bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of CYP19A1 gene variants with differences in disease progression in breast cancer patients from different racial/ethnic backgrounds.
Authors: Villareal Reina , Meisner Angela W. , Aguirre Lina , Kulkarny Vibhati , Shah Vallabh , Qualls Clifford , Dayao Zoneddy Ruiz , Royce Melanie 
Published: March 2020

1558 Background: Polymorphisms in the aromatase (CYP19A1) gene result in differences in the risk for breast cancer and response to treatment. We hypothesize that allele frequencies in the CYP19A1 gene vary according to race and may result in differences in progression of breast cancer among women from different racial backgrounds. The objectives of this study are: 1) to determine the allele/genotype frequencies in the CYP19A1 gene among women with breast cancer from different racial backgrounds, and, 2) to determine the association between disease progression and CYP19A1 gene variants. Methods: Clinical data and stored DNA from 327 patients participating in the Expanded Breast Cancer Registry (EBCR) program at the University of New Mexico were analyzed. These patients were followed-up for a period of 1 to 6 years. Comprehensive genotyping for CYP19A1 gene single nucleotide polymorphisms (SNPs) was performed using microarray (Illumina). Results: Data from 164 non-Hispanic white and 119 Hispanic women were analyzed. Four SNPs (rs1259269, rs17703883, rs16964211, rs28757101) were associated with differences in genotype/allele frequencies between the 2 racial groups. Furthermore, 3 SNPs (rs4646, rs17647478, and rs6493486) were associated with differences in disease progression. The rare allele (G) for the rs17647478 (G/T) is associated with poor progression compared those without the allele (41.7% vs. 17.1%, p=0.04). Similarly the minor (A) allele for the rs4646 (A/C) and the rs6493486 (A/G) is also associated with a greater chance of worsening disease (23.2% vs. 12.4%, p=0.02 and 23.4% vs. 12.4%, p=0.02, respectively). A significant percentage of women carrying the A allele for both rs4646 and rs6493486 and the T allele for the rs17647478 have more advanced disease at the time of presentation. None of the SNPs analyzed result in racial differences in breast cancer progression. Conclusions: Polymorphisms in the CYP19A1 gene influence overall disease progression in breast cancer patients but have no impact on the racial differences of disease behavior. Women carrying the risk alleles present at a more advanced stage and are also at greater risk of progression.
The effects of BR-DIM (BioResponse 3, 3’-Diindolylmethane) administered pre-prostatectomy on the androgen receptor (AR).
Authors: Heath Elisabeth I. , Hwang Clara , Cher Michael L. , Heilbrun Lance K. , Powell Isaac , Menon Mani , Li Jing , Chitale Dhananjay , Gupta Nilesh , Sethi Seema , Bolton Susan , Smith Daryn W. , Sarkar Fazlul H. 
Published: March 2020

1560 Background: Consumption of cruciferous vegetables is associated with decreased risk of prostate cancer (PCa). 3,3’-diindolylmethane (DIM), an in vivo active compound formed after consumption of cruciferous vegetables, down-regulates the AR, and causes its nuclear exclusion which results in in vitro growth arrest and apoptosis of PCa cells. We conducted a biomarker trial evaluating BR-DIM in pre-prostatectomy patients with the primary objective of measuring DIM levels in prostate tissue and in plasma. Methods: Patients with organ-confined PCa who were candidates for surgery were treated with BR-DIM at a dose of 225 mg orally twice daily for a minimum of 14 days. Patients did not receive any androgen deprivation therapy. Patients received their last dose of BR-DIM the day before surgery. Blood samples for DIM levels were collected pre-treatment and just prior to surgery. DIM concentration was measured in the plasma and in prostate tissue specimens using a validated high-performance liquid chromatographic method with tandem mass spectrometric detection. AR was evaluated by immunohistochemistry (IHC). Results: 36 patients were treated at 2 institutions. The 26 evaluable patients had median age of 60 years (range 41 - 76), 14 were Caucasian, and 10 were African American. Reasons for inevaluability included change in surgery date (n=4), inadequate BR-DIM treatment (2), withdrawal from study (2), canceled surgery (1), and other (1). Toxicity was minimal; only two patients with grade 3 headache. Post dosing, DIM was found at a mean trough level of 10.2 ng/ml (range, 0.5 to 24.7) and 12.3 ng/gm of tissue (range, 0.0 to 26.8) in plasma and in prostate tissue, respectively. PSA levels had a slightly downward trend after BR-DIM treatment. In 18 of 20 evaluable PCa specimens, IHC showed nuclear exclusion of AR. Conclusions: BR-DIM was well tolerated, and DIM was detected in both plasma and prostate tissues at ~12 h post dosing. Nuclear exclusion of AR was found in 90% of PCa specimens post BR-DIM dosing, suggesting in vivo inactivation of AR activity. PSA levels were slightly reduced overall. Accrual is ongoing and nearly complete. Additional studies with BR-DIM in PCa are warranted.
