bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity at diagnosis and breast cancer (BC) recurrence risk based on the 21-gene assay recurrence score (RS).
Authors: Ridolfi Kimberly , Zhang Chong , Onitilo Adedayo A. , Ledesma Wendy M. , Andreason Molly , Engel Jessica Marie , Kim KyungMann , Wisinski Kari Braun , Tevaarwerk Amye , Charlson John A. 
Published: March 2020

555 Background: Obesity at diagnosis has been associated with poorer overall survival in BC patients. The Oncotype Dx 21-gene assay RS has been shown to predict the risk of distant recurrence in estrogen receptor (ER) positive BC. This study aimed to evaluate if an association exists between body mass index (BMI) and RS. Methods: Retrospective chart review of patients (pts) with BC diagnosed 2005-2010 and a 21-gene assay was performed. Risk factors including BMI, hormone use, and menopausal status were collected as well as tumor characteristics such as ER/PR/HER2 status, stage, and grade. Univariate analysis of the association between BMI level (<30 vs ≥30), and RS (≤18 vs >18), stage (I vs II), and grade (1 vs 2 vs 3) was conducted using Chi square test. Correlation of BMI with RS (0-100) was also assessed via Spearman’s correlation. All tests were at a two sided significance level of 0.05. Results: Of 495 pts with a RS value, 482 had a BMI within 6 months of diagnosis. Median BMI was 27.7 kg/m2 (range 17-63). BMI for pts presenting with stage 2 disease is significantly higher (30±6.9) than those with stage 1 (29±7.8), p=0.04 (Wilcoxon rank sum test). No association was found between BMI level and stage, grade or RS. See Table. Mean RS was 18.8 vs 18.2 (BMI <30 vs ≥30), p=0.79 (Wilcoxon rank sum test). Conclusions: This is the largest study of the association between BMI and the RS. Obesity (BMI≥30) has been associated with increased recurrence and death from BC. However, we found no association between BMI and RS. This suggests that poorer outcomes among obese ER+ breast cancer patients may not be due to intrinsic tumor biology (as reflected in the RS), but to other non-tumor factors, whether higher circulating estrogen levels, reduced efficacy of aromatase inhibitors, other comorbidities, difficulty with chemotherapy or other unidentified factors. Further study is warranted. [Table: see text]
Patient-reported symptoms following IMRT alone for oropharynx cancer: A survivorship study.
Authors: Gunn Gary Brandon , Fuller Clifton David , Garden Adam S. , Frank Steven J. , Morrison William H. , Beadle Beth Michelle , Phan Jack , Mendoza Tito R. , Hanna Ehab Y. , Ang K. Kian , Cleeland Charles S. , Rosenthal David Ira 
Published: March 2020

5561 Background: Patients (pts) with favorable oropharynx cancer (OPC) are often treated with single modality RT with excellent disease control. We present the pattern of pt-reported symptoms in OPC survivors treated with IMRT alone. This will represent a benchmark for later comparison to pts treated with other modalities (e.g., proton therapy, transoral surgery). Methods: Pts eligible for this cross-sectional questionnaire-based study had OPC treated with IMRT (no systemic therapy), in remission >18 mos, completed the MD Anderson Symptom Inventory – Head and Neck Module (MDASI-HN). Clinical data were tabulated and analyzed using non-parametric statistics. Results: 89 pts participated. OPC sub-site was tonsil in 58, base of tongue (BOT) in 30, and soft palate in 1 pt. 65% were TX/1, 28% T2, and 7% T3/4, while 53% were NX/1 with 47% N2. Mean RT dose was 66 Gy (SD±2.5). Median age was 54 years (SD±11). Mean follow-up at MDASI-HN was 74 months (SD±15). Mean MDASI-HN symptom rating (0 to 10 scale) was 1.3 (95% CI 0.97-1.6), with no significant difference by OPC sub-site. No single MDASI-HN items showed significant difference in the percentage of pts with moderate to severe (M/S) reports by OPC site, thou dry mouth approached significance (p=0.054), 53% in BOT vs. 32% for tonsil. Overall, 14% of pts were entirely symptom free (i.e. “0” across all 22 symptom items), 33% reported only mild symptoms, 23% only moderate symptoms, and 31% reported any symptom as severe . The top 7 symptoms were dry mouth, swallowing, sleep, taste, fatigue, distress, and teeth and these were reported at M/S levels by 39%, 24%, 19%, 17%, 16%, 14%, and 10% of pts, respectively. For those with any M/S symptom, the median number of symptoms reported at M/S levels was 3. 1/89 pts had a feeding tube at the time of MDASI-HN completion. Conclusions: The late symptom burden for long-term OPC survivors following IMRT alone was low, with nearly half of pts with only minimal symptoms across all items. Considering other endpoints (e.g. disease control, acute toxicity, second malignancies, and functional measures), future treatment strategies should seek to match or exceed these results. Future RT symptom prevention/reduction strategies should focus on the top symptoms identified here.
Predicting the Oncotype DX score: An inexpensive guesstimation.
Authors: Pesce Catherine , Stempel Michelle , Eaton Anne , Patil Sujata , Brogi Edi , Potz Brittany , Hudis Clifford , El-Tamer Mahmoud 
Published: March 2020

