bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot intervention addressing sexual dysfunction after risk-reducing oophorectomy.
Authors: Bober Sharon , Garber Judy , Recklitis Christopher J , Patenaude Andrea Farkas 
Published: March 2020

9644 Background: Women at high risk for ovarian cancer due to BRCA1 or BRCA2 mutation or family history are recommended to undergo prophylactic bilateral salpingo-oophorectomy (PBSO) after age 35 or completion of childbearing. This potentially life-saving surgery leads to premature menopause, frequently resulting in profound sexual dysfunction. We developed and piloted the first psychoeducational intervention for managing sexual dysfunction in young women after PBSO. Methods: This single-arm multi-modal pilot intervention study included a single half day session with educational modules about sexual health education, relaxation training, and cognitive behavioral therapy (CBT) skills to manage symptoms, followed by tailored telephone counseling. Self-report assessments, including the 19-item Female Sexual Function Index (FSFI) and a 10-item measure of sexual knowledge after PBSO were completed at baseline and two months post-intervention. Eligible women had PBSO for risk-reduction, current age ≤ 49, and endorsed at least one symptom of sexual dysfunction. Study endpoints include feasibility and effectiveness. Results: 36 women enrolled and completed pre- and post- assessments. Median age was 44 years (range 36-49) and median time since PBSO was 3.2 years (range 0.75-12.3). FSFI scores improved significantly from baseline to post-intervention for the desire (p = 0.003), arousal (p = 0.001), and satisfaction (p = 0.031) domains, as well as on the full scale score (p = 0.005). In addition, 60% of participants demonstrated improved knowledge scores about managing sexual dysfunction after PBSO following the intervention. Conclusions: The current intervention builds upon recent advances in CBT and sexual health education to address this much-neglected problem after PBSO. Results from this promising pilot intervention provide compelling preliminary data to move toward conducting a randomized clinical trial. Reducing post-PBSO distress, a valuable goal in its own right, may ultimately improve uptake of this potentially life-saving procedure in a high-risk population, as loss of sexual functioning is one of the reasons mutation carriers give for rejecting surgical risk-reduction.
Impact of oncology drug shortages.
Authors: Emanuel Ezekiel J. , Shuman Katie , Chinn Derek , Gogineni Keerthi 
Published: March 2020

CRA6510 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.
Efficacy of different anti-HER2 drugs in first-line therapy for advanced breast cancer: Systematic review and meta-analysis.
Authors: Sasse Andre Deeke , Carcano Flavio Mavignier , dos Santos Lucas Vieira , Lima Joao Paulo Da S.N. 
Published: March 2020

e11500 Background: Anti-HER2 therapy has brought major gains to therapy of advanced breast cancer (ABC), however it is still not know if there are difference in efficacy between trastuzumab and lapatinib. We execute a systematic review and meta-analysis in order to measure the impact of anti-HER2 therapy on ABC outcome and to assess if any particular drug is more effective in this scenario. Methods: Randomized controlled trials comparing first-line antineoplastic drug plus minus antiHER2 therapy (either trastuzumab or lapatinib) in ABC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), progression-free survival (PFS), tumor response and safety. Meta-analyses were performed using random-effects model and outcomes measured by hazard ratio (HR) and pertinent 95% confidence intervals were calculated. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of anti-HER2 drug used over the estimated effect size. Results: eight trials (1848 patients) were included, two trials used lapatinib whereas six used trastuzumab. In two trials, anti-HER2 therapy was combined to hormone therapy. All trials, except the one by Slamon, demanded tumors to be ISH+ or IHC 3+. The methodological quality of included trials was moderate to good. Either trastuzumab or lapatinib improved overall survival (HR 0.79; 95% CI 0.69-0.91; P=0.0008; I2=0%) with no difference bet drugs (test for difference P=0.75). PFS was also increased with antiHER2 addition with similar activity of trastuzumab and lapatinib (HR = 0.58; 95% CI 0.51-0.66; P<0.0001; I2=0%, test for difference P= 0.42). Conclusions: The present meta-analysis confirmed the role of antiHER2 drugs as a valid first-line therapy for ABC. Furthermore, we failed to show any difference in efficacy between lapatinib and trastuzumab when combined to systemic therapy, both being acceptable options for antiHER2 therapy for ABC.
Health economic analysis of breast cancer index in patients with ER+, LN- breast cancer.
Authors: Gustavsen Gary , Schroeder Brock , Kennedy Patrick , Pothier Kristin Ciriello , Schnabel Catherine A. , Erlander Mark G. 
Published: March 2020

