bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of neutrophil-to-lymphocyte ratio on pathological complete response in triple negative breast cancer.
Authors: Enriquez Daniel , De la Cruz Ku Gabriel Antonio , Fernandez Margiory , Eyzaguirre Eduardo , Luque Renato , Paitan David , Luján Maria , Saavedra Antonella , Valcárcel Bryan , Morante Zaida , Fuentes Hugo Alejandro , Neciosup Silvia P. , Gomez Henry Leonidas
Published: September 2018

e12012

Background: Immune response in Triple Negative Breast Cancer (TNBC) plays a critical role in pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Therefore, neutrophil to lymphocyte ratio (NLR) could be an interesting biomarker to evaluate systemic inflammation in TNBC. Our aim was to evaluate the effect of NLR, also progression free survival (PFS) and overall survival (OS) as secondary objectives. Methods: We reviewed 338 medical records of II-III CS TNBC patients treated with NAC, in the 2000-2014 period, at Instituto Nacional de Enfermedades Neoplasicas. Patients were grouped in NLR < 3 and ≥3. Survival differences were assessed by log-rank test in the univariate analysis and prognostic factors were then investigated by Cox regression analysis. Results: Mean age was 47y [range:24-79], 54% were premenopausal, 90.9% had clinical T3-T4 tumor and 80.5% clinical nodal involvement. There were 44 and 294 pts with II and III CS, respectively. From 338 patients, 259 had NLR < 3 and 79, ≥3. No significant clinical differences were noted between these groups, except a higher mean BMI among patients with NLR < 3 (28 vs 26Kg/m2, p = 0.01). pCR rate was higher in NLR < 3 patients (22% vs 15.2%, p < 0.001) and partial response was reached on 70.7% and 62% of pts with NLR < 3 and ≥3, respectively. At 5 year median follow-up, 5-year DFS was higher among patients with NLR < 3 (47 vs 34%, HR = 0.69, 95%CI: 0.50-0.95, p = 0.02) and so was 5-year OS (55 vs 40%, HR: 0.61, CI95%: 0.43-0.85, p = 0.004). At multivariate analysis, premenopausal status, non-pCR and nodal involvement were associated with worse DFS. Otherwise, NLR < 3 (HR: 0.61, 95%CI: 0.43-0.86, p = 0.005) and pCR were predictors of better OS, nonetheless nodal involvement had negative impact on OS. Conclusions: NLR is a valuable predictive biomarker of pCR and OS in TNBC patients. We report less pCR rates due to higher stages among peruvian population.
Reducing doxorubicin cardiotoxicity in rats with mammary tumors by dantrolene.
Authors: Todorova Valentina K , Kaufmann Yihong Jiang-Cao , Kumarapeli Asangi R , Siegel Eric R , Owen Aaron , Aronson Julia H , Makhoul Issam , Wei Jeanne , Theus Sue A , Klimberg Suzanne
Published: September 2018

e12013

Background: Doxorubicin (DOX), widely used in breast cancer, is known for its cardiotoxicity. Preventing DOX-cardiotoxicity without affecting its antitumor efficacy has not been successful. DOX-cardiotoxicity results from oxidative stress that increases intracellular calcium levels by promoting the release of Ca2+ from sarcoplasmic reticulum (SR) and impairing Ca2+ clearance in cardiomyocytes. Dantrolene (DNT), a postsynaptic muscle relaxant inhibits the release of Ca2+ from SR by inhibiting the ryanodine receptor (RYR). The aim of this study was to examine the effect of DNT on cardiotoxicity and anti-tumor efficacy of DOX in a rat model of breast cancer. Methods: Female F344 rats with implanted MatBIII breast cancer cells were randomized into 3 groups of 12 rats/group and were treated as follows: “DOX” group was injected i.p. with DOX 2x week for 3 weeks (cumulative dose 12 mg/kg); “DNT” group received daily DNT (5mg/kg/day) by oral gavage; and “DOX+DNT” group was treated with DOX 2x week for 3 weeks and daily DNT (5mg/kg). The presence of cardiac alterations was examined by echocardiography before and after the experiment. Body weight, tumor size and volume were measured at sacrifice. H&E stainings of the hearts and tumors was examined. Blood glutathione (GSH) levels were determined. Results: Mortality in the groups of rats treated with DOX alone, DNT+DOX and DNT was 40%, 16% and 0%, respectively. Histopathologic analysis of hearts of the surviving rats showed reduced DOX induced cardiotoxicity in the group treated with DOX+DNT as shown by reduced interstitial edema, cytoplasmic vacuolization and myofibrilar dysruption, compared to DOX only treated hearts. DNT significantly increased cardiac output and stroke volume, and improved the decline of left ventricle ejection fraction (LVEF) induced by DOX by 50%. Also, reduced breast tumor volumes with increased tumor necrosis was observed in rats treated with DOX+DNT compared to DOX alone. Rats treated with DNT lost less body weight and had a higher blood GSH levels. Conclusions: These data indicate that DNT is able to provide protection against DOX cardiotoxicity while maintaining its antitumor efficacy. Further preclinical studies are needed to determine the optimal dosing of DNT.
Likelihood of late relapse assessed by the Breast Cancer Index (BCI) in LN-invasive lobular compared to invasive ductal carcinoma.
Authors: Nunes Raquel , Salganik Max , Liu Junmei , Schnabel Catherine A. , Richardson Andrea Lynn
Published: September 2018

