bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of further chemotherapy (CT) after capecitabine as first-line chemotherapy (CT) for metastatic breast cancer (MBC)
Authors: Debled M. , Trainaud A. , Durand M. , Floquet A. , Brouste V. , Mauriac L. 
Published: March 2020

1095 Background: Based on results of randomized trials of Xeloda (X) vs CMF or taxanes (T) as first-line CT for MBC, very favorable tolerability, and patients’ (pts) preference for oral therapy, front-line X is now often used in our institution, especially for slowly progressing disease. As other CT regimens, especially T, have demonstrated improved OS, we analyzed post-X CT in these pts. Methods: Analysis was restricted to pts who began X before Jan 05, all of whom have now discontinued because of progression or toxicity. Results: In 90 eligible pts, median TTF and OS from initiation of X are 9 [95% CI 7–11] and 26 [22–30] months, respectively. 75% of pts received second-line CT. Three subgroups can be analyzed: (A) 65 pts (median age 58y, range 34–84) received further CT (median 2 regimens, range 1–6) after stopping X, including T (85% of pts), anthracycline (a/c: 42%), vinorelbine (45%), or mitomycin C (20%). 24 pts received =2 regimens including a/c and T; 7 pts received neither T nor a/c (vinorelbine, n = 6; UFT, n = 1). Median OS from initiation of X was 30 months [95% CI 27–32]. 30 pts are alive after a 16-month median follow-up since X failure; they may receive another CT; (B) 3 pts are currently receiving endocrine therapy after X failure and may receive another CT later; (C) 22 pts (24%) (median age 77y, 19 =70y) died without receiving further CT. Median OS from initiation of X was 11 months (range 0.5–23). 4 of these pts (aged 57, 71, 74, and 84y) received endocrine therapy for 2–10 months. Ability to administer further CT varies with age: of pts <75y, 89% received subsequent CT (T: 75%), whereas 37% of pts =75y received second-line CT. Conclusions: TTF and OS indicate that capecitabine is very active as first-line CT for MBC. For a large majority of pts <75y, first-line X does not compromise administration of further CT including T. No significant financial relationships to disclose.
Gemcitabine/paclitaxel compared to gemcitabine/vinorelbine in metastatic breast cancer: An interim analysis
Authors: Bensalem A. , Bouzid K. 
Published: March 2020

1097 Background: New combinations and strategies have been developed over the past 10 years including new drugs such as taxanes and gemcitabine. It is not clear whether the activity of the gemcitabine-paclitaxel (GP) combination regimen would translate into better progression-free or overall survival (OS) when compared with gemcitabine-vinorelbine (GV) especially in metastatic breast cancer. This study was conducted to evaluate the overall response rate (RR) of GP Vs GV. Secondary objectives included individual responses of GP and GV, time to progression (TTP), time to treatment failure (TTF), OS, and toxicities. Methods: Patients(pts) with histological diagnosis of stage IV or recurrent breast cancer who had PS =2 and measurable disease were randomized to receive GP (Gemcitabine: 1,250mg/m2 D1 & D8- paclitaxel: 175 mg/m2 D1, D1=D28) or GV (Gemcitabine: 1,250mg/m2 D1 & D8 - vinorelbine: 25mg/m2 D1 & D8, D1=D21). Pts received anthracycline and/or capecitabine chemotherapy in adjuvant and/or metastatic setting. Results: Of 47 patients enrolled, 24 patients were randomized to GP arm and 23 to GV arm. 72% of patients were stage IV and 28% recurrent disease. To date, all patients were qualified for safety, TTF, TTP and OS analysis. Hematologic toxicities were: Neutropenia in 23% in GP Vs 17% in GV, Anemia in 12% in GP Vs 9% in GV. Non hematologic toxicities were essentially nausea and vomiting grad 2–3 in 27% in GP Vs 31% in GV. Anti-emetic agents were administrated to decrease them. The Complete Response (CR) was 27% in GP Vs 30% in GV, the Partial Response (PR) was 23% in GP Vs 17% in GV; with an Overall Response Rate (ORR) of 50% in GP Vs 47% in GV. Median TTF in weeks was 12 in GP Vs 14 in GV. Median TTP (weeks) was 14 in GP Vs 19 in GV. Median OS (weeks) was 32 in GP Vs 50 in GV. Conclusions: In our experience, schedules incriminating gemcitabine are efficient and produce clinical benefit and there activities are very interesting. The analysis of the useful of paclitaxel or vinorelbine associated to gemcitabine demonstrates that these associations are active with no significant differences in toxicities. Therefore, the questions are what regimens, for what patients to what high responses in pre-treated metastatic breast cancer. No significant financial relationships to disclose.
