bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA1 and BRCA2 germline mutation carriers have a lower breast density compared to high risk women without such mutations
Authors: Sharma P. , Klemp J. R. , Kimler B. F. , Khan Q. J. , Smith E. J. , Fabian C. J. 
Published: March 2020

1517 Background: High mammographic breast density, a known risk factor for breast cancer is influenced by both genetic and non genetic factors. It is not clear if there are differences in breast densities between BRCA1/2 mutation carriers and high-risk non carriers. The aim of this study was to compare breast density in high-risk women with and without BRCA1/2 mutation. Methods: Women at high risk for development of breast cancer (based on family history, prior precancerous disease or prior breast cancer) who underwent genetic testing at the University of Kansas Breast Cancer Prevention Center between 1998 and 2005 were identified under an IRB approved protocol. BRCA1/2 full sequencing was performed at Myriad Genetic Laboratories. The earliest digitized mammogram of these subjects was identified from a preexisting mammogram database. All mammograms had to be prior to/at least one year from any chemoprevention intervention. For subjects with prior breast cancer, mammogram of the uninvolved breast was used. Breast density was assessed on the left craniocaudal mammographic view by computer assisted method, Cumulus. Frequencies of categorical variables were assessed using chi-square analysis. Continuous variables were assessed using Mann-Whitney non parametric test. Multiple regression analysis was used to investigate whether differences are due to variables other than mutation status. Results: The study population consisted of 284 high-risk women who underwent BRCA1/2 testing and for whom a mammogram was available. 30 (11%) had BRCA1 and/or 2 deleterious mutation. There was no difference between mutation carriers and non-carriers for BMI, 5 year Gail risk, parity, menopausal status and HRT use. Mutation carriers were younger (median age 42 vs. 46, p=0.020) and more likely to have a positive family history (100% vs. 85%, p=0.020). Older age (p<0.001), higher BMI (p<0.001) and having a BRCA1/2 mutation (p=0.025) were significantly associated with a lower breast density. Conclusion: Among high risk women, possession of a deleterious BRCA1/2 mutation is associated with lower breast density after adjusting for factors known to affect breast density. This suggests that breast density may be governed by genetic factors other than BRCA1/2 mutation status. No significant financial relationships to disclose.
Analysis of 94 patients with advanced biliary tract cancer
Authors: Andritzky B. , Adler S. , Burkholder I. , Thöm I. , Schuch G. , Görn M. , Schilling G. , Edler L. , Bokemeyer C. , Laack E. 
Published: March 2020

15172 Background: Cholangiocarcinoma or gallbladder cancer are often diagnosed at an advanced stage with limited treatment options. Methods: Between 1994 and 2004, 94 patients (pts) (47 male, 47 female) with advanced biliary tract cancer were treated at the Department of Oncology and Hematology, University Hospital Hamburg-Eppendorf. Clinical and histopathological characteristics, response to chemotherapy, and survival were investigated in a retrospective analysis. Median age was 59 years (range 30–80) and median Karnofsky performance status was 90%. Predominant histologic type was adenocarcinoma (94.7%). Primary tumor sites were extrahepatic bile duct (29.9%), gallbladder (28.7%), intrahepatic bile duct (10.6%), ampulla of Vater (2.1%), not specified (28.7%). Predominant localizations of metastases were liver (73 pts (77.7%)), lymph nodes (49 pts (52.1%)) and the peritoneum (14 pts (14.9%)). 33 pts (35.1%) underwent surgery of the primary tumor at time of diagnosis. Results: 72 of 94 pts (76.6%) received a first-line chemotherapy, all together 10 different chemotherapy regimens were used. The median number of cycles was 2.5 (range 1 - 12). A single agent chemotherapy with gemcitabine was the most often adminstered regimen (23 pts (31.9%)), followed by carboplatin and etoposide plus whole body hyperthermia (12 pts (16.7%)) and 5- fluorouracil and folic acid (10 pts (13.9%)). The overall response rate was 8.3% (95% CI 3.1 - 17.3) (34.7% SD, 47.2% PD, 9.7% not evaluable). Second-line chemotherapy was given in 27 patients, which induced no tumor response, but a stable disease rate of 22.2%. Median time to follow- up was 44.8 months. Survival was calculated for all 94 pts since time of diagnosis. Median overall survival was 12.2 months and median progression-free survival 9.2 months. The median overall survival time for the 72 pts who were treated with chemotherapy was 14.0 months, and for the 22 pts who did not receive chemotherapy 10.7 months (p=0.2). Conclusions: Our analysis showed a poor prognosis for patients with advanced biliary tract cancer. Response rate to chemotherapy was low. Therefore, well tolerated cytotoxic agents should be used and new treatment strategies (including molecular targeted therapy) should be further investigated. No significant financial relationships to disclose.
The risk of thrombotic events in patients with primary versus secondary hepatic malignancies who are undergoing surgical resection
Authors: Yates T. J. , Abouljoud M. , Lambing A. , Kuriakose P. 
Published: March 2020