e11504 Background: Numerous studies have demonstrated the cost utility of gene expression-based assessment of recurrence risk in breast cancer. Cost savings rely primarily on decreased use of adjuvant chemotherapy in patients predicted to be low-risk. Breast Cancer Index (BCI) is a gene expression-based test that significantly predicts overall risk of recurrence, late (≥5y) recurrence and likelihood of benefit from extended (≥5y) endocrine therapy in patients with ER+, LN- breast cancer. This study evaluated the potential cost utility of BCI from a US third-party payer perspective. Methods: A fact-based economic model was developed which projected the cost and effectiveness of BCI in a hypothetical population of patients with ER+, LN- breast cancer compared to standard clinicopathologic diagnostic modalities. Patients flowed through the model based on patterns of care and BCI data. Costs associated with adjuvant chemotherapy, toxicity, follow-up, endocrine therapy, and recurrence were modeled over 10 yrs. Model inputs were based primarily on published literature, and supplemented by interviews with disease experts and payers. Sensitivity analyses were performed around key inputs to estimate effects on the model. Results: Use of BCI is projected to be cost saving in this patient population, with a net cost savings of $4,005 per patient tested after accounting for BCI cost. Gross cost savings were projected to be achieved through targeted use of adjuvant chemotherapy ($5,785), reduced recurrence in patients receiving extended endocrine therapy based on BCI ($2,350), and reduced recurrence in previously non-compliant patients ($370). Sensitivity analyses demonstrated that results were most sensitive to chemotherapy utilization in low- and intermediate-risk patients, cost of adjuvant chemotherapy, cost of recurrence, and percentage of patients classified as low risk. Conclusions: BCI is projected to be cost saving in an ER+, LN-, breast cancer patient population. Cost savings are achieved through projected impact on adjuvant chemotherapy use, extended endocrine therapy use, and endocrine therapy compliance. These findings require validation in additional cohorts, including studies of real-world clinical practice.
Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients: 2-year update.
Authors: Cagossi Katia , Razzini Giorgia , Ferrari Alessia , Lazzaretti Maria Grazia , Leporati Meri , Silvestri Rosangela , Iadanza Manlio , Artioli Fabrizio 
Published: March 2020

e11515 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, prior systemic therapy for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression. Primary objective was time to progression (TTP) and safety. Results: Fifteenpatients were included. Median age was 52 years old (range 42-77). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 6 months (2-14). No complete response was observed. Eight out of fiftten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and were still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited significant reduction of serum marker concentrations. No grade 3-4 skin toxicity was reported. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The combination of lapatinib with metronomic chemotherapy may lead to effective palliation despite extensive pretreatment at least in bone metastatic patients. The treatment appears to be less toxic than lapatinib and capecitabine at full dosage, especially in heavily pretreated MBC patients. The preliminary results suggest the need of a clinical trial to confirm a role of this combination to delay lapatinib resistance.
Evaluation of risk recurrence in early breast cancer assessed by Oncotype DX and tumor cell dissemination to blood and bone marrow.
Authors: Aktas Bahriye , Bankfalvi Agnes , Heubner Martin Leonhard , Kimmig Rainer , Kasimir-Bauer Sabine 
Published: March 2020

