prevention study was to evaluate the effect of anastrozole on surrogate endpoint biomarkers in breast tissue and serum of women with breast cancer who are at increased risk for developing a contralateral second primary breast cancer. Methods: Women with a history of stage I, II breast cancer who were scheduled to start anastrozole for standard adjuvant treatment were eligible. After signing informed consent, patients underwent baseline fine needle aspiration (FNA) of the unaffected breast and serum collection for biomarker analysis before starting anastrozole at 1 mg per oral /day. A repeat FNA and serum collection were performed after 6 months of therapy. Biomarker endpoints included changes in ER and KI-67 expression in breast tissue analyzed by immunohistochemistry and insulin-like growth factor binding protein (IGFBP-1) in serum analyzed by ELISA. The difference in biomarkers before and after treatment was assessed using a Wilcoxon signed-rank test. Results: Forty two patients were enrolled and accrual has been completed. Median age was 58.8 (range 48–75). There was no change in ER or Ki-67 expression in pre- and posttreatment FNA samples. However, there was a statistically significant difference in pre- and posttreatment serum IGFBP-1 levels (p = 0.014); with pre-and post- mean treatment levels being 9.2 ng/mL and 13.5 ng/mL, respectively. Conclusions: We found a significant modulation of IGFBP-1 levels with 6 months of anastrozole treatment in women at increased risk of developing contralateral breast cancer. Anastrozole is currently being studied as a prevention agent in a large phase III trial, and our results provide support for continued evaluation of IGFBP-1 as a surrogate endpoint biomarker in prospective breast chemoprevention studies. [Table: see text]
Stage-size relationship in long-term repeated CT screening for lung cancer: Anti-Lung Cancer Association project
Authors: Seki N. , Eguchi K. , Kaneko M. , Ohmatsu H. , Kakinuma R. , Matsui E. , Kusumoto M. , Tsuchida T. , Nishiyama H. , Moriyama N. 
Published: August 2020

1540 Background: We have investigated the individualized benefit of CT screening as Anti-Lung Cancer Association projects (presented at ASCO 2006–2008). However, there has not been enough information about the relationship of lung cancer stage to tumor size in repeated CT screening. Therefore, we evaluated the stage-size relationship of these asymptomatic lung cancer cases diagnosed by long-term repeated screening with low-dose helical CT. Methods: Among 2,120 participants (mean age 63 years, 87% male, and 83% smoker) at baseline screening, 1,877 underwent semiannually repeated screening from 1993 to 2004. Nineteen (0.90%) prevalence cancers and 57 (0.32%) incidence cancers were detected. Within categories of tumor size, the distribution of pathological stage, histology, lymph node status, and distant metastases was determined. Results: Pathological stage has a strong relationship to tumor size at baseline screening (spearman r = 0.63, p = 0.013) and repeated screening (r = 0.65, p < 0.001). In the analysis of all 76 cases, lymph node status (r = 0.59, p < 0.001) and distant metastases (r = 0.55, p = 0.005) have also a strong relationship to tumor size. The percentages of cases with no metastases (N0M0) were 100% (0/21), 89% (17/19), 62% (8/13), 83% (10/12), 50% (4/8), and 33% (1/3) for the categories 10 mm or less, 11 mm to 15 mm, 16 mm to 20 mm, 21 mm to 30 mm, 31 mm to 40 mm, and 41 mm or greater, respectively. Histology for the categories 15 mm or less was localized bronchioloalveolar carcinoma in 13 cases, adenocarcinoma with mixed subtype in 11 cases, invasive adenocarcinoma in five cases, other non-small cell carcinoma in 10 cases, and small cell carcinoma in one case. Accumulated 10-year hazard ratio of above histology was 2.4, 2.5, 2.6, 4.1, and 0.7. In multivariate analyses, pathological stage was related to only tumor size (standardized regression coefficient beta = 0.59, p < 0.001) whereas histology was related to tumor size (beta = 0.43, p < 0.001) and smoking index (beta = 0.28, p = 0.016). Conclusions: These results provide direct evidence of a stage-size relationship in long-term repeated CT screening for lung cancer. Furthermore, early detection of lung cancer of 15 mm or less in diameter leads to the detection of early-stage (N0M0) lung cancer in repeated CT screening. No significant financial relationships to disclose.
Web-based resources for sun protection information: A French-language evaluation
Authors: Mahé E. , Beauchet A. , Saiag P. 
Published: August 2020