15178 Background: The increased risk of thromboses is well documented in patients with malignancies, and those undergoing abdominal surgery. Furthermore, patients requiring hepatic resection for underlying malignant disease have been reported to be at increased risk for thrombotic complications. However, guidelines for thromboprophylaxis in this patient population are still under investigation. A cursory review performed at our institution determined the incidence of thrombotic events to be comparable to that reported in the literature. We, therefore, went further to study if there was a difference in the risk of thromboses between those undergoing resection for primary hepatic cancer, versus metastatic disease. Methods: We performed a retrospective chart review of patients undergoing surgical resection for hepatic malignancies. The primary end point was to determine whether there was a difference in the incidence of thrombotic events between primary and secondary malignancies. Results: A total of 99 patients at our institution underwent surgical resection for either primary or secondary hepatic malignancies in the past 5 years. There were 7 patients who developed thrombotic events within three months of their resection. Of these patients, all 7 underwent resection for secondary hepatic malignancies. Based on the nature of this study, and its lack of standardized thromboprophylaxis, statistical analysis was not performed. Conclusions: Patients undergoing surgical resection of hepatic malignancies appear to be at increased risk of thrombotic events, and may require more specific standardization of their thromboprophylaxis. Furthermore, based on our observation it appears those associated with metastatic disease may derive an even greater benefit from this. Future prospective studies will be required to evaluate this difference in thromboses, and to better define the guidelines for thromboprophylaxis. No significant financial relationships to disclose.
Gemcitabine for patients with chronic renal failure on hemodialysis
Authors: Matsuda M. 
Published: March 2020

15189 Background: Numerous studies of gemcitabine (GEM) as an agent for advanced pancreatic carcinoma (APC) have been reported. Although significant and/or unexpected toxicities of GEM have been reported even at low doses in patients (pts) with impaired renal function, no dosing recommendations have been developed for chronic renal failure (CRF). Methods: In this report, we present five APC pts with CRF and discuss the use of GEM for pts on hemodialysis (HD). Results: CASE 1. A-74-year old man with CRF (not on HD) received GEM (800 mg) on days 1 and 8. Grade 3 hematological toxicity (neutropenia and thrombocytopenia) occurred on day 9, which recovered immediately after HD was performed. Ten courses of GEM (800 mg x q2w) with HD initiated 6 h after administration have since been administered without any side effects. CASE 2. A-48-year old man underwent Whipple’s operation and received GEM (1000 mg x3 q4w) as adjuvant chemotherapy. After 10 cycles, he developed hemolytic uremic syndrome (HUS), which recovered immediately after performance of HD. HD was initiated 24 h after GEM (1000 mg), and this sequence was repeated 53 times until recurrence occurred. CASE 3. A-78-year old woman with recurrent pancreatic carcinoma developed HUS after 29 cycles of GEM (800 mg x q2w). After remission of HUS by starting HD, GEM was commenced again (HD was initiated 24 h after GEM at 1000mg x q2w), and has been administered 18 times. Both CASE 4 (a 65-year- old woman) and CASE 5 (a 56-year-old man) are APC pts with a long history of HD. Although HD was initiated within 24 h after GEM (1000mg) administration, Grade 3 hematological toxicity (neutropenia and leukocytopenia) occurred in these pts and we had to give up GEM after several courses. Conclusions: GEM (800–1000 mg) can be administered safely to pts with CRF on HD, especially soon after commencing HD, as long as HD is initiated within 24 h after GEM administration. In pts with a long history of HD, however, GEM should be administered with caution. No significant financial relationships to disclose.
Effect of familial breast cancer outcomes on health behaviors of relatives
Authors: Fisher S. G. , Mumby P. , Kohli S. 
Published: March 2020