A phase II study of weekly low-dose paclitaxel plus 24-hour infusion of cisplatin as first-line chemotherapy for metastatic breast cancer (MBC)
Authors: Shen Y. , Hsu C. , Kuo S. , Lu Y. , Lin C. , Huang C. , Cheng A. 
Published: March 2020

1100 Background: The dose and schedule of paclitaxel have been evolving in the past 15 years. However, the lowest effective dose of weekly paclitaxel remains unclear. In this study, we examined if a very low dose of paclitaxel can be effective in MBC. Except for the dose of paclitaxel, the chemotherapy regimen and the patient population of this study were very similar to one of our previous report (Cancer 2002; 95:2044–50). Methods: Women with chemotherapy-naïve metastatic BC, adequate performance status and organ functions were eligible. All patients received paclitaxel, 50 mg/m2 iv 1 hr on D1, 8 and 15, and cisplatin, 40 mg/m2 iv 24 hrs on D1 and 8, every 4 weeks. Patients continued this low-dose regimen until progressive disease (PD) or prohibitive toxicities occurred. Patients who had PD or stable disease (SD) without clinical benefit were shifted to paclitaxel 80 mg/m2 iv 1 hr on D1, 8 and 15, and cisplatin, 40 mg/m2 iv 24 hrs on D1 and 8, every 4 weeks. The primary endpoint was overall response rate (ORR). Simon’s optimal two-stage design (P0, P1,a, and βare 20%, 40%, 0.05, and 0.2, respectively) was adopted. More than 4 objective responses were needed in the first 13 patients, and a total of 43 patients will be enrolled. Results: After a median follow-up duration of 16.5 months, 27 patients were evaluable for response and toxicity. Their median age was 52.7 years (range: 30.1∼69.4). Twenty patients were hormone receptor (+), while 6 patients were Her-2/neu (+). A total of 121 cycles of protocol treatment were administered as of Dec. 2006. There were 0 complete response and 14 partial responses, for an ORR of 51.9%. Nine of 14 responders remain progression-free. The PFS was 9.6 months (95% of CI: 5.53∼13.67%) and the OS not reached. Grade 3–4 anemia, neutropenia, liver toxicity, thrombocytopenia, and skin toxicities were reported in 8, 6, 2, 1, and 1 patients, respectively. Neurotoxicity was common (22/27), but all were grade 1 or 2. Conclusions: The preliminary results of this study suggest that weekly low-dose paclitaxel is as effective as conventional-dose paclitaxel, and the treatment-related toxicities were more acceptable. No significant financial relationships to disclose.
The role of transvaginal ultrasound in early diagnosis of tamoxifen-related endometrial cancer: An Italian experience
Authors: Martella F. , Giannessi P. G. , Coltelli L. , Giuntini N. , Safina V. , Falcone A. 
Published: March 2020

11021 Background: women treated with tamoxifen for ER-positive early breast cancer are at a two to seven fold increased risk of endometrial cancer. Even though published data fail to support the use of transvaginal ultrasound (TVU) for screening of endometrial cancer, this is still a very common clinical practice in this subset of patients (pts). Methods: we have conducted a retrospective analysis to investigate the value of TVU in early detection of tamoxifen-related endometrial cancer. The screened population consists of pts treated with adjuvant tamoxifen in our institution from January 1999 up to December 2003 receiving a TVU annually or in case of gynaecologic symptoms. Results: 491 evaluated pts performed a total of 1634 TVUs in asymptomatic conditions. FIGO stage I endometrial cancers have been diagnosed in 3 patients (0.32%) who are still alive after total hysterectomy. A vaginal bleeding anticipated the examination in 33 women (3.2%) and represented the first symptom in two cases of tumor. Only one endometrial cancer has been detected with the screening procedure. Median increase of endometrial thickness has been 7.6 mm (range 1–34 mm) and those patients with abnormal images at TVU underwent an hysteroscopy with endometrial biopsies (169) resulting in a benign histology (polyps, cystic atrophy, hyperplasia) in most cases. Conclusions: therefore we have performed more than 1500 transvaginal ultrasound to detect only one asymptomatic cancer so we agree with literature in supporting that women receiving tamoxifen should undergo only an annual gynaecologic examination reserving the TVU to patients with vaginal bleedings or discharges. No significant financial relationships to disclose.
