bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term rates of breast cancer in a population of women with ductal carcinoma in situ treated by breast-conserving surgery.
Authors: Rakovitch Eileen , Nofech-Mozes Sharon , Narod Steven , Hanna Wedad , Saskin Refik , Tuck Alan , Sengupta Sandip , Done Susan , Miller Naomi , Youngson Bruce , Paszat Lawrence Frank 
Published: March 2020

1123 Background: Ductal Carcinoma in Situ (DCIS) is a non-invasive form of breast cancer which is often treated by breast-conserving surgery. The addition of radiotherapy to surgery has been shown to reduce the risk of local recurrence (LR), but use of radiotherapy varies. It is not known to what extent women with DCIS are at risk for recurrent cancer due to the omission of radiation therapy. We studied a large provincial cohort of women with DCIS who were treated with breast-conserving surgery for factors which predict local recurrence and estimate the impact of radiotherapy on local recurrence and long-term rates of breast preservation. Methods: All women diagnosed with DCIS in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. Women treated with breast-conserving surgery, alone or with radiotherapy, were included. Survival analyses were used to study local recurrence (DCIS or invasive) in relation to patient characteristics, tumour characteristics and treatment. Results: The cohort included 3975 women who were treated with breast-conserving therapy; of these, 1949 (49%) received radiation. At 10 years median follow-up, 736 developed LR(19%). LR developed in 259 of 1949 women who received radiotherapy (13%) and in 477 of 2026 women who did not (24%;p<0.001). The differences were significant for both invasive LR (7% vs. 14%; p<0.001) and DCIS recurrence (6% vs.9%; p<0.001). The 10-year cumulative rate of mastectomy was 13% for women who received radiotherapy compared to 17% for those who did not (p<0.01).We estimate that 29% (N=214) of all local recurrences diagnosed in Ontario in women treated for DCIS between 1994 and 2003 would be prevented if all patients received radiotherapy. Conclusions: The omission of radiation therapy after breast-conserving surgery in women with DCIS resulted in a substantial number of local recurrences that might have been avoided and lower rates of breast preservation. Improvements in guidelines that facilitate the selection of women in whom radiotherapy can be avoided are needed.
Phase I/II trial of partial breast irradiation (PBI) with various concurrent chemotherapy regimens.
Authors: De Souza Lawrence Lana Maria , Shah Amit , Young Mary Elizabeth , Stearns Vered , Asrari Fariba , Frassica Deborah Anne , Tsangaris Theodore N. , Fetting John H. , Lange Julie R. , Jacobs Lisa K. , Myers Lee , Wolff Antonio C. , Zellars Richard C. 
Published: March 2020

1128 Background: Potential benefits of concurrent chemo-radiation include: shorter duration of treatment, smaller interval between surgery and adjuvant therapies, and synergistic effects. We have previously shown that PBI with concurrent dose dense doxorubicin and cyclophosphamide (ddAC) is well tolerated (Zellars JCO 2009). We performed a follow-up feasibility trial of PBI delivered concurrently with other various chemotherapy regimens. Methods: Women with T1-2, N0-1 breast cancer s/p lumpectomy with ≥2 mm margins were eligible. Chemotherapy regimen was at the discretion of the medical oncologist (Table). PBI (40.5 Gy in 15 daily 2.7 Gy fractions) was delivered within the first 2 cycles of chemotherapy. Primary endpoints were hematologic and non-hematologic toxicities graded according to Common Terminology Criteria for Adverse Events manual (v. 3.0). Results: Thirty-four patients enrolled with median f/u of 19.2 mos. (4.0 - 38.6). Mean tumor size was 1.8 cm (+/- 0.7 cm), 71% pN0, 68% HR +, 18% Her2 +. All patients completed concurrent chemo-radiation. Three patients had a 3-8 day delay in chemotherapy (1 grade 2 thrombocytopenia; 1 Grade 2 liver enzymes; 1 T desensitization). There was 1 local (DCIS) and no regional/distant recurrences or deaths. Toxicity: 2 grade 4 neutropenia (ddAC, TCarboH); 1 grade 3 neutropenia (post-AC paclitaxel); 1 Grade 3 hyponatremia and DVT (TC); 1 syncope (TAC). None had > grade 2 radiation dermatitis. Conclusions: PBI and concurrent chemotherapy is associated with minimal toxicity and appears to be well tolerated. These results deserve further investigation. Funded by The Breast Cancer Research Foundation. [Table: see text]
Evaluation of the stage IB designation of the 7th edition of the AJCC Staging System.
Authors: Dallas Nikolaos Andreas , Yi Min , Hunt Kelly , Shah Ruchita R. , Kuerer Henry Mark , Litton Jennifer Keating , Wu Yun , Caudle Abigail Suzanne , Meric-Bernstam Funda , Sahin Aysegul A. , Mittendorf Elizabeth Ann 
Published: March 2020

