bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective pilot study of serum lipid levels and the risk of breast cancer
Authors: Raghupathy R. V. , Seidler C. W. , Emani S. , Rooney J. 
Published: March 2020

10539 Background: Prior prospective cohort studies have provided conflicting data regarding lipid levels as a breast cancer risk factor. These studies were either designed to study cardiovascular diseases or included a small number of incident cases. This retrospective pilot study compared the lipid profiles of breast cancer patients to a normal cohort obtained from a large community based HMO database. Methods: Fallon Clinic automated outpatient billing and laboratory databases were used to identify patients with breast cancer (ICD9–174.9) and retrieve average lipid profiles at least two years prior to the first identified diagnosis date. The outpatient billing record of a central Massachusetts HMO was used to randomly generate a control group without an ICD9 diagnosis of breast cancer. Patients were classified into two groups based on age to approximate menopausal state (pre menopausal <50 yr, post menopausal ≥50 yr). T-tests were conducted to compare the total cholesterol, LDL, HDL and triglycerides of the two groups. Results: See table. Conclusions: In the pre-menopausal population, total cholesterol and LDL were significantly higher in the breast cancer group. In the post-menopausal group, triglycerides were higher and HDL lower. Though the HDL association is in concurrence with two large prior studies, other associations have not been demonstrated. An average of fasting levels obtained more than two years before diagnosis eliminates the lipid profile response to meals, variability in isolated values and influence of pre-clinical cancer on the data. However, the patients have not been matched for other breast cancer risk factors or variable menstrual phase while obtaining samples in the pre-menopausal population. [Table: see text] No significant financial relationships to disclose.
Cardiac tolerability of trastuzumab in metastatic breast cancer (MBC) patients previously treated with high-dose chemotherapy (HDC) with autologous hemopoietic support: Retrospective analysis from Gruppo Italiano Trapianto Midollo Osseo (GITMO) Solid Tumor Working Party
Authors: Bengala C. , Zamagni C. , Pedrazzoli P. , Matteucci P. , Ballestrero A. , Da Prada G. , Martino M. , Rosti G. , Danova M. , Jovic G. , Conte P. 
Published: March 2020

10558 Background: HER-2 overexpression is associated to a poor prognosis in high-risk and MBC patients treated with HDC. HER-2 status is also a predictive factor of response to trastuzumab: when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant DFS and/or survival improvement has been observed in HER2+ early and MBC. Unfortunately, in both settings, trastuzumab was associated with an increased risk of cardiac dysfunctions (CD). Patients and Methods: In order to evaluate the cardiac safety of trastuzumab after HDC, we have reviewed the clinical charts of HER2-overexpressing MBC patients treated with HDC and trastuzumab at 11 centres of the GITMO group. Age, baseline LVEF, radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. Cardiac dysfunction (CD) was defined as: 1) decline of LVEF ≥ 10% to below 50%, 2) decline of LVEF between 5 and 9% to below 50% with symptomatic (NYHA class III-IV) congestive heart failure (CHF), 3) any symptomatic CHF event. Results: Fifty-three patients treated between 1999 and 2005 have been included in the analysis. Median age was 47 years (range 29–66). Median interval between HDC and trastuzumab was 6 months. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only) it was 55% (p = 0.01). Five out of the 28 (17.9%) pts experienced CD. Two out of 53 (3.8%) pts developed a symptomatic (NYHA class III) CHF. Age ≥ 50 years was the only factor significantly associated with CD. However age ≥ 50 years and multiple transplant procedure were associated with a significant decline of LVEF (p: 0.02). Conclusion: The incidence of CD is not superior to that reported with trastuzumab after standard chemotherapy. However pts with age ≥ 50 years or receiving multiple course of HDC, should be considered at risk for CD. No significant financial relationships to disclose.
Combination therapy with gefitinib and capecitabine in metastatic breast cancer (MBC): A phase I trial
Authors: Mayer E. L. , Harris L. N. , Partridge A. H. , Gelman R. S. , Schumer S. T. , Comanaru R. S. , Long M. , Sampson E. , Burstein H. J. , Winer E. P. 
Published: March 2020