e12025

Background: Women with HR+ breast cancer remain at risk for late distant recurrences (DR) despite optimal adjuvant therapy. Invasive lobular carcinoma (ILC) is the 2nd most common subtype of invasive breast cancer. When compared to invasive ductal carcinoma (IDC), ILC has distinguishing clinical and pathologic characteristics that may result in different response to therapy and long term prognosis. BCI is a validated gene expression-based assay for pts with early stage HR+ breast cancer that provides risk of late (5-10 y) DR and predicts likelihood of benefit of extended endocrine therapy (EET). Here, we compared BCI assay results in pts with HR+, LN- ILC vs IDC. Methods: The BCI Clinical Database for Correlative Studies is an IRB-approved de-identified database that contains >50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice (N=14,463). Molecular variables include BCI Prognostic score, HoxB13/IL17BR ratio (H/I), and molecular grade index (MGI). Clinicopathologic variables were abstracted from pathology reports (available for a subset of cases). LN- pts with available pathologic data were analyzed. Chi-squared tests were used to compare BCI results between IDC and ILC subgroups. Results: Analyses included 2554 LN- pts with available histologic subtype data (80.7% IDC; 13.7% ILC; 2.6% mixed; 2.9% other). Median age was 59.3y (range 27-89y; 74% ≥ 50y). BCI Prognostic had a broad distribution of individual risk assessment in both IDC and ILC. However, BCI Prognostic had a lower median BCI scores (P<0.0001) in ILC, and classified a smaller proportion of pts with ILC as high risk for late DR compared to IDC (36.5% vs 53.1%; P<0.0001). IDC had a higher median molecular proliferative status (MGI) compared to ILC (P<0.0001). BCI Predictive (H/I) identified a slightly decreased proportion of pts with ILC benefiting from extended endocrine therapy compared to IDC (38.2% vs 41.1%). There was no difference in quantitative ER or PR (by PCR) between groups. Conclusions: BCI identified a smaller proportion of pts with ILC at high risk of late DR compared to IDC. Further studies evaluating outcomes are warranted to further validate BCI in pts with ILC.
Feasability of contrast-enhanced CT in breast conservation surgery for invasive and non-invasive breast cancer.
Authors: Kamada Yoshihiko , Tamaki Kentaro , Uehara Kanou , Tamaki Nobumitsu
Published: September 2018

e12084

Background: MRI imaging has become the standard for planning breast conservation surgery for breast cancer. However, due partly to lack of resources of a small clinic practice, we have been utilizing contrast enhanced CT facilitated with ultrasound for this purpose. The aim of this presentation is to assess the feasability of contrast-enhanced CT in breast conservation surgery. Methods: We used GE Brightspeed-8 CT, with HP Z440 workstation (for free line masking). 100 mld of Iopamidol contrast medium was injected at a rate of 3 ml/sec and image capture was done at the 60 or 180 second phase. Images were taken with the patient in a supine position. We evaluate a total of 2057 cases operated in a ten year period between 2005.1.1 to 2014.12.31, excluding cases receiving preoperative chemotherapy. 1,757 cases (85%) were invasive and 300 cases (15%) were non-invasive breast cancer cases. Results: Lesion localization by contrast-enhance CT was acceptable by predefined criteria in 72% of invasive carcinoma cases, and 89% non-invasive carcinoma cases. The breast conservation rate was 77% and 83% for invasive and non-invasive breast cancer cases, respectively. Surgical margins were positive “on ink” for 8 cases (0.6%), and positive within 5 mm (including DCIS) in 340 cases (25.1%) of the 1,357 invasive cancer cases treated with BCT. There were 7 completion total mastectomies and 3 partial mastectomies for the patients with positive margins (11/340 = 3.2%). Surgical margins were positive for 78 cases (31.3%) of the 249 DCIS cases undergoing BCT. There was 1 completion mastectomy and 2 partial mastectomies for the patients with positive margins (3/78 = 3.8%). Local recurrence rates for invasive and non-invasive breast cancer cases undergoing BCT were 2.6% (average observation period 65.0 months) and 2.8% (average observation period 64.4 months), respectively. Conclusions: Contrast-enhanced CT facilitated with ultrasound imaging is an effective and easy to implement modality for planning breast conservation surgery in invasive and non-invasive breast cancer, possibly in part due to imaging that corresponds closely to the breast position during surgery.
Postmastectomy radiation in women with node positive breast cancer in the Ontario population.
Authors: Latosinsky Steven , Jenkyn Krista Bray , Li Lihua , Shariff Salimah
Published: September 2018