Breast cancer risk reduction among patients with DCIS.
Authors: Palomares Melanie R. , Banzet Michelle , Lu Kelley , Justus Jacob , Ottesen Rebecca A , Niland Joyce C. 
Published: March 2020

1562 Background: The incidence of ductal carcinoma in situ (DCIS) has dramatically increased with widespread mammographic screening. Although risk of recurrence of DCIS is low, it is associated with a higher risk for subsequent contralateral breast cancer (CBC), for which preventive measures are available. We evaluated the uptake of surgical and pharmacologic interventions to reduce CBC risk at our institution and investigated factors that may influence treatment choices for DCIS. Methods: City of Hope (COH) DCIS patients were identified using two sources, the Circulating Breast Tumor Marker (BrTM) Registry and the National Comprehensive Cancer Network (NCCN) database. Datasets were linked together, and treatment variables were cross-tabulated with patient and tumor characteristics. Results: Of 782 patients with breast malignancy diagnosed since 1997, 370 were excluded due to concurrent or prior invasive disease, 8 due to suspected misclassification based on therapies received, and 4 due to treatment on protocol. Of the remaining pure DCIS patients, treatment choices were recorded for 289. Of those, 40 (14%) chose bilateral risk reduction mastectomy (BRRM), 82 (28%) unilateral mastectomy, 165 (57%) lumpectomy, and 2 had no surgery. Hormonal therapy (HT) was recorded for 215 individuals who did not pursue BRRM: 124 (57%) took tamoxifen, 3 of whom switched to raloxifene, 5 (2%) started with raloxifene, and 7 (3%) took an unspecified hormonal agent, for a total HT uptake of 55%. This included 8 of 29 women with ER-negative DCIS who chose HT for CBC risk reduction. Younger age at diagnosis was associated with BRRM (24% of women diagnosed before age 50, 10% of those diagnosed 50-64, and 5% of women 65+ had BRRM, p<0.001) and HT (59% of women <65 chose HT compared to 40% of women 65+, p=0.009). Within ethnic minorities, more Asian women chose BRRM (22% vs 7% of other minorities, p=0.08). Interestingly, fewer high grade DCIS women opted for HT (39% vs 55% for low to intermediate grade, p=0.06). Conclusions: Young women tend to pursue surgical prophylaxis. Among women who keep their breasts, HT uptake was high across all age and ethnic groups, except for those older than 65 at diagnosis. It is unclear if this is due to patient choice or reflects age bias in physician recommendation.
ABO blood group and the risk of breast cancer: Multicenter, case-control, observational study.