e11516 Background: The OncotypeDX assay is a validated genomic test that predicts the likelihood of breast cancer (BC) recurrence, patients’ (pts) survival within 10 years of diagnosis and benefit of chemotherapy in early-stage, N0, ER-pos BC. In addition, disseminated tumor cells (DTC) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood, especially stemness like tumor cells (slCTCs) including cells being able to perform epithelial-mesenchymal transition (EMT), have been associated with worse outcome in BC. Here we use OncotypeDX as well as the presence of DTCs, CTCs and slCTCs to evaluate the risk for recurrence in early BC pts. Methods: In total, 90 pts with newly diagnosed HER2-neg early stage BC received breast conserving surgery and sentinel lymphonodectomy. 17 pts were ER-/PR-, 12 pts ER+/PR-, 3 pts ER-/PR+ and 59 pts were ER+/PR+. Analysis of OncotypeDX and KI67 were performed. In case of G2 tumors, UPA and PAI1 were determined as further proliferation markers in tissue samples. Two BM aspirates from these patients were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. Furthermore, 2 x5 ml blood were analyzed for CTCs with the AdnaTest BreastCancer for the detection of EpCAM, MUC-1, HER-2, and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for the presence of slCTCs using the AdnaTest EMT (multiplex RT-PCR for TWIST, AKT2, PI3K), and the AdnaTest TumorStemCell (ALDH1). Results: OncotypeDX was performed in 68/91 cases. 30/68 pts (44%) had a low RS, 29/68 pts (43%) an intermediate RS and 9/68 pts (13%) a high RS, respectively. BM aspiration could be performed in 70/91 pts with a positivity rate of 34% (24/70) for DTCs. CTCs were detected in 16/68 (25%) evaluable pts and slCTCs in 27/62 (44%) pts, respectively. In preliminary statistical analysis, KI67, PR and grading are showing association to RS as well as the presence of slCTCs. Tissue samples of patients with G2 tumors (N=65) underwent evaluation for UPA/PAI1analysis. Conclusions: Final statistical analysis for the complete data set including correlations to RS with all evaluable parameter will be available for presentation at the ASCO.
Benefit of chemotherapy after third line and evaluation of post-progression survival (PPS) in metastatic breast cancer (MBC): A single institution study.
Authors: Forcignano Rosachiara , Ciccarese Mariangela , Chiuri Vincenzo Emanuele , Cairo Giuseppe , Lupo Laura Isabella , Petrucelli Luciana , Gambino Abbondanza , Ronzino Graziana , Licchetta Antonella , Gnoni Antonio , Giannarelli Diana 
Published: March 2020

e11517 Background: MBC remains an incurable disease with median survival of 2-3 years despite new drugs. The gain of benefit from third-line chemotherapy (CT3) in MBC is unknown. The validation of PPS as surrogate endpoint and its correlation to OS is under debate. Methods: From 2006-2012 we analyzed retrospectively consecutive 114 pts treated for MBC, 67 with at least 3 lines CT, to show the gain of benefit after CT3 and predictive factors of response to multiple lines of therapy. Moreover, we evaluated PPS for each line and its relation to OS. Results: Median age at M+ diagnosis was 58 years (29-87), median site of disease 2 (1-6), 66.7% visceral, HER-2+ pts 31.1%, median number of anti-Her-2 treatment 2 (1-6); 56.1% received a maintenance treatment (37% M1, 13% M2), median number of treatment 3 (1-8). Median OS for all pts was 47.1 (95%CI: 36.5-57.6). No difference in OS for pts with maintenance treatment vs not, respectively 49.1 vs 45.6 P=0.17. Multivariate Cox analysis showed that OS is related with ER/Pgr status (positive vs negative p=0.03) number of lines ( >3 vs ≤ 3) p< 0.0001 and number of metastatic sites (>2 vs ≤2) p=0.01. We evaluated relation between PFS and OS and PPS and OS until 6th line of therapy with a linear regression model. Conclusions: These results supported the use of chemotherapy after CT3. PFS and PPS are related to OS until 6th line of treatment. PPS as surrogate endpoint of OS is a valid hypothesis to be evaluated in prospective trials of MBC [Table: see text]
Correlation between body mass index and clinical and pathologic characteristics of breast tumor intrinsic subtypes.
Authors: Bas Murat , Yalcin Selim , Rahatli Samed , Kucukoztas Nadire , Dizdar Omer , Altundag Ozden 
Published: March 2020