A phase I/II study of imatinib and docetaxel as neoadjuvant therapy in locally advanced breast cancer
Authors: Haley B. B. , Ashfaq R. , DeHaas M. , Ramaswami A. , Sikder K. , Tripathy D. 
Published: March 2020

11039 Background: Imatinib mestylate(Gleevec,G) is a tyrosine kinase inhibitor of platelet derived growth factor receptor(PDGFR) and KIT(CD117). In breast cancer(BC),PDGFR signaling regulates tumor interstitial fluid pressure(IFP). PDGFR inhibition lowers IFP enhancing tumor drug delivery and chemo effect. KIT’s role in BC growth is unclear.PDGFR and KIT signal pathways regulate proliferation and cell cycle progression.Receptor blockade may enhance anti-tumor activity combined with chemo.This study evaluated tolerability,toxicity and efficacy of imatinib and docetaxel and treatment changes in biomarker expression and downstream mediators. Methods: Eligibility:Total 12 women, invasive LABC(T2–4,No-2,Mo)IHC + for KIT and/or PDGF, ECOG 0–2,bidimensional disease.Treatment:Assigned to 1of 3 G dose levels(400,600,800mg) taken daily 2 weeks then combined with D30mg/m2 IV weekly x3 Q28 days. Three completed G(400mg D) and protocol modified to G600 and 800mg dose for 1 week then combined with D30mg/m2 IV weekly x12. Tumor(T)measured pretreatment and at definitive surgery at conclusion of G+D.T biopsy done preG, postG and at end of G+D for tissue markers. Three treated G400, 5G600 and 4G800mg dose. Results: 12 patients median age 51 (range 39–62), ECOG PS O, 4 pre/8 post menopausal treated. Clinical pretreatment (C-PRx) tumor size (TS)median 6cm (range 3- 12cm).C-PRx node status 7cN0 and 5cN1.PRx x-ray TS median 4.5 cm (range 2.5–8.5cm). Response:OR 25% 1 near CR+2 PR(3/12) at 400 and 600mg dose levels.Two SD(G800mg),3 progressed/off study,2 withdrew/toxicity(G3 rash/edema and G4 N/V), 2 NR.Surgery:5PM and 7MRM. Toxicity:Non- hematologic:nausea(1G4/G400mg),vomiting(1G4/G600mg),diarrhea(1G3/G800mg),fatigue(2G3/G800mg),myalgia(1G3/G800mg),rash(1G3/G600m g) and hypophosphatemia (2G3/G600mg). Hematologic toxicity mild neutropenia/anemia G1/2.One hospitalized for G3 odonophagia/stomatitis,G800mg.Dose Delay:2 missed 1 week of D+G (G600mg),2 missed 2 weeks of D+G (1G600mg and 1G800mg). Conclusion: Imatinib and docetaxel in neoadjuvant LABC is feasible and tolerable with low G3/4 toxicity and acceptable activity.G400mg dose best tolerated. Tissue IHC and molecular profiles to be reported separately.
Oblimersen (O) in combination with docetaxel (T), adriamycin (A), and cyclophosphamide (C) as neoadjuvant systemic therapy (NST) in primary breast cancer (PBC): Final results of a multicentric phase I study
Authors: Rom J. , Schlehe B. , Marmé F. , Schuetz F. , Eichbaum M. , Sinn H. , Buechele T. , Sohn C. , von Minckwitz G. , Schneeweiss A. 