e12104

Background: Despite two randomized controlled trials first published in 1997 showing improvements in both locoregional control and survival, postmastectomy radiation for node positive breast cancer patients has not been universally accepted; particularly for patients with 1-3 positive nodes. Subsequent favorable meta-analyses have resulted in more recent guidelines supporting postmastectomy radiation. We examined the rate and predictors of postmastectomy radiation receipt in node positive breast cancer patients in Ontario (population 13.2 million). Methods: We used the Ontario Cancer Registry, a population-based, prospectively-collected registry, to identify all node positive female breast cancer patients in the province with a diagnosis date between April 1, 2010 and Sept 30, 2014. Patient records were linked to prospectively maintained health administrative databases. Through these databases, the universal single-payer health care system in Ontario can capture details for each patient for all health care encounters, hospitalizations, procedures (mastectomy), prescription medications, systemic cancer therapy and radiation. Logistic regression modeling using generalized estimating equations was employed to determine the association between patient, tumor and treatment characteristics and receipt of radiation, while accounting for the possible clustering effect by health regions. Results: Of the 6,535 women with node positive breast cancer who had undergone a mastectomy 73.9% received radiation. Of the 4227 women with 1-3 positive nodes, 68.7% received radiation, and of the 2308 women with > 3 positive nodes 83.4% received radiation. Receipt of radiation was positively associated with younger age ( < 70 years), increasing cancer stage and a lower Charlson comorbidity index. Conclusions: In a setting with universal healthcare, the majority of women with node positive breast cancer in Ontario received postmastectomy radiation, including women with 1-3 positive nodes. Older women, those with higher stage and those who had increased co-occurring medical conditions were less likely to receive radiation therapy.
Immune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer (BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev).
Authors: Waks Adrienne Gropper , Barry William Thomas , Gjini Evisa , Dillon Deborah , Rodig Scott , Brock Jane E. , Baltay Michele , Savoie Jennifer , Stover Daniel G. , Winer Eric P. , Krop Ian E. , Tolaney Sara M.
Published: September 2018

e12134

Background: Though preliminary study of the BC immune microenvironment suggests that HR+ tumors are less immune-active than other subtypes, immune biomarkers may have important clinical implications in HR+ BC pts. Methods: 78 HR+/HER2- BC pts were enrolled on a prospective trial of preop bev followed by bev with adriamycin/cyclophosphamide/paclitaxel dose-dense chemo. Tumor samples were collected at diagnosis and surgery (pre-tx and post-tx). PD-L1 expression (by immunohistochemistry) and tumor-infiltrating lymphocytes (TILs) were scored. Whole transcriptome sequencing and Nanostring PanCancer Immune Profiling Panel were performed. Pathologic response at surgery was assessed by Miller-Payne (MP) and residual cancer burden (RCB) scores. We calculated adjusted correlations by linear/logistic regression for RCB/dichotomized MP, respectively. Results: 55 pts who received trial tx and had >1 analyzable specimen are included. Pre-tx TILs and tumor PD-L1 (tPD-L1) scores (see table) were slightly positively correlated (Spearman rho 0.23, p=0.1). Large changes (>5%) in TILs or tPD-L1 from pre-tx to post-tx were rare: 2 pts each had large changes in TIL or tPD-L1 score (N=38 and N=31 pairs, respectively). Higher pre-tx TILs or tPD-L1 were significantly associated with more favorable RCB and MP (all Spearman p<0.01) in unadjusted analyses. After adjustment for age and tumor grade, higher pre-tx TILs and tPD-L1 were associated with more favorable RCB (p<0.01 for both), and higher pre-tx tPD-L1 correlated with more favorable MP (p=0.03). Pathologic complete response occurred in 4 pts; all 4 had high pre-tx TILs, pre-tx tPD-L1, or both. Analysis of immune-related RNA signatures is ongoing. Conclusions: High levels of tumor-immune interaction were seen in only a minority of untreated HR+ breast tumors, and did not typically change after tx with chemo plus bev. Nonetheless, TILs and tPD-L1 are significantly associated with pathologic response to preop tx in HR+ disease. [Table: see text]
Trastuzumab combined with doublet or single-agent chemotherapy as a first-line treatment for HER2-positive metastatic breast cancer.
Authors: Yu Yunfang , Wang Ying , Chen Kai , Fu Tuping , Yao Herui
Published: September 2018

e12511

Background: To investigate the efficacy and safety of doublet vs. single-agent chemotherapy (CT) plus trastuzumab as first-line treatments for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). Methods: We searched for randomized clinical trials (RCTs) that investigated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcome measures for this analysis included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Meta-analyses and trial sequential analyses (TSA) were conducted. The study quality was evaluated using the GRADE framework. The PROSPERO registry number is CRD42016043766. Results: The results from four RCTs that included 1,044 participants were pooled. Moderate-quality evidence indicated that doublet CT+H better correlated with prolonged PFS (hazard ratio [HR] = 0.69, 95% confidence interval (CI) 0.63 to 0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88 to 0.92, P < 0.0001) than did single-agent CT+H; however, moderate-quality evidence indicated there was no significant difference between the two drug regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98 to 1.17, P = 0.157), as confirmed by TSA, which indicated that the cumulative Z-curve entered the futility area. There was moderate-quality evidence that the treatment-related grade 3 to 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000; number needed to treat to harm (NNTH) = 20), nausea/vomiting (RR = 4.26, P = 0.002; NNTH = 25), diarrhea (RR = 2.81, P = 0.002; NNTH = 25), and stomatitis (RR = 5.02, P= 0.003; NNTH = 25) were more frequent with doublet CT+H than single-agent CT+H. Conclusions: Doublet CT+H is associated with longer PFS and OS than single-agent CT+H when used as a first-line therapy for HER2-positive MBC.
Infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy.
Authors: Mortimer Joanne E. , Yuan Yuan , Jung Jae J , Stewart Daphne B. , Chung Samuel , Koehler Stephen , Cooper Jill , Kruper Laura , Wong Louise , Dadwal Sanjeet
Published: September 2018

