bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical value of Ki67 in risk-stratifying HR-positive breast cancer.
Authors: Bulbul Ajaz , Araujo-Mino Emilio Paul , Bautista Adriana , Rashad Sadaf , Khorsand-Sahbaie Masoud 
Published: May 2019

e12540 Background: Oncotype DX (ODX) is a validated clinical tool requiring efficient utilization. Ki67 protein immunohistochemistry (IHC) may represent a screening approach correlating with the Recurrence score (RS) in resource limited setting. Methods: We retrospectively studied 242 patients (Jan. 1989 – Oct. 2017) across rural practices in NM. Median time to follow-up was 8.9 (0.03, 26.8) yrs. ODX candidates evaluated included node positive (NP), negative (NN), hormone receptor (HR) positive and HER2 negative cohort. Ki67 <20% (LKi-n=196) vs >20% (HKi-n=46) was compared to Low/Intermediate (LODX-n=202) vs High risk ODX (HODX-n=40). Descriptive statistics, Chi-square, Kaplan Meier survival and Cox proportional hazard models were used. Results: Median age was 64 ± 13.2. Stage I (54.1%), II (42.6 %), and III (3.3%); Grade 1 (24.2%), 2 (46.7%), 3 (24.9%). LKi in (196/242) 81%, HKi in (46/242) 19%. LODX in (202/242) 83.4%, HODX in 40/242 (16.5%). LKi was associated with stage I (87%), II (78%) vs. Stage III (25%) (p=0.015). LKi was associated with lower grades 1 (100%), 2 (92%) vs grade 3 (40%) (p=<0.001). LKi was associated with LODX (190/242) 94% and HKi with HODX (34/40) 85% (p <0.001). ODX recategorized 3% (6/196) LKi into HODX and 26% (12/46) HKi to LODX. LKi vs HKi 10-year FFP was 0.97 + 0.01 vs 0.73 + 0.08 HR 8.31 (3.12, 22.14)(p=<0.01) and 10-year OS was 0.87 + 0.03 vs 0.78 + 0.08 HR 1.77 (0.84, 3.78) (p=0.13), respectively. Ten-year OS in LKi was 0.98 + 0.02 vs 0.97 + 0.02 HR 0.42 (0.04, 3.62) (p= 0.43) with (n=46) or without (n=121) adjuvant chemotherapy respectively. Conclusions: LKi is predictive of excellent outcomes. It may have a role in risk stratification when access to ODX is limited. Lack of standardization of Ki67 reiterates the value of ODX. Prospective data are needed to confirm these findings.
Learning from every patient: Real-world clinical outcomes of patients with metastatic triple-negative breast cancer treated in the community oncology setting.
Authors: Khanna Anchit , Bowers Elani , Haiderali Amin , Slancar Michael Marian , Rainey Natalie Heather , Teo Lee Na , Collins Ian M. , Tafreshi Ali , Pokharel Khageshwor , Sabbah Ream , Bohensky Megan 
Published: May 2019

