bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting triple-negative breast cancer by conversion into HER2-positive cancer: A novel therapeutic approach.
Authors: Bernemann Christof , Huelsewig Carolin , Kiesel Ludwig , Liedtke Cornelia 
Published: March 2020

e11534 Background: Triple negative breast cancer (TNBC) is defined by the lack of estrogen-receptor alpha (ERα) and progesterone receptor (PGR) expression as well as absence of human epidermal growth factor receptor2 (HER2/neu) overexpression. This type of breast cancer is characterized by a poor prognosis and significantly reduced survival rate compared to other BC subtypes. This is mostly due to the lack of targeted agents like endocrine or anti HER2 targets. Breast cancers which overexpress HER2 are usually treated by chemicals targeting HER2; either by blocking the extracellular domain through trastuzumab or the intracellular domain through the small molecule lapatinib. Both therapeutics lead to inhibition of downstream pathways like MAPK and PI3K, resulting in increased apoptosis as well as reduced proliferation. Methods: We hypothesize that downstream effects might be induced in TNBC cells when HER2 is artificially overexpressed and cells get treated as HER2 positive cells. Therefore, triple negative breast cancer cell lines were transfected with HER2. These cells were treated with anti-HER2 agents. Molecular analyses will demonstrate whether transfection with HER2 will yield a HER2 positive breast cancer phenotype in that all downstream signaling mechanisms act similarly to a priori HER2 positive cells. Results: Preliminary experiments suggest that proliferation of TNBC cells transfected with HER2 does not change significantly. Treatment with HER2-blocking antibody trastuzumab leads to significant decrease of proliferation in HER2 transfected, initially triple negative MDA-MB-231 breast cancer cells. Only a moderate decrease in proliferation was observed when lapatinib, a molecule directed against both EGFR and HER2, was used in both MDA-MB-231 wildtype and HER2-transfected cell lines. Conclusions: We surmise that firstly, conversion of cancer might become a clinical tool to treat cancer of poor prognosis and secondly that our results might shed light on future therapeutic approaches e.g. small molecule compound screening for endogenous HER2 reactivation / overexpression and subsequent targeted treatment of triple negative breast cancers.
Docetaxel-carboplatin-bevacizumab (TCV): A novel combination that promises a high activity in triple-negative breast cancer: A pilot study.
Authors: Chacon Jose Ignacio , Rubio Salvador(2) Ana Rosa , Cordero Franco(1) Nazaret , Martinez Carrasco (1) Begona , Alonso Soler(1) Sonia , Diaz Paniagua(1) Laura , Fernandez Franco(1) Lourdes , San Juan del Moral(1) Alberto , Esteban Esteban(1) Carmen , Moya Gomez(2) Paloma , Cruz Mora(1) Miguel Angel 
Published: March 2020

e11543 Background: Triple negative breast cancer (TNBC) is an anthracycline resistant subtype, for which there is no standard chemotherapy. Taxanes, platinum-derived drugs and bevacizumab all seem to be active drugs in this setting, but definitive data are still lacking. Our purpose is to report our experience with the combination Docetaxel-Carboplatin-Bevacizumab (TCV) in TNBC. Methods: We retrospectively analysed our database using medical claims for patients diagnosed with TNBC and treated with TCV in neoadjuvant (NAJ) or metastasic( MD), between July 1, 2009, and December 31, 2011. Informed consent was obtained from all patients. Results: 13 pts have received 86 TCV cycles, 8 in NAJ and 5 for MD. NAJ: Median age: 48(28-60) y. T3-T4 tumors: 62,5% . N+: 62.5%. All pts received 6 TCV cycles, except 1 pt, still on therapy. 5 (62.5%) pts received quadrantectomy, 2(25%) mastectomy as surgical treatment after TCV. One pt has not received surgery yet. Sentinel lymph node biopsy was done in 5/8 (62.5%) pts, the other 3 received axillary dissection for clinically N+ metastasis. After surgery, pathologic complete response (pCR) in breast in 6/7 pts (85.7%); in axillary nodes, pCR in 5/7 pts (71,4%). One has not been surgically evaluated yet. Median follow-up: 10 months (2-18). Only one pt has relapsed with cerebral metastasis. MD: Median age: 54.4 (40-71) y. 4 pts received TCV as first line, one as third line therapy. 3 pts obtained complete response, 2 partial responses, but both progressed in three months. Median follow-up: 14.4 months. Only one of these pts has died. Toxicity: Was mild, without any grade 3 or 4 toxic effect. Only one pt showed grade 2 hypertension after bevacizumab infusion. Neutropenia was not evaluable for use of G-CSF per protocol. Conclusions: Although this is a short series, it suggests that TCV may be a highly active combination in TNBC with a good tolerability profile. These data warrant continuing testing of this combination in TNBC.
Does progesterone protect from chemotherapy-induced peripheral neuropathy? A retrospective audit of breast cancer patients.
Authors: Prabhu Aruna Laxman , Singh Akshita , Kaushik Rucha Vishal , Nair Nita S. , Hawaldar Rohini W , Vanmali Vaibhav , Parmar Vani , Gupta Sudeep , Badwe Rajendra A. 
Published: March 2020