1130 Background: Recent data from large cooperative group trials have questioned the relevance of small volume metastases identified in the sentinel lymph nodes (SLN) of early stage breast cancer patients. The 7th ed. of the AJCC staging system differentiates node negative patients (stage IA) from those with micrometastases (stage IB) or macrometastases (stage II or III). This study was undertaken to determine the utility of the stage IB designation. Methods: Review of a prospectively maintained database identified 3474 patients who underwent SLN biopsy between 1993 and 2007. Clinicopathologic and outcomes data were recorded and patients staged according to the 7th ed. AJCC system. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results: AJCC stage distribution included: 2246 (65%) stage IA, 207 (6%) stage IB, 685 (20%) stage IIA, 209 (6%) stage IIB, and 127 (3%) stage III. For patients with stage IB disease, SLN micrometastasis was identified by H&E in 173 (84%) and immunohistochemistry (IHC) in 34 (16%); suggesting that 16% would have been staged IA if enhanced evaluation had not been performed. Median follow-up was 6.1 yrs (range 0-17.2). The 5-yr RFS,DSS and OS rates for patients with stage IB disease were 98.0%, 99.5%, and 95.9% respectively, which did not differ significantly from patients with stage IA disease who had 5-year RFS,DSS and OS rates of (97.5%, p=.9), (98.8%, p=.7) and (96.2%, p=.8). When all stage I patients (IA and IB) were evaluated by ER status or grade (grade 1 vs 2 vs 3), these biologic factors were able to significantly discriminate patients with respect to RFS, DSS and OS. Conclusions: Differentiating patients with micrometastases from node negative patients does not stratify patients with respect to survival. Biologic factors (ER status and grade) are better discriminants of survival than the presence of small volume nodal metastases in patients with early stage disease. These data do not support routine use of IHC or alterations in adjuvant therapy decisions based on identification of SLN micrometastases.
BMI, long-term changes in BMI, and risk of cancer mortality in a large cohort study.
Authors: Taghizadeh Niloofar , Vonk Judith M. , Boezen H. Marike 
Published: March 2020

1502 Background: There are indications of an association between Body Mass Index (BMI) and risk of different cancer types. There is dispute whether this association differs between males and females. Methods: We studied the association of BMI at the first survey with risk of mortality from the most common types of cancer (lung, colorectal, breast and prostate cancer) in a large general population-based cohort study (Vlagtwedde-Vlaardingen, 1965-1990) with follow-up on mortality status until 2009. Additionally, we assessed this association based on tertiles of the annual change in BMI (defined as the difference between BMI at last survey and first survey divided by the time between last and first survey). We used 3 categories of BMI (< 25 kg/m2, 25-30 kg/m2, and ≥ 30 kg/m2) and changes in BMI (< 0.02 kg/m2/yr, 0.02-0.2 kg/m2/yr, and > 0.2 kg/m2/yr) in the analyses. The multivariate Cox regression model was adjusted for age, smoking, gender. Analyses were additionally stratified by gender and smoking. Results: Among all 8645 subjects, 1194 died due to cancer (lung cancer: 275; colorectal cancer: 134; breast cancer: 117; prostate cancer: 83). Mortality from all types of cancer was significantly increased in subjects with BMI > 30 kg/m2 (HR (95 % CI)) = 1.22 (1.00-1.48)), especially in females (1.38 (1.06-1.81)) and in never smokers (1.39 (1.02-1.90)). Prostate cancer mortality was significantly increased in males with BMI 25-30 kg/m2 (2.04 (1.90-3.83)) and > 30 kg/m2 (2.61 (1.02-6.67)). This association between prostate cancer mortality and BMI was higher in smokers. Lung cancer mortality risk was decreased in subjects with BMI 25-30 kg/m2 (0.71 (0.54-0.93)) and > 30 kg/m2 (0.82 (0.50-1.32)), especially in males, in smokers, and in smoking males. There were no significant associations between BMI and colorectal or breast cancer mortality nor between change in BMI and mortality from all analyzed types of cancer. Conclusions: We show that an increase in BMI is associated with an increased risk of mortality from all types of cancer in females and with an increased mortality risk from prostate cancer in males but with a decreased lung cancer mortality risk, especially in males. More research is needed into the biological mechanisms that link BMI to cancer.
A multi-institution study of the accuracy of BRCAPRO in predicting BRCA1/BRCA2 mutations in women with ovarian cancer.
Authors: Daniels Molly S , Babb Sheri , King Robin , Urbauer Diana , Amos Christopher I. , Brandt Amanda C. , Buchanan Adam , Mutch David Gardner , Lu Karen H. 
Published: March 2020