e11532 Background: In this study it is aimed to investigate the association between body mass index between the clinical and pathological characteristics of breast tumor intrinsic subtypes defined by ER, PR and HER-2 expression status. Methods: 885 breast cancer patients followed-up at the Medical Oncology Departments of Baskent University Faculty of Medicine from 1983- 2012 were evaluated. In accordance with the criteria of the WHO, patients with BMI (kg/m²) <18,5 were classified as underweight; 18.5-24.9 as normal; 25-29.9 as overweight, 30-34.9 as obese class I; between 35-39.9 as obese class II; and > 40 as obese class III (morbid). Results: Median age of the 885 patients included in the study was 53.9. The number of pre-menopausals were 348 (43.2%). Average BMI was 27.2 kg/m². Compared to Luminal B and HER-2 positive groups, the rate of T1 tumors were significantly higher (p=0.002 and p=0.006) in Luminal A group. There was a statistically significant (p=0.046) difference in LVI rates between the groups, with the Luminal B group showing a higher rate of LVI. There was a statistically significant difference in PR positivity between groups as PR positivity was more frequent in the group with BMI between 30.0-34.99 kg/m² compared to the groups with BMI less than 25 kg/m² and BMI between 25.0-29.99 kg/m² (p=0.035 and p=0.003). There was a statistically significant difference in HER-2 between groups as the rate of HER-2 negatives was significantly higher, and the rate of HER-2 positives were significantly lower in the group with 30.0-34.99 kg/m², compared to the group with BMI less than 25 kg/m² (p=0.002 and p=0.048). Conclusions: Our results indicate the association between body mass index and clinical characteristics of breast tumor intrinsic subtypes. Further research is needed to explore biological role of BMI on tumor intrinsic subtypes.
Identification of the activated form of the estrogen receptor (ER) in breast cancer (BC).
Authors: Gilles Erard M. , Bosq Jacques , Fuqua Suzanne A.W. , Zukiwski Alexander A. , Caillaud Jean-Michel , Gilles Barthelemy , Bonneterre Jacques 
Published: March 2020

e11535 Background: : About 50% of ER positive (ERpos) BC are resistant to hormone treatment. In absence of ligand, ERs are evenly distributed in nuclei in normal tissue. Upon ligand binding, ERs dimerizes and form a discrete focal subnuclear distribution pattern (FDP), which are associated with transcriptional activation of ER. This ER FDP is observed in BC. We hypothesized that in BC that the presence/absence of ER in the FDP could predict antiestrogen activity. This study describes an immunohistochemistry (IHC) method, by which a biomarker could be developed to investigate this hypothesis. Methods: 37 paraffin embedded, formalin fixed archived BC samples were processed using 4 ER-alpha antibodies (Ab) under different IHC conditions to develop and refine this biomarker, the ER nuclear morphology was analyzed with standard microscopy at x1000. Interpretation of the IHC slides was done by an experienced pathologist. Standard ER, progesterone receptor (PR), and Ki67 testing were done. Tumor grade was obtained from the patients’ records. Analysis of the different Ab was with the kappa statistics. Comparison of the IHC technique to immunofluorescence (IHF) was done on 8 samples. Results: Consistent with prior research observations, tumors had two ER nuclear morphologies: 1. Diffuse pattern (D) where the ER was distributed evenly in a fine granular pattern, 2. Aggregate pattern (A) where the ER is distributed in distinct clumps or aggregates. This defined 3 tumor phenotypes: A cells only (A) 1% (4/37), D cells only (D) 65% (24/37), and a heterogenous mix of A + D cells (AD) 18% (7/37), ER Neg 14% (5/37). IHC and IHF analysis for ER nuclear morphology was concordant. The ER activation status (A/AD or D) was not correlated with staining ER intensity, ERpos %, PRpos%, but was correlated with % Ki67 staining (p=0.09) and tumor grade (0.035). Conclusions: ERpos early BC biopsies can be grouped in two categories based on ER nuclear morphology: A group with diffuse and homogenous nuclear staining, and a different group with heterogeneous area of cells having a nuclear pattern consistent with a functional or activated ER. These observations warrant clinical pathological studies to determine if this biomarker is potentially predictive of clinical outcomes.
An empirical assessment of breast cancer treatment charges by survival status.
Authors: Stenehjem David D. , Dahal Arati , Bellows Brandon Kyle , Brixner Diana I. 
Published: March 2020

