Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. Methods: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3-9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. Results: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed >= 1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (>= 7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. Conclusions: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases. (C) 2021 The Authors. Published by Elsevier Ltd.

Selenium is an essential trace element with roles in musculoskeletal health (1,2) . Osteoclast inactivation is associated with selenium supplementation in vitro and selenium status is correlated negatively with markers of bone health (3,4) . However, the impact of selenium supplementation on bone turnover markers (BTM) has not been studied. This study investigated the effects of selenium supplementation for up to 5 years in older people on BTM including osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks and bone alkaline phosphatase. 490 Danish men and women (60 – 74 y) were randomised to receive 0, 100, 200 or 300 μ g of selenium daily as selenium-enriched yeast. Plasma selenium concentration was measured using inductively-coupled-plasma mass spectrometry and BTMs were measured using an autoanalyser at baseline, 6 months and 5 years in non-fasted

Abstract Funding Acknowledgements The Danish Heart Foundation, Copenhagen (grant number: 14-R97-A5188-22839 and 15-R99-A5940). The Research Fond of the Region of Southern Denmark. Background Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. The possibility to detect signs of acute myocardial deterioration at treatment initiation is not thoroughly investigated. Accordingly, the aim of this study was to assess changes in GLS and biomarkers within the first two weeks of trastuzumab treatment. Methods In a prospective cohort study 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8% (SD ± 3.6), GLS -19.9% (SD ± 2.1), 40% hypertension) were included. Examinations including echocardiography and measurement of troponin T and NT-proBrain Natriuretic Peptide were conducted before initiation of trastuzumab, at day 3, 7 and 14 and after 3, 6 and 9 months. Results A significant deterioration in LVEF, GLS, s’, e’ septal and s’RV occurred during the 9 months study period and was proceed by significant changes in all these parameters within the first 14 days. After 14 days 12 patients (27%) had an increase in GLS ≥10 %, which was associated with significantly lower LVEF at nine month at 55.2% (SD ± 4.1) vs. 59.5% (SD ± 3.5) (p = 0.001) compared to patients with <10 % early increase in GLS (Figure 1). No difference in plasma concentrations of cardiac biomarkers was observed between the two groups. Conclusion In this cohort study deteriorations in key echocardiographic parameters were detected within the first two weeks of trastuzumab treatment, and an early 10 % increase in GLS was associated with a lower LVEF at nine months. Abstract P1533 Figure 1

Abstract Background: The international, randomized, placebo-controlled phase III ExteNET trial showed that a 1-year course of neratinib after trastuzumab-based adjuvant therapy significantly improved 2-year invasive disease-free survival (iDFS) in patients with early-stage HER2+ breast cancer (BC) (hazard ratio 0.67; 95% CI 0.50–0.91; p=0.009) [Chan et al. Lancet Oncol 2016]. The significant iDFS benefit with neratinib was maintained after a median 5 years' follow-up (hazard ratio 0.73; 95% CI 0.57-0.92; p=0.008) [Martin et al. ESMO 2017]. At both time-points, marked benefit with neratinib was evident in patients with hormone receptor (HR)+ tumors, whereas in patients with HR– disease, initial improvements with neratinib diminished after completing treatment. We report exploratory analyses from the ExteNET trial done to better characterize the effects of neratinib in the HR+ subgroup. Methods: Patients with early-stage HER2+ BC were randomly assigned to oral neratinib 240 mg/day or placebo for 1 year after standard primary therapy and trastuzumab-based adjuvant therapy. Randomization was stratified by HR status (locally assessed), nodal status, and trastuzumab regimen. Adjuvant endocrine therapy was recommended for patients with HR+ disease. Data concerning disease recurrences were collected prospectively during year 1-2 post-randomization, and from medical records during year 3–5 post-randomization. Primary endpoint: iDFS. Secondary endpoints: DFS including ductal carcinoma in situ (DFS-DCIS); time to distant recurrence (TTDR); distant DFS (DDFS); cumulative incidence of central nervous system (CNS) recurrences; overall survival (OS). Hazard ratios (95% CI) were estimated using Cox proportional-hazards models. Data cut-off: March 2017. Clinicaltrials.gov: NCT00878709. Results: 2840 patients were randomized (neratinib, n=1420; placebo, n=1420); 1631 (57%) patients had HR+ tumors (neratinib, n=816; placebo, n=815). 93% and 94% of HR+ patients in the neratinib and placebo groups, respectively, were receiving adjuvant endocrine therapy at baseline. Efficacy outcomes in the HR+ cohort after a median follow-up of 5.2 years are shown in the table. In subgroup analyses of the HR+ cohort, hazard ratios for iDFS were 0.49 in centrally confirmed HER2+ patients (n=951), and 0.58 in patients who had completed prior trastuzumab ≤12 months before randomization (n=1334). CNS recurrence and OS data are not yet mature. Updated 2-year analysis5-year analysis Hazard ratiobP-value Hazard ratiobP-value Δ, %a(95% CI)(2 sided)Δ, %a(95% CI)(2 sided)iDFS4.10.49 (0.31–0.75)0.0014.40.60 (0.43–0.83)0.002DFS-DCIS4.80.45 (0.29–0.69)<0.0015.10.57 (0.42–0.79)<0.001DDFS3.10.52 (0.32–0.84)0.0084.00.60 (0.42–0.85)0.004TTDR2.90.52 (0.31–0.85)0.013.80.61 (0.42–0.86)0.006a. Difference in event rates between neratinib vs placebo; b. Neratinib vs placebo Conclusions: Neratinib was associated with an absolute iDFS benefit of 4.4% in patients with HR+/HER2+ BC after 5 years' follow-up. HR/HER2 receptor cross-talk may underpin the notable effect of neratinib in patients with HR+ tumors when given in combination with endocrine therapy. Citation Format: Chia SKL, Martin M, Iwata H, Moy B, Lalani AS, Holmes FA, Mansi J, von Minckwitz G, Buyse M, Delaloge S, Ejlertsen B, Yao B, Murias Rosales A, Hellerstedt B, Cold S, Inoue K, Shen Z-Z, Galeano T, Barrios CH, Chan A. Effects of neratinib after trastuzumab-based adjuvant therapy in hormone receptor-positive HER2+ early-stage breast cancer: Exploratory analyses from the phase III ExteNET trial [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 P1-13-03.

