Background CT-P6 is a proposed biosimilar to reference trastuzumab. This trial (NCT02162667) evaluated the similarity of CT-P6 and reference trastuzumab for both efficacy and safety in HER2 positive EBC patients. The primary endpoint, pathological complete response (pCR) rate was entirely within the pre-defined equivalence margin (Stebbing et al., Lancet Oncology 2017). Efficacy and safety were similar between the two treatment groups. We aimed to investigate the cardiotoxicity in the 1 year treatment and follow-up period. Methods A total of 549 patients with HER2 positive EBC were randomized to receive CT-P6 (n=271) or reference trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin and cyclophosphamide (FEC, Cycles 5-8) in the neoadjuvant setting. CT-P6 or reference trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received monotherapy of CT-P6 or reference trastuzumab up to 10 cycles in the adjuvant setting. Left ventricular ejection fraction (LVEF) was evaluated by ECHO or MUGA at baseline, every 3 or 4 cycles during treatment and every 6 months thereafter. If LVEF decreased by ≥10 points from baseline and <50%, a reassessment was performed within 3 weeks and the patient was withdrawn from the study treatment if the cardiac toxicity was confirmed. Results Median follow-up period was 19 months. In total, 96% of patients completed 8 cycles of taxane and anthracycline combination therapy during the neoadjuvant period and 90% of patients in each group received 1-year treatment of CT-P6 or reference trastuzumab. The relative dose intensity of study drug was similar, indicating good tolerability of CT-P6 and reference trastuzumab (97.5% and 97.3% during the neoadjuvant period; 98.5% and 98.8% during the adjuvant period). Docetaxel and FEC combination therapies were administered approximately 96% of dose intensity in the two groups. All patients had normal LVEF (≥55%) at baseline. Mean LVEF value was maintained more than 60% during 1-year treatment and follow-up period. Heart failure cases with LVEF decrease (≥10 points from baseline and <50%) were reported to be similar between two groups. Three patients in each group were withdrawn due to LVEF decrease. Adverse events of cardiac disorders were reported to be similar between two groups. All cases were mild or moderate except two cases. Table 1. Summary of heart failure with LVEF decrease and cardiotoxicity CT-P6 (N=271)Reference Trastuzumab (N=278)LVEF decrease ≥ 10 points and below 50%9 (3.3%)7 (2.5%)- Asymptomatic9 (3.3%)6 (2.1%)- Symptomatic01 (0.4%)- Confirmed2 (0.7%)4 (1.4%)- Withdrawn3 (1.1%)3 (1.1%)Cardiac disorder by AEs31 (11.4%)38 (13.7%)- Grade 1 to 230 (11.0%)37 (13.3%)- Grade 3 to 51 (0.4%)11 (0.4%)21 Grade 3 of Adams-Strokes syndrome occurring 5 months after the completion of 1-year treatment; 2 Grade 5 of acute myocardial infarction occurring 10 days after Cycle 1 of the neoadjuvant therapy Conclusions Combination therapy of CT-P6 with taxane/anthracycline and monotherapy of CT-P6 over 1 year period were well tolerated and cardiotoxicity was similar to reference trastuzumab. Citation Format: Esteva FJ, Chung HC, Royce ME, Lee SY, Lee SJ, Stebbing J. Cardiotoxicity in 1 year of treatment with reference trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early stage breast cancer (EBC) patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-14.
Background ACOSOG Z1041 (Alliance) found pathological complete response rates in women with operable HER2-positive breast cancer were similar with FEC → P+T (Arm 1) and P+T → FEC+T (Arm 2) where treatment was administered as 5-FU 500 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 day 1 of a 21-day cycle x 4; paclitaxel 80 mg/m2 weekly x 12 and trastuzumab 4 mg/kg once then 2 mg/kg weekly x 11. We now report DFS and OS results with a median follow up of 4.4 years (range: 26 days to 6.2 years). Methods All patients who began study treatment were included in the analyses. Stratified log rank tests and stratified proportional hazard models were used to assess differences in DFS and OS from randomization between treatment arms. Results From September 15, 2007 to December 15, 2011, 282 women with HER2-positive breast cancer were enrolled. Two patients randomized to arm 1 withdrew consent prior to treatment and are excluded from these analyses. Patient and disease characteristics of the remaining 280 women (arm 1, n=138; arm 2, n=142) were similar between treatment arms. Recurrences and deaths are shown in the table. DFS were not found to differ with respect to treatment arm (stratified logrank p=0.6870; HR stratified (Arm2/Arm1)=0.88; 95%CI: 0.48-1.61). Also, OS was not found to differ with respect to treatment arm (stratified logrank p=0.8790; HR stratified (Arm2/Arm1)=1.07; 95%CI: 0.43-2.69). Conclusions Concurrent administration of trastuzumab with anthracyclines offers no additional benefit in terms of achieving pathologic complete response or improving survival and is not needed. FEC → P+TP+T → FEC+T Arm 1Arm 2n138142Recurrences2022Deaths811 Grant Support: U10 CA76001 The study is registered with ClinicalTrials.gov, number NCT00513292. Citation Format: Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig GW, Royce ME, Ewer MS, Hunt KK. Disease-free (DFS) and overall survival (OS) data from ACOSOG Z1041 (Alliance) a randomized neoadjuvant trial comparing FEC followed by paclitaxel plus trastuzumab (FEC → P+T) with paclitaxel plus trastuzumab followed by FEC plus trastuzumab (P+T → FEC+T) in HER2-positive operable breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-02.