e11552 Background: Paclitaxel is an integral component of chemotherapy for breast cancer but its benefit comes at the risk of peripheral neuropathy. There are experimental models of peripheral nerve injury in which progesterone is protective, possibly through remyelination and other mechanisms. Methods: We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel induced peripheral neuropathy, in a retrospective audit of breast cancer patients. Patients who had received paclitaxel chemotherapy for breast cancer were characterized as having CIPN or not by clinical history/examination. Results: 256 women treated with paclitaxel at our institution were assessed for CIPN. Of these 133(52%) were premenopausal and 123(48%) postmenopausal at diagnosis. 22(8.6%) had preexisting diabetes mellitus. Of the 133 premenopausal women 97(72.9%) developed chemotherapy induced amenorrhea (CIA). The incidence of CIPN was 23.1% in persistently premenopausal patients 47.4% in patients with CIA and 57.7% in postmenopausal patients. In patients with DM 81.8% had CIPN. In a multivariate logistic regression model, increasing age (continuous variable RR=1.04 95%CI 1.02-1.08 p=0.001) DM (RR=4.39 95% CI 1.42-13.38 p=0.01) and postmenopausal/CIA status (RR=2.48 95% CI 1.05-5.88 p=0.03) were risk factors for CIPN. Because patients developed CIA at variable times and circulating progesterone levels at the time of neurotoxin insult maybe variable in them such patients were excluded in the second model, which included only patients with continuing menses (n=36) and postmenopausal at diagnosis (n=123). In the latter model postmenopausal status (RR=3.5 95%CI 1.18-10.39 p=0.02) and DM (RR=6.8 95%CI 1.44-31.82 p=0.01) were associated with CIPN but increasing age (RR=1.03 95% CI 0.98-1.07 p=0.21) was not. Conclusions: These results suggest a neuroprotective effect of premenopausal status, possibly related to higher circulating levels of progesterone. We hypothesize that progesterone administration prior to taxane chemotherapy may protect against CIPN. This will be tested in a RCT.
Oxidative stress induced by early cycles of combination chemotherapy in chemonaive and radionaive breast cancer patients.
Authors: Kok Victor C. , Ko Wan-Seng , Guo C.H. , Chen P.C. 
Published: March 2020

e11561 Background: Chemotherapy-induced oxidative stress (CIOS) can be altered multifactorially in time course of treatment. Initial changes of CIOS in the breast cancer patients are not clear. OBJECTIVES: IRB-approved prospective study of the changes of CIOS in chemo-naïve and radiotherapy-naïve breast cancer patients who undergo chemotherapy(CT) or radiotherapy(RT) in either adjuvant or metastatic settings. Methods: Exclusion criteria: Patient who has prior exposure to CT or RT, active infection, connective tissue disorder, been taking antioxidant agent(s), active hepatitis, liver cirrhosis, renal insufficiency and no written informed consent. Blood samplings were done before CT or RT and day 22 since chemotherapy or day 29 since RT. Serum analyzed for glutathione peroxidase(GSH-Px), glutathione reductase(GR), Vit.E, malondialdehyde (MDA), and trace elements including Zn, Cu, Fe, Se. Results: 10 patients and 10 healthy volunteers were entered. Median age: 47.5 (R: 38~80); Tumor type; infiltrating ductal ca: 8 pts; lobular ca: 1; mucinous: 1. Stage: IIA: 4 pts; IIB: 1; IIIA: 3; IIIB: 0; IIIC: 1; Relapsed: 1. ECOG 0/1: 9/1 pts; Regimens: FEC: 5 pts, CAF: 1, EC: 2, CMF: 1; RT: 1. After 1 cycle of CT or 28 days of RT: GSH-Px was significantly increased (P=0.0003); GR increased (P=0.0002); Vit. E increased (1-sided P=0.028); MDA decreased (P=0.0073) and Zn decreased (P=0.0162). Contrary to some oncologists initial expectations, the early changes after chemotherapy or radiotherapy are elevation of body's antioxidative capacity. Conclusions: Spontaneous counterbalance of CIOS after initial cycles of chemotherapy is suggested from this study.
Patterns of in vitro chemotherapy (CT)-induced apoptosis (APOP) in recurrent/metastatic breast carcinoma (CA): Comparisons of generic multisource drugs (generics) with proprietary single-source drugs (proprietaries).
Authors: Bosserman Linda D. , Rogers Karl , Davidson Dirk C. , Willis Carl Rogaston , Rutledge James , Hallquist Allan , Young Tracy , Rajurkar Swapnil Padmakar , Karimi Misagh , Presant Cary A. 
Published: March 2020