Authors: Urun Yuksel , Koru-Sengul Tulay , Altundag Kadri , Utkan Gungor , Onur Handan , Akbulut Hakan , Demirkazik Ahmet , Icli Fikri 
Published: March 2020

1572 Background: The role of genetic factors in the development of cancer is widely accepted. ABO blood type is an inherited characteristic and previous studies have observed an association between ABO blood group and risk of certain malignancies, including pancreatic and gastric cancer. The data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. Methods: All patients who had breast cancer (BC) and treated between 2000-2010 at the Departments of Medical Oncology of both Ankara and Hacettepe Universities (Ankara, Turkey) with defined ABO blood type and Rh factor were included in our retrospective reviews of tumor registry records. A group of volunteer healthy women donors of Turkish Red Crescent between 2004-2011 were identified as a control group, without any matching factors. The relationship of ABO blood types and Rh factor with various prognostic factors such as age at diagnosis, menopausal status, family history of breast cancer, and ER/PR/HER2 status were evaluated from 1740 BC patients. We compared the distributions of ABO blood types, Rh factors among 1740 patients and 204,553 healthy controls. Among BC patients, differences between each of aforementioned ABO blood groups and Rh factors with respect to various prognostic factors were explored, respectively. Results: Overall distributions of ABO blood groups as well as Rh factor were comparable between patients (44% A, 8% AB, 16% B, 32% O, 88% Rh+) and controls (41% A, 8% AB, 16% B, 35% O, 87% Rh+). However, there were statistically significant differences between patients and controls with respect to A vs. nonA (p=0.019) and marginal significance (p=0.051) for O vs. nonO. Among patients, there were statistically significant differences between A and nonA with respect to HER2 (p=0.0421), M stage (p=0.0447), T stage (p=0.0020). Only T stage (p=0.0337) were significantly different between O vs nonO. Grade (p=0.0227) and M stage (p=0.0107) were significantly different between Rh factors. Conclusions: In our study sample, ABO blood type was statistically significantly associated with breast cancer. Additional studies are necessary to determine the mechanisms by which ABO blood type may influence the risk of breast cancer.
Hepatitis B reactivation risk in patients with solid tumors receiving single-agent capecitabine versus doxorubicin-based chemotherapy.
Authors: Ling Winnie Hui Yee , Pang Angela , Lee Soo-Chin 
Published: March 2020

1575 Background: Reactivation of hepatitis B virus (HBV) in cancer patients on chemotherapy is a challenge especially in Asia where HBV infection is endemic. Risk of HBV reactivation differs according to cancer type, chemotherapy regimen, and concomitant use of steroids. The United States Centre for Disease Control and Prevention recommends universal screening for chronic HBV infection for all patients before chemotherapy although screening for low-risk chemotherapy regimens may not be cost effective. Methods: We sought to assess and compare HBV reactivation risk and effectiveness of prophylactic anti-viral therapy in preventing HBV reactivation in patients receiving a ‘high-risk’ (doxorubicin-based) chemotherapy regimen for which prophylactic anti-viral therapy for hepatitis B carriers is generally accepted versus a ‘low-risk’ (single agent capecitabine) chemotherapy regimen for solid tumours at a tertiary cancer centre. The electronic medical records of eligible patients were reviewed between January 2007 and December 2010. Results: A total of 708 patients were identified, including 434 and 274 who received doxorubicin-based chemotherapy and single agent capecitabine respectively. HBV screening rate was 42.6% (51% for doxorubicin-based chemotherapy, 30% for single agent capecitabine, p<0.0001). 15/302 (5%) screened patients were found to be hepatitis B carriers (6 on doxorubicin, 9 on capecitabine). Overall, 3/708 patients (0.4%) developed HBV reactivation (all from the unscreened doxorubicin group, 3/214 (1.4%) compared to 0/192 (0%) unscreened patients in the capecitabine group, p<0.0001). All 15 identified hepatitis B carriers received prophylactic anti-viral therapy (14 received lamuvidine, 1 had entacavir) and none had HBV reactivation. Conclusions: Not all chemotherapy regimens are associated with risk of HBV reactivation. Routine hepatitis B screening and prophylaxis for low-risk chemotherapy regimens such as single agent capecitabine may add morbidity and may not be cost effective.
Castration resistance and high-risk disease among nonmetastatic (M0) prostate cancer (PC) patients on androgen deprivation therapy (ADT).