557 Background: Oncotype DX Recurrence Score [RS] is used to predict the benefits of chemotherapy added to adjuvant hormone therapy in ER positive early stage breast cancer. It is also prognostic. However, its expense may be a concern in some health care systems and communities. In addition, it is labor intensive, requiring shipment of tissue samples to a single laboratory with an average 10-14 day turnaround time (in the US). A reliable and inexpensive estimator of the Oncotype DX risk score using readily available pathologic variables from tumor specimens could be useful. Methods: We reviewed our prospective database of patients with Oncotype DX results obtained over 2.5 years (1155 specimens with Oncotype DX scores, September 2008 – March 2011) and identified 766 invasive ductal carcinomas with known ER status, PR status, histologic grade, and nuclear grade. Through linear regression analysis, we predicted recurrence score for each tumor using these four parameters. After categorizing according to the same risk classification as in Oncotype DX (low risk: RS<18, intermediate risk: RS 18-30, or high risk: RS>30) we compared our predicted recurrence score to actual Oncotype DX recurrence score. Results: Overall 69.7% of specimens were assigned the same risk category as with the Oncotype DX level. In the predicted low risk group, 1.7% of patients were actually high risk. None of the predicted high risk patients had a low score. Conclusions: We found a strong correlation between scores estimated using our model and actual reported Recurrence Scores. If validated, our model could provide a clinically useful estimation of risk at lower cost. [Table: see text]
Genetic alterations in HRAS gene in relation to outcome and response to cetuximab in head and neck squamous cell carcinoma.
Authors: Rampias Theodoros , Giagini Athina , Matsuzaki Hiroumi , Bartzi Valentina , Siolos Spyros , Vaja Elena , Haralambakis Nick , Katsaounis Panagiotis , Scorilas Andreas , Psyrri Amanda 
Published: March 2020

5574 Background: Aberrant signaling through RAS/MAPK pathway is implicated in resistance to EGFR-targeted agents in cancer. Genetic alterations in Hras gene such as mutations and specific polymorphisms are associated with aggressive phenotype in several smoking-related malignancies. We sought to determine the impact of Hras genetic alterations on response to cetuximab and prognosis in HNSCC. Methods: Clinical outcome according to Hras status was investigated in a retrospective cohort of 140 HNSCC specimens. Primary endpoints were overall survival (OS) and disease-free survival (DFS) and secondary endpoint was treatment response. For statistical analysis, T-test was used for continuous data and x2 –test for categorical data. Cetuximab-resistant cell lines harboring mutant Hras (BB49, T24) were infected with lentivirus expressing shRNA targeting the Hras or a scrambled- shRNA. MTT assay was used to determine the effect of cetuximab on growth of lentivirus infected cells. Biochemical analysis involved immunoblotting for pERK1/2. Results: Mutationanalysis of tumor samples showed that 5.7% participants harbored Hras mutations and 16.42% harbored Hras polymorphisms (rs12628, rs41258054) that are associated with tumorigenesis. Patients bearing tumors with mutated Hras had inferior mean OS ( 22.13vs 35.20, p=0.02) and a non-significant trend for inferior mean DFS. Patients with tumors containing Hras genetic alterations (mutation or polymorphism) had significantly inferior mean OS (p=0.02) compared to those harboring wt Hras and trended towards inferior DFS (p=0.07). Patients had received various treatments such as surgery plus/minus RT and various chemotherapy regimens. A subgroup analysis of 38 patients treated with cetuximab-based regimens showed that wt Hras was associated with higher likelihood of attaining CR or PR to treatment of borderline significance (p=0.06) due to small sample size. Silencing of Hras in Hras-mutant cell lines restored sensitivity to cetuximab and caused a direct downregulation of pERK1/2 levels. Conclusions: Hras genetic alterations are associated with aggressive clinical course and may affect response to cetuximab in HNSCC.
The role of postoperative radiotherapy (PORT) in the management of parotid gland malignancy (PGM).
Authors: Harrison Louis Benjamin , Hu Kenneth , Shourbaji Rania Ayman , Culliney Bruce , Li Zujun , Urken Mark , Persky Mark , Mourad Waleed Fouad 
Published: March 2020