e11562 Background: Therapy of metastatic breast CA involves choices between Generics and Proprietaries, and between combination CTs (Combos) and single-agent CTs. This study determined the relative in vitro CT induced APOP of Generics versus Proprietaries, and Combos versus single agents. Methods: Purified breast CA cells from 67 patient (Pt) biopsies were placed in short-term culture with CT using the microculture kinetic (MiCK) assay. APOP was analyzed every five min over 48 hrs. APOP was defined in kinetic units (KU) of apoptosis. Significant APOP was > 1.0 KU. Significant difference between individual assays was > 0.57 KU based on replicate analyses. Results: 43 Pts were evaluable for comparison of Generics versus Proprietaries. Generics produced APOP > Proprietaries in 36/43 Pts (84%) and = to Proprietaries in 6 Pts (14%). Proprietaries produced APOP > Generics in 1 Pt (2%). In-class comparisons indicated epirubicin had mean APOP > doxorubicin (P=0.01), cisplatin had APOP > carboplatin (P<0.01); vinorelbine had APOP > vincristine (P=0.02); docetaxel had APOP > nab-paclitaxel (P=0.01); whereas docetaxel and paclitaxel APOP were not different (P=0.85). However, in individual Pts, docetaxel had APOP > paclitaxel in 37% of Pts, whereas paclitaxel was better than docetaxel in 31%. For Combos, cyclophosphamide + doxorubicin produced APOP > single agents in 25%, while single agents had APOP = or > cyclophosphamide plus doxorubicin in 67%. Cyclophosphamide plus docetaxel had APOP > single agents in 33%, but single agents had APOP = or > cyclophosphamide plus docetaxel in 66%. Other comparisons will be presented. Conclusions: Generics APOP is often equal to or better than Proprietaries APOP. In individual Pts single agents frequently produced higher APOP than Combos. The MiCK APOP assay can identify individual Pts with metastatic breast CA for whom Generics or single agents produce higher APOP than Proprietaries or Combos. Prospective clinical trials confirming these predictive differences are warranted. These differences could result in significant savings in health care costs.
Albumin component of nab-paclitaxel and skin toxicities in Chinese breast cancer patients.
Authors: Hu Xi-Chun , Tang Lichen , Wang Biyun , Sun Si , Zhang Jian , Jia Zhen , Lu Yunhua , Di Genhong , Zhimin Shao 
Published: March 2020

e11567 Background: This phase II study was to explore the efficacy and safety of weekly nab-paclitaxel and cisplatin combinationin Chinese advanced breast cancer (ABC) patients. While all other safety profiles were similar and expected based on published clinical trial results conducted in Western patients, the incidence of skin rash was unexpectedly higher. Methods: Nab-paclitaxel(125 mg/m2) was administered on days 1, 8, 15, followed by cisplatin (75 mg/m2) on day 1 every 28 day cycle until disease progression, intolerable toxicities or the maximum of 6 cycles. Patients who received at least one injection of the study drug were included in this analysis of the incidence of skin rash among Chinese patients. Toxicity was graded using the CTCAE4.0. The incidences of skin toxicity with conventional- and nab-paclitaxel were obtained from published trial results in both Chinese and Western patients. Results: 73 patients enrolled were qualified to be analyzed, and a total of 384 cycles were administered before the datalock on Oct 1st, 2011. Rash was presented in 27 patients (37.0%). The most common sites involved were face (14/27), neck (14/27), limbs (18/27) and frictional parts of the trunk (10/27). Macular and papular rash with pruritus commonly occurred 2 (1-7) days after the first day of chemotherapy. Only one patient developed Grade 3 skin toxicity with generalized erythroderma and disfigurement of the face requiring dose reduction. The rash gradually regressed 2 (1-10) days after antihistamines using and pigmentation remained in 13/27 cases. The incidence rate of skin toxicity was significantly higher in Chinese patients than Western counterparts (P<0.0001), while no difference was found with conventional paclitaxel. Conclusions: A higher rate of skin toxicity occurred in Chinese breast cancer patients treated with weekly nab-paclitaxel comparing to Western patients. The albumin component of nab-paclitaxel maybe the cause of the skin disorder. [Table: see text]
A phase II study of weekly nanoparticle albumin-bound paclitaxel combined with cisplatin in patients with metastatic breast cancer.
Authors: Wang Biyun , Hu Xi-Chun , Sun Si , Zhang Jian , Tang Lichen , Wang Zhong Hua , Wang Lei Ping , Lv Fangfang , Zhang Qunling , Zheng Chunlei , Jia Zhen , Lu Yunhua 
Published: March 2020