Authors: Pirolli Melissa , Hernandez Rohini Khorana , Cetin Karynsa , Quigley Jane , Grant-Huerta Yanina , Stryker Scott , Smith Paul , Adams John , Liede Alexander 
Published: March 2020

1581 Background: Prostate-specific antigen (PSA) is a well-known PC biomarker. In the M0 setting, rising PSAs despite ADT is an indication of the development of castration-resistant prostate cancer (CRPC). In this disease state, men are at risk for developing bone metastasis (BM), which is associated with significant morbidity and may negatively affect survival. Using real-world data, we explored PSA-based criteria to identify patients who develop CRPC while on ADT and the subsets that may be at increased risk of BM. Methods: We used the Oncology Services Comprehensive Electronic Records (OSCER) database, which includes electronic medical record (EMR) data on cancer patients from 328 urology and oncology clinics in the US. Eligible patients were adult men with M0 PC with ≥1 PSA recorded between 3/1/2010 and 2/28/2011 and currently receiving ADT (gonadotropin-releasing hormone agonists or bilateral orchiectomy) for ≥6 months (mos). We defined CRPC as two sequential PSA rises while on ADT and high risk for BM as any PSA ≥8 ng/mL or PSA doubling time (DT) ≤10 mos, as described by Smith MR et al, Lancet 2012. We explored subsets of CRPC patients who may be at even higher risk of BM using PSA thresholds (≥8 ng/mL and ≥20 ng/mL) and DT (≤4, 6, 8, and 10 mos). Results: Of 1,818 men with M0 PC receiving ADT ≥6 mos, 36% (N=646) met the CRPC definition, of whom 80% (N=517) had PSA ≥8 ng/mL and/or PSA DT ≤10 mos (high risk). PSA DT alone explained 63% (44% / 70%) to 93% (65% / 70%) of subgroup eligibility (Table), and emerged as a main driver in defining increased risk of BM for CRPC subsets. Conclusions: In this analysis of EMR data, over one-third of men with M0 PC on ADT met criteria for CRPC, and most CRPC patients (80%) may be considered at high risk for BM. Requiring ≥3 PSAs to define CRPC may be a limitation; however, because PSAs are closely monitored in patients on ADT, these definitions of CRPC and high risk may be useful in practice. These data suggest that PSA DT may be a more clinically meaningful measure of defining CRPC subsets than absolute PSA thresholds. [Table: see text] .
An exploratory study to determine if BRCA1 and BRCA2 mutation carriers have higher risk of cardiac toxicity.
Authors: Ismail-Khan Roohi , Sajjad Monique , Sun Weihong , Soliman Hatem Hussein , Han Hyo S. , Minton Susan E. , Lancaster Johnathan M. , Pal Tuya 
Published: March 2020

1585 Background: Anthracycline related cardiac toxicity (CT) is a concern in treating women with breast cancer. The prevalence of heart failure (HF) affects 2% of the population, less so in women. Patients receiving anthracycline based therapy (ABT) have a dose-dependent risk of reduction in ejection fraction. Recent work by Dr. Verma suggests that BRCA-deficient mice manifest increased levels of cardiac failure. We sought to explore the risk for CT and evaluate the association between ABT and HF in female BRCA mutation carriers. Methods: An online survey was developed to collect information about breast cancer treatment (including HF) in BRCA mutation carriers through the national BRCA patient advocacy organization FORCE via their 2011 conference and their website as well as the Moffitt-based Inherited Cancer Registry (ICARE). The prevalence of CT and HF was calculated in both BRCA 1 and 2 breast cancer patients and compared to general population risks. Data from those that received ABT was compared to published HF rates from ABT. Results: Our sample included 227 BRCA1 carriers and 164 BRCA2 carriers in whom 6.4% reported cardiac toxicity (i.e., either HF and/or CT). This included similar proportions in BRCA1 vs BRCA2 carriers (i.e., 6.6% and 6.1%, respectively). These proportions are significantly higher than the published rate of 2% (all p-values < 0.001). Specifically regarding ABT, 112 mutation carriers had doxorubicin (Adriamycin) for treatment of whom 8% reported HF, similar to the 11 who had Epirubicin (11 patients), of whom 9% reported HF. Conclusions: Our data suggests that BRCA mutation carriers may have an increased risk of CT compared to the general population. In particular, women with BRCA mutations treated with ABT also appear to have a higher risk of developing CT and/or HF. This exploratory study provides the basis upon which larger retrospective and prospective studies are currently being planned. The high percentage of CT observed in this study requires confirmation as they could inform recommendation for cardiac screening and review of the current standard for ABT use in this population.