Published: March 2020

11047 Background: The Bcl-2 downregulator O in combination with standard cytotoxic chemotherapy leads to synergistic antitumor effects in preclinical trials. To evaluate maximum tolerated dose (MTD), safety and preliminary efficacy of O in combination with TAC as NST in PBC we performed a multicentric phase I study. Methods: Previously untreated patients with PBC T2–4a-c N0–3 M0 received escalating doses of O as a 24 hour continuous infusion on day (d) 1–7 in combination with T 75mg/m2, A 50mg/m2 and C 500 mg/m2 on day 5 followed by five three weekly cycles of TAC without O. Results: A total of twenty-eight patients with a median age of 50 years were enrolled. 61% of tumors were T2, 43% grade 3, 68% ductal-invasive, and 64% hormone receptor positive. Patients received O in a dose of 3 mg/kg/d (cohort I, 9 patients), 5 mg/kg/d (II, 9 patients), and 7 mg/kg/d (III, 10 patients), respectively. No dose-limiting toxicity occurred. Most common adverse events [all National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade = 2] were fatigue, nausea, alopecia, headache and flue-like symptoms observed in 78% (I), 89% (II), and 90% (III) of patients, respectively. Following OTAC the most severe hematological toxicity was neutropenia (NCI-CTC grade 1–2/3/4) which developed in 0/0/56% of patients (I), 11/0/56% of patients (II), and 20/20/50% of patients (III), respectively. At least 50% reduction in tumor volume was oberved in 14 patients. Five patients (18%) achieved a pathologic complete response (3 patients in cohort I, 2 patients in cohort II). Conclusions: O up to a dose of 7 mg/kg/d given as a 24 hour infusion on day 1–7 can be safely administered in combination with standard TAC on day 5 as NST in patients with PBC. The preliminary efficacy warrants further evaluation of this combination in a randomised trial. No significant financial relationships to disclose.
HER2-negative metastatic breast cancer patients receiving first-line docetaxel: Survival data and prognostic factors
Authors: Deblock M. , Esterni B. , Tarpin C. , Charaffe-Jauffret E. , Extra J. M. , Viens P. , Goncalves A. 
Published: March 2020

1105 Background: Modern management of metastatic breast cancer (MBC) patients (pts) is currently based on molecular stratification according to HER2 status and first-line taxanes. We sought to examine outcome data and prognostic factors in a prospectively characterized cohort of HER2 negative MBC pts receiving first-line docetaxel in a routine setting. Methods: Medical records from 162 HER2-, MBC pts treated at the Institut Paoli-Calmettes with first-line docetaxel-based regimen between 1997 and 2005 were reviewed. These patients had been treated with docetaxel single-agent or in combination according to standard institutional protocols. Univariate and multivariate analysis according Cox regression model were employed to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: Pt characteristics were the following: median age (ys), 51 (24 -75); Histological type (ductal/lobular/other, %) 81/15/4; Grade (1/2/3, %); Hormonal Receptivity (HR) (yes/no, %) 83/17; Adjuvant chemotherapy (CT) (yes/no; %) 66/34; Disease-free interval (DFI) (<24 months/>24 months, %) 47/53; visceral disease (yes/no, %) 46/54; number of metastatic sites (<3/>3,%) 78/22; liver metastasis (yes/no, %) 31/67; bone metastasis (yes/no, %) 65/35. After a median follow-up of 33 months, median PFS and OS were 11.7 months (95%CI , 9.7 -14.8) and 35 months (95%CI, 28.1–52.1), respectively. By univariate analysis, HR- (p=7.9 e-06), visceral disease (p=0.015), shorter DFI (p=0.027) and previous adjuvant CT (p=0.0038) were negatively associated with PFS, while HR- (p=6.3e-07), visceral disease (p=0.0094) and shorter DFI (p=0.01) were also negatively associated to OS. 14. These parameters retained independent prognostic significance by multivariate analysis, the strongest being HR-(p=2.4e-5) for OS. HR- pts had a PFS of 6.87 months [95%CI, 4.27 - 11.0] Vs 14 months [95%CI, 11.84 - 18.5] in HR+ pts (log-rank test p= 3.16e-06). 2-year OS were 38% [95%CI, 21.9–65] and 76%[95%CI, 68.7–84.4] (p = 6.52e-08) in HR- and HR+ pts, respectively. Conclusions: In the taxane era, median OS of HER2- MBC pts is nearly 3 yrs. Triple negative pts (HER2-, HR-) are a very poor-risk group requiring innovative therapeutic strategies. No significant financial relationships to disclose.