1521 Background: While the disease outcomes of breast cancer probands do not affect the objective risk of first degree relatives (FDR), the morbidity and mortality experience may impact their subsequent perceptions and health behaviors. This study examines the influence of a proband’s disease course on screening behaviors, perceived risk, self-efficacy, traumatic stress and related mood disturbances of FDR. Methods: A cross-sectional sample of 149 FDR was recruited (79% of respondents) by invitations distributed by 545 probands. Respondents were categorized into a ‘high impact’ group whose familial proband had expired, relapsed or undergone intensive chemotherapy (n=55), and a ‘low impact’ group whose proband was disease-free after surgery ± radiation (n=94). This sample provided a power of 84% for detection of a 1.5 unit difference in screening indices and a 10% difference in perceived risk between groups with a two-sided alpha level of 0.05. Parameters were measured by self-administered, mailed surveys of newly-developed and established instruments. Objective risk assessments were completed by a genetic counselor. Statistical analyses included parametric and non-parametric methods, as appropriate. Results: While the high impact group reported perceptions of greater familial proband suffering (8.6 vs.5.8) and greater anxiety and doubt regarding mammography benefits (11% vs. 1%) (p<0.01), there was no statistically significant difference between groups in screening behaviors or perceived risk. The high impact group experienced sleep disturbances (28%), emotional stress (52%), and mood swings (61%) more often than the comparison group (p<0.001). FDR with the highest objective risk had significantly higher scores on screening indices and perceived risk (p<0.01) but significantly lower knowledge regarding breast cancer (p=0.04). Conclusions: This study suggests that while morbidity and mortality of familial probands is not associated with screening practices of FDR, it does have a negative impact on their psychological well-being. Enhanced strategies to educate and support FDR regarding familial breast cancer risk and potential psychological repercussions of the proband’s experience are warranted. No significant financial relationships to disclose.
Health-related quality of life among high-risk women in an MRI surveillance study
Authors: Bradbury A. R. , Cummings S. A. , Dignam J. J. , Patrick-Miller L. , Verp M. , White M. A. , Dudlicek L. , Newstead G. , Abe H. , Schmidt R. , Olopade O. I. 
Published: March 2020

1522 Background: The quality of life (QOL) and psychological impact of incorporating MRI into breast cancer screening programs for high-risk women (HRW) has not been well studied. Psychological and biological risk factors, e.g. cancer history, BRCA mutation, imaging recall, generalized anxiety or clinical depression may mediate QOL outcomes. Methods: 100 HRW undergoing intensive surveillance including yearly mammography, semiannual breast ultrasound and breast MRI have completed QOL (SF-36), anxiety (STAI) and depression (Beck) questionnaires at semi-annual visits. 56 HRW have completed 3 screenings. Differences in QOL measures over time were evaluated using longitudinal regression models. Differences between participants and population norms (PN), women with/without a history of cancer and with/without a BRCA mutation were assessed using t-tests. Results: QOL scores increased over time and were statistically significant for the general health (GH) subscale (p=0.016). All QOL subscales were higher than PN at baseline and were significantly higher than PN at 12 months. Mean GH score at 12 months = 80.0, PN 72.7 (SD14.2, p<0.01). Mean mental health score at 12 months = 78.9, PN 73.4 (SD14.9, p<0.01). At baseline, BRCA carriers had lower QOL scores than non-carriers and women with a history of cancer had higher QOL scores than unaffected participants, although these differences were not statistically significant. Conclusions: These data suggest that intensive breast cancer screening incorporating breast MRI may have a positive effect among HRW. Continued enrollment will allow for multi-variate characterization of psychological and biological predictors of change in QOL and psychological well-being among high-risk women undergoing intensive screening. No significant financial relationships to disclose.
Effect of coronary heart disease (CHD) risk factors and medications on invasive breast cancer risk in the Raloxifene Use for The Heart (RUTH) trial
Authors: Mershon J. , Geiger M. , Barrett-Connor E. , Collins P. , Kornitzer M. , Dowsett S. , Zheng S. , Song J. , Wenger N. 
Published: March 2020

