bluuebunny/crossref_metadata_2025 huggingface dataset:
Overuse of sentinel lymph node biopsy with breast conserving surgery for clinical DCIS.
Authors: Jones Natalie Beckman , Ottesen Rebecca A , Niland Joyce C. , Breslin Tara M. , Weeks Jane C. , Hughes Melissa E , Agnese Doreen Marie , Edge Stephen B.
Published: March 2020

1125

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend against sentinel lymph node biopsy (SLNB) for ductal carcinoma in-situ (DCIS) treated with breast conservation surgery (BCS). SLNB is appropriate with mastectomy because it precludes subsequent SLNB if invasive cancer is identified. However, SLNB is commonly performed with BCS for DCIS. We hypothesize SLNB use in the setting of BCS for DCIS varies and may be over used in some cancer centers. Methods: We examined 6,070 cases with initial biopsy showing DCIS presenting to 13 institutions participating in the NCCN Breast Outcomes Database from 1998-2009. Receipt of SLNB was defined as SLNB performed at any point in primary treatment for those with a final diagnosis of DCIS or at the first surgical procedure for those upstaged to invasive cancer. Characteristics of patients who did and did not have SLNB were compared using Chi-square tests. Logistic models adjusting for clinical and pathologic variables were performed to assess factors associated with use of SLNB. Results: Of 3,725 treated with BCS, 778 (20.9%) had SLNB. Among 2,345 treated with mastectomy, 1,484 (63.3%) had SLNB. Within BCS, patients presenting with clinical symptoms (vs. screening detected) were more likely to have SLNB (p=0.0006, OR: 1.76; 95% CI 1.31-2.36). For both groups, presence of comedo necrosis, year of diagnosis, and treating institution were predictors of SLNB (p<0.0001). 1,171 (19.3%) were upstaged from DCIS at initial biopsy to invasive cancer on final pathology. 212 (18.1% invasive cancer group) had positive nodes. Use of SLNB increased over time from 1998-2009 in mastectomy group. Among BCS group, SNLB use decreased over the first half of the study period and then remained stable at approximately 15% across all centers. Conclusions: Although use of SNLB has decreased over time, a substantial percentage of patients undergoing BCS for DCIS receive SNLB. Practices vary considerably across centers. SLNB can be performed as a second procedure for those treated with BCS and identified with invasive cancer, thereby avoiding unnecessary risk of significant morbidity. Breast programs should review their practices to curtail the use of unnecessary surgery for women with DCIS.
Axillary lymph node status in breast cancer staging: What patient and tumor factors affect the accuracy of ultrasound-guided fine needle aspiration?
Authors: Chacko Celin , Reig Beatriu , Koenigsberg Tova
Published: March 2020

1126

Background: The purpose of the study is to evaluate the accuracy of ultrasound-guided fine needle aspiration (FNA) of axillary lymph nodes(ALNs) in patients with breast cancer and to determine factors that influence accuracy of ultrasound-guided FNA. Methods: Retrospective review of patients with breast cancer who had FNA of ALNs as well as sentinel lymph node excision or complete axillary dissection. Patients treated with neoadjuvant chemotherapy were excluded. 55 axillary FNAs in 54 patients were included in the final analysis. Pathology reports were reviewed for size of the primary tumor, FNA results, number of positive ALNs, and greatest tumor size in ALNs. FNA was performed if a suspicious lymph node was identified. Surgical sentinel lymph node biopsy or full axillary dissection were the reference standard. Micrometastases (< 0.2 mm) and isolated tumor cells in the lymph node were included in the negative group. Atypical and nondiagnostic FNA results were considered negative cytologic results. Significance was analyzed using the Mann-Whitney test. Results: Size of the primary cancer ranged from 0.3 mm to 8.5 cm. The sensitivity of FNA was 73%, with positive predictive value of 97% and negative predictive value of 52%. The NPV of FNA for primary tumors <1 cm, 1.1-2, 2.1-5 and >5 cm is 100%, 36%, 50% and 66% respectively. Correlation of primary tumor size with sensitivity of FNA was not statistically significant. The sensitivity of FNA for lymph nodes with metastatic deposit < 5mm, 6-10mm, 11-15mm, 16-20mm, and 21mm+ is 0%, 57%, 59%, 89%, and 100%, which is statistically significant (p = 0.007). The number of positive ALNs at axillary dissection is not correlated to the sensitivity of FNA. The sensitivity of FNA for 1-3, 4-9 and 10+ positive ALNs is 78%, 64% and 80%. Conclusions: Our findings indicate that FNA of suspicious axillary lymph nodes is valuable even in small tumors, which differs from the literature. The overall negative predictive value of FNA is 52%, so sentinel lymph node biopsy is essential after negative FNA. Sensitivity of FNA increases with the size of the metastatic deposit in the lymph node, but is not correlated to the number of positive ALNs found at dissection.
Breast cancer in older women.
Authors: Pearlstone David B. , Stewart Tyler , Afshari Ashkan , Nguyen Lyly , Garofalo Rosemary
Published: March 2020