e12524

Background: We observed an increased incidence of severe skin and nail infections in HER2 positive patients whose treatment regimens included pertuzumab to trastuzumab-based chemotherapy; a previously unrecognized toxicity. Methods: We developed a registry for patients (pts.) who were identified by their treating physician to have severe skin/nail infections attributed to this dual HER2-directed treatment. A single infectious disease specialist (SD) oversaw the attribution of infection to drug or non-drug. Physicians were encouraged to assess quantitative immunoglobulins. Results: To date, 44 women were identified to have 62 individual episodes of infection, often at more than one site. Treatment was given as neoadjuvant therapy -24, as adjuvant therapy - 6, and for metastatic disease -14. The median age was 57 (Range 25-73); 24 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH); 22 pertuzumab, trastuzumab, and a taxane; 2 were on pertuzumab and trastuzumab alone. Folliculitis of the scalp, abdomen, chest wall and/or buttocks was observed in 31 patients; abscesses developed in 15;6 required surgical interventions. Paronychial infections involving one to 16 digits were observed in 6, 3 of whom required surgical intervention. With the exception of 2 pts, all had adequate WBCs. Cultures were obtained in 20 pts., and identified MSSA in 8, MRSA in 5, and Streptococcal species in 3. Two pts. with cellulitis had negative cultures; 1 pt. was cultured after initiation of antibiotics, and 1 pt. died of gram positive cocci sepsis on cycle 2 day 7 of PTCH. Her WBC on day 1 was 13.0, and she received pegfilgrastim on day 2. Immunoglobulins were found to be low in 16 of 29 (41%) women tested. In the absence of culture data, infections were managed with cephalexin, doxycycline, or topical antibiotics. The majority of patients continued on chemotherapy, but pertuzumab was deleted from the regimen in 2 pts. Conclusions: We continue to see a significant increase in gram positive invasive skin and nail infections in women with HER2 positive breast cancer treated with pertuzumab and trastuzumab-based regimens. Low levels of quantitative immunoglobulin in select patients suggest a possible mechanism.
Prediction of exemestane benefit in patients with advanced breast cancer based on diagnostic biopsy mRNA analysis.
Authors: Christensen Troels Dreier , Buhl Anna Sofie Kappel , Christensen Ib Jarle , Nelausen Knud Mejer , Balslev Eva , Knoop Ann Søegaard , Brix Eva Harder , Vestlev Peter Michael , Ejlertsen Bent , Kumler Iben , Luczak Adam , Langkjer Sven Tyge , Linnet Soeren , Jakobsen Erik , Bogovic Jurij Antonovic , Glavicic Vesna , Buhl Ulla Hald , Jensen Peter Buhl , Knudsen Steen , Nielsen Dorte
Published: September 2018

e12532

Background: Exemestaneis a steroidal aromatase inhibitor used in the treatment of postmenopausal patients with estrogen receptor(ER)-positive adjuvant and advanced breast cancer. We aimed to determine the predictive value of a multigene mRNA-based mathematical algorithm (Drug Response Predictor (DRP)) for benefit of exemestane. The DRP is founded on measuring the full cancer transcriptome in sensitive and drug resistant cell lines compared with expression patterns in tumors and broadly validated in several studies (Wang et al. JNCI (2013) 105 (17): 1284-1291.) (Knudsen, S. et al. PLoS One (2014) 9(2): e87415.) (Christensen, TD et al. J Clin Oncol (2016) 34: suppl; abstr e12056.) (Kappel, IB et al. J Clin Oncol (2016) 34: suppl; abstr e20007.). Methods: Among 838 consecutive patients from a DBCG cohort with advanced breast cancer treated at 10 participating sites we identified 163 patients who between November 2008 and November 2015 initiated exemestane. All but one patient were ER-positive. Patients were evaluated every 3 to 4 months using CT scans and clinical examination. After patient informed consent mRNA was extracted and assayed on Affymetrix Gene Chip U133p2 arrays from formalin fixed paraffin embedded diagnostic biopsies. The primary endpoint was progression free survival (PFS). Analysis of the DRP’s ability to predict PFS was performed using a Cox regression model adjusted for treatment line. Results: Median PFS was 8.5 months. Of the 163 patients, 101 received prior adjuvant antihormone therapy and 60 did not. Data regarding adjuvant therapy was inaccessible for two patients. Hazard ratios for patients with predicted good vs. poor effect of exemestane are shown in the table. Conclusions: In a clinical setting, a mathematical algorithm using mRNA from a diagnostic biopsy can in patients unexposed to previous adjuvant endocrine therapy with statistical significance predict who will benefit from exemestane. [Table: see text]
Comparative efficacy with endocrine-based combination versus monotherapy among postmenopausal women with HR+/ HER2- metastatic breast cancer: A network meta-analysis.
Authors: Tang Derek , Ayyagari Rajeev , Patterson-Lomba Oscar , Zhou Zhou , Xie Jipan , Niravath Polly Ann
Published: September 2018