e12554 Background: Triple-negative breast cancer is a biologically aggressive disease that accounts for 15% of all breast cancers, of which around 4-5% are metastatic (mTNBC) at diagnosis. Notably, there is no standard of care for mTNBC in the first line (1L) setting. This, in addition to higher relapse rates and poor long-term survival, warrants evaluation of real-world treatment patterns, especially in the 1L setting, to better inform on clinical outcomes. Methods: This observational, retrospective, chart review study included a cohort of twenty-six mTNBC patients from six different sites Australia, who commenced 1L treatment between July 1, 2012 and June 30, 2015. Medical records of eligible patients were abstracted using electronic case report forms after gaining relevant ethics approvals. Data on treatment patterns and clinical outcomes in the 1L setting were then collected from the index date until the end of data abstraction or death. The index date is defined as the date of initiation of 1L systemic therapy for mTNBC. Results: In the 1L setting, patients that received combination (52%) chemotherapy was slightly higher than single-agent (48%) chemotherapy. The commonest combination used was Carboplatin-Gemcitabine (12%), and the most common monotherapy was Nab-Paclitaxel (24%). The overall response rate and disease control rate were estimated to be 32% and 60% in the 1L setting. The median duration of treatment and the median time to next line of therapy were calculated to be 98 days and 12.45 (95% CI 2.79, 20.30) months respectively. Importantly, the median progression free survival (sensitivity analysis) and the median overall survival were estimated to be 3.17 (95% CI 1.91, 5.09) and 10.41 (95% CI 5.36, 16.53) months respectively. Conclusions: Chemotherapy is currently the mainstay of treatment for mTNBC. However, disease progression and chemo-related toxicities warrant stratified use of more efficacious and tolerable treatment options, especially in the 1L setting. Results from this study could be useful in comparing the efficacy and cost effectiveness of these emerging targeted and immuno-therapies outside the clinical trial setting.
Real-world data regarding the efficacy of neoadjuvant carboplatin-paclitaxel followed by dose-dense adriamycin-cyclophosphamide for triple-negative early breast cancer.
Authors: Bhojwani Ajay Ashok , Flint Helen , Hall Benjamin James , Wong Helen , Innes Helen , Cliff Joanne , Ahmed Eliyaz , Malik Zaf , O'Hagen Julie , Tolan Shaun , Hall Allison , Hayat Khizar , Errington Douglas , Alam Farida , Thorp Nicky , O'Reilly Susan , Law Andrea , Cicconi Silvia , Jackson Richard , Palmieri Carlo 
Published: May 2019

e12559 Background: Platinum based regimens in the neoadjuvant (NA) setting for triple negative breast cancer (TNBC) have resulted in a significant increase in the pathological response (pCR) rate but at the cost of worse hematological toxicities. Despite these data such NA regimens are not widely used as yet for TNBC. Currently, no real world evidence exist regarding the efficacy and toxicity of this treatment regimen. Methods: Patients treated with neoadjuvant carbo-pac-ddAC between December 2015 and May 2018 at Clatterbridge Cancer Centre NHS Foundation Trust were identified via pharmacy records. Clinical records were reviewed, and clinico-pathological information and toxicity data were recorded. Data lock was January 16, 2019. Results: 53 female patients were identified with a median age of 48 years (IQR: 40.0-55.5). At presentation: Median tumour size 29mm (IQR: 20.0-40.0), 45% (24/53) were LN +, 8% (4/53) were ER+. Of 30 patients tested for germ line susceptibility, 23% (7/30) were found to have a BRCA mutation (full details to be presented). Delivery of planned CT : 4% (2/53) discontinued early for progressive disease or patient choice; of the remaining patients there were a total of 36 deferrals and 8 dose reductions. Surgical details: Breast: 42% (22/53) mastectomy & 58% (31/53) WLE, Ax management: 37% (19/51) Ax clearance & 63% (32/51) sentinel node biopsy (2 patients underwent previous axillary treatment for prior BC). Of 24 patients LN+ at presentation 58% (14/24) underwent Ax clearance; of these 64% (9/14) had no Ax involvement. pCR rate (ypT0/is, N0) (cases with prior ipsilateral Ax surgery excluded) was 53% (27/51) & pCR breast alone: 60% (31/52). Radiotherapy: 90% (47/52) received radiotherapy post-surgery. Outcome: At a median follow up 42.4 wks (IQR: 34.2-54.4), 6% (3/52) patients had disease recurrence resulting in 2 deaths. Conclusions: These initial real world data confirm the efficacy of NA therapy with carbo-pac-ddAC, with pCR rates consistent with literature. These results support the use of platinum based chemotherapy in the NA management of TNBC. Updated outcomes will be presented based on pCR versus no pCR; and BRCA status.
Somatic mutations in triple-negative breast carcinoma and high-grade serous ovarian carcinoma from young women.
Authors: Serio Pedro Adolpho MP , Pereira Glaucia Fernanda Lima , Katayama Maria Lucia Hirata , Maistro Simone , Lopez Rossana Veronica Mendoza , Roela Rosimeire Aparecida , Rodrigues Livia Munhoz , Koike Folgueira Maria A. A. 
Published: May 2019