1520 Background: 10-15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation, with significant management implications for both patients and relatives. Genetic testing decisions are guided in part by the estimated likelihood of identifying a mutation. The BRCAPRO model uses personal and family history of breast and ovarian cancer to calculate the likelihood of a BRCA1/2 mutation. This study’s purpose was to assess the ability of BRCAPRO to accurately determine this likelihood. Methods: BRCAPRO scores were calculated using CancerGene v5.1 for 589 ovarian cancer patients referred for genetic counseling at three institutions. The study population was divided into quintiles by BRCAPRO score, with cutpoints chosen such that each quintile represented 20% of the sample. Chi-square goodness-of-fit test was used to compare observed BRCA1/2 mutations to the number predicted. ANOVA models were used to assess factors impacting BRCAPRO accuracy. Results: 180/589 (31%) ovarian cancer patients tested positive for a BRCA1/2 mutation. At BRCAPRO scores under 40%, more mutations were observed than expected (93 observed vs. 34.1 expected, p<0.001). If patients with BRCAPRO scores <10% had not been offered genetic testing, almost one-third of mutations (51/180, 28%) would have been missed. Multivariate analysis demonstrated that BRCAPRO underestimated risk for high grade serous ovarian cancers but overestimated risk for other histologies (p<0.0001), underestimation increased as age at diagnosis decreased (p=0.02), and model performance varied by institution (p=0.02). Conclusions: Ovarian cancer patients classified as low risk by BRCAPRO are more likely to test positive than predicted, therefore the BRCAPRO prediction could falsely reassure patients considering genetic testing. BRCAPRO performance could be improved by incorporating factors such as ovarian cancer histology. Alternatively, given the high prevalence of BRCA1/2 mutations in high grade serous ovarian cancer and the apparent limitations of using family history to predict mutation probability, BRCA1/2 genetic testing could be offered to high grade serous ovarian cancer patients regardless of family history.
Genetic polymorphisms of the OPG gene associated with breast cancer.
Authors: Assmann Gunter , Juhasz-Boess Ingolf , Gruenhage Frank , Graeber Stefan , Wieczorek Stefan , Pfreundschuh Michael , Solomayer Erich-Franz , Ney Jasmin Teresa 
Published: March 2020

1523 Background: The receptor activator of NfkappaB (RANK) and osteoprotegerin (OPG) cascade system have been reported to play a role in the pathogenesis of breast cancer (BC). Genetic variations in the genes coding for RANK, RANK ligand (RANKL), and OPG are supposed to play a role in the susceptibility of breast cancer. Methods: In the present case-control study genomic DNA was obtained from 307 BC patients (age: median 56) and 396 healthy female controls (healthy blood donors, HC; age median: 45). We studied six single nucleotide polymorphisms (SNPs) in the genes coding for RANK (2 SNPs, rs1805034, rs35211496), OPG (2 SNPs, rs3102735, rs2073618), and RANKL (2 SNPs, rs9533156, rs2277438) using TaqMan assay-guided PCR for the respective SNPs. The genotype and allelic frequencies comparing BC with HC were analyzed with χ2 test for 2x3 and 2x2 tables, respectively. Results: The genotype distributions as well as the allelic frequencies of the SNP rs3102735 in the OPG gene differed significantly (p=0.006 and p=0.019, respectively) between BC patients and HC; the genotypes containing the minor allele were more frequent in BC patients (table). In the OPG SNP rs2073618 the minor allele C was significantly less frequent in BC patients compared to HC (43.8 vs. 49.7%; OR: 0.788; p=0.031). In addition, BC patients carried less frequently the homozygous genotype of the minor allele compared to major allele (18.6 vs. 23.9%, p=0.083). No significant risk was detected for the other SNPs investigated in this study. Conclusions: This is the first study reporting a significant association of the SNP rs3102735 in the OPG gene with the susceptibility to develop BC in the Caucasian population. The minor allele C of OPG SNP rs2073618, however, seems to be protective against BC disease. The impact of the OPG SNP rs3102735 (location: 5`near region, chromosome 8q24) and of the OPG SNP rs2073618 (a missense SNP, leading to amino acid exchanges Leu3Asn) on the pathogenesis of BC are unclear. [Table: see text]
Clinical characteristics and natural history of patients with squamous cell lung carcinoma with FGFR1 amplification.
Authors: Bos Marc Christiaan Allardt , Gardizi Masyar , Heukamp Lukas Carl , Schildhaus Hans-Ulrich , Nogova Lucia , Ko Yon-Dschun , Schlesinger Andreas , Brockmann Michael , Serke Monika Heidi , Gerigk Ulrich , Hekmat Khosro , Stoelben Erich , Reiser Marcel , Engel-Riedel Walburga , Schnell Roland , Schmitz Stephan H. , Frank Konrad , Buettner Reinhard , Wolf Juergen , Zander Thomas 
Published: March 2020