10564 Background: Preclinical models have suggested synergy between the EGFR tyrosine kinase inhibitor gefitinib (G) and the 5-FU prodrug capecitabine (C), an active treatment for MBC. This phase I study was designed to explore the safety of this all-oral regimen in patients (pts) with MBC. Methods: Pts were treated in sequential cohorts (n = 3–6) using a fixed dose of G (250 mg qd continuously) and escalating doses of C (1500 mg/m2/day, 1750 mg/m2/day, and 2000 mg/m2/day) in a 21-day cycle. An additional 10 pts were enrolled in a validation cohort at the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was defined during the first cycle as any grade 3/4 toxicity or a delay >3 weeks due to unresolved toxicity. The primary endpoint was safety; secondary endpoints included assessments of tumor response (using RECIST criteria), adherence to the oral regimen, and biomarker measurements. Results: 19 pts were enrolled; the mean age was 49 y, 58% of tumors were hormone receptor positive, and 10% were HER2 positive. The mean number of prior MBC chemotherapy regimens was 1.2 and 74% had visceral spread. No pts in dose escalation cohorts had DLT during cycle 1. The 10 pts in the validation cohort (MTD C 2000 mg/m2) had 3 DLTs in cycle 1 and 1 DLT in cycle 2 (95% CI 12–74%). For all pts at C 2000 mg/m2 (n = 13), there was no grade 4 toxicity, however 5 (38%) had grade 3 toxicity, 7 (54%) required a C dose reduction, and 2 (15%) came off study for persistent toxicity. 3 pts (23%) experienced grade 3 diarrhea, and 4 pts (31%) had moderate to severe hand/foot syndrome. There were no objective responses (PR or CR) observed out of 18 evaluable pts. The mean number of completed cycles of therapy was 4.8, and 3 pts (16%) were treated for > 24 weeks. An exploratory analysis of serum EGFR measurements demonstrated no association of pre- or post-therapy values with lack of progression. Monitoring adherence to oral therapy using a microelectronic monitoring system (MEMS) was feasible, and detailed data will be presented. Conclusions: In this phase I dose escalation trial of G/C therapy in women with MBC, treatment was generally well tolerated, with a confirmed C MTD of 2000 mg/m2. Moderate toxicity and dose reductions were common. In this small cohort, the G/C combination did not appear to have substantial anti-tumor activity. [Table: see text]
Circulating regulatory T cells in advanced breast cancer patients
Authors: Karamouzis M. V. , Perez S. A. , Gritzapis A. D. , Ardavanis A. , Skarlos D. V. , Baxevanis C. N. , Rigatos G. , Papamichail M. 
Published: March 2020