e12561 Background: High grade serous ovarian carcinoma (HGSOvCa) and triple negative breast cancer (TNBC) share characteristics, such as poor prognosis, BRCA1 germline mutations and TP53 somatic mutations. Our aim was to analyze somatic mutations from HGS-OvCa and TNBC from young patients aged ≤ 40 years. Methods: Whole genome or exome sequencing data for TNBC (n = 83) or HGS-OvCa (n = 21) was recovered from COSMIC or cBioPortal. Data was searched for cancer driver genes catalogued in Cancer Gene Census (CGC) or Candidate Cancer Gene Database rank A or B (CCGD) and for DNA repair genes. Results: TNBC mainly consisted of ductal carcinomas (78/83). A median of two cancer causing genes was affected in both TNBC and HGS-OvCa and TP53 was mutated in at least 2/3 of the samples. Only 7/83 and 2/19 of TNBC and HGS-OvCa samples, respectively, did not present variants in known cancer causing genes. C > T substitutions were the most frequent events in both TNBC and HGS-OvCa, however transversions were more frequently detected in TNBC. Besides TP53, another 33 genes were mutated in both tumor types, including PIK3CA, RYR2, TARBP1, CSMD3, DNAH11, MYO3A, NF1, TNRC6A, CACNA1E, HCMN1, PRKDC. Conclusions: Although many similarities were detected, TNBC in young patients presents a higher number of transversions and almost 25% of HGSOvCa present somatic mutations in HR genes. [Table: see text]
Longitudinal treatment patterns and adverse events (AEs) in younger patients (Pts) with metastatic triple-negative breast cancer (mTNBC): A real-world landscape analysis.
Authors: Kuderer Nicole Maria , Varghese Della , Hill Kala , Lyman Gary H. , Botteman Marc 
Published: May 2019

e12562 Background: While no uniform standard of care exists for mTNBC, conventional chemotherapy remains the treatment mainstay. This retrospective analysis of U.S. commercial claims data was conducted to characterize real-world longitudinal chemotherapy treatment patterns and predictors of AEs in mTNBC. Methods: We assessed all pts with mTNBC aged 18-60 years starting first-line (1L) chemotherapy from 01/01/2011 to 12/31/2015 in the IMS LifeLink database, which does not report on investigational therapies. Longitudinal treatment patterns, treatment duration, and AEs were characterized by line-of-therapy (LOT). The primary and secondary endpoints were any AE and treatment duration. Multivariable logistic and Cox regression analyses were used to identify clinical risk factors for AEs and predictors of longer treatment duration, respectively. Results: 1,447 mTNBC pts receiving ≥1 LOT were identified (median [range] age, 51 [24-60] years), of which 54% received ≥2 and 8% ≥3 LOT. Combination therapy (combi-Tx) was used as 1L for 73%, second-line (2L) for 22%, and third-line (3L) for 32% of pts. The most common combi-Tx was cyclophosphamide/doxorubicin (1L: 40%; 2L: 5%), and carboplatin/gemcitabine in 3L (17%). The most common 1L and 2L monotherapies (mono-Tx) were taxanes (10% and 66%), and 3L capecitabine (13%). Median treatment duration for 1L to 3L was 56-58 days, and for combi- vs mono-Tx in 1L, 50 vs 71 days. The proportion of pts experiencing any AE was 34% during 1L, 38% during 2L, and 56% during 3L therapy. After adjusting for key confounders including Charlson comorbidity index, independent risk factors for AEs were later LOT, 3L vs 1L (OR = 3.20, 95%CI: 2.13-4.79), and younger age groups vs age 55-60 (OR = 1.94, 95%CI: 1.48-2.55). Additional analysis will assess independent predictors of treatment duration. Conclusions: This real-world study reveals considerable treatment heterogeneity and short treatment durations even with conventional combination chemotherapies. Among non-Medicare mTNBC pts, younger age is a risk factor for AEs possibly due to more aggressive therapies. More treatment options are needed for pts with mTNBC.
Chronobiological assessment of triple-negative breast cancer.
Authors: Revazishvili Pati , Tavartkiladze Alexandre , Tavartkiladze Levan , Sordia Teimuraz , Gvajaia Ani 
Published: May 2019