Phase II trial of neoadjuvant exemestane [EXE] and celecoxib [CELE] in breast cancer: Results of biomarkers
Authors: Shapiro C. L. , Povoski S. P. , Jiminez R. , Dehart J. , Ottman S. , Shiels D. R. , Xiaobia L. , Brueggemeier R. 
Published: March 2020

11056 Background: Aromatase [CYP19] activity and expression is increased by prostaglandin E2, thus providing a rational for combining the COX-2 inhibitor, CELE, with an aromatase inhibitor. To evaluate the effects of these drugs on proliferation and other biomarkers, we conducted a neoadjuvant trial of EXE alone followed by the combination of EXE and CELE. The primary endpoint was the assessment of biomarkers and the secondary endpoint was toxicity. Methods: Clinical stages II/III, postmenopausal, estrogen [ER] and/or progesterone receptor [PR] positive, previously untreated, ECOG 0–1 were eligible. Excluded were inflammatory breast cancer, history of myocardial infarction, and documented allergy to aspirin, NSAIDs, or sulfonamides. After initial core biopsy pts received 8 weeks (wks) of EXE 25 mg daily. They then received a second core biopsy followed by 8 wks of EXE and CELE 400 mg twice daily. After 16 wks, pts had definitive surgery. Compliance was assessed by pill counts at study visists every 4 wks. At baseline, 8, and 16 wks, pts had tumor measurements by physical exam, mammogram, and ultrasound. A tissue microarray [TMA] was contructed and immunohistochemical [IHC] staining with commercially available antibodies for Ki-67, COX-2, HER-2, ER, and PR was performed. Two independent pathologists scored intensity and percentage of cells staining and were blinded to treatment and the timimg of specimen acquistion. Statistical analyses were performed using Wilcoxon signed-rank test Results: Twenty pts with a median age 62 (range 56–87) were enrolled. CELE was discontinued in 3 (15%) pts for grade 1 rash-1 pt; grade 1 creatinine elevation-1 pt; and grade 1 melena-1 pt. Three (15%) pts-partial response, 16 (80%)-stable disease, and 1 (5%)-progressive disease. None of the differences in biomarkers between 0 and 8 wks and 8 and 16 wks were significant. A trend toward decreasing mean Ki 67 was observed from 0 to 8 wks (20% vs 9%, p=0.19) and 8 to 16 wks (9% vs 7%, p=0.7) Conclusions: Neoadjuvant EXE followed by EXE/CELE was well tolerated with anti-tumor activity. Tumor cell proliferation decreased by about 50% during EXE, but small sample size precluded reaching statistical significance. Frozen tissue was collected and the results of CYP 19 mRNA expression will be presented. [Table: see text]
Biweekly neoadjuvant gemcitabine, epirubicin, and nano-particle albumin bound (nab) paclitaxel (GEA) with tumor SPARC analysis correlated with pathologic responses: Results of a multicenter phase II trial
Authors: Daniel B. R. , Doss H. , Gian V. , Meluch A. A. , Murphy P. B. , Peacock N. W. , Raefsky E. , Yardley D. A. , Simons L. , Inhorn R. C. 