1132

Background: Recent guidelines recommend minimizing breast cancer screening for women over the age of 75. This study examines the presentation and outcome of older patients with breast cancer to determine if increasing screening among older patients may result in better outcomes. Methods: A prospective database at Hackensack University Medical Center was queried for all patients with breast cancer diagnosed between 1/1/2006 and 1/1/2011. Numerical values compared by Student’s t -test; categorical values by Fisher exact test. Median time to events determined by Kaplan-Meier; outcomes compared by log-rank test. Results: 2200 patients were identified (> 75 years, n=335, < 75 years, n=1865). Among the older cohort, mean age was 81 +/- 4 years (range: 75 – 101); mean tumor size was 2.3 +/- 0.1 cm (range: .1 – 12). Most tumors were invasive and localized (in-situ: 12.7%, localized: 57.3%, node positive: 24.0%, metastatic: 5.8%) and most commonly ductal histology (ductal: 77.0%; lobular: 16.6%, mixed:6.2%). Only 10.0% of patients with invasive disease and 29.2% with positive nodes received systemic therapy; 90.2% underwent surgical resection. Disease-free and overall 5 year survival was 54.9% and 62.9% (in-situ: 82.2%; localized: 67.1%; node positive: 57%; metastatic 22%). Older patients had larger tumors (2.30 +/- .11 v. 1.91 +/- .04 cm; p<0.001), more locally advanced (T4) disease (6.7% v. 1.7%, p<.001), more invasive disease (89% v. 84%, p<.01). Older patients had less positive family history (21.7% v. 37.3%, p<.0001). There was no difference between the groups in race, presentation with stage IV disease, tumor grade, lymphovascular invasion, histologic subtype, triple negativity, or nodal positivity. Overall and disease free five year survival were significantly worse for older patients (OS: 90.2% v. 63.9%, p< .0001; DFS: 80.9% v. 54.9%, p<.0001). Conclusions: Breast cancer among older women leads to worse outcomes compared to younger patients, regardless of histology, invasiveness of disease, hormonal status, nodal status or tumor grade. Older women present with more invasive disease, larger tumors and more locally advanced disease, despite having less family history. This implies that continued screening beyond age 75 may lead to less advanced presentation and better outcomes.
Scoring system for prediction of having three or more involved axillary nodes for breast cancer.
Authors: Ahn Soo Kyung , Kim Ji sun , You Jee Man , Shin Hee-Chul , Moon Hyeong Gon , Han Wonshik , Noh Dong Young
Published: March 2020