1530 Background: RUTH enrolled 10,101 postmenopausal women at increased risk for major coronary events. Women were not enrolled based on their risk for breast cancer. The incidence of invasive breast cancer in the placebo group was low for this older population of women (mean age 67.5 years). The aim of this analysis was to determine whether CHD risk factors and selected cardiac medications were protective against invasive breast cancer in this population at increased risk for coronary events. Methods: Covariates assessed were baseline factors that are known CHD risk factors and selected medications ( Table ). Univariate analyses were performed for all covariates using placebo data. Results: The effect of baseline CHD risk factors and selected cardiac medications on the incidence of invasive breast cancer in women receiving placebo in RUTH (N=5057) Conclusions: In these postmenopausal women at increased risk for major coronary events, baseline CHD risk factors and selected cardiac medications assessed individually did not protect against invasive breast cancer. The low incidence of invasive breast cancer in the RUTH population does not appear to be due to the presence of CHD risk factors or use of cardiac medications. [Table: see text] [Table: see text]
Gene expression as a predictive marker of outcome for high-risk transitional-cell carcinoma (TCC) of the bladder in patients (pts) randomized to adjuvant chemotherapy with cisplatin-gemcitabine (PG) or observation (OBS) after radical cystectomy
Authors: Pollera C. F. , Pessina G. , Nelli F. , Felici A. , Moscetti L. , Ruggeri E. , Mottolese M. , Gallucci M. , Sperduti I. , Cognetti F. 
Published: March 2020

15502 Background: A randomized phase III trial comparing PG vs OBS in muscle-invasive TTC of the bladder is currently ongoing. ERCC1 and RRM1 genes are involved in the nucleotide excision repair pathways, and their up-regulation by tumor has been clearly related to resistance of cisplatin and gemcitabine, respectively. Preliminary correlations in patients with bladder cancer randomized to PG were already presented (Proc ASCO 2005, Abstract No: 4589). In the present study, we have examined the predictive value of ERCC1 and RRM1 as markers of tumor progression, as well as their potential correlation with other known prognostic factors also in patients randomized to OBS. Methods: Thirty-nine paraffin-embedded TTC samples of a subset of patients entered the trial were collected. The characteristics were: pT2 23%, pT3 54%, pT4a 23%, pN1–2 46%; G3–4 98%; M/F 10%/90%, median age: 65 years (range 53–74); PG/OBS: 49%/51%. Analysis consisted of real time RT-PCR quantification of mRNA levels of ERCC1 and RRM1. Results: After a median follow-up of 25 months (range 12–51), 17 patients relapsed and 10 deceased. A good correlation was found between mRNA expression levels of both genes. Three-year disease-free survival (DFS) was 74% vs 33% for patients with low and high ERCC1 expression (p=0.03), and 64% vs 22% for those with low and high RRM1 expression (p=0.26), respectively. Comparable result in favour of patients showing lower ERCC1 mRNA levels was found in both groups of patients randomized to PG or obs. Multivariate analysis demonstrated that only the presence of N1–2 and low expression level of ERCC1 were significant prognostic factor for better DFS (HR 4.358, 2.775 and p value = 0.006 and 0.046, respectively). Conclusions: Determination of ERCC1 mRNA expression level in muscle-invasive bladder cancer can make a contribution as an independent predictor of DFS after radical cystectomy. It’s still unclear if quantification of ERCC1 gene expression level could interact with adjuvant chemotherapy. Longer follow-up will help to address this issue (Supported by CNR-MIUR grants 02.00447, 03.00387-ST97). No significant financial relationships to disclose.
Romidepsin (FK228), a histone deacetylase inhibitor: Final results of a phase II study in metastatic hormone refractory prostate cancer (HRPC)
Authors: Parker C. , Molife R. , Karavasilis V. , Reid A. , Patterson S. G. , Riggs C. , Higano C. , Stadler W. M. , McCulloch W. , de Bono J. S. 
Published: March 2020