e12564 Background: Triple Negative Breast Cancer (ER-, PR-, Her2/neu-., TNBC) constitutes 15-18 per cent of all malignant breast cancers. It is characterized by aggressive course and high lethality. Methods: We assessed chronobiological features of 19 patients with TNBC (medium age group 34-71). We used data of Melatonin and Cortisol circadian secretions for assessment parameters. During the month, we took blood from patients on every third day, from 02:00-04:00 pm to 02:00-04:00 a.m time intervals. The control group was composed of 14 patients with breast cancer, histological type: ER/PR+ and Her2/neu-. Results: As the result of the research, meaningful differences have been revealed between the investigated and control group. In patients with TNBC, the medium day-time concentration of Melatonin during the day was 1.1 pg/ml (normal range - up to 20 pg/ml), while at night its level increased by 4.2 pg/ml. In the control group, the average day-time level was 5.7 pg/ml, and at night - 12.5 pg/ml. Regarding Cortisol, in the investigated group, in day-time hours its average concentration in blood was 2.1 μg/dl (normal tange - 2.5 - 11.9 μg/dl, at afternoon), while at night - 0.7 μg/dl (normal range < 1.8 μg/dl, at night). In the control group, at day-time, the average cortisol concentration was 4.095 μg/dl (normal range - 2.5 - 11.9 μg/dl, at afternoon), at night - 0.94 μg/dl (normal nange < 1.8 μg/dl, Night). Conclusions: The study results have showed significant biochemical differences between ER/PR+/ Her2/neu- and TNBC- patients. Reduction of circadian secretion of Melatonin, as a major biochemical marker, directly correlates with the degree of cancer aggression, as it is seen fom the study. Furthermore, in patients whose Melatonin concentration was critically low, ductal (CK5/6+ and/or EGFR+) and metaplastic (epidermal: CK5/6+, EGFR+, Ck14+, p63+) forms were histochemically detected, which are extremely aggressive subtypes of TNBC. Regarding Cortisol levels in patients with critically Melatonin level, the Cortisol concentration was at critically low margin as well, that is considered to be the additional chronobiological marker for the aggressive course and rapid progression of cancer.
Efficacy of platinum-based regimens as the first-line therapy in Chinese patients with advanced TNBC and deleterious BRCA1/2 mutations.
Authors: Wang Nan , Li Kun , Kong Wei-Yao , Liu Xiao-Ran , Tan Meng-Yao , Jiang Han-Fang , Song Guo-Hong , Di Lijun , Wang Quanren , Wang Amy , Yu Jianjun , Jia Shidong , Li Huiping 
Published: May 2019

e12565 Background: Platinum-based therapy remains an effective treatment for triple-negative breast cancer (TNBC), however, the usage is largely limited due to its side effect and rapidly developed drug resistance. High prevalence of BRCA1/2 mutations are reported in TNBC. Here we explored efficacy of platinum-based regimens as the first-line treatment for Chinese patients (pts) with advanced TNBC, and analyzed its association with mutations of germline BRCA1/2 (gBRCA). Methods: We retrospectively analyze 220 patients diagnosed as advanced TNBC who were treated at the Dept. of Breast Oncology, Peking University Cancer Hospital in 2013-2018, and routinely evaluated by RECIST 1.1. Statistical analysis is performed in R 3.5.1. Cox proportional-hazard models are used for survival analysis. Results: 129 pts received non-platinum chemotherapy (NPCT) as the first-line therapy, and 91 pts received platinum-based chemotherapy (PBCT). The clinical benefit rate (CBR) and median PFS were not statistically different between NPCT and PBCT groups The median OS was 30.0 and 22.5 months for PBCT and NPCT group respectively (P = 0.09, HR = 0.70). Among them, 114 pts had BRCA gene tested, of which 14 had deleterious gBRCA mutations, 7 in each group. In PBCT group, the CBR was 85.7% and 35.1% for pts with and without deleterious gBRCA mutations respectively (P = 0.04). The median PFS, OS were 14.9 months and 5.3months (P = 0.001), 26.5 and 15.5 months (P = 0.16) for pts with and without the gBRCA mutations. No significant difference was observed between NPCT pts with and without gBRCA mutations as regards the CBR, PFS and OS. PBCT Pts had significantly more grade 3-4 anaemia (5.5% vs 0%) and thrombocytopenia (8.8% vs 0%) while higher percentage of palmar-plantar erythrodysesthesia (PPE) (12.4% vs 0%) and peripheral neuropathy (8.6% vs 1.1%) were observed in NPCT pts. Conclusions: The efficacy of platinum-based regimens as the first-line treatment of advanced TNBC insignificantly differs from that of non-platinum therapy. However, they are more effective for patients with deleterious gBRCA mutations, suggesting a BRCA1/2 genetic testing may be warranted for such patients.
Phase II study of eribulin mesylate for treatment of CNS metastases (mets) in metastatic breast cancer (mBC).
Authors: Nelson Ariel Ann , Manjappa Shivaprasad , Choudhary Yuvraj , Thompson Cheryl L. , Agler Jeanine , Lawrence Bethany , Ahluwalia Manmeet Singh , Silverman Paula 
Published: May 2019

