bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer pathology patterns in Armenia.
Authors: Zohrabyan Davit , Bardakhchyan Samvel , Mkhitaryan Sergo , Safaryan Liana , Arakelyan Jemma , Tamamyan Gevorg , Harutyunyan Lilit , Avagyan Armen , Mkhitaryan Armen , Mkrtchyan Gohar , Rushanyan Marine , Harutyunyan Martin 
Published: May 2020

e12586 Background: Breast cancer (BC) is the most common malignancy among the women in Armenia (AM). Currently there is a knowledge gap regarding the morphology distribution of the BC in AM. Methods: The data on patients with BC diagnosed in 2015-2016 in the pathology lab “Davidyants Labs” in AM were retrospectively reviewed. Pts with Her2+ results by IHC were excluded from the study, due to unavailability to perform FISH or CISH analyses. Overall 361 pathology reports were evaluated. Results: The median age was 54 years; range [19-82]. Histopathological subtypes were defined for 305 pts, from which lobular carcinoma 57.4% of cases (175/305), ductal carcinoma 26.9% (82/305), mucinous carcinoma 2.6% (8/305), mixed type carcinoma (lobular and ductal) 2.6% (8/305), DCIS 2% (n = 6/305), non specified carcinoma 2% (6/305), medullary carcinoma 1% (n = 3/305) and others 5.6% (17/305). Within the cohort 8.5% (23/270) were grade 1, 65.9% grade 2 (178/270); 25.6% grade 3 (n = 69/270). Vascular or lymphatic invasion was present in 59.5% (50/84) and 64.7% (55/85), respectively. Staging distribution, based on pT pN data for 92 pts who went to primary surgery, was: 0 stage 7.6% (7/92), I stage 22.8% (21/92), II stage 41.3% (38/92), III stage 28.3% (26/92). Staging distribution based on ypT ypN data for 27 pts who went to surgery after neoadjuvant chemo was 0 stage 25.9% (7/27), I stage 18.5% (5/27), II stage 29.6% (8/27), III stage 25.9% (7/27). ER and PR were defined for 244 patients. ER positive 89.8% (219/244) of cases, PR pos. 73% (178/244), ER/PR pos. 72.5% (177/244) cases. Her receptor was defined for 237 patients. Her3+ 16.9% (40/237); Her2+ 12.7% (30/237); Her1+ 38% (90/237); Her0 32.5% (n = 77/237). We could not evaluate Her2+ status by FISH or CISH, so these results were excluded from the analysis. Ki67 was low (≤20) in 42.1% (101/240) of cases and high ( > 20) in 57.9% (139/240). Within the group Luminal A type was 41.4% (84/203); Luminal B 32.5% (66/203); Her positive 19.7% (40/203) and triple negative 6.4% (13/203). p53 and perineural invasion (Pn) was present in 32% (16/50) and 52% (26/50), respectively. Tumor leukocyte infiltration was determined for 16 patients. Leukocyte infiltration was positive in 43.7% (7/16) cases, negative in 25% (4/16) cases, minimal in 31.3% cases (5/16). Conclusions: BC in Armenian women presents with different epidemiological characteristics in comparison with other ethnicities. Lobular type BC is the most frequent type among Armenian women, however, differential diagnosis between lobular/ductal carcinomas was done without IHC (E-Cadherin), which rises the need for further studies on that regard.
Phenotype variants of invasive breast cancer differ in associations between the primary tumor size and its Ki-67 value.
Authors: Kurbel Sven , Dmitrovic Branko , Vrbanec Damir , Separovic Robert 
Published: May 2020