1533 Background: FGFR1 amplifications have been described as a promising oncogenic target in squamous cell lung cancer. Here we aimed at describing the clinical characteristics and natural history of FGFR1amplified squamous cell lung cancer patients. Methods: From 01/2011 to 01/2012 we screened 553 squamous cell lung cancer patients in our Network for Molecular Screening of Lung Cancer for the presence of FGFR1 amplifications by FISH analysis in accordance with the local ethics committee. FGFR1 was defined as amplified if the ratio of FGFR1 copies to centromeric copies was above 2 or if more than 50% of tumor cells showed 5 copies or if more than 15% of tumor cells demonstrated clusters of FGFR1. Clinical data were collected by extracting information from medical records, the local cancer registry and by questioning treating physicians and patients. Results: FGFR1FISH analysis could be performed in 95% of the cases and was amplified in 16%. Of the amplified cases 75 % were male and 25% female without significant enrichment for male or female. The median age of the patients at diagnosis was 67 yrs (range 46 - 82). Stage at presentation was: 16% I; 17.3% II; 26.7% IIIa, 40% IIIb/IV. 97,3% of the patients were former or active smokers with a median of 40 pack years. The median progression free survival of patients with stage IIIb/IV disease was 11 months (95% CI 8-14; n=14). The median overall survival was not yet reached after a median follow-up time of 14 months (95% CI 11 - 17; n=24). We further screened for co-existing genetic lesions such as mutations in EGFR, BRAF, KRAS, PIK3CA as well as translocations of ALK and amplifications of ERBB2. Two patients demonstrated co-occurring PIK3CA mutations and one a BRAFmutation. Conclusions: Screening for FGFR1 is feasible under routine clinical conditions. By implementation of a regional molecular screening network the ability to screen for FGFR1 amplification was successfully expanded to non-academic centers and private practices. FGFR1 amplifications in squamous cell cancer of the lung are frequent (16%) and associated with smoking history. Screening for FGFR1 might pave the way for the application of new FGFR1 directed targeted drugs in squamous cell lung cancer.
Molecular epidemiological prospective study of EGFR mutations from Asian patients (pts) with advanced lung adenocarcinoma (PIONEER).
Authors: Yang Pan-Chyr , Shi Yuankai , Au Joseph Siu-kie , Srinivasan Sankar , Cornelio Gerardo H. , Tsai Chun-Ming , Thongprasert Sumitra , Heeroma Dr Karin , Yohji Itoh , Khoa Mai Trong 
Published: March 2020