e12535

Background: Endocrine-based therapies (ETs) are used to treat postmenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer (ABC). This study synthesizes the available evidence on progression-free survival (PFS), overall response rate (ORR) and clinical benefit rate (CBR) with ETs, as monotherapy and in combination with targeted therapy (TT), in postmenopausal HR+/HER2- ABC using a mixed treatment comparison (MTC). Methods: A systematic literature review of Medline, EMBASE, Cochrane Library and key conferences (2013-2016) was performed to identify randomized clinical trials satisfying the following criteria: 1) included women with HR+/HER2- ABC, 2) included ET monotherapy and ET+TT combination arms, 3) reported PFS, ORR or CBR, and 4) was published in 2007 or later (when HER2 testing was standardized). Pairwise hazard ratios (HRs), relative risks (RR) and their corresponding 95% credible intervals (CrIs) were obtained via a Bayesian MTC. Efficacy was studied in first-line and aromatase inhibitor (AI)-failure (included patients who previously failed an AI or chemotherapy as first-line therapy) settings separately. ETs included letrozole, fulvestrant and exemestane, while ribociclib, palbociclib and everolimus were the TTs identified. Results: Three trials were eligible in the first setting for all three outcomes. TT+ET had significantly longer PFS vs. ET (HR = 0.56, 95% CrI 0.48-0.65), and also had significantly higher ORR (RR = 1.34, 1.17-1.51) and CBR vs. ET (RR = 1.17, 1.12-1.23). In the AI-failure setting, three trials were eligible for PFS, two for ORR, and none for CBR. TT+ET significantly improved PFS vs. ET (HR = 0.47, 0.41-0.53) and had significantly higher ORR vs. ET (RR = 3.52, 2.26-5.39). Conclusions: These results consistently indicate that the hazard of progression or death was approximately halved and that overall response and clinical benefit rates were significantly improved across patient settings for patients receiving TT+ET relative to ET monotherapy among postmenopausal women with HR+/HER2- ABC women.
The impact of stereotactic radiotherapy to metastatic site on systemic treatment decision in oligometastatic breast cancer patients.
Authors: Besen Ali Ayberk , Mertsoylu Huseyin , Kose Fatih , Yıldırım Berna , Gozel Sedat , Sedef Ali Murat , Ucar Aysenur , Onal Cem
Published: September 2018

e12564

Background: Patients with oligometastatic disease achieve long-term survival with multimodality treatment strategies. However, little attention has been paid to the effect of adjusting systemic therapy after local therapy in clinical studies. The aim of this study was to investigate the effects of changing or continuing the same treatment regimen following local therapy on survival parameters. Methods: Out of 350 metastatic breast cancer patients, treated between 2012 and 2016, 43 patients (12%) with oligometastatic disease were included in our study. Oligometastasis was defined as < 5 metastatic sites in the same or different organs. Results: At a median follow-up of 32 months (7–53 months), 29 (67.4 %) patients had died. The one- and two-year overall survival (OS) rates were 95% and 78%, respectively, and the one- and two-year progression-free survival (PFS) rates were 77% and 51%, respectively. Following stereotactic body radiotherapy (SBRT) to oligometastatic sites, systemic treatment protocols were changed in 28 (65.1%) patients, while systemic treatment was continued unchanged in 15 (34.9%) patients. Changes to systemic treatment were significantly higher in patients with two organ metastases compared to patients with one organ metastasis ( p= 0.04). In the univariate analysis, estrogen receptor (ER) status and triple negative disease were significantly predictive of OS. The ER status and the number of metastatic organs were identified as significant predictors of PFS. In the multivariate analysis, only age emerged as a significant independent predictor of OS, while the number of initial organs involved and triple negative disease were significant factors for PFS. Conclusions: A hybrid treatment strategy is associated with higher survival rates in oligometastatic breast cancer patients. Post-SBRT systemic treatment change had no significant impact on OS and PFS in this study.
Serum phosphatidylcholine is lower among breast cancer patients on systemic chemotherapy.
Authors: Li Xin , Lim John , Kolatkar Anand , Welter Lisa , Waitman Kathryn , Hwang Eun-Sil Shelley , Lu Janice M. , Kuhn Peter , Nieva Jorge J.
Published: September 2018