Outcomes of male breast cancer in the United States: A SEER database analysis from 1973 to 2008.
Authors: Hossain Akm Mosharraf , Bobba Ravi Kiran , Kardinal Carl G. , Freter Carl 
Published: March 2020

1586 Background: Male breast cancer (MBC) is rare compared to female breast cancer (FBC). There has been no systemic study to examine the epidemiology of MBC in USA in the past decade. Methods: We examined 6,157 cases of MBC reported in SEER database from 1973-2008 (released 2011). We performed rate, frequency and survival sessions to examine age, sex, stage, grade, treatment modalities and survival using the SEER*Stat Software 7.0.5. These variables were compared with that of 877,885 FBC cases reported in SEER 1973-2008. Results: The incidence rate was 1.3 (MBC) and 124 (FBC) per 100,000, respectively. Median age of diagnosis was higher in MBC compared to FBC (72 vs. 61 yrs. P<0.001). 18% of MBC were seen at age less than 60 years compared to 32% in FBC (p<0.001). FBC tend to be more hormone receptor positive (74% vs. 61%; p<0.001). There were 5,145 Caucasians (WH), 701 African Americans (AA), 258 Hispanics and 42 Asian patients. Stage III and IV, Grade III and IV histologies were more common in MBC. Staging and Grading did not differ among the different ethnicities except for Grade IV histology in AA 19%, Asians 20% when compared to WH 13% (p<0.001). Treatment modalities included, surgery (MBC 78% vs. FBC 93%; p<0.001), chemotherapy (MBC 82% vs. FBC 43%; p<0.001) and radiation therapy (MBC 19% vs. 36% FBC; p<0.001). Treatment modalities were similar among WH and AA. Survival was higher in FBC compared to MBC (table) but improved over time in MBC. AA and Asians had lower 1-5 year survival compared to WH. Conclusions: MBC presents at a later age, higher stage and grade, predominantly requiring chemotherapy with an overall poor survival compared to FBC. But 1-5 year survival improved over time in MBC. This can be explained by early diagnosis, better treatment and other factors. Further studies should be performed in this regard. [Table: see text]
Evaluation of perioperative therapy for stage II and III rectal cancer in California, 1994-2009.