1133

Background: Completion axillary lymph node dissection (ALND) is currently the standard of care in the event of a positive sentinel lymph node biopsy (SLNB). However, result from Z0011 indicate that women with a one or two involved axillary nodes and clinical T1-T2 tumors undergoing lumpectomy with radiation therapy followed by systemic therapy do not benefit from completion of ALND in terms of survival. The purpose of this study was to define possible predictors of having three or more involved axillary node to provide information for surgeons making decision about sparing intraoperative frozen section analysis of sentinel lymph node and completion ALND. Methods: We reviewed the records of 1215 patients with clinical T1-T2 invasive breast cancer. None of these patients were in situ cancer on initial gun biopsy nor received neoadjuvant chemotherapy. Factors associated with having three or more involved axillary nodes were evaluated by univariate and multivariate logistic regression analysis. Results: Among 1215 patients, 321 patients had three or more positive nodes. On a multivariate analysis, having three or more positive nodes was associated with primary tumor size by breast US, axillary LN grade according to cortical thickness by US, presence of axillary LN enlargement on chest CT and age. A scoring system to predict the probability of having three or more nodes based on patients’ data and preoperative image findings was developed from the multivariate logistic regression model. The area under the ROC curve was 0.827 (95% CI: 0.793-0.860), and negative predictive value was 90.2% for a score ≤2.7. Similar findings were observed for a validation dataset of 505 patients. Conclusions: Patients with a low probability of having three or more positive nodes can be identified from preoperative image finding. The scoring system developed will be helpful to surgeons making decision about sparing intraoperative frozen section analysis of sentinel lymph node and completion ALND.
A phase III prevention trial of low-dose tamoxifen in HRT users: The HOT trial.
Authors: Bonanni Bernardo , Maisonneuve Patrick , Serrano Davide , Varricchio Clara , Rotmensz Nicole , Cazzaniga Massimiliano , Lazzeroni Matteo , Santillo Barbara , Di Pace Raffaella , Latronico Antuono , Belloni Carlo , Rosselli Del Turco Marco , Segnan Nereo , Masullo Pietro , Andreoli Claudio , Monti Nadia , Vella Alessandro , D'Aiuto Giuseppe , Veronesi Umberto , De Censi Andrea
Published: March 2020

1500

Background: Primary prevention trials have shown that tamoxifen (T) lowers ER+ breast cancer (BC) incidence, but adverse events are a barrier to its broad use. The Italian Tamoxifen Prevention Trial showed a positive risk/benefit ratio in the subgroup of hormone replacement therapy (HRT) users in the T arm, with fewer BC and no cardiovascular disease (CVD) excess. In a dose-ranging study, T 5 mg/day showed a favorable biomarker modulation in HRT users. We conducted a multicentre, phase III, BC prevention trial in current or de novo HRT users, randomized to either T 5 mg/day or placebo (P) for 5 yrs, with 5yrs follow-up. Methods: The study was powered to detect a 40% decrease of BC on T from an annual rate of 4/1000 on P with 20% dropout and 5y recruitment. All analyses were performed on ITT basis. The cumulative incidence of events was determined using Kaplan-Meier methods. The two treatment groups were compared by using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals were obtained using Cox proportional regression model. All P values were two-sided. Results: Due to the WHI-HRT trial results, recruitment was lower than anticipated, with a total of 1884 subjects being randomized (946 P and 938 T arm, respectively). 79% were >50 years old at study entry. 66% were normal weight, 21% were hysterectomized; 80% were already on HRT at baseline, 53% were on trasdermal route and 28% had 5y-Gail risk>1.5%. At 7.7y mean follow-up, 43 BC were diagnosed, 24 (annual rate 4.1/1000) on P and 19 (3.3/1000) on T (HR 0.80, 95%CI 0.44-1.46). The efficacy of T was greater in luminal-A type (HR=0.32, 95% CI, 012-086). CVD events were rare (including 1 DVT on T), with no statistical difference between arms. A HR of 4.74 (95% CI, 1.96-11.5) was observed for benign endometrial polyps, but no increase of uterine cancers (3 on P vs 1 on T). Menopausal symptoms were more frequent on T, whereas headache was less frequent on T. Conclusions: The combination of low-dose T and HRT is safe and provides a promising way to retain the benefits while reducing the risks of either agent. While the insufficient power of our study prevents firmer conclusions, it supports further studies of low-dose T in the prevention setting.
Diabetes, related factors, and breast cancer risk.
Authors: Boyle Peter , Boniol Mathieu , Koechlin Alice , Robertson Chris , Rosenstock Julio , Bolli Geremia , Autier Philippe
Published: March 2020