e12571

Background: Chemotherapy-induced cognitive impairment, also known as 'chemobrain', is widely recognized as a frequent adverse effect of chemotherapy, occurs in 10-40% of all cancer patients. Those cancer survivors suffer from poor concentration, memory, abstract reasoning, and motor dysfunction. The etiology is unclear. In our study, we analyzed the metabolite panels in breast cancer patients with vs. without chemotherapy trying to identify metabolic mediators of neurologic injury. Methods: We obtained plasma sample from 18 breast cancer patients, 9 received chemotherapy prior to blood drawn; while the other 9 had no systemic therapy. The plasma samples were sent for mass spectroscopy. Each metabolites level was normalized, and the two groups were compared in each metabolite by t-test with statistical significance corrected for multiple comparisons using the Holm-Sidak method. Results: We identified 57 amines and their metabolites; 106 carbohydrate related metabolites, and 228 lipid molecules. While amino acid, and carbohydrate did not show significant difference, phosphatidylcholine level in the chemotherapy treated group demonstrated lower level in the patients received chemotherapy. Among 59 phosphatidylcholine identified, 6 variants were significantly lower in the chemo group compare with non chemo group. Additionally the sum of all phosphatidylcholine variants was diminished in the chemotherapy treated patients compared with untreated controls. No other differences in plasma lipid levels were identified. Conclusions: Phosphatidylcholine is a major component of cell membranes and lipid rafts which are critical elements in nerve conduction. It also plays a role as the precursor to the neurotransmitter acetylcholine. The finding that phosphatidylcholine is significantly different between chemotherapy treated vs. the no chemotherapy group raises the possibility that lipid metabolism contributes to chemotherapy-induced cognitive impairment and further experiments are planned to explore this hypothesis.
Breast cancer molecular subtypes association with clinical outcomes and race.
Authors: Sadek Ramses F. , Zhang Li fang , Abdul Sater Houssein Talal
Published: September 2018

e12575

Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.
Triple negative breast cancer (TNBC): Analysis of age and stage distribution and survival between African American and Caucasian women in a predominant low-income population.
Authors: Tano Sheeba V. , Kavanaugh Mindie Michelle , Peddi Prakash , Mansour Richard P. , Shi Runhua , Burton Gary Von
Published: September 2018

e12586

Background: Triple negative breast cancers (TNBC) represent roughly 15% of all breast cancer and are associated with decreased overall survival. A higher incidence of TNBC has been seen in younger and African American patients. We investigated the effect of age and race relative to outcomes of patients with TNBC seen at a state charity hospital system. Methods: This retrospective review identified 194 pts with TNBC diagnosed between 1993-2011 at LSUHSC-Shreveport, a state charity hospital. TNBC was defined as ER/PR both <1% and HER2neu not overexpressed by FISH analysis. The patient’s race, age at diagnosis, stage at diagnosis, treatment, relapse free survival (RFS), overall survival and survival following confirmed metastatic disease were analyzed. Results: There was no statistical difference in frequency of stage between groups. Although not statistically significant, there was a trend to worse RFS in AA and in young pts of both races. Younger age at diagnosis did have an inferior median survival as compared to older pts regardless of race or stage (p=0.0476). There was no difference in median survival following confirmation of metastatic disease between races (p=0.3574) or between age groups (p=0.8548); (median survival = 31 mos, 2.56-204 mos). Conclusions: In a predominantly low income patient population the incidence of TNBC was higher in the AA and in the young (age ≤ 50) as expected. There was no difference in stage or frequency within the populations. However, outcomes appeared to be worse in the younger pts and in AA patients with higher recurrence rate. Survival following first recurrence was similar regardless of age and race. Further analysis of etiologies for racial and age disparities is needed. [Table: see text]
Comparison of genomic and gene expression profile between cancer and healthy samples.
Authors: Papasotiriou Ioannis , Ntanovasilis Dimitrios , Apostolou Panagiotis
Published: September 2018

e13001

Background: A variety of chromosomal aberrations underlie developmental abnormalities and cancer. Use of techniques such as microarrays provides an opportunity to perform gene expression analysis. A recent approach is the use of array based comparative genomic hybridization (aCGH) to detect genomic abnormalities in human tumors. The aim of this study is to compare genomic and gene expression profile between cancer patients and healthy individuals. Methods: DNA and RNA were isolated from peripheral blood mononuclear cells from 9 patients, with different types of cancer and 4 normal donors. aCGH (Agilent-60K) and gene expression microarrays (Microarrays Inc.-whole genome platform) were performed using commercial reference samples. Data were analyzed with Array-Pro analyzer and Cytogenomics software. Results: The aCGH data demonstrated the majority of gains and amplifications were observed in cancer samples, while the deletions and losses were higher in normal individuals. Among aberrations, common genes in both types of samples were detected. These genes included ACAD8, ACP1, B3GAT1, IDI1, IDI2, IGSF9B, IRX1, IRX2, JAM3, MYT1L, NTM, OPCML, PXDN, THYN1, TPO. However, there were abnormalities that included genes, which appeared only in cancer samples, like cadherins ( CDH11, CDH8 and CDH5) and EPHA5, while genes such as ACOX1, PTPRN2, TYMS and genes of zinc-finger proteins were observed only in normal samples. No statistical significant difference in gene expression, between cancer and normal samples, was observed. On the contrary, overexpression was observed in genes that were not detected in aCGH. Conclusions: Whereas it is acceptable that great achievements have been carried out in cancer field, the mechanism of tumorigenesis is not clear understood. The present study demonstrated that even though genomic aberrations exist, these are not always representative at gene expression level. However, the combination of both techniques could be used for more accurate and reliable data. This requires study in more samples including different cancer types so to be used at clinical level.
Implementation of reflexive genomic profiling in non-squamous NSCLC: Results of single center experience.
Authors: Brown Jacqueline T , Moore Andrew R , Reuss Joshua E , Simon Nicholas I , Gentzler Ryan D. , Hall Richard Delmar
Published: September 2018