e12588 Background: Epidemiological studies report that Ki-67 values are higher in larger invasive breast cancers (IBC). This relation was investigated in 1040 consecutive IBC patients with various immunohistological phenotypes (ER+/-; HER2 0, 1+ to 3+), all treated at a single Croatian hospital. Methods: A scatter plot of 1040 Ki-67 values with their cancer diameter (in cms) have produced an LOWESS nonparametric curve that almost overlapped with the logarithmic function of the same data set (Ki-67% = 18.39+20.63*log(D), where D is a tumor diameter in cm). The next step in using this logarithmic function as a model, was to convert D values into log(D) for linear correlations, amenable to tests of significance. Results: Among all 1040 pts, only ER positive phenotype variants Ki-67% correlated with log(D): Among ER positive tumors, the HER2 expression has decreased the correlation significance and the slope of regression lines, suggesting that the HER2 presence increases Ki67% in small tumors, while larger tumors have Ki67% less augmented than among HER2 absent tumors. Thus the highest slope of the line was found among HER2 absent ER+ patients. Conclusions: Since only ER positive tumors have shown correlation of Ki67% with the log of their tumor size, tumor biology (estimated by Ki67%) of the ER negative IBCs seems unrelated with their size. This possibly suggests that the clinical course of ER negative IBC patients is less predictable due to some etiological distinction the ER positive and ER negative breast cancers. [Table: see text]
Concordance of multispectral immunofluorescence (mIF) with programmed death ligand 1 (PD-L1) and stromal tumor infiltrating lymphocyte (sTILs) clinical assays in early-stage breast cancer (BC).
Authors: Sanchez Katherine , Chang Shu-Ching , Kim Isaac , Martel Maritza , Wu Yaping , Redmond William L , Sun Zhaoyu , Waddell Dottie , Laxague Deborah R. , Bernard Brady , Shah Monil , Urba Walter John , Page David B. 
Published: May 2020

e12589 Background: There is growing need for surrogate immune-based biomarkers in BC to enhance prediction accuracy and to facilitate comparisons of therapeutic activity in the context of clinical trials. We report mIF as a high-dimensional biomarker that is highly concordant with both PD-L1 (SP142) and sTIL clinical assays (H&E), but with greater precision to quantify on-treatment pharmacodynamic effects. We also demonstrate how statistical modeling can be employed to improve precision of PD-L1/sTIL estimates, and reduce sample size requirements for biomarkers-driven comparative clinical trials. Methods: Samples were obtained from a recently-reported pre-surgical cytokine-based phase Ib immunotherapy (IRX-2) clinical trial (NCT02950259). Pre-treatment and resection tissues (n = 30) were analyzed for sTIL score, PD-L1 status, and mIF (PerkinElmer Vectra) using antibodies to quantify BC cells (cytokeratin), immune cells (CD3, CD8, CD163, FOXP3), and per-cell PD-L1 expression. Mixed effects regression models were employed to correct for intratumoral heterogeneity and enhance statistical precision. Monte Carlo simulations were employed to evaluate whether regression modeling could reduce sample size required to detect treatment-related increases in sTIL/PD-L1 in pre-surgical clinical trials. Results: Results: mIF sTIL estimates were highly correlated with H&E sTIL score (pre-treatment samples: r = 0.59, p > 0.001; excisional samples: r = 0.63, p > 0. 001). mIF PD-L1 estimates were highly correlated with the PDL1 SP142 assay, with average densities increasing concordantly according to SP142 IC category (IC0 v. IC1, p = 0.04; IC0 v. IC2/3, p = 0.003). Our regression modeling approach dramatically improved power to demonstrate treatment-related changes in sTIL and PD-L1. The estimated sample size requirement to show the observed effect on sTIL score (1.80 fold change, CV 0.83) was n = 25 with conventional t-testing of means, versus n = 13 with regression modeling. Conclusions: mIF is concordant with SP142 and sTIL prognostic assays, but with increased precision to quantify treatment related changes. Regression modeling can dramatically improve the utility of mIF as a surrogate immune-based biomarker. Our approach is being utilized in ongoing phase II studies to compare the activity of pembrolizumab +/- locoregional cytokines (IRX-2) in triple negative BC, and paclitaxel/trastuzumab +/- pembrolizumab +/- pertuzumab in HER2-positive BC.
A systems medicine-based approach for finding metabolic targets applied to primary basal-like breast cancer.
Authors: Cook Daniel , Nielsen Jens , Braun Eduardo 
Published: May 2020