#6103 Background: Paravertebral block (PVB) is a form of regional block that has long been used in surgical procedures, including breast surgery. PVB provides intraoperative and postoperative analgesia, decreasing the need for narcotics (NA). It also decreases amounts of general anesthesia (GA) required. NA and GA contribute to postoperative nausea and vomiting, which is decreased with PVB. There has not been a modern cost analysis of PVB in breast surgery. The purpose of this study is to evaluate patient comfort and cost effectivness of PVB in breast surgery.
 Materials and Methods: A retrospective chart review of 461 breast cases was performed. Mastectomy with or without axillary staging and lumpectomy with axillary staging were included (n=188). Minor breast biopsies, lumpectomies alone, and combined reconstructions/other procedures were excluded. Data collected included whether or not PVB was performed (based on surgeon/patient/anesthesiologist preference), length of stay (LOS), postoperative requirements for NA and antiemetics (AE), and complications from PVB. Patients (pts) were scheduled as inpatient (IP) or outpatient (OP) based on procedure and comorbidities. The data was analyzed for IP and OP groups for LOS. Cost was calculated from NA and AE use and overnight stay.
 Results: 188 total procedures (125 IP; 63 OP). 88/125 IP had PVB (70%). 57/63 OP had PVB (90%). IP LOS < 24 hrs had 4/5 with PVB (80%); 1/5 without (20%). LOS 24-36 hrs had 46/63 with PVB (73%); 17/63 without (27%). 57 had LOS > 36 hrs; 38/57 with PVB (67%); 19/57 without (33%). OP LOS 0-2 hrs had 41 pts; 39/41 with PVB (95%); 2/41 without (5%). 22 had LOS > 2 hrs; 18/22 with PVB (82%); 4/22 without (18%). There was an overall shorter LOS for both IP and OP with PVB than without (p=0.0151). 152/188 pts required NA (81%). 112/152 received PVB (74%); 40/152 did not (26%). 36/188 did not require NA (19%). 32/36 received PVB (89%); 4/36 did not (11%). There was a difference between those who did and did not receive PVB and NA use (p=0.0257). 86/188 required antiemetics (46%). 59/86 received PVB (69%); 27/86 did not (31%). 102/188 did not require AE (54%). 86/102 received PVB (84%); 16/102 did not (16%). There was a difference between those who did and did not receive PVB and requirements for AE (p=0.0143). Number of doses of NA and AE were summarized as cost values per pt. The average cost for these medications for an IP with PVB was $184 vs $213 without. OP medicine costs with and without PVB was $39 and $111. Overall average cost difference was $29 for IP, $72 for OP. OP also saved $800 overnight charge. For all pts combined, there was a statistical cost difference (p=0.0085). 1/188 pts had a complication (pneumothorax).
 Discussion: PVB results in less use of postoperative NA and AE in breast surgery. Not only is this reflected in pt comfort, but also a statistically significant cost reduction for both IP and OP procedures and LOS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6103.