5581 Background: To report the role of PORT in the management of PGM and to analyze the prognostic factors for optimal locoregional (LRC) and distant control (DC) Methods: This is a single institution retrospective study. From March 2001-2011, a total of 118 patients with PGM were treated with surgery and PORT (100%) of which 75% were treated with IMRT, 20 and 10% received concurrent carboplatin and CDDP respectively. Indications for PORT were: recurrent or gross residual disease, +ve or close margins, nerve invasion and +ve lymph nodes (LN). PORT fields comprehended parotid bed and ipsilateral neck. Median PORT doses delivered were 70, 63, 54 Gy (at 1.8-2 Gy/fraction) for gross, microscopic disease, and ipsilateral neck respectively. All PORT was delivered via 4-6 MV photons with daily 3-5 mm bolus. The median age was 52 (18-89). Females and Caucasian made up 56% and 64% of the population, respectively. Histologic findings were adenoid cystic carcinoma 20%, mucoepidermoid carcinoma 19%, adenocarcinoma 18%, pleomorphic carcinoma 16%, salivary duct carcinoma 9%, acinic cell carcinoma 8%, ex-pleomorphic carcinoma 7%, and sarcoma 3%. Pathological stages I, II, III, IV were 10, 30, 20 and 40% respectively Results: With a median follow up of 56 months (12-124), the LRC and DC for the whole cohort were 96% (5/118) and 93% (8/118) respectively. The median duration of PORT was 45 days (40-60). The median time to LR failure (LRF) and distant metastases were 16 (12 - 30) and 28 months (24-48) respectively. Late RT toxicity was; grade I xerostomia 30%, altered taste 15%, trismus 6%, dysphagia and neck stiffness 2%. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100%. Chi square and regression analysis tests show significant relationship (P=0.001) between salivary duct ca (70%) and distant metastases (DM), also males are at higher risk (17%) to develop LRF and DM, compared to females (6%). Poor prognostic features for DM and LRF were salivary duct ca, stage IV, PNI, and multiple LN involvement. Conclusions: Our data show that surgery followed by PORT to the tumor bed and ipsilateral neck provide excellent long standing oncologic and functional outcomes. Further studies are warranted to optimize the management of patients at higher risk of DM despite LRC and RT ± chemotherapy administered.
Association of the phosphorylation of the estrogen receptor at serine 118 and 167 with prognosis in postmenopausal breast cancer patients.
Authors: Beelen Karin J. , Opdam Mark , Koornstra Rutger H.T. , Vincent Andrew D. , Vermorken Jan Baptist , van Diest Paul J. , Sanders Joyce , Wesseling Jelle , Linn Sabine C. 
Published: March 2020

562 Background: The sensitivity of the estrogen receptor (ERα) to anti-estrogen therapy can be affected by phosphorylation events. In premenopausal breast cancer patients, phosphorylation of the ERα at serine 118 (ERαS118-p) is predictive for benefit from adjuvant tamoxifen. Since ERαS118-p represents the common hallmark of different signaling cascades that differ in E2 dependency, the resulting effect on estrogen sensitivity may differ between pre- and postmenopausal patients. Phosphorylation of serine 167 (ERαS167-p) has been associated with favorable disease outcome, but whether ERαS167-p can predict tamoxifen sensitivity is currently unknown. We tested the predictive value of both ERαS118-p and ERαS167-p for benefit from adjuvant tamoxifen in postmenopausal breast cancer patients. Methods: We collected primary tumor blocks from 563 ERα positive (stage I-III) postmenopausal patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial). The median follow-up of patients without a recurrence event was 9.4 years. Immunohistochemistry was performed on a TMA using monoclonal antibodies for ERαS118-p and ERαS167-p. The percentage of positive nuclei was scored and a score of ≥ 10 % was considered as positive. Multivariate Cox models were used to assess hazard ratios (HRs) for recurrence free interval and the interaction between these phosphorylations and tamoxifen treatment. Results: We did not find a significant interaction between either ERαS118-p (p=0.99) or ERαS167-p (p=0.44) and tamoxifen, suggesting that the relative benefit from adjuvant tamoxifen in postmenopausal patients is not dependent on the presence of one of these phosphorylations. Both tamoxifen treated patients as well as control patients had a better prognosis when their tumor was positive for ERαS118-p (adjusted HR 0.60 p=0.02) or ERαS167-p (adjusted HR 0.62, p=0.02) compared to patients whose tumor did not express these ERα phosphorylations. Conclusions: In postmenopausal patients ERαS118-p and ERαS167-p are both associated with better prognosis, but do not predict differential benefit from tamoxifen.
Synchronous bilateral breast cancer (SBBC): Concordance of receptor status between right and left breast.
Authors: Desai Palak , Braun Eduardo , Dehghan-Paz Irene , Gattuso Paolo , Canar Jeff , Cobleigh Melody A. 
Published: March 2020