e13010

Background: Identification of oncogenic driver mutations (ODM) and targeted therapies have increased the number of treatment options for patients (pts) with non-squamous non-small cell lung cancer (ns-NSCLC). Different methods exist to detect ODM and there is no standard approach. This study examines the changes in detection of ODM over a 2-year period before and after implementing reflexive genomic testing using next generation sequencing (NGS) in January 2015. Methods: We retrospectively reviewed ns-NSCLC cases (stages I-IV) in 2014 and 2015 using the UVA Cancer Registry. We identified pts with pathologically-confirmed ns-NSCLC and reviewed any genotyping - single gene pyrosequencing, NGS, or FISH for gene rearrangements - within 90 days of pathologic confirmation. Comprehensive genomic profiling (CGP) was defined as both NGS and ALK/ROS1 FISH. Chi-square analyses were generated using SAS 9.4. Results: A total of 360 pts were included. 60% had genotyping while 19% underwent CGP. Mutations are summarized in the table below. From 2014 to 2015, genotyping increased from 50% to 69% (p<0.001), with CGP increasing from 2% to 48% of testing performed (p<0.001). Detection of oncogene driver mutations increased from 28% to 46% (p=0.009). Doubletons (pts with 2 driver mutations) increased from 0% to 5% (p=0.036). Conclusions: Reflexive CGP significantly increased the rate of detection of ODM at our center with results similar to previous studies. Previous studies detected low rates of doubleton mutations, perhaps due to lack of uniform NGS testing. Utilization of NGS may increase detection of doubleton mutations, for which further study is necessary to evaluate efficacy of targeted therapies. For centers without reflexive CGP, implementing this approach is likely to increase rates of ODM detection and expand treatment options. [Table: see text]
Genetics in the development of endometrial cancer: How does it affect East Asians?
Authors: Gubernick Lindsay , Lee Jessica , Chern Jing-Yi , Gerber Deanna , Boyd Leslie R. , Curtin John Patrick , Levine Douglas A. , Pothuri Bhavana
Published: September 2018

e13022

Background: Obesity and Lynch syndrome are well-known risk factors for the development of endometrial cancer. However, there is a paucity of data comparing patients across multiple ethnicities. Methods: All patients diagnosed with endometrial cancer or complex atypical hyperplasia between 2012 and 2015 were retrospectively identified and evaluated. Comparative statistical analyses were performed and stratified by ethnicity with appropriate two-sided statistical tests. Results: A total of 506 patients were diagnosed with endometrial cancer (n = 447) or complex atypical hyperplasia (n = 59) and of these, 31 were East Asian (EA, 6.3%). The remaining 475 patients (93.9%) were of Caucasian, black, Latino, South Asian, Southeast Asian or other unspecified ethnicity. Compared to other patients, EA were diagnosed at a younger age (median age 53 vs 62, p = 0.0003) and had lower body mass indices (BMI) (median BMI 23.0 vs 30.7, p < 0.0001). There were no differences in stage, tumor grade or histology. Differences in age and BMI remained significant despite controlling for these factors on multivariate analysis. Of the EA group, 10 of 31 patients (32.3%) underwent genetic testing and of these, three (30.0%) were found to have a germline mutation in a mismatch repair (MMR) gene. All three patients were of Chinese ancestry, and two had mutations in MLH1 and one in MSH2. In comparison, 69 (14.5%) of the remaining 475 had genetic testing, and six (8.7%) were diagnosed with Lynch syndrome. Chinese patients were more likely to have Lynch syndrome (42.9% vs 8.7%, p= 0.04). There were no differences found in family history of Lynch-related cancers between Chinese and other patients. There was no correlation between germline mutations and MMR testing on tumor immunohistochemistry. All three Chinese patients with Lynch syndrome had negative MMR tumor testing. Conclusions: EA patients with endometrial cancer are diagnosed at younger ages and with lower BMIs compared to patients of other ethnic backgrounds. Chinese patients have a high rate of germline Lynch mutations despite negative tumor MMR testing. EA, particularly Chinese patients, may represent a high-risk cohort, and referral for genetic counseling regardless of tumor MMR testing should be considered.
Do fears of getting cancer and family history of cancer influence participation in opportunistic screening or organized screening for gastric cancer?
Authors: Hahm Myung-Il , Choi Kui Son , Lee Hoo-Yeon , Suh Mina , Lee Yoon Young , Shin Dong Wook , Kim Bokmi
Published: September 2018