10567 Background: It has been recently shown that regulatory CD4+CD25bright T cells (Tregs) are increased in patients with several malignancies and this increase correlates with advanced stage and dismal prognosis. Breast cancer (BC) patients represent a heterogeneous population with unpredictable natural history, even at advanced stages. We sought to monitor advanced stage (III and IV) BC patients, overexpressing HER-2/neu (HER) or not, for circulating Tregs before, during and after the administration of chemotherapy, either alone or in combination with Trastuzumab. Methods: Determination of circulating Tregs was performed in 50 μl whole peripheral blood by a Lyse NoWash FACS procedure and staining for CD45, CD4 and CD25. Tregs were determined as the lymphocytes expressing lower CD4 within the CD4+ T cell compartment and higher CD25 expression compared to the CD4 negative lymphocytes. Clinical evaluation of the patients was done according to RECIST criteria. Results: 24 HER+ and 19 HER- stage III / IV BC patients have been compared to 14 healthy donors, before therapy. The percentage of Tregs among the CD4+ T cell population of HER+ patients was significantly increased compared to both HER- patients and healthy donors (8,74 ± 2,68 vs 6,07 ± 1,85 and 6,55 ± 1,49, respectively). Trastuzumab combined with chemotherapy resulted in a progressive decrease in the percentage of circulating Tregs, reaching normal levels after the fourth cycle of treatment (6,95 ± 1,17). On a per patient basis, decrease in Tregs correlated either with documented partial response or stable disease, while increased Tregs during treatment coincided with progressive disease. No statistically significant change in the percentage of Tregs after chemotherapy was observed in HER- patients. Conclusions: 1) Increased Tregs do not directly correlate with clinical stage in BC, as stage III and IV HER (+) and (−) patients exhibit significantly different Tregs profiles. 2) HER+ advanced BC patients exhibit increased percentages of circulating Tregs and respond to the combination of Trastuzumab and chemotherapy by decreased Tregs. This decrease is either due to a reduction of the tumor burden or neutralization of circulating HER antigen by Trastuzumab, or a combination of both. No significant financial relationships to disclose.
Pegylated liposomal doxorubicin (PLA) at a metronomic schedule for patients with advanced breast cancer (ABC)
Authors: Nolè F. , Verri E. , Sanna G. , Munzone E. , Catania C. , Ascione G. , Adamoli L. , Dellapasqua S. , Colleoni M. , Goldhirsch A. 
Published: March 2020

10571 Background: The anti-angiogenic efficacy of chemotherapy (CT) is probably best obtained by administration of low doses of cytotoxics on a frequent or continuous schedule. The aim of this pilot study was to assess feasibility, clinical efficacy and tolerability of PLA, using a “metronomic” schedule in ABC. This schedule has been previously tested in the treatment of Kaposi sarcoma. Methods: From January to November 2005, 36 pts with ABC were treated with PLA, at a dose 20 mg/m2 q14. Almost all the pts were heavily pretreated for ABC and 44% of them received previous anthracycline therapy in adjuvant or metastatic setting. Results: Thirty-four pts were evaluable for toxicity and 29 for response. One pt (3%) had CR, 3 (11%) PR, 12 (41%) NC and 13 (45%) PD, for an overall clinical benefit of 28%. Median response duration was 2.59 mos; median TTP was 3.38 mos (95% CI 2.11–4.64). Treatment was well tolerated with neither G3-G4 NCI-CTC hematological toxicity. Only one pt experienced G3 palmar-plantar erythrodysesthesia (PPE). PPE was observed in other 15 pts (39%), with G2 occurring in 7 (21%). Other common G2 non-hematological toxicities were mucositis in 3 pts (9%) and constipation in 3 pts (9%) Dose reduction, due to subjective or hematological toxicity, was required in 10 pts (36%). No decrease in LVEF > 10% from baseline was observed. Conclusions: Metronomic PLA schedule in pretreated ABC pts seems to be an active and well-tolerated regimen. As to dose-dense CT, targets of metronomic CT might be, in addition to malignant cells, also endothelial and other stromal cells of the progressing metastasis, leading ultimately to the stability and eventually regression of the neoplastic lesion. The lower toxicity profile of the metronomic schedules make their use in pts with ABC very attractive and their testing in the adjuvant setting extremely challenging. No significant financial relationships to disclose.
Incidence of brain metastases after first line chemotherapy in breast cancer patients treated with or without trastuzumab
Authors: Ferretti G. , Felici A. , Pino M. , Carlini P. , Fabi A. , Nuzzo C. , Sperduti I. , Cognetti F. , Papaldo P. 
Published: March 2020