572 Background: This analysis was prompted by a patient who presented with SBBC who had and ER+, HER2- cancer in one breast and an ER-, HER2+ cancer in the other. Since both breasts have the same genetic background and environmental exposures, concordance should be virtually identical unless other factors are at play. Methods: SBBC was defined as bilateral cancer diagnosed concurrently or within 6 months of each other. Cases were identified retrospectively from patients seen at Rush University Medical Center. This analysis was limited to invasive SBCC (ISBBC). Estrogen receptor (ER) and Her2/neu (HER2) status were assessed according current ASCO/CAP guidelines. Correlation between ER and HER2 status was determined using κ statistic. Results: From January 1998 to December 2012, 33 cases of ISBBC were diagnosed. In 65% of cases synchronous disease was diagnosed concurrently. The average age at diagnosis was 56. The majority were multiparous and 79% post menopausal. About half of the patients (55%) had at least one first degree relative with a history of breast or ovarian cancer and 9% of the cohort had a deleterious mutation in BRCA1 or BRCA2. Infiltrating ductal was most common (74%) followed by infiltrating lobular (21%). 53% of breasts specimens also contained ductal carcinoma in situ. 68% of tumors were ER positive and 8% were HER2 positive. Concordance in ER status was seen in 73% of cases (kappa coefficient 0.14) and in HER2 status was 64% (Kappa coefficient 0.35). Conclusions: Despite identical hereditary and environmental exposure, some patients develop ISBBC cancers with discordant receptor status. While this is the exception, it suggests that other factors influence important tumor characteristics. [Table: see text]
In situ quantitative measurement of mRNA to predict response to trastuzumab in a cohort of metastatic breast cancer patients.
Authors: Vassilakopoulou Maria , Bordeaux Jennifer , Neumeister Veronique , Cheng Huan , Schalper Kurt , Skarlos Dimosthenis V. , Pectasides Dimitrios G. , Pavlidis Nicholas , Koutras Angelos , Linardou Helena , Razis Evangelia , Bobos Mattheos , Kotoula Vassiliki , Rimm David , Fountzilas George , Psyrri Amanda 
Published: March 2020

573 Background: Trastuzumab therapy is currently selected based on assessment of HER2 by either immunohistochemistry (IHC) for protein over-expression or fluorescence in situ hybridization (FISH) to detect gene amplification. We sought to determine the predictive value of in situ quantitative measurement of mRNA on a cohort of trastuzumab-treated metastatic breast cancer patients. Methods: A tissue microarray composed of ninety metastatic breast cancers treated with various chemotherapy regimens combined with trastuzumab was constructed. HER2 intracellular domain (ICD), HER2 extracellular domain (ECD) and HER2 mRNA were assessed using the AQUA method for quantitative immunofluorescence. For HER2 protein evaluation CB11was used to measure ICD and SP3 to measure ECD of the HER2 receptor. In addition, HER2 mRNA status was assessed using the RNAscope assay ERRB2 probe according to manufacturer’s protocol modified for detection with Cy-5 Tyramide. Cytokeratin was used in order to create the tumor mask and signal was quantified within the mask. Primary endpoints included time to progression (TTP) from trastuzumab initiation and overall survival (OS) times. Statistical analysis was performed using Kaplan-Meier analysis and the Cox proportional hazard model. Results: HER mRNA was tightly correlated with ICD HER2, as measured by CB11 (r2=0.35), but not with ECD HER2 as measured by SP3 (r2=0.14). Both ICD HER2 and HER2 mRNA were predictive of response to trastuzumab, but ECD was not. Multivariate analysis including age, histological grade and hormone receptor status shows the ICD to be predictive of TTP (p=0.0377). HER2 mRNA levels were significant for prediction of TTP (p=0.0344) in multivariate analysis including age and histological grade. Conclusions: The expression of ICD, as detected by CB11 and HER2 mRNA levels were significantly associated with TTP in this trastuzumab-treated metastatic cohort. The ECD, as detected by SP3 is neither predictive of response, nor tightly correlated with HER2 mRNA. In situ assessment of HER2 mRNA has the potential to identify breast cancer patients who derive benefit from trastuzumab treatment.
Relationship between body mass index (BMI) at diagnosis of ER+ node negative breast cancer (BC) and Oncotype DX recurrence score.
Authors: Lohrisch Caroline A. , Davidson Ashley , Chia Stephen K. L. , Gelmon Karen A. , Shenkier Tamara Nina , Ellard Susan , Woods Ryan , Wong Linda , Pope Janice 
Published: March 2020