1509

Background: Diabetes and breast cancer are both common conditions in women and may share common risk factors. Methods: To shed clarification on the potential association between diabetes, related factors and breast cancer risk, a comprehensive literature review and formal meta-analysis was carried out, planned, conducted and reported following PRISMA guidelines regarding meta-analysis of observational studies. Variables studies in relation to breast cancer risk were adiposity, physical activity, glycaemic load, glycaemic index, diabetes, IGF-1, fasting glucose, fasting insulin and C-peptide, adiponectin, metformin and glargine use. The Summary Relative Risk (SRR) and the corresponding 95% Confidence Interval (CI) was calculated. Results: For breast cancer at all ages, the calculated risks were as follows: diabetes (SRR=1.23 95% CI (1.12, 1.34); physical activity (SRR=0.88, 95% CI (0.85, 0.92)); glycaemic load (SRR=1.05, 95% CI (1.00, 1.10)); glycaemic index (SRR=1.05, 95% CI (1.00, 1.09)); fasting glucose (SRR=1.14, 95% CI (0.94, 1.37)); serum insulin (SRR=1.26, 95% CI (0.86, 1.84)); c-peptide (SRR=1.29, 95% CI (0.91, 1.82)); adiponectin (SRR=1.16, 95% CI (0.93, 1.46)); metformin (SRR=0.97, 95% CI (0.82, 1.16)); and glargine (SRR=1.10, 95% CI (0.94, 1.30)). An increase of 5 units in Body Mass Index (a weight increase if 14.5 kg in a person 1.70 metres tall) was associated in post-menopausal breast cancer (SRR=1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR=0.83, 95% CI (0.72, 0.95)). Serum insulin was associated with breast cancer at post-menopausal ages but not at pre-menopausal ages whereas with c-peptide there was a significant association at pre-menopausal ages but not post-menopausal. For IGF-1, Hodge’s Standardised Mean Difference (HSMD) was calculated and there was no significant association with breast cancer at all ages (HSMD=-0.026, 95% CI (-0.031, 0.084)), at post-menopausal ages (HSMD=0.007, 95% CI (-0.068, 0.082)) or at pre-menopausal ages (HSMD=-0.065, 95% CI (-0.009, 0.140)). Conclusions: Key risk factors for breast cancer appear to be adiposity and physical activity which are both related to the risk of developing diabetes.
Second malignant neoplasms (SMN) among 18,627 testicular cancer survivors (TCS) after chemotherapy (CHEM) or surgery (SURG).
Authors: Fung Chunkit , Fossa Sophie D. , Milano Michael T , Yu Mandi , Worman Melissa , Travis Lois B.
Published: March 2020