15507 Background: Romidepsin is a bicyclic depsipeptide that inhibits histone deacetylase (HDAC). Translocations fusing TMPRSS2 gene and ERG oncogenic factor is associated with elevated HDAC-1 expression. HDAC inhibition results in accumulation of hyperacetylated histone proteins resulting in G1 and G2/M arrest, differentiation of transformed cells and apoptosis. Romidepsin can also inhibit HSP90, ablating androgen receptor expression. This is the 1st study to report activity of an HDAC inhibitor in HRPC. Methods: Romidepsin was administered intravenously at 13mg/m2 on days 1, 8 and 15 of a 28-day schedule. A 2-stage design was used. Eligibility criteria included: no prior chemotherapy, metastatic disease, QTcB <470msec, Karnofsky PS =80. The primary endpoint was to determine rate of disease control (complete response [CR], partial response [PR], stable disease [SD] for 6 months). Secondary endpoints were PSA response rate (RR), time to PSA and objective disease progression, safety profile, effect on disease related symptoms and pharmacokinetics (PK) of romidepsin. Results: Thirty-one patients were enrolled. Median age: 64 years (range 43–82). Twenty-one patients are evaluable for radiological and PSA response: 1 patient achieved a confirmed radiological PR lasting >6 months (m), and 2 confirmed SD for 6m. Four patients had SD lasting 5m (n=2) and 4m (n=2). The PSA RR was 7%. A 3rd patient had a 40% fall in PSA lasting 5m. The most common drug related adverse events were (all grades, %): nausea (84%), fatigue (77%), vomiting (65%), anorexia (61%), constipation (45%), dysguesia (35%), diarrhea (32%), thrombocytopaenia (32%), anemia (28%) and neutropenia (25%). There were no grade 4 events. Non-specific asymptomatic ST segment changes on ECG were seen in 15 % of patients; there was no evidence of significant QTc prolongation on ECG confirmed by manual calculation. Conclusions: Treatment with single agent romidepsin is associated with a disease control rate of 14% and a PSA RR of 7%. Constitutional toxicities are prominent, no grade 4 events have been observed and only minimal cardiac toxicity has been reported. Further investigation in combination with other active agents in HRPC is warranted. [Table: see text]
Identification of occult prostate malignancy using a stereotactic transperineal prostate biopsy technique
Authors: Moran B. J. , Braccioforte M. H. 
Published: March 2020

15520 Background: This study investigates the detection rate of non-palpable, isoechoic occult prostate malignancy using a stereotactic transperineal prostate biopsy (STPB) technique in patients with previously negative transrectal ultrasound-guided prostate biopsy. Methods: 327 consecutive patients with continued rising total prostate specific antigen (PSA) with a minimum of 1 prior benign transrectal prostate biopsy (range 1–8), underwent STPB at a single out-patient institution between 05/2004 and 11/2006. Median patient age, total PSA and prostate volume and number of specimens obtained were 62 years, 8.3 ng/ml, 46.1 cm3 and 40 specimens, respectively. Similar to a prostate brachytherapy procedure, the prostate was positioned on the implant grid. Specimens were obtained according to x, y, and z coordinates from eight equal octants with pathology reported accordingly. A greater number of specimens were obtained from the apical half than the basilar half of the prostate; this was attributed to smaller glands in which the apical specimens sufficiently sampled the anterior curvature of the gland. Results: STPB yielded adenocarcinoma in 125/327 (38%) patients. The number of biopsy cores obtained per patient approximated the prostate gland volume in cm3. Multivariate analysis (paired samples t-tests) demonstrated there was a significant difference in detection rates with the apex having a higher incidence of malignancy than the base of the prostate gland (p=.000). Furthermore, the anterior apex harbored significantly more adenocarcinoma when compared to the posterior apex (p=.026) ( Table 1 ). Conclusions: STPB is efficacious for diagnosis of non-palpable, isoechoic occult prostate malignancy. A possible explanation for the significant finding in this study that occult malignancies occupy a higher percentage of apical biopsies using STPB may be related to difficulty and limitations of apical sampling using a standard transrectal biopsy approach. [Table: see text] No significant financial relationships to disclose.