PURPOSE: We developed a novel, quantitative and high-speed MR spectroscopic imaging (MRSI) method to map total Choline (tCho), a sensitive biomarker of breast tumor status, as an adjunct to enhance the limited specificity of routine dynamic-contrast enhanced (DCE) MRI. Quantitative tCho maps measured in 7 minutes were compared with tCho obtained with conventional Single Voxel Spectroscopy (SVS). METHOD AND MATERIALS: Measurements on a total of 18 healthy female subjects (mean age: 25.6±5) were performed using 3T MR scanners (Siemens Trio, Erlangen, Germany) located at the two partner sites equipped with 4-channel breast coil (Siemens, Erlangen, Germany) or 8-channel breast coil (Sentinelle Medical, Toronto, Canada). 2D MRSI data of an entire oblique slice were collected using Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) [1] with MEGA lipid suppression. Acquisition parameters were: TR/TE=1500ms/125ms, matrix size=32x32, voxel size=2x2x2mm3 (8cc), number of signal averages= 16 with weighted k-space sampling and total acquisition time=7 minutes. PRESS SVS data were acquired with 8 cc voxel size using identical TR/TE and acquisition time. The absolute metabolite concentration was calculated in reference to tissue water (millimoles of tCho per kilogram of solute) using LCModel (s-provencher.com) fitting to estimate the Choline peak baseline and subsequent spectral integration using a Cramer-Rao lower bound threshold of 25%. RESULTS: tCho was detected in 7 of the 15 subjects (47%) in both SVS and PEPSI data. In the PEPSI data sets, tCho was detected in multiple voxels (Fig. 1). Subjects in which tCho was detected exhibited narrower water line width and smaller lipid content than subjects in which tCho was not detectable (2-tailed t-test, P<0.01). The absolute tCho concentrations corrected for relaxation effects in these 7 subjects using SVS and PEPSI was 0.43±0.34 mmol/kg and 0.51±0.19 mmol/kg, respectively. In comparison with SVS data (21.8±8.6Hz), PEPSI spectra demonstrated larger water line width (33.9±12.6Hz) and displayed greater lipid contamination from adipose tissue areas and larger baseline distortion due to the spatial point spread function. CONCLUSION: Despite less favorable shimming and lipid suppression conditions compared to SVS, it is feasible to quantitatively map tCho in healthy breast tissue using high-speed MRSI, with concentration values that are consistent with those from SVS. Studies in breast cancer patients are in progress to assess the feasibility of breast cancer diagnosis and treatment monitoring with MRSI. Results will be reported at the Symposium. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing systemic therapy (i.e. chemotherapy, endocrine therapy) for breast cancer and to develop an improved screening protocol for high risk patients. Fig. 1: PEPSI slice localization (left) and spectral array (right) with superimposed LCModel fit and integrated tCho peak Ref: (1) Posse et al. Magn. Reson. Med. 2007;58(2):236-244. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-16.
Introduction: In New Mexico (NM), Hispanic women have a 1.6-fold increased risk of breast cancer-specific death compared to non-Hispanic white women. In previous studies, race/ethnic minority women have been less likely to receive recommended adjuvant treatments, including radiation in women undergoing breast conservation, and hormonal therapy. Objective: To determine whether non-receipt of recommended therapies contributed to disparate survival. Methods: We conducted a case-cohort study of breast-cancer-specific survival within a population-based cohort of first invasive breast cancer diagnosed in white females from 1997-2009 in six NM counties, identified through Surveillance Epidemiology End Results (SEER). We selected fifteen percent of all women diagnosed with breast cancer and all breast cancer deaths. After IRB approval, data were collected from comprehensive medical chart reviews, supplemented by SEER information. Receipt of standard of care, vs. not, was defined based on age, diagnosis year and tumor characteristics, according to changes in treatment guidelines. Women who had a reported contraindication or refused therapy were omitted from assessment of quality of care for that therapy. Cox proportional hazards models for case-cohort were conducted using weighted estimates, with calculation of robust variance and hazard ratios (HR) and 95% confidence intervals (CI), using an alpha level of .05. Analyses were restricted to women of age 70 or less who survived at least 12 months. The proportional hazards assumption was verified by Schoenfeld residuals. All analyses were adjusted for age. Results: Comprehensive medical records reviews were completed for 91% of eligible women (674 cohort members, 519 breast cancer deaths; median follow up 7.8 years). All others were omitted from analysis. Of women eligible for guideline-based treatment, receipt of guideline-appropriate therapy did not differ by Hispanic ethnicity for any treatment, and Hispanic women were slightly more likely overall to receive appropriate therapy (difference not significant). Among guideline-eligible women, at least 91% received radiotherapy, 78% received chemotherapy, 82% received endocrine therapy, and 89% received anti-HER2 targeted agents. After adjustment for other treatment, lack of receipt of guideline-appropriate therapy was related to an increased risk of breast cancer death for endocrine (HR 1.76; 95% CI 1.09-2.84) and radiation therapy (HR 2.05; 95% CI 1.14-3.69). The few HER2-positive women not treated precluded further assessment. After accounting for endocrine and radiation therapy the survival disparity HR of 1.6 in Hispanic women was reduced to 1.57 suggesting only 2% of the disparity was due to differences in receipt of these treatments. Conclusion: Limitations include likely undercounts of appropriate therapy, thus proportions cited are minimal estimates. Appropriate therapy includes only documented receipt as therapy completion could not always be assessed. Hispanic women have a disproportionately higher breast cancer mortality despite apparently receiving adjuvant therapies to a similar degree as non-Hispanic white women. Equalizing standard of care and attempting to reduce treatment disparities may not be sufficient to address the disproportionate mortality in Hispanic women. Citation Format: Friend SC, Royce ME, Kang H, Lomo L, Barry M, Wiggins C, Prossnitz E, Hill DA. Survival disparities: Quality of care apparently not the answer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-05.
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