1536

Background: Increased risks of SMN after radiotherapy (RT) for testicular cancer (TC) are well established. Few population-based studies, however, have focused on SMN risk among a contemporary group of TCS managed initially with non-RT approaches, including CHEM. Methods: Standardized incidence ratios (SIR) of SMN stratified by site and time since TC diagnosis were calculated for 18,627 TCS reported to the SEER program (1980-2008) who initially had CHEM (n=8,058) or SURG (n=10,569) alone without RT, with each cohort accruing 65,398 and 92,681 person-years (PY) of follow-up respectively. Results: After CHEM, significantly increased risks of solid cancers (n=154; SIR 1.3; 95% CI 1.1-1.5; absolute excess risk (AER) 5.4 per 10,000 PY) and leukemias (n=18, SIR 3.9; 95% CI 2.3-6.1; AER 2.0) were observed. Solid cancer risk remained elevated for > 20 yrs, whereas excess leukemias were concentrated within 10 years after diagnosis. SIRs for solid cancers during the <1, 1-4, 5-9, 10-14, 15-19, and 20+ yr periods were 2.0 (95% CI 1.03-3.5), 1.4 (95% CI 0.97-2.0), 0.8 (95% CI 0.5-1.2), 1.3 (95% CI 0.9-1.8), 1.6 (95% CI 1.05-2.2), and 1.5 (95% CI 0.95-2.2) respectively (P-trend 0.5) whereas SIRs for leukemia were 3.2, 9.9 (P<0.05), 2.6, and 2.3 respectively, with no cases reported in the latter 2 intervals. Median latencies to the development of solid cancers and leukemia were 12.5 yr (0.1-28) and 2.5 yr (0.1-14) respectively. Increased site-specific risks were apparent for cancers of liver (SIR 1.9; 95% CI 0.6-4.4); pancreas (SIR 2.1; 95% CI 0.8-4.6); soft tissue (SIR 4.9; 95% CI 2.1-9.7); bladder (SIR 1.9; 95% CI 1.02-3.3); kidney (SIR 2.6; 95% CI 1.4-4.3); brain/CNS (SIR 1.8; 95% CI 0.7-3.7), and thyroid (SIR 3.9; 95% CI 2.1-6.6). Secondary leukemias included 16 non-lymphocytic and 2 lymphocytic leukemias. In contrast, among TCS managed initially with SURG alone, no excess solid cancers were observed (n=198; SIR 1.0; 95% CI 0.8-1.1), albeit an increased risk of leukemia (n=15; SIR 1.9; 95% CI 1.1-3.2, AER 0.8) was seen. Conclusions: Future analytic studies should further evaluate the site-specific risks of SMN after modern CHEM for TC and the baseline risk among patients managed with non-cytotoxic approaches.
Cost sharing and hereditary cancer risk: Predictors of willingness-to-pay for genetic testing.
Authors: Matro Jennifer Madeline , Ruth Karen , Wong Yu-Ning , McCully Katen C. , Rybak Christina , Hall Michael J.
Published: March 2020

1544

Background: The increasing availability of genetic testing (GT) in cancer (CA) care has been paralleled by increasing cost-sharing practices by payors that are intended to reduce overuse of health care services. Patients referred for hereditary CA risk assessment may be subject to financial deterrents such as high out-of-pocket (OOP) costs. Little is known about what factors may influence high-risk patients' willingness-to-pay (WTP) for GT. Methods: The Gastrointestinal (GI) Tumor Risk Assessment Registry includes individuals referred for evaluation of genetic CA risk based on personal and/or family hx. At enrollment, participants complete a survey collecting detailed demographic, CA hx, and psychosocial items related to CA risk. Baseline data on 406 participants were available; 21 who did not respond to WTP items were excluded. WTP items included intention for: GT only if paid by insurance; GT even if paid by self; and amount WTP (7 levels, $25 to $2000). Multivariable models examined predictors of WTP (self vs only if paid by insurance) (model 1, logistic), and predictors of amount WTP (model 2, ordinal logistic, 5 levels). All statistical tests are two-sided (α=0.05). Results: Most participants were women (73%), white (92%) and aged 45-64 (58%). 51% had ≥ 4 yr college degree; 22% had household income >$75,000; 42% had hx of GI CA; 56% had > 1 1st degree relative (FDR) with colorectal CA (CRC). Overall, 82 (21.3%) were willing to have GT only if paid by insurance, and 303 (78.7%) were WTP OOP. Of those WTP, 271 (89%) stated an amount. Independent predictors of WTP (model 1) were: 1) expectation of positive result, 2) confidence to control CA risk, 3) fewer perceived barriers to CRC screening and 4) benefit of guiding screening (all p<0.05). Subjects WTP a higher amount (model 2) were male, more educated, and had greater CA worry, fewer FDR with CRC (all p<0.05), and more positive attitudes toward GT (p<0.01). Conclusions: Patients who are WTP some OOP costs for GT anticipate benefits to control of CA risk afforded by GT. Women and less educated patients may face greater barriers from high co-pays. Identifying patient-level factors associated with WTP for genetic services is increasingly important as GT is integrated into routine CA care.
Profiling uptake of single site testing (SST) for familial cancer (CA) risk in an administrative genetic testing database.
Authors: Hall Michael J. , McCully Katen C. , Devarajan Karthik , Kaldate Rajesh R. , Daly Mary Beryl
Published: March 2020