e12590 Background: Although metabolic disfunction is one of the hallmarks of cancer and metabolism-based therapies are a key class of chemotherapeutics, there remains no systematic way to identify metabolism-based targets for therapeutic intervention. Because of this deficiency, metabolism-based therapies offer a largely untapped area for therapeutic discovery, especially for difficult to target tumors, like basal-like breast cancer (BLBC). Adding to the challenge of discovering metabolism-based therapeutics for BLBC, however, is the heterogeneity of tumor behavior across patients, both in terms of aggressiveness and molecular regulation. Methods: We addressed these challenges by introducing a systems medicine-based technique integrating metabolic network modeling with single-patient RNA-sequencing (RNA-seq). We then applied this technique to investigate metabolic weaknesses in primary BLBC. We constructed a genome-scale metabolic model of breast cancer (ecBRCA) along with RNA-seq profiles constructed from The Cancer Genome Atlas (TCGA) to predict metabolic targets whose inhibition is lethal to BLBC tumors. We then evaluated the effectiveness of drugging these targets across patients by simulating the effect of a targeted knock-out on primary tumors with published RNA-seq profiles from 534 BLBC patients in TCGA and the Swedish Cancerome Analysis Network for Breast (SCANB). Results: We found multiple metabolic targets that may prove clinically useful for complementary treatment of primary BLBC tumors. Among these, we found UDP-Glucose 6-Dehydrogenase (UGDH) and Heparan Sulfate 2-O-Sulfotransferase 1 (HS2ST1) to be particularly promising protein targets for chemotherapy in BLBC, with 80-100% of simulated BLBC tumors responding to their inhibition. Currently FDA-approved drugs down-regulating these proteins, such as metformin (for UGDH) and surfen (for HS2ST1), are potentially viable complementary treatments for BLBC patients. Additionally, we found several metabolite targets whose inhibition may inhibit BLBC growth, including leukotriene A4, creatinine, vitamin D3, and the oncometabolites 2- and 3-hydroxy-glutarate. Conclusions: Taking a systems medicine-based approach to understanding BLBC metabolism allows for a systematic way to identify metabolic targets for therapeutic intervention. Additionally, certain metabolic weaknesses appear to be conserved in BLBC tumors across patients, including a dependence on UGDH and HS2ST1, which could be treated with currently available drugs like metformin and surfen.
Tolerance of concurrent CDK inhibitor and radiation therapy in metastatic breast cancer patients.
Authors: Beddok Arnaud , Arsene-Henry Alexandre , Porte Baptiste , Cao Kim , Scher Nathaniel , Otz Joelle , Minsat Mathieu , Bidard Francois Clement , Fourquet Alain , Cottu Paul H. , Kirova Youlia 
Published: May 2020

e12598 Background: Palbociclib, a small-molecule inhibitor of cyclin-dependent kinases (CDK4 and CDK6), combined with letrozole increases progression-free survival among patients with previously untreated ER-positive, HER2 negative advanced breast cancer. The purpose of our study was to retrospectively evaluate the tolerance of the concomitant association of Palbociclib and radiation therapy (RT) at Curie Institute. Methods: Between April 2017 and August 2019, 30 women with ER-positive, HER2 negative metastatic breast cancer received locoregional (LR) and/or symptomatic irradiation at a metastatic site concurrently with Palbociclib at a daily dose of 125 mg, from d1 to d21 every 28 days. Palbociclib was always associated with endocrine therapy: letrozole (with or without an LHRH analogue) or fulvestrant. Thirty-five sites were irradiated: nine patients received post-operative locoregional RT, including the chest wall or breast and lymph node areas, and 26 sites of metastases were irradiated: 17 at the spine, 7 peripheral skeletal lesions, 1 brain lesion and 1 choroidal lesion. The dose prescribed for locoregional mammary radiotherapy was 50 Gy in 25 fractions and varied for the treatment of metastatic sites: 20 Gy in 5 fractions (n = 13), 30 Gy in 10 fractions (n = 10) and 8 Gy in 1 fraction (n = 2). The brain metastasis was stereotactically treated (1 fraction of 18 Gy). The primary endpoint was toxicity scored according to the common terminology criteria for NCI adverse events, version v5.0. Results: Mean number of days of Palbociclib during RT was 8.8 days (range, 1 to 24 days). The most common acute toxicities were dermatitis (12/35, including 2 grade 2) and neutropenia (12/35, including 9 grade 2). Palbociclib had to be stopped during the RT of two patients (2/30): one patient treated locoregionally (bilateral breast and lymph nodes irradiation) developed a grade 3 dermatitis and febrile neutropenia, another treated locoregionally developed grade 2 dysphagia. After a median follow-up since the end of RT of 17 months (6 – 31 months, SD 8), none of the patients have so far exhibited late toxicity. Conclusions: Concomitant administration of palbociclib with RT was reasonably well tolerated in our series of 30 patients. Given this experience, palbociclib should not be discontinued during radiation therapy. Nevertheless, our findings should be confirmed in prospective registration studies collecting larger number of patients.
Risk factors of ipsilateral breast tumor recurrence in triple-negative or HER2-positive breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy.
Authors: Tazo Mizuho , Kojima Yasuyuki , Yoshida Atsushi , Nakayama Sayuka , Tokui Ryu , Ogawa Tomoko , Kuwayama Takashi , Nakayama Takahiro , Yamauchi Hideko , Tsugawa Koichiro , Nakamura Seigo , Hayashi Naoki , Ishitobi Makoto 
Published: May 2020