582 Background: Inferior stage-adjusted survival for BC among obese (O) women has been reported. This may reflect differences in treatment planned for O women, in treatment received (due to toxicity), or in tumor biology arising in different cellular environments, such as high serum insulin levels, which are associated with a higher risk of recurrence. Methods: We examined whether overweight (BMI 25-30) or obese (BMI >30) women had a higher Oncotype Dx Recurrence Score (RS) after ER+, node negative (NN) or N0i+ BC than normal weight women. Included were all participants at the BC Cancer Agency in a RS clinical utility study in consecutive ER+ NN, N0i+ BC (n=156) at the BC Cancer Agency and in the TAILORx trial (n=56). Sixteen were excluded (n=5 withdrew consent; 1 triple negative; 3 test failed; 2 her2+; 1 neoadjuvant treatment, n=4 height and weight missing). Results: A similar proportion of O patients had low, intermediate, and high RS tumors. Cancers with a high RS were more likely to be grade 3 (55% of grade 3 tumours had high RS, 33% intermediate RS, 12% low RS) and fewer were strongly ER positive (69% of high RS versus 97% of intermediate and low RS). Conclusions: While this data does not support differences in tumor risk arising in O versus non obese environments in ER+, NN BC, examination of a larger data set may be more informative. [Table: see text]
Correlation, comparison, and combined analysis of Ki-67 and histological grade for early luminal breast cancer.
Authors: Naito Yoichi , Fujii Satoshi , Itoh Kuniaki , Nezu Masahiko , Matsubara Nobuaki , Sasaki Masaoki , Wada Noriaki , Yoneyama Kimiyasu , Mukai Hirofumi 
Published: March 2020

585 Background: Both Ki-67 and histological grade are established prognostic factors in patients with early breast cancer. Recent international expert consensus employs Ki-67 to classify luminal breast cancer, and histological grade is described as an alternative. We investigated the prognostic value of Ki-67, histological grade, and their combination. Methods: Patients with early breast cancer treated with surgery between January 2000 and December 2008 were retrospectively reviewed. Inclusion criteria were as follows: estrogen receptor positive, HER2 negative, available for Ki-67 and histological grade. Clinicopathological data were retrieved from medical records. Ki-67 labeling index was investigated using MIB-1 antibody and subdivided into three categories: low 0-9%; intermediate 10-19%; high >20%. Histological grade was scored between 1 and 3. Disease-free survival (DFS) was defined as time from surgery to the first documented disease recurrence or death. Ki-67 categories and histological grade were analyzed respectively and then concomitantly for prognostic impact on DFS. Results: A total of 606 patients were included. Median age was 58 and 28.1% were over 65 years. 65.4% were postmenopausal women. Progesterone receptor was positive in 84.0% of patients. 29.6% received neoadjuvant or adjuvant chemotherapy. Number of lymph node metastasis was 0 in 70.0%, 1-3 in 21.3%, and >4 in 8.7% of patients. Ki-67 categories and histological grade showed weak but significantly correlation (Spearman’s rho = 0.385, p<0.001). High Ki-67 and histological grade 3 were correlated with worse prognosis to the same extent (HR 2.518, p = 0.002 and HR 2.541, p = 0.048, respectively). For combined analysis, patients represented concomitant with high Ki-67 and histological grade 3 showed worse prognosis compared with those with Ki-67 low and histological grade 1 (HR 3.137, p = 0.021). Conclusions: Ki-67 and histological grade were significantly but weakly correlated. Combined use of these two factors could better predict recurrence of early luminal breast cancer.