1550

Background: Among the anticipated social and cost-saving benefits to identifying a mutation in a CA predisposition gene in an individual is the subsequent opportunity to perform SST in close relatives to confirm risk status and to guide risk-reducing interventions. Despite ample research into uptake of primary genetic testing for Lynch syndrome (LS) and hereditary breast ovarian syndrome (HBOS) among moderate- and high-risk individuals, few studies have focused on the resultant cascade of SST that is predicted to follow in families. Methods: Administrative data on 2,631 consecutive single-site mutation tests performed over a 3-month interval (12/1/10-2/28/11) were obtained from a commercial genetic testing database maintained by Myriad Genetic Laboratories. 14 subjects (29 tests) were excluded due to multiple entries. Demographic, personal/family history (hx), and provider data are collected on a Test Requisition Form included in kits. All statistical tests are 2-sided (α=0.05). Results: Women had SST more often than men (HBOS 82.8%; LS 65.5%). Mean age at time of SST was 42.7 yrs, and was higher for HBOS than LS (p=0.01). Among subjects with hx of CA, mean age at CA diagnosis (dx) was similar (HBOS 48.6; LS 48.7 yrs). Subjects reported CA in >1 relatives (range 1-16) with a mean age at dx 40.1 yrs. Compared to HBOS, those tested for LS were more likely to report CA in a 1st degree relative (81.3 vs 74.4%, p=0.001) and a lower age of youngest CA dx in the family (p<0.001). Non-European ancestry was more common for HBOS SST than LS (30.0 vs 24.8%) (p=0.05). SST positive test rate was no different by syndrome or ancestry, but was higher for men (47.5 vs 42.0%, p=0.02). Conclusions: Uptake of commercial SST in high-risk families is uneven by age, sex, ancestry and CA syndrome. While between-syndrome variability in CA risks may explain some differences, more research is needed to understand barriers to uptake of SST among at-risk individuals if CA prevention goals are to be realized. [Table: see text]
A comparison of simple single-item measures and the NCI Common Toxicity Criteria version 3.0 measure of peripheral neuropathy.
Authors: Puttabasavaiah Suneetha , Liu Heshan , Qin Rui , Kottschade Lisa A. , Barton Debra L. , Loprinzi Charles L. , Grothey Axel , Soori Gamini S. , Sloan Jeff A.
Published: March 2020

1557

Background: Peripheral neuropathy (PN), a common and intrusive side effect of chemotherapy in clinical trials, has been assessed via the clinician-rated common terminology criteria for adverse events (CTCAE) and/or patient-reported outcome (PRO) measures (Morton, ASCO, 2005). We assessed the relative sensitivity of CTCAE and PRO measures for evaluating interventions for preventing and ameliorating CIPN. Methods: Data from285 patients in two prevention trials (N05C3, N04C7) and 432 patients from three intervention trials (N00C3, N01C3, N06CA) were analyzed separately. CTCAE version 3.0 item for neuropathy was compared to 2 NCCTG numerical analogue CIPN items, 6 EORTC CIPN20 individual items, 2 McGill Pain Questionnaire items, and one Brief Pain Inventory item. The sample size provided over 80% power to detect a true Spearman rank correlation of 0.15 assessed the relationship between CTCAE and PRO measures. Results: Results from both the prevention and treatment trials were similar in terms of the relationship between the CTCAE and PRO measures. No correlation coefficients between the CTCAE and any of the PRO items at baseline were above 0.35, with the majority around 0.2. Higher scores for the numbness items were observed than for the CTCAE in 47% of the patients at baseline and 39% during treatment in the treatment trials. Many patients had severe numbness PRO scores but mild CTCAE scores (12%) at baseline and (8%) during treatment in the treatment trials. Results for the numbness and tingling PRO measures were redundant. The correlations of the CTCAE with pain were weak, all below 0.35 at baseline with differences as much as 29 points on average on a 0-100 transformed scale. Conclusions: The CTCAE and PRO measures of PN measure different constructs. The CTCAE includes both functional and ADL/motor aspects which may or may not be related to the singular constructs of pain, numbness, tingling, or adjectival characteristics of pain assessed by the PRO measures. The two measures cannot be used in place of each other.
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.