e11568 Background: This prospective phase II study was to investigate the efficacy and toxicity of weekly albumin-bound paclitaxel (nab-paclitaxel) and cisplatin combination in patients with metastatic breast cancer. Methods: Females with unresectable, recurrent or metastatic breast cancer were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m2 on d1, 8, 15, followed by cisplatin 75 mg/m2 on d1, repeated every 28 days with a maximum of 6 cycles. The primary objective was overall response rate (ORR) and the second objectives were progression free survival (PFS), safety, and overall survival (OS). Results: Seventy-three women were enrolled into this study. A total of 384 chemotherapy cycles were administered with a median of 6 cycles. A high overall response rate (67.1%) was achieved in the whole population. The highest response rate was observed in the first line patients (80.6%) and in patients who had not received taxane previously (80%). After a median follow-up of 12.8 months, the median PFS was 10.5 months. For the patients receiving first-, second- and third-line or more,median PFS was 12.3, 9.0 and 7.7 months, respectively (P=0.006). Subgroup analysis showed that the highest response rate was obtained in Her-2 positive patients, followed by patients with triple negative and luminal subtypes, yielding a response rate of 77.8%, 68.8% and 63.9%, respectively (P=0.584). The corresponding median PFS was 13.6, 12.7 and 10.0 months, respectively (P=0.83). While grade 4 neutropenia occurred in 46 patients (63.0%), febrile neutropenia occurred only in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%), 13 of whom had to stop chemotherapy due to no recovery to grade 2 or less within 2 weeks. Other common toxicities included alopecia, nausea, vomiting and rash. Conclusions: The results of this trial add to the clinical evidence that doublet of nab-paclitaxel and cisplatin has high efficacy and a good safety profile in treatment of patients with metastatic breast cancer. Further evaluation of this regimen in metastatic breast cancer, especially triple negative subtype, is justified.
Thrombocytopenia in hematologic malignancy and solid tumors in the United States.
Authors: Bennett Dimitri , Suppapanya Nittaya , Grotzinger Kelly 
Published: March 2020

e12001 Background: Thrombocytopenia (TCP) frequently occurs in patients with hematologic or solid malignancies resulting from the underlying disease processes or a complication of cancer treatments. Severe TCP may both increase the risk of bleeding, interrupt or reduce optimal dosing with therapies. Epidemiological data on these patients are limited. Therefore, to increase our knowledge, we identified patients with hematologic & solid malignancies & assessed the frequency of primary, secondary & TCP not otherwise classified, following diagnosis & through treatment using a large US claims database. Methods: Hematologic & solid malignancy adult cases were identified during the calendar year 2008 in the Integrated Healthcare Information Service, a medical & prescription claims database comprised of ~101.7 million members from 46 health plans in the US. Malignancies were defined using ICD-9 diagnosis codes; 2 codes were required to confirm cancer. TCP was defined as the presence of at least 2 claims with ICD-9 codes 287.3 or 287.4 or 287.5 within 365 days of the first malignancy diagnosis in 2008. All grades of TCP thus might be reflected as platelet counts were not used to verify diagnostic coding. Adults on active cancer therapy as well as those for whom cancer therapy was not yet initiated & those who have completed their therapeutic regimen are included in the analyses. Results: The frequency of TCP was higher among patients with hematologic malignancies compared to those with solid tumors. Among hematologic cancers, TCP was more common among patients diagnosed with acute myeloid leukemia 33.4% & acute lymphoblastic leukemia 19.1%, followed by aplastic anemia 13.6%, MDS 12.6%, multiple myeloma 9.4%, chronic lymphocytic leukemia 6.9%, chronic myelogenous leukemia 5.9% & non-Hodgkin’s lymphoma 5.1%. Of all patients with solid tumors, the greatest proportion with TCP were observed among those with small cell lung cancer 9.4%; TCP was relatively rare among patients with cancers of the ovary 3.1%, non-small cell lung cancer 2.9%, cervical cancer 2.3%, bladder 1.6%, uterus 1.1%, & breast cancer 0.7%. Conclusions: Overall, TCP occurrence varies widely by cancer type but is commonly higher among patients with hematological malignancies than solid tumors.
Lung cancer and benign lung diseases in patients with serious vitamin D deficiency in eastern China.
Authors: Li Rong , Wu Jing , Xiong Liwen , Han Baohui 
Published: March 2020