e13045

Background: Cancer is the leading cause of death in Korea. Individuals with a family history of cancer might overestimate their personal risk for getting cancer and report high cancer-related worry or concern. Those factors could positively or negatively influence on cancer screening behavior. Although Korea has a universal screening program for common cancers, some people still choose opportunistic screening program with out-of-pocket costs. This study was to identify association between fears of getting cancer and participation on opportunistic anc organized screening programs for cancer. Methods: The study population was derived from the Korean National Cancer Screening Survey 2013, which is annual survey conducted by National Cancer Center of Korea in order to investigate trends of participation rates among general population in cancer screening. 3,004 individuals aged over 40 years were finally selected as study subjects. Chi-square tests and multinomial logistic regression model were used to identify factors associated with being screened for gastric cancer. Results: A total of 2,078 of the subjects (69.2%) underwent gastric cancer screening, of which 311 individuals (10.4%) participated in opportunistic and 1,767 individuals (58.8%) participated in organized screening programs. After adjusting socio-demographic factors and health behaviors, worry and concern about cancer were identified as factors positively associated with being screened for gastric cancer. ORs for undergoing gastric cancer screening were elevated for both screening programs according to the level of worry and concern about cancer (p for trend < 0.05). We did not found relationship between family history of gastric cancer and participation. Conclusions: The results of this study suggest that fears of getting cancer such as worry and concerned about cancer had a stronger influence on participation in not only organized screening program but also opportunistic screening program. We could identify that ORs for undergoing the opportunistic screening were slightly higher than those for undergoing the organized screening in terms of cancer worry and cancer concern.
Pathologic findings at risk-reducing salpingo-oophorectomy in germline BRCA mutation carriers: Optimal age of bilateral RRSO.
Authors: Kim Yong-Man , Lee Shin-Wha , Lee Young-jae
Published: September 2018

e13046

Background: Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age of 40. Methods: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2013 to 2015. Both fallopian tubes of all cases were examined according to the SEE/FIM protocol and immunohistochemically (IHC) staining was performed when a precursor lesion was suspected. Results: RRSO was performed in 55 patients. The median age at RRSO was 44 years (32–73 years). Of the 36 patients with IHC staining, 7 showed p53 overexpression, 1 showed Ki-67 overexpression, 2 showed serous tubal intraepithelial carcinoma, 2 showed occult cancer, and 1 showed metastatic cancer of breast origin. All occult invasive cancer cases were tubal origin and detected in patients older than 40 years. The detection rate of premalignant lesions or cancer was 21.8% (12/55). Among patients who underwent RRSO under the age of 40, premalignant lesions were found only in BRCA 1 mutation carriers (40.0% vs 0%). In BRCA 2 mutation carriers, premalignant lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of premalignant lesions in BRCA1 mutation carriers. Conclusions: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers, especially in BRCA 1 mutation carriers.
Age standardized pattern of cancers in Pakistani population from 2008 to 2014.
Authors: Syed Binafsha Manzoor , Mangi Fayaz Hussain , Qureshi Jawaid Naeem , Shaikh Noshad Ahmed , Ujjan Ikram Uddin , Laghari Naeem Ahmed
Published: September 2018

e13060

Background: Cancer is a heterogeneous disease, influenced largely by gender, genetic makeup and environmental factors. This study was therefore aimed to assess age-standardized pattern in both males and females in Pakistani population. Methods: During the period of seven years (January 2008 to December 2014) prospectively collected institutional data was retrieved. All patients presented with primary cancers were included and pattern of top ten tumors was assessed. The data was analyzed using SPSS 21.0. Results: During the study period, a total of 15,906 patients with primary cancer were reported. Pattern of distribution is given in the table below. Conclusions: Among males and females there has been a different pattern of cancers. However among young males oral cancers remains at the top while lung at the older age and breast cancer among females remains at the high rate regardless of age. [Table: see text]
Anion gap and cancer mortality: Insight from NHANES database.
Authors: Verma Ashish , Qayyum Rehan
Published: September 2018

e13068

Background: The serum anion gap is an effective tool to analyze acid- base disorders for the past 40 years. Anion gap and non-anion gap acidosis is prevalent in cancer patients and contributes to morbidity and mortality The aim of the present study was to investigate the independent association of serum anion gap with cancer mortality. Methods: We examined the 34,370 participants ( ≥ 20years of age) using National Health and Nutrition Examination survey data (1999-2010) combined with National Death Index for mortality status through December 2011.The serum anion gap was calculated by subtracting sum of chloride and bicarbonate from sodium concentrations in meq/l. We divided the data set in to four quartiles of serum anion gap. Cox proportional hazard models were made to estimate the hazard ratios for cancer mortality for each unit increase in serum anion gap. The models were adjusted from demographic and confoundig variables. Results: The mean age of participants was 49.59±18.42 years. Out of total population 33,717(98.1%) were alive and 651 (1.9%) were dead secondary to cancer. The mean period of follow up was 5.55±3.53 years. In univariate regression model using serum anion gap as continuous variable, we found 6% (HR-1.06;95%CI,1.0-1.1), increase in cancer mortality with each unit increase in serum anion gap. After adjusting for potential confounders using multivariate regression model we found 8%(HR-1.08;95%CI,1.03-1.14), increase in cancer mortality with each unit increase in serum anion gap. In univariate regression model using quartiles, we found 47% (HR-1.47;95%CI,1.04-1.93), increase in cancer mortality with each unit increase in serum anion gap in highest quartile compared to the lowest quartile. After adjusting to the potential confounders the risk for cancer mortality increases to 60% in highest quartile comparison to lowest quartile (HR-1.60;95%CI,1.12-2.26). Conclusions: We found a linear association between serum anion gap and cancer mortality. A high serum anion gap is associated with increase in cancer mortality and may be the prognostic indicator of cancer mortality in general population. This should be validated by performing further investigation.