e11541 Background: Breast cancer treatment can be costly, but it remains unknown if charges differ between patients who die during treatment compared to survivors. The objective of this study was to assess annualized mean charges by survival status in patients with a diagnosis of breast cancer. Methods: The University of Utah Enterprise Data Warehouse was used to analyze patients ≥18 years with a diagnosis of breast cancer identified by ICD-9 code (initial diagnosis defined as index date) treated at the Huntsman Cancer institute (HCI) from 2002-2010. The HCI Tumor Registry was used to determine stage at diagnosis and other cancers. Cause and date of death was captured from the Utah Population Database. Cancer-related (CR) and non-CR charges were by ICD-9 codes from index date until death or end of the follow-up period, were weighted by the inverse probability of survival, and annualized. Generalized linear models (GLM) with gamma distribution and log link function were used to examine charges by survival status, while adjusting for baseline characteristics including demographics, stage, and comorbidities. Results: There were 1783 patients included, of which 296 (17%) died. Compared to survivors, deceased patients were older (mean age 62 vs. 56), more were diagnosed with stage IV disease (17% vs. 3%), and fewer with stage I (24% vs. 45%); all p<0.001. Mean unadjusted annualized CR charges were not different between groups (deceased $34,310 vs. alive $32,797; p=0.64), but non-CR charges were higher for deceased patients ($39,926 vs. $16,538; p<0.001). GLM results indicated deceased patients had 90% higher annualized CR charges relative to survivors (p<0.001) and higher charges for stages I, II, and III (125%, 86%, and 69%, respectively; all p<0.001). Deceased patients had 124% higher annualized non-CR charges relative to survivors (p<0.001) and higher charges for stages I, II, and III (174%, 146%, and 107%, respectively; all p<0.001). Charges did not differ between groups for stage IV patients. Conclusions: When adjusting for confounders, death was associated with higher CR and non-CR charges, except in patients with stage IV disease at diagnosis. Patients who died during treatment may have had more aggressive disease leading to higher charges.
Attitude of Italian oncologists toward fertilty preservation in patients with early breast cancer.
Authors: Frassoldati Antonio , Barni Sandro , Amoroso Domenico , Collovà Elena 
Published: March 2020

e11547 Background: Patient’s desire for fertility preservation is a frequently underestimated problem in oncology clinical practice. Even if several different approaches have been suggested to maintain fertility in early stage breast cancer patients undergoing adjuvant chemotherapy, few women undergo to such procedures or are referred to a specialized team. Methods: Between April and July 2011, an electronic questionnaire regarding the treatment attitude in early breast cancer in premenopausal women was submitted to Italian oncologists, and 611 (female 52%, age range 25-65, 81% from general hospitals, 19% from research institute) filled in the questionnaire. Among the items, we explored also the issue of fertility preservation in women candidate for adjuvant chemotherapy and hormones. We compared the survey results (examined according to sex, age, working institution and geographic origin) with the recommendations available from guidelines of oncology and gynecology societies. Results: A pregnancy test before starting chemotherapy is considered mandatory only by 49.5% of oncologists, independently from age and type of treatment. In order to maintain fertility, several guidelines recommend eggs or embrio freezing, whereas the use of LHRH-analogs is recommended only in the contex of research trials. In our survey, the eggs freezing is considered the preferred method by 24,8% of Italian oncologists only, while 6% suggest cryopreservation of ovarian tissue. Embrio freezing is preferred by <1% of oncologist. However, the majority of Italian oncologists considers the administration of LHRH-analog the treatment of choice to maintain fertility (independently from the hormone receptor status of the tumor in 83% of cases). No significant differences as by type of institution, geographic location, and physician’s age has been observed. Conclusions: The use of LHRH-analog is the preferred method by Italian oncologists for fertility preservation. A recent analysis of literature regarding the use of LHRH-analogs by Italian Society for Medical Oncology using the GRADE method suggest an important role of this drugs, even if not yet conclusive for their efficacy (level of evidence 1+, Recommendation “slightly positive”).