e12599 Background: To date, patients undergo breast surgery after neoadjvant chemotherapy (NAC) even though they achieve clinical complete response (cCR). The safety of omitting breast surgery for the patients who are predicted to be pCR has recently investigated in some research, however we still have not reached to a definite consensus yet. We may consider the breast surgery omission on the assumption that the rate of ipsilateral breast tumor recurrence (IBTR)after achieving pCR is acceptably low. The purpose of this study is to examine the rate of and evaluate the clinical features of IBTR in patients achieving pCR after NAC. Methods: In this study, a total of 278 patients with HER2-positive or Triple negative type primary breast cancer were enrolled from4 institutions. They were all diagnosed as ypT0 after breast conserving surgery and received postoperative radiotherapy. Occurrence of IBTR and other clinicopathological factors were collected by retrospective chart review. Results: Of the 278 patients, 49 patients (18%) were ER+/HER2+, 106 patients (38%) were ER-/HER2+ and 123 patients (44%) were ER-/HER2-. We found breast recurrence in 11 patients (4%) as a first recurrence. The 5-year breast recurrence rate was 4.5% in total, 2.2% in ER+/HER2+, 4.0% in ER-/HER2+ and 4.6% in ER-/HER2-, respectively. There was no significantly difference among subtypes. Interestingly, the 5-year breast recurrence rate of patients under 40-year-old was 12.3% which was significantly higher than patients with and above 40-year-old (3.1%, p=0.002). Conclusions: We should be extremely careful when consider omitting breast surgery for patients younger than 40 even if they achieved pCR after NAC.
Accuracy of sentinel lymph node biopsy in invasive lobular carcinoma of the breast.
Authors: Guo Ruby , Brabham Case E. , Fahrner-Scott Kelly , Abel Mary Kathryn , Wong Jasmine , Alvarado Michael , Esserman Laura , Ewing Cheryl Ann , Mukhtar Rita A. 
Published: May 2020

e12604 Background: The safety of the sentinel lymph node biopsy procedure (SLNB) in the surgical management of breast cancer relies upon a false negative rate (FNR) being less than 10%. The accuracy of SLNB in invasive lobular carcinoma (ILC), the second most common type of breast cancer, has not been evaluated. Because of high rates of false negative imaging and the diffuse growth pattern in ILC, less accurate pre-operative staging and a potentially unreliable lymphatic drainage pattern may impact the accuracy of SLNB in this tumor type. We therefore sought to characterize the accuracy of SLNB in a cohort of patients with ILC. Methods: We queried an institutional database of 707 patients with ILC and identified 196 patients who underwent SLN mapping with excision of both sentinel and non-sentinel nodes. A false negative was defined as having negative sentinel lymph nodes and a positive non-sentinel node. We calculated the FNR and sensitivity of SLNB and evaluated clinicopathologic variables. Results: Of 196 cases, 183 were clinically node-negative, 9 were clinically node-positive, and 4 had unknown clinical node status. Of the 183 clinically node-negative patients, 69 (37.7%) patients had node-positive disease at surgery. Overall, 7 of 196 cases had false negative SLNB, yielding an FNR of 8.97%. The sensitivity of SLNB was 91%. Patients with a false negative SLNB were significantly older than patients without (mean age 63 versus 54.7 years, p = 0.041). Significantly fewer sentinel and non-sentinel nodes were removed in women aged 50 years or older compared to those under 50 (1.9 vs. 2.5 sentinel nodes, p = 0.0158; 4.7 vs. 7.9 non-sentinel nodes, p = 0.0077). There were no differences in tumor receptor subtype, grade, stage, presence of lymphovascular invasion, or receipt of neoadjuvant therapy in those with a false negative SLNB compared to those without. Conclusions: The high rate of nodal positivity in clinically node negative patients highlights the challenges of clinical nodal assessment in ILC. Despite this, the SLNB procedure had a FNR that fell within the acceptable range, supporting its use in ILC. The relationship between number of sentinel nodes removed and FNR deserves further study, particularly in older women where extent of nodal surgery continues to decline.
The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC).
Authors: Yariv Orly , Yerushalmi Rinat , Moore Assaf , Shohat Tzippy , Rotem Ofer , Yasmin Korzets Ceder , Goldvaser Hadar 
Published: May 2020