Background: DBCG 07-READ was designed to compare sequential EC followed by D with DC in patients with early, TOP2A normal breast cancer as a retrospective evaluation of the DBCG 89D trial suggested that these patients would not benefit from an anthracycline. Methods: This is a multicenter open-label randomized phase III trial. Three groups of women were eligible following completely resected unilateral invasive TOP2A normal (TOP2A gene to centromere 17 ratio of 0.8 to 2.0) breast cancer by mastectomy or breast conserving surgery in combination with axillary clearance or a negative sentinel node biopsy; 1: Age 18 to 39 years; 2: Age 40 to 75 years and estrogen receptor (ER) negative ( 20 mm. Eligible patients were required to have a Charlson Comorbidity (CC) Index Results: Between July 2008 and December 2012 we (12 DBCG centers) randomly assigned 2006 eligible patients to DC (N=1008) or EC-D (N=998). Patient and tumor characteristics were balanced by treatment groups. The median estimated potential follow-up is 5.4 years and the 5-year DFS was 88.0%; 95% CI 85.8 to 90.0 in the EC-D arm and 87.9%; 95% CI 85.7 to 89.9 in the DC arm. No significant difference in the risk of DFS events HR=1.03; 95% CI 0.80 to 1.32; p=0.84 or mortality HR=1.11; 95% 0.79 to 1.56; p=0.55 was observed in the intent to treat analysis. Patient-reported toxicity will be compared for the two chemotherapy regimens. Conclusion: The READ trial gives evidence to support no outcome benefit from anthracycline in patients with TOP2A normal ealy breast cancer. Citation Format: Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen M-B, Knoop AS, Hoejris I, Ewertz M, Balslev E, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. DBCG 07-READ: A randomized phase III trial comparing six cycles of docetaxel and cyclophosphamide (DC) to three cycles of epirubicin and cyclophosphamide followed by three cycles of docetaxel (EC-D) in patients with early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S6-03.