10582 Background: Brain metastases during trastuzumab therapy have been frequently observed. Only a few studies have compared the risk of brain metastases in patients (pts) treated with or without trastuzumab. Methods: In our hospital, between Jun 2000 and September 2005, we conducted a retrospective study in 72 metastatic breast cancer pts treated with first-line mono-chemotherapy (CT) with paclitaxel or docetaxel or vinorelbine ± Trastuzumab (T). Results: Thirty-five pts with HER2 pos disease were treated with T associated with 1st line CT, while 37 pts (16 with HER2 positive tumor, 21 HER2 negative) were not treated with T (NT). Ten HER2 pos NT pts subsequently received T. The median follow-up was 21 months (range1–129); the median age was 54 (range 32–82); the median treatment duration was 5 months (range 1–29). The incidence of recurrence (R), progressive disease in brain (BR), progression free survival (PFS) after first line CT, and overall survival (OS) were reported below: (see Table) Conclusions: This study showed that, after first line chemotherapy, the use of T did not affect the incidence of BR in HER2 pos metastatic breast cancer pts. On the other hand, Her-2 neg seems to predict ‘per se‘ a lower incidence of cerebral spread of disease. [Table: see text] No significant financial relationships to disclose.
Clinical availability of chemotherapy response assay using adenosine triphosphate in breast cancer patients
Authors: Jeong J. , Lee S. , Yoon S. , Jung W. , Lee H. , Lee I. 
Published: March 2020

10592 Background: The response to chemotherapeutic agents of breast cancer is heterogeneous from patient to patient. Several methods were developed to decide chemotherapeutic agents which were sensitive to individual patients but so far, there are no ways which is commonly used in the clinic to tailor the treatment. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. Methods: From March 2004 to February 2005, 65 breast cancer patients were enrolled in this study. After elimination of normal contaminated cells, cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer(doxorubicin, epirubicin, 5-FU, paclitaxel, docetaxel, vinorelbine, and gemcitabine). 7 Drug-treated cancer cells and untreated cancer cells were cultured for 48 hours and then ATP was measured. To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean death rate of doxorubicin, epirubicin and paclitaxel by HER-2 status. Results: The ATP-CRA was performed sucessfully in 62 patients. (95.4%) In all cases, we can get the results within 7 days. The range of cell death rate was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean cell death rate (35.7%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.58 and 0.2 between paclitaxel and epirubicin. In HER-2 positive group, mean cell death rate of epirubicin and paclitaxel was significantly higher than in HER-2 negative group (p = 0.017, p = 0.036) and same trend was seen in doxorubicin but not statistically significant (p = 0.060). Conclusions: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. With indirect comparison, it showed similar results with in vivo studies but for clinical use, the prospective randomized controlled trial should be preceded. No significant financial relationships to disclose.
Pharmacogenomic analysis of needle biopsies obtained before preoperative docetaxel/capecitabine/FEC (TX/FEC) chemotherapy for breast cancer
Authors: Holmes F. A. , O’Shaughnessy J. A. , Hellerstedt B. , Pippen J. , Vukelja S. , Kocs D. , Asmar L. , Fenske E. , Lin F. , Symmans W. F. , Pusztai L. 
Published: March 2020

10595 Background: Our goal was to evaluate the feasibility of obtaining fine needle biopsies, for pharmacogenomic analysis, in community based oncology practices and develop gene expression-based predictors of pathologic complete response (pCR) to preoperative sequential docetaxel/capecitabine and 5-fluorouracil, epirubicin, cyclophosphamide chemotherapy. Methods: One hundred seventy-five patients were accrued at 29 sites in the US Oncology Research network. FNA specimens were mailed to a central laboratory (MDACC) and gene expression profiling was performed on Affymetrix U133A chips. Results: RNA extraction was started on 140 specimens, 112 of these (80%) yielded ≥1 μg total RNA, 69 were hybridized and 65 (94%) gene expression profiles have passed quality control as of abstract submission date. The analysis plan is to develop a multigene predictor of pCR from the first 80 cases and test its performance independently in the remaining cases. Conclusions: Collection of mandatory research FNA biopsies for pharmacogenomic research is feasible in community practice. Approximately 80% of biopsies yield sufficient RNA for gene expression profiling. In 20% of patients, either technical factors, which can be addressed, or tumor biology (necrotic, rapidly growing tumors) were limiting. Supported by Roche Laboratories, Inc., Nutley, NJ; Pfizer, New York, NY; and Precision Therapeutics, Pittsburgh, PA. [Table: see text]
Improved differentiation of 300 breast lesions using real-time elastography
Authors: Thomas A. , Kümmel S. , Landt S. , Warm M. , Fritzsche F. , Lichtenegger W. , Fischer T. 
Published: March 2020