e12606 Background: Oral contraceptives (OC) and hormone replacement therapy (HRT) are well-established risk factors for ER positive breast cancer. Infertility is associated with an increased breast cancer risk and there is conflicting data on the influence of fertility treatments on breast cancer risk. The impact of exogenous estrogen exposure on breast cancer characteristics is not well described. Methods: A single center retrospective cohort study comprising all women with ER positive, human epidermal growth factor receptor 2 (HER2) negative, EBC whose tumors were sent to OncotypeDX analysis treated in our institute between 2005 and 2012. Data on exogenous estrogen exposure were collected including: OC and HRT use and prior fertility treatments. The impact of these exposures was assessed on pre-specified histopathological features including: tumor size, nodal status, ER and progesterone receptor (PR) staining, grade, Oncotype recurrence score (RS), ki67, lymphovascular and perineural invasion. Results: A total of 620 women were included, 79% were postmenopausal. Prior exposure to OC, HRT and fertility treatments was documented in 19% (103), 30% (136) and 11% (62), respectively. OC use was associated with smaller (≤1cm) tumors (30% vs. 20%, p = 0.023) and were less likely to have grade 3 disease (10% vs. 19%, p = 0.049). No other associations were found between exogenous estrogen exposures and tumor characteristics (Table). Conclusions: Use of OC may be associated with breast cancer with a distinct features compared to women with luminal breast cancer without history of OC use. Large scale studies are needed to better characterize these findings. [Table: see text]
Magseed localisation for loco-regional breast and lymph node recurrences: Placement prior to chemotherapy to allow focused removal of the initially diseased tissue.
Authors: Benn Carol , van Loggerenberg Dominic , Shaw Vernon Adrian robert 
Published: May 2020

e12610 Background: Multi-disciplinary meeting decisions may suggest chemotherapy prior to surgery. Prior to chemotherapy, localisation of the diseased tissue is important to ensure accurate retrieval. Magseed is induced to become a magnet when used in conjunction with a detector. The aim of this study was to assess the accuracy of placement, retrieval, and localisation of a Magseed into a radiologically suspicious loco-regional recurrence in patients requiring chemotherapy. Methods: Patients with loco-regional recurrence that had been assessed in the multidisciplinary meeting as requiring chemotherapy, as well as being potential candidates for surgery post-chemotherapy, were referred for placement of a Magseed prior to commencing chemotherapy or during treatment. The seed was placed by a senior radiologist in the unit. Ten patients have currently completed chemotherapy and surgery. Two patients had more than one Magseed placed. Giving a total seed placement number of 14 seeds. Results: Seed localisation with the Sentimag probe was successful in all cases at 100% localisation, however the retrieval rate was less at 93% due to a case where a lymph node underwent fibrosis. The maximum number of days between the seed placement and surgery was 249 days. Conclusions: Magseed is successful and accurate in localising and retrieving loco-regional recurrences in patients requiring surgery post chemotherapy. Retrieval is possible due to high recordings on the sensor in all cases. Magseed thus provides the treating clinician with an alternative to conventional radiological markers with the added benefit of a single placement to retrieval methodology.