Authors: Cho Myung Mi , Morgan John , Chenna Sumana , Knutsen Raymond , Kazanjian Kevork 
Published: March 2020

1587 Background: Surgical treatment of stage II and III rectal cancer changed little during the past two decades, while ancillary therapies have undergone two evolutionary changes. We sought to evaluate changes in chemoradiation (chemoRT) practices for patients receiving radical operations for stage II and III rectal cancer in California, 1994-2009. Methods: We extracted age, sex, race/ethnicity (R/E), socioeconomic status (SES) (demographic variables) and chemoRT variables for stage II and III rectal cancer cases in California. We used unconditional logistic regression to compute independent odds ratios of receiving preoperative chemoRT (PreOP Tx) to postoperative chemoRT (PostOP Tx) during Early (1994-1999), Middle (2000-2003), and Late (2004-2009) time-periods using the late time-period as the referent group. Results: Logistic regression analyses assessing time-period and demographic variables reveal trends and odds ratios with 95% confidence intervals (OR; CI) for chemoRT variables. Our findings showed a stepwise increase in the odds of PreOP Tx to PostOP Tx across Early, Middle, to Late time-periods (OREarly/Late=0.11; 0.10, 0.13, ORMiddle/Late=0.36; 0.32, 0.40). Age <40 and 40-49, independently predicted higher odds of PreOP Tx than PostOP Tx compared to age 50-74, while the findings for subjects age 75+ were similar to those seen in the age 50-74 group (OR<40/50-74=1.63; 1.30, 2.05, OR40-49/50-74=1.18; 1.03, 1.36, OR75+/50-74=1.04; 0.90, 1.18). Females showed lower odds of PreOP Tx to PostOP Tx than males (ORFemale/Male=0.85; 0.77, 0.93). Odds of PreOP Tx to PostOP Tx were significantly lower among Asian/Other (A/O) and Hispanic relative to Non-Hispanic White (NHW), while findings were similar to NHW for Non-Hispanic Black (NHB) (ORA/O/NHW=0.85; 0.74, 0.98, ORHispanic/NHW=0.84; 0.73, 0.96, ORNHB/NHW=0.92; 0.73, 1.15). SES did not predict odds of PreOP Tx versus PostOP Tx. Conclusions: These findings depict independent increases in PreOP Tx across the three time-periods among stage II and III rectal cancer patients receiving radical operations. Further analyses will evaluate survival characteristics predicted by changes in perioperative therapies for stage II and III rectal cancer patients.
Second primary gynecologic neoplasms among breast cancer survivors.
Authors: Barretina Ginesta Maria Pilar , Beltran Miguel , Buxo Maria , Sala Nuria , Baste Neus , Munoz Silvia , Vilardell Loreto , Brunet Joan , Marcos Rafael , Izquierdo Angel 
Published: March 2020

1588 Background: Excess of risk of several second primary malignancies after treatment for breast cancer (BC) has been reported. This risk can be related with shared risk factors, cancer susceptibility genes or prior treatments received. Hormonal factors and hormone therapy are known to be risk factors for both BC and some gynecological malignancies. The aim of this study was to asses gynecological cancer risk as a second neoplasm among BC patients in our population. Methods: Patients diagnosed with invasive BC (CIE10: C50.0-C50.9) and registered in the Girona Cancer Registry from 1980 to 2006 were included in our study. We analyzed their incidence of second gynaecological malignancies except for contralateral BC. Standardized Incidence Ratios (SIR) and absolute excess of risk (AER) of these patients compared to general population were calculated. Results: 6.209 patients were diagnosed of invasive BC in this period, with median age at diagnosis 62 years, median follow-up 4 years. 84 of them developed a second malignancy of gynaecological origin (SIR 1,98 CI 95% 1,59-2,44; AER 104,01/100.000 person-year). We observed 4 uterine cervix (SIR 0.64 IC95% 0,20-1,54), 3 vulvar-vaginal (SIR 0,96 IC95% 0,24-2,60), 13 ovarian (SIR 1,13 IC95% 0,63-1,89) and 63 uterine corpus neoplasms (UC), as well as 1 genital female tract neoplasm unspecified. High and statistically significant SIR was observed for gynecological malignancies in general and specifically for UC(SIR 3.14 IC 95% 2,44-4,00). With this finding, histology of UC cases was reviewed. 12 out of 63 were malignant histologies, not otherwise specified. Among the remaining 51, there were 8 type II (1 clear cell and 7 serous adenocarcinoma, 15.7%), 34 type I (endometrioid adenocarcinoma, 66.7%) and 6 carcinosarcomas (11.8%). There were also 2 adenosarcomas (3.9%) and 1 mucinous adenocarcinoma (1.9%). Conclusions: Women with previous BC have an elevated risk of developing a second primary gynecological malignancy compared with general population, particularly for UC. These patients should be followed up for its early detection. We detected a slight increase in unfavourable uterine carcinoma histologies respect to the general population. Further investigation of this finding is warranted.