10608 Background: Differences in tissue elasticity are useful in the diagnosis of breast tumors. With elastography the elastic properties of breast tissue can be imaged in real time by means of color-coded superimposition on the B image and then used for evaluating focal lesions. The goal of the present study was to compare the sensitivity and specificity of elastography with that of B-mode sonography. Methods: A total of 300 patients with histologically confirmed breast lesions (168 benign, 132 malignant) were included in the study. The patients’ average age was 51 years, the range 16 to 86 years. Evaluation was by means of the 3D finite-element method. The data is color-coded and superimposed on the B-mode ultrasound scan (HITACHI EUB 8500). A second examiner was employed to improve the objectivity of the method. The results were compared with histology and the data obtained by previous ultrasound investigations. Sensitivities and specificities were calculated. Results: B-mode sonography yielded a sensitivity of 95.5% and a specificity of 84%. The two examiners were almost in complete agreement in their evaluation of the elastography images (McNemar Test: weighted kappa: 0.86): elastography yielded a sensitivity of 82%, a specificity of 88%. Conclusion: The diagnostic results for elastography in breast lesions showed a higher specificity and a somewhat lower sensitivity in comparision with B-mode sonography. No significant financial relationships to disclose.
Raman spectroscopy to distinguish progression stages in breast cancer
Authors: Clare S. E. , Neubauer H. , Schuetz C. , Kurek R. , Solomayer E. , Wallwiener D. , Dye D. F. , Zaleski J. M. , Goulet R. J. , Fehm T. 
Published: March 2020

10619 Background: The concept of early breast cancer detection has evolved to mean the discovery of a premalignant lesion or an early stage invasive lesion prior to metastasis. Therefore, methods must be developed to identify the actual primogenitors of cancer, those lesions which with certainty will progress to cancer. Currently, two technologies are employed for routine imaging of the breast: mammography and ultrasonography. Neither of these techniques can unequivocally distinguish between benign and malignant tissue limiting them to detection but not diagnosis. We hypothesize that differences in Raman spectra will enable the accurate discrimination of breast lesions one from one another and from normal breast epithelia. Therefore, preliminary studies were performed to investigate the potential of Raman spectroscopy. Methods: Cyropreserved breast tissue was selected, sectioned (10 μM) and stained with Hematoxylin and Eosin to verify the histologic diagnosis and to guide the acquisition of Raman spectra from a consecutive section (30 μM). This “analysis” section is mounted on Permanox (polyolefin; Nunc, Rochester, NY) over an area of the slide perforated with small holes (dia. 1mm) to provide the laser with direct access to the tissue without background Raman scattering from the polyolefin. Using a Raman microscope spectra were obtained from multiple areas of five breast tumors to address the reproducibility of spectral similarities across different tumors, to identify spectral differences between malignant and benign tissue, to identify spectral differences between invasive and ductal carcinoma in situ (DCIS) and to optimize the integration time. Results: In general, the spectral profiles for each tissue type are conserved with distinct differences in the predominance and peak widths of specific vibrations. Even in the absence of complex algorithms, malignant vs. benign tissue identification is possible. An analysis of the ability to reliably distinguish between invasive ductal carcinoma and DCIS will have to await additional spectra. A sound vibrational fingerprint of the tissue, consistent with that of the high signal/noise scan at 10 minutes, can be obtained within 30 seconds. Conclusions: Raman spectroscopy with short collection times shows promise and warrants further investigation. No significant financial relationships to disclose.
Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer
Authors: McDaniel S. A. , Krontiras H. , Carpenter J. T. , Nabell L. M. , Bland K. I. , Urist M. M. , Falkson C. I. , Forero A. 
Published: March 2020

10622 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity. No significant financial relationships to disclose.