1534 Background: The epidemiological, multicenter prospective study (NCT01185314; PIONEER) assessed EGFR mutation (M) rates in pts from Asia with newly diagnosed advanced lung adenocarcinoma (ADC). Influence of demographic and clinical factors on EGFR M rates was investigated. Methods: Pts were aged ≥20 years, with treatment naïve stage IIIB/IV lung ADC. Tumor sample (biopsy, surgical specimen, cytology) EGFR M status (primary endpoint; positive [M+], negative [M-], undetermined [MU]) was determined using Scorpion ARMS (Therascreen EGFR RGQ kit). EGFR M frequency was calculated and compared between demographic/clinical factor subgroups (chi-square/Fisher’s exact test). Factors with p<0.05 in the univariate analysis were further analyzed by multivariate logistic regression at 1% significance level to take the large dataset into consideration. Results: Of 1482 pts from 7 Asian countries, 43.4% were female, mean age was 60 years (range 17-94), and 52.6% were never-smokers. EGFR M status was evaluated in 1450 patients (32 [2.2%] were MU): 746 (51.4%) were M+, 704 (48.6%) were M-. Country, gender, ethnicity, smoking status, pack years, metastasis, (all p<0.001) and disease stage (p=0.009) correlated significantly with EGFR M status. EGFR M+ rate by country: Vietnam 64.2% (77/120), Taiwan 62.1% (108/174), Thailand 53.8% (63/117), Philippines 52.3% (34/65), China 50.2% (372/741), Hong Kong 47.2% (76/161), India 22.2% (16/72). EGFR M+ rates were 61.1% in females, 44.0% in males, 60.7% in never smokers, and 31.4% in heavy smokers (>50 pack years). EGFR M+ rates were 37.5% in male regular smokers (113/301), 34.8% in female regular smokers (8/23), 56.5% in male never smokers (104/184) and 62.0% in female never smokers (358/577). Ethnic group (p<0.001) and pack years (p<0.001) were identified as important factors by logistic regression; gender was not significant when adjusted for smoking status. Conclusions: The overall EGFR M+ rate in unselected ADC was 51.4%. Ethnicity and pack years were found to have a statistically significant association with EGFR M rates. There was no association between gender and EGFR M rates when adjusted for smoking status.
Correlation of breast cancer risk in European BRCA2 mutation carriers with birth cohort.
Authors: Tea Muy-Kheng Maria , Kroiss Regina , Muhr Daniela , Fuerhauser-Rappaport Christine , Wagner Teresa M. U. , Singer Christian F. 
Published: March 2020

1537 Background: Mutations in the Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2) lead to an elevated risk of developing breast (BC) and ovarian cancer (OC). However, risk estimates vary, depending on the study population. Furthermore, there are indications that birth cohort can influence the cancer risk. We investigated the risks for BC and OC associated with BRCA2 mutations in a cohort of female mutation carriers of a genetically heterogeneous central European population who were identified by molecular genetic testing in our institute. Methods: This study included 171 Caucasian women from Austria who underwent genetic counseling and where molecular genetic analysis identified a mutation in the BRCA2 gene at the Medical University of Vienna, Division of Senology, in Austria. A total of 57 healthy and 114 affected BRCA2-carriers were detected. The risk was estimated using the product limit method. The log rank test was used to compare different strata. Results: The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 77–93%) and 31% for OC (95% CI 16–46%) in our BRCA2 study population. Female BRCA2-carriers born in 1958 or later were at a significantly higher risk of developing BC (p<0.001; 88% vs. 46% to age 40) but not of OC (p is not significant; 0% vs. 2% to age 40) compared to mutation carriers born earlier. Conclusions: We conclude that female BRCA2 mutation carriers should also be counseled about their cohort-dependent cancer risk, especially for breast cancer. Further research about variables that may affect cancer risk like lifestyle-related factors should be considered.
Breast cancer in Irish families with Lynch syndrome.
Authors: Jordan Emmet , Farrell Michael P. , Cadoo Karen Anne , Clarke R. M. , Nolan C. , Kell M. R. , McCaffrey John , Maher Michael A. , Connolly E. M. , Boyle Terence , Kennedy M. John , Morrison P. J. , Muldoon C. , Gallagher David J 
Published: March 2020

1543 Background: Breast cancer is not among the recognised malignant manifestations of Lynch Syndrome which include colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical (IHC) expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland. One kindred was omitted due to a biallelic MMR and BRCA1 mutation.The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status, and a genotype phenotype correlation was investigated. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in sixteen pedigrees were as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Of the 7 LS kindreds containing breast cancer, 6 MSH2 mutations and 1 MSH6 mutations were identified. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. 5 samples were available for IHC evaluation. 3 out of 5 cases showed loss of MMR expression, all showed loss of MSH2 and MSH6 expression. One of the two cases with normal IHC expression in breast tissue belonged to a kindred where 3 siblings with colorectal cancer and documented deleterious mutations demonstrated no IHC loss. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All identified breast cancer were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.