e12571 Background: There is no approved drug therapy for CNS mets from mBC. Eribulin mesylate (eribulin) is a microtubule inhibitor approved for treatment of mBC patients (pts) who have received at least 2 prior chemotherapy regimens. Previously reported cases have demonstrated significant CNS responses in mBC pts treated with eribulin. This study evaluates the CNS response in pts with mBC treated with eribulin. Methods: CASE7113 was a prospective phase II single-arm study to evaluate the 12-week CNS progression free survival (12-wk CNS-PFS) of pts with mBC and CNS mets treated with eribulin. 20 pts were to be enrolled to demonstrate a 40% 12-wk CNS-PFS (95% CI, 8.5% - 61.5%). All pts had radiologically confirmed mBC CNS lesions with at least one lesion that did not receive prior radiation or surgical resection. Eribulin was administered at standard dose of 1.4mg/m2 IV on days 1 and 8 of a 21 day-cycle. Pts underwent baseline and 12-week brain MRI. The study was closed due to slow accrual; an analysis of enrolled pts was performed. Results: 9 female pts were enrolled; median age was 56 (32-82) years. 55% and 67% had ER+ and/or PR+ and Her2+ mBC respectfully. 1 pt had triple negative breast cancer (TNBC). Median number of prior therapies was 3 (0-12). The 12-wk CNS-PFS (95% CI) was 88.9% (51.8% - 99.7%), the median PFS (95% CI) was 22.6 (4.3 - 31.9) weeks, the median OS (95% CI) was 15.7 (4.0 - 27.3) months. 4 pts achieved stable disease and 1 pt had a partial response. There were no unexpected toxicities. Conclusions: For mBCa pts with CNS mets, this estimate of 12-wk CNS-PFS suggests activity of eribulin and merits further investigation in this population in the context of clinical trials. Clinical trial information: NCT02581839.
Detection of brain metastasis by metabolomics methods in metastatic breast cancer patients.
Authors: Özer Özge , Nemutlu Emirhan , Eylem Cemil Can , Kır Sedef , Reçber Tuba , Aktas Burak Yasin , Kars Ayse , Aksoy Sercan 
Published: May 2019