1549 Background: With the dramatic increase in ultraviolet-induced skin damage, including melanomas and skin carcinomas, advocating the benefits of reasonable and moderate exposure to sunlight is a public health priority in most Western countries. Objective: The aim of this study was to investigate the nature and quality of the information posted on the Internet about the effects of the sun on health and about sun protection. Methods: We used eight terms with eight search engines to identify relevant websites providing sun protection advice on the French-speaking web. This information was compared to the recommendations issued by nine official organizations. Influence of website quality and commercial links on the quality of the advice provided was evaluated. For the purposes of this comparison, we attributed marks to the following four criteria: 1) risks and benefits of sun exposure; 2) sun avoidance; 3) clothing recommendations; and 4) sunscreen use. Results: The search identified 1,551 links. After exclusion of sites duplicated either within or between search engines, and of websites used as references, we found 129 web pages dedicated to sun protection advice. Data on the effects of the sun and sun protection were deficient in most websites in comparison to official organization websites. It was even better than the web pages or websites respecting quality criteria. Commercial links tended to score poor marks for 1, 2, and 3 but better marks for 4 (sunscreen use). Conclusions: We showed the limits of web-based resources on the French-speaking web regarding sun protection advice. Poor quality of most of the websites and commercial conflict of interest with sunscreen manufacturers may explain these limits. No significant financial relationships to disclose.
A phase II study of chemoradiation followed by adjuvant temozolomide and poly-ICLC in patients with newly diagnosed glioblastoma: 12- and 18-month survival data (NABTT 0501)
Authors: Rosenfeld M. R. , Chamberlain M. , Grossman S. A. , Peereboom D. M. , Lesser G. J. , Batchelor T. T. , Desideri S. , Salazar A. M. , Ye X. 
Published: August 2020

2002 Background: Polyinosinic-polycytidylic (poly-ICLC), is a double-stranded RNA that stimulates a variety of host defense mechanisms including T-cell and natural killer cell activation, cytokine release and specific anti-proliferative and anti-viral effects. The objective of this study was to determine the safety and efficacy of poly-ICLC when added to adjuvant treatment for newly diagnosed glioblastoma. Methods: Newly diagnosed patients > 18 years with histologically proven glioblastoma received standard external beam radiation with concurrent low-dose temozolomide (TMZ) (75 mg/m2) followed by adjuvant cycles of TMZ for 5 days (150–200 mg/m2) (week 1) then intramuscular injections of poly-ICLC (20 mcg/kg) 3 times a week (weeks 2–8; total 21 injections) with week 9 off and no limit to the number of adjuvant cycles (TMZ + poly-ICLC). Imaging evaluations were performed before every cycle. Results: There were 97 patients enrolled (60 men); median age 56 yrs (range 21–85); median KPS 90 (range 60–100). Fourteen patients did not start adjuvant treatment (5 patient request and 4 investigator withdrawal; 2 progressive disease; 1 death; 1 toxicity; 1 other). The most frequent CTC grade 3–4 toxicities occurring in > 5% of subjects at least possibly related to poly-ICLC were leukopenia (20%), thrombocytopenia (14%), anemia (13%), neutropenia (10%), and SGPT (9%) or alkaline phosphatase (7%) elevation. Two deaths during adjuvant treatment were considered unlikely related to poly-ICLC. To date 71 of 97 patients have survived at least 12 months from diagnosis. The estimated median survival for the entire cohort was 17.2 months (95% CI: 15.5–19.3 months). Overall survival for the cohort at 12 months was 73.2% (95% CI: 63%-82%) and at 18 months 47.4% (95% CI: 37–58%). For only those subjects 18–70 years, overall survival at 18 months was 51.8% (95% CI: 41–63%). This is contrasted with EORTC 26981/22981 that reported an 18 month overall survival of 39.4% (95% CI: 33.8–45.1). Conclusions: The addition of poly-ICLC to a modified adjuvant treatment regimen for newly diagnosed GB is well-tolerated. Survival data at 12 and 18 months suggest increased efficacy compared to chemoradiation with adjuvant TMZ only. [Table: see text]