Abstract Background: DBCG 07-READ was designed to compare sequential EC followed by D with DC in patients with early, TOP2A normal breast cancer as a retrospective evaluation of the DBCG 89D trial suggested that these patients would not benefit from an anthracycline. Methods: This is a multicenter open-label randomized phase III trial. Three groups of women were eligible following completely resected unilateral invasive TOP2A normal (TOP2A gene to centromere 17 ratio of 0.8 to 2.0) breast cancer by mastectomy or breast conserving surgery in combination with axillary clearance or a negative sentinel node biopsy; 1: Age 18 to 39 years; 2: Age 40 to 75 years and estrogen receptor (ER) negative (<10% positive) and/or HER2 positive tumor; and 3: Age 40 to 59 years and ER ≥ 10% positive and either node positive, ductal carcinoma and grade II-III, or tumor size > 20 mm. Eligible patients were required to have a Charlson Comorbidity (CC) Index < 2 and to be without signs of distant metastasis. Patients were randomized to receive 6 cycles of DC (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks or 3 cycles of EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) followed by 3 cycles of D (docetaxel 100 mg/m2) every 3 weeks. In case of a CC Index of 1 or 2 chemotherapy was administered at a reduced dose-intensity. Adjuvant endocrine treatment, trastuzumab and radiotherapy were administered according to the guidelines of the DBCG. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS) and distant disease-free survival (DDFS). Results: Between July 2008 and December 2012 we (12 DBCG centers) randomly assigned 2006 eligible patients to DC (N=1008) or EC-D (N=998). Patient and tumor characteristics were balanced by treatment groups. The median estimated potential follow-up is 5.4 years and the 5-year DFS was 88.0%; 95% CI 85.8 to 90.0 in the EC-D arm and 87.9%; 95% CI 85.7 to 89.9 in the DC arm. No significant difference in the risk of DFS events HR=1.03; 95% CI 0.80 to 1.32; p=0.84 or mortality HR=1.11; 95% 0.79 to 1.56; p=0.55 was observed in the intent to treat analysis. Patient-reported toxicity will be compared for the two chemotherapy regimens. Conclusion: The READ trial gives evidence to support no outcome benefit from anthracycline in patients with TOP2A normal ealy breast cancer. Citation Format: Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen M-B, Knoop AS, Hoejris I, Ewertz M, Balslev E, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. DBCG 07-READ: A randomized phase III trial comparing six cycles of docetaxel and cyclophosphamide (DC) to three cycles of epirubicin and cyclophosphamide followed by three cycles of docetaxel (EC-D) in patients with early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S6-03.

To the Editor,Neoadjuvant chemotherapy (NAC) plays an important role in patients with locally advanced breast cancer (LABC). Achievement of pathologic complete response (pCR) at surgery is a surrog...

The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1.We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20–80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0–1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m2 per day), S-1 only (80 mg/m2 per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m2) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082.We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2–57·6) and that of sequential treatment was 57·2% (53·4–60·8; hazard ratio [HR] 0·92, 95% CI 0·80–1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2–56·6) and that of the S-1 group was 58·2% (54·4–61·8; HR 0·81, 95% CI 0·70–0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3–4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3–4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively).Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan.Epidemiological and Clinical Research Information Network.

Background: Chronic pain is often reported after surgery for breast cancer. This study examined pain and sensory abnormalities in women following breast cancer surgery.Methods: Sensory tests were carried out on the operated and contra‐lateral side in 55 women with chronic pain after breast cancer treatment and in a reference group of 27 pain‐free women, who had also undergone treatment for breast cancer. Testing included a numeric rating score of spontaneous pain, detection and pain threshold to thermal and dynamic mechanical stimuli and temporal summation to repetitive pinprick stimulation. The neuropathic pain symptom inventory was applied for participants with chronic pain.Results: The mean age was 58.6 years for the pain patients and 60.6 years for the pain‐free patients. Thermal thresholds were significantly higher on the operated side than on the contra‐lateral side in both groups and side difference in warmth detection threshold was significantly higher in the pain group than in the pain‐free group (mean 3.8 °C vs. 1.1 °C, P=0.01). The frequency of cold allodynia was higher in participants with pain than in pain‐free participants (15/53 vs. 1/25, P=0.01), and the frequency of temporal summation evoked by repetitive pinprick was higher in participants with pain than in pain‐free participants (23/53 vs. 2/25, P=0.0009). The frequency of dynamic mechanical allodynia did not differ significantly between the two groups.Conclusion: These findings suggest that chronic pain after surgery for breast cancer is associated with sensory hyperexcitability and is a neuropathic pain condition.