e12572 Background: The aim of this study was to identify markers for the early diagnosis of brain metastasis by metabolomic methods in breast cancer patients. Methods: A total of 88 breast cancer patients with distant metastases were included the study. The patients were divided into two groups according to their metastasis status as patients with brain metastases and patients with distant metastases without any brain metastases. For metabolomic analyses, liquid chromatography quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) and gas chromatography mass spectrometry (GC-MS) analysis methods were used. Results: 88 patients were included the study. 33 of the 88 patients had brain metastasis group and 55 patients had distant metastases without brain metastasis. A total of 79 metabolites were identified by the GC-MS analysis. Of these, 11 of them (alanine, sphingosine, fructose, fumaric acid, glycine, lactic acid, phenylalanine, pyroglutamic acid, serine, threonine, and valine) were found at statistically significantly higher levels in the patient group with brain metastases (p < 0.05). In LC-qTOF-MS analysis 47 metabolites were identified with statistically significant results between the two groups. Predictive accuriecies for idendification of the brain metastasis with 5 and 10 metobolites models were 94.6% and 95.2%, respectively.Amino acyl tRNA biosynthesis, arginine and proline metabolism, nitrogen metabolism, cyanaminoacid metabolism, nicontic and nicotinicamide metabolism, glycine, serine and threonine metabolism pathways have been involved more significantly in patients with brain metastasis (p < 0.05). Conclusions: Although these results need to be confirmatory prospective studies, these data promising for early detection of the brain metastasis by markers in sera.
Chronobiological features of melatonin receptors (MT1) expression in breast cancer cells.
Authors: Tavartkiladze Alexandre , Gvajaia Ani , Revazishvili Pati 
Published: May 2019

e12581 Background: According to WHO data, Breast Cancer is the most prevalent malignancy in women. The biological role of Melatonin in the etiology and pathogenesis of the tumour disease has already been approved by a number of research studies. The purpose of our investigation was the assessment of features of Melatonin receptor circadian expression in circulating tumour cells of breast cancer (CTCs). Methods: We observed 34 patients (aged 36-68) with breast cancer (various immunophenotypes). CTCs were separated from patients’ venous blood every third day, in 02:00-04:00 pm and in 02:00-04:00 am intervals. The cells were taken from each patient 4 times. On CTCs, MT1 – receptor expression was assessed using immunocytochemical method. Results: Results of the study revealed that Melatonin receptor expression in breast cancer patients is characterised by the noticable circadian rhythmics. MT1–receptor expression peak by CTCs was detected at 02:00-04:00 am i.e. at night. The less aggressive tumor the higher is the extent of the receptor expression (density). Respectively, in hormone dependent and Her2/neu (negative) tumors the highest expression of the MT1–receptor occurs in hormone dependent and Her2/neu(positive) tumors–medium expression and in triple negative breast Cancer (TNBC) cells–the lowest expression, while in some TNBC–circulating tumor cells MT1 receptor expression has not been detected at all. Conclusions: Hence, based on our the results, we can conclude that Melatonin as the expression of main biochemical marker receptors of bio-rhythms in breast cancer cells, has highly expressed chronobiological nature and directly correlates with histological types of tumor, that provides conditions for the development of new chronotherapeutic strategies in breast cancer treatment.
Tracking the tumor evolution of patients with recurrence of ipsilateral breast tumor.
Authors: Song Yane , Peng Li , Zhou Wei , Niu Yiru , Yang Wanning , Mao Beibei , Guo Xianchao , Han Wenbo , Zhang Henghui , Chen Weizhi , Mao Feng 
Published: May 2019

e12582 Background: After primary surgical resection, quite a proportion of breast cancer survivors would experience local recurrence within 5 years. Whether local recurrent tumors arise independently or from the primary tumors, which is critical for diagnosis and appropriate treatment, remains a clinical dilemma. Phylogenetic analysis between the primary and recurrent tumor provides a new strategy helpful for determining the origin of the local recurrent tumor. Methods: DNA was extracted from FFPE samples of the primary and recurrent tumors from 12 patients with recurrence of ipsilateral breast tumor. Phylogenetic analysis between the primary and recurrent tumors in the same individual was performed based on whole exome sequencing. PyClone and SciClone were employed to detect subclones. Results: The median time to recurrence of the 12 patients was 15 months (9 to 52 months). 9 (75%) of the 12 patients recurred within 2 years. Each patient had one shared somatic mutation clone between the primary and recurrent tumor, with shared somatic mutation number ranging from 5 to 59. This observation suggests that the recurrent tumor maybe originate from the primary tumor. Conclusions: The shared somatic mutation clone indicates the primary and recurrent tumor could be of the same origin and the recurrent tumor was metastasis from primary lesion. This may provide some information to help selecting the most appropriate treatment for patients.