Published: March 2020

11060 Background: The triplet combination of gemcitabine (G), anthracyclines and taxanes have demonstrated significant activity in the metastatic as well as neoadjuvant breast cancer setting with objective response rates of 90% and pathologic CRs of 20–25% with a variety of schedules. SPARC, a poor prognostic indicator, is a glycoprotein expressed in many solid tumors, including breast cancer, and is thought to mediate active tumor transport of nab paclitaxel resulting in high intratumoral concentrations. The present tumor analysis correlates SPARC expression with pathologic responses to neoadjuvant GEA. Methods: Patients with clinical T1c-T4d and/or N0–3, M0 (T1N0M0 excluded) breast cancer, chemo naive, ECOG PS 0–2, normal LVEF, adequate organ function were treated with neoadjuvant G 2000 mg/m2, epirubicin 50 mg/m2, nab paclitaxel (A)175 mg/m2 IV q14 x 6 cycles followed by surgery. Postoperative therapy: G 2000 mg/m2 and A 220 mg/m2 q14 x 4 cycles. Neulasta 6 mg sc D2 was given with all cycles although alternative granulocyte stimulating factors was permitted. Enrollment planned for 120 pts. Results: 72 pts are enrolled, 48 patients evaluable for toxicityand pathologic responses available for 35 pts. Median age: 48 years (29–73), ECOG PS 0 - 45 pts (96%), 1 - 3 (6%), median tumor size 4.5 cm, 79% ductal, 4% lobular, 13% inflammatory. 54% ER-/PR-, 81% HER2 negative. 21 (60%) were triple negative, basal subtype. Heme toxicity was minimal: G3/4 neutropenia: 4 (8%) pts, thrombocytopenia: 3 (6%) pts. There were no episodes of febrile neutropenia. Nonheme toxicity significant for G3/4 arthraglias: 5 (10%) pts & fatigue in 3 (6%) pts. 3 pts hospitalized (infection, PE, abd pain). 1 pt developed PD during neoadjuvant therapy; 5 pts did not complete post op chemo (pt compliance: 2, PD: 2, MD discretion: 1). pCR was noted in both breast and LNs in 7 pts (20%) and pPR in 26 (74%). Conclusions: Neoadjuvant dose dense GEA is feasible and extremely well tolerated. Significant activity with a pCR of 20% is evident with the basal subtype of breast cancer. SPARC tumor analysis correlations with observed pathologic responses will be presented and updated with the continuing accrual to this trial. No significant financial relationships to disclose.
Ductal carcinoma in situ (DCIS) breast specimens need to be embedded completely in order to determine the correct extent of the disease
Authors: Bendrat K. , Georgiev G. , Corterier H. , Friedrichs K. , Lindner C. , Niendorf A. 
Published: March 2020

11061 Background: The processing of breast specimens suspicious of ductal carcinoma in situ (DCIS) is hampered by the fact that DCIS is not regularily visible at the gross level. There is no general consensus as how to process those breast specimens. Suggestions lead from examination of the entire tissue sample with a special focus on the resection margins to algorithms such as cutting only those paraffin blocks containing calcifications. Methods: In order to identify the influence of the diagnostic method on the measured extent of a DCIS lesion we compared two approaches. One was based on the examination of a single section and the other on examination of the entire specimen, i.e. cutting multiple 0.5 cm slices to be analyzed as max. 52 x 76 mm whole mount sections. 187 consecutive breast specimens from 186 patients (median patient age 60 years, range 31 to 87 years) from three gynecological institutions between Jan 2004 and Nov 2006 were searched for DCIS. We compared the largest tumor diameter from a single section of a specimen (‘apparent diameter‘, AD) with a ‘reconstructed diameter‘ RD calculated on the basis of the number of 0.5 cm slices taken from a sample and the number of slices containing the DCIS lesion. Results: Complete histological examination of these 187 cases (90 high and 97 low grade DCIS lesions) revealed a statistically significant difference (p=7.5E-9) between the apparent diameter AD (mean 22.4 mm, range 2 to 80 mm) and the reconstructed diameter RD (mean 31.6 mm, range 6 to 76 mm). In 138 cases (73.8%) the true extent of the disease would have been underestimated (RD > AD) if the diagnosis had been based only on a single exemplary section, the mean difference RD-AD being 14.8 mm (range 1–50 mm). In addition, we found 40 invasive cancers (multifocal inside the DCIS lesion, unifocal inside the DCIS and unifocal outside the DCIS). Conclusions: We conclude that the complete examination of a breast specimen helps to determine the true extent of DCIS and additionally helps to identify cases that turn out to be already invasive. Both findings may have important impact on the patients’ further treatment and outcome. No significant financial relationships to disclose.