e12010 Background: Vitamin D deficiency is a global problem. Methods: We estimated the 25-hydroxyvitamin D (25(OH)D) concentrations to confirm whether patients with lung diseases in eastern China showed vitamin D deficiency and whether this deficiency was related to the risk of lung cancer.We used chemiluminescence to estimate the 25(OH)D concentrations in 250 patients from eastern China, of whom 197 had untreated stage III/IV lung cancer and 53 had benign lung diseases. Results: The mean serum 25(OH)D concentration of patients with lung cancer was 10.63 ± 7.04 ng/mL and that of patients with benign lung disease was 9.62 ± 6.37 ng/mL. Although there was no significant difference between the values, the mean serum concentrations of 25(OH)D obtained in patients with lung cancer and benign lung diseases were lower than the normal value (>20 ng/mL); p values in both cases were less than 0.0001. Among the 250 patients, 90 showed low serum 25(OH)D levels of ≤ 4 ng/mL. Conclusions: Patients with lung diseases in eastern China show low serum levels of 25(OH)D, and the average serum 25(OH)D level is much below the normal vitamin D level. Presently it cannot be concluded whether the low levels of 25(OH)D is a risk factor for lung cancer, because the average serum 25(OH)D levels in patients with lung cancer or benign lung diseases are very low.
Characteristic and management of lung cancer as a secondary malignancy.
Authors: Pluzanski Adam , Badurak Pawel , Kowalski Dariusz M , Glogowski Maciej , Zajda Katarzyna , Krzakowski Maciej Jerzy 
Published: March 2020

e12011 Background: New diagnostic and therapeutic strategies increase survival in cancer patients. Etiology and management of primary lung cancer (LC) are well established, but little is known about incidence of LC as a secondary neoplasm. The study analyzes the clinical characteristic, pathology and management of LC as a secondary neoplasm. Methods: We reviewed medical records of patients (pts) treated in our institution from Feb.1998 to Aug.2011 with diagnosis of LC as a second malignancy. The analysis included median age at the time of diagnosis of primary cancer, histology, type of treatment and time until diagnosis of LC. Results: 84 pts were analyzed – median age at the time of diagnosis of primary cancer was 62 years (range 35-79) (65 years in men and 58 years in women p<0,05). The most frequent primary was: breast -21 pts (25%), larynx -19 pts (23%), colon - 9 pts (11%). According to etiology, tobacco-related primary cancers occurred in 37 (44%) pts. Radiotherapy/chemoradiotherapy was the treatment for primary cancer in 42 (50%) pts, surgery alone in 31 (37%) and chemotherapy in 11 (13%) pts. Adenocarcinoma as a secondary LC was diagnosed in 43 pts (51%), squamos-cell carcinoma in 30 pts (36%), small-cell lung cancer or carcinoid in 6 pts (7%), other types of non-small cell lung cancer in 5 pts (6%). Median time between diagnosis of primary cancer and LC was 50 months (range 0-354). Stage I or II LC was found in 56 pts (67%) and stage of III or IV in 26 (31%) pts (contrary to staging observed in pts diagnosed with LC as a primary malignancy in our institution concurrently). After diagnosis of LC radical and palliative treatment was offered in 65 (77%) pts and 19 (23%) pts respectively. After median follow-up of 84 months, progression of LC was noted in 27 pts (32%) and median time to progression was 16 months (range 2-89). Conclusions: Patients after treatment of tobacco-related cancers are at risk of developing LC as a second malignancy. LC as a secondary cancer is observed also after treatment of breast cancer and radiotherapy use. Close surveillance after treatment of primary malignancy allows detection of LC at early stage with a chance of radical treatment.