Abstract Background: Obesity is associated with an increased risk of dying from breast cancer. There may be several explanations for this such as obese women being diagnosed at a more advanced stage of disease or that treatment is less effective in obese patients. The aim of this study was to examine the influence of obesity on the risk of recurrence and death from breast cancer or other causes in relation to adjuvant treatment.Material and methods: From the database of the Danish Breast Cancer Co-operative Group (DBCG) we identified 53816 women who received treatment for early breast cancer according to the DBCG protocols between 1977 and 2006 with complete data on follow up. Information was available on age and menopausal status at diagnosis, tumor size, number of lymph nodes removed, number of positive lymph nodes, deep fascia invasion, histological type, grade of malignancy, estrogen receptor status, treatment regimen, and protocol version (year), while data on height and weight to derive the body mass index (BMI, weight in kilograms divided by the square of height in meters) were available for 18967 patients or 35 % of the patients. The chemotherapy regimens included cyclophosfamide, metotrexate, and fluorouracil (CMF) up to 1999 and cyclophosfamide, epirubicin, and fluorouracil (CEF) from 1999 onwards. Endocrine therapy included mainly tamoxifen of durations from one to five years depending on time period. Associations between BMI (<25 vs ≥25,<30 vs ≥30) and other prognostic factors were analyzed by using the chi square test. Cause specific survival and invasive disease-free survival (type of first failure) were analysed by univariate and multivariate methods using Cox proportional hazards regression models.Results: Compared with patients with a BMI less than 25, those with a higher BMI were older, more often postmenopausal, had larger tumors, more lymph nodes removed and more positive lymph nodes, more often invasion into deep fascia (all p<0.0001), and more often grade III tumors (p=0.04). Univariate analyses showed that the risk of a loco-regional recurrence was not related to BMI while the risk of distant metastases increased with increasing BMI after 3 years of follow up. The risk of dying from breast cancer remained elevated for patients with high BMI throughout 30 years of observation. Adjusting for the effect of other prognostic factors, multivariate analyses confirmed an independent prognostic effect of obesity. Within the first 10 years of follow-up chemotherapy and endocrine treatment were equally effective in lean and obese patients. However, after 10 or more years of follow-up, the treatment effect did not last in obese patients who had a poorer survival despite treatment.Conclusion: Results from this population-based cohort of almost 19000 patients followed for up to 30 years confirmed that obesity is associated with a poorer prognosis after breast cancer. This is likely to be due to obese patients having a higher risk of developing distant metastases than lean patients and that adjuvant treatment seems to loose its effect more rapidly in obese patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 18.

1015 Background: Gemcitabine (G), either as a single agent or in combination with taxanes, has demonstrated efficacy in MBC in phase II and III studies. We conducted a phase III study to compare time to progression (TTP) of G plus docetaxel (T) versus (vs.) T alone. The secondary endpoints included overall survival (OS), overall response rate (ORR), and toxicity. Methods: Females with HER-2-negative locally advanced or MBC and a WHO performance status ≤ 2 were randomized to GT (G 1,000mg/m2 day 1 + 8; T 75mg/m2 day 1) or T (100mg/m2 day 1) every 21 days. Pts were previously untreated, had prior anthracycline-based (neo)adjuvant chemotherapy or had received a single prior anthracycline-bsed chemotherapy regimen for MBC. Time-to-event endpoints were estimated using the Kaplan-Meier method, and the log-rank test was applied for comparisons between regimens. The planned sample size was 254 evaluable pts with α I and β of 0.05 and 0.90, respectively. Results: A total of 336 pts were randomized (170 GT; 166 T), data from one centre are yet missing and the present evaluation is based on data from 306 pts (155 GT; 151 T). The pts had a median age of 58 years in both regimens; range 36–73 years and 30–74 years, respectively. The median TTP was 7.5 months for the GT regimen vs. 6.5 months for the T regimen. The GT arm demonstrated an ORR of 44% vs. 38% in the T arm with 4 and 3 % complete responses, respectively. The OS was 13.4 vs. 13.2 months in the GT and T arm, respectively. Hematologic toxicity was common, especially grade 3–4 neutropenia (GT = 69%; T = 61%); infection was reported in 22 and 20% of the pts, respectively (none of the pts received G-CSF). The most commonly reported non-hematologic toxicities of grade 3–4 included mucositis (GT = 2%; T = 5%), diarrhea (GT = 4%; T = 7 %), fatigue (GT = 6%; T = 11%), oedema (GT = 10%; T = 3%), and peripheral neuropathy (GT = 9%; T = 28%). Conclusions: Preliminary data of GT as first- or second-line chemotherapy demonstrates a TTP advantage among HER-2-negative pts with advanced breast cancer. Updated results and proper statistical analyses will be presented. No significant financial relationships to disclose.

Numerous genetic linkages, association studies have been performed in different ethnic groups and revealed many susceptibility loci and genes for nicotine dependence. However, limited similar researches were performed in Han Chinese. This study was designed to investigate the association of candidate genes with nicotine dependence in Han Chinese. We genotyped 384 SNPs within 45 candidate genes with nicotine dependence in a Han Chinese population consisting 223 high nicotine dependent subjects and 257 low nicotine dependent subjects by employing GoldenGate genotyping assay (Illumina). Following association analysis was performed using PLINK software. Individual SNP-based association analysis revealed that nine SNPs located in DRD3 (rs2630351), DRD5 (rs1967550), MAP3K4 (rs2314378), DDC (rs11575461), CHRNB3 (rs4954), GABBR2 (rs2779562), DRD2 (rs11214613 and rs6589377) and CHRNA4 (rs2236196) were significantly associated with FTND after correction for multiple testing with the p values from 2.59 × 10− 7 to 9.99 × 10− 5. Haplotype-based association analysis revealed haplotype G-A-A formed by rs2630351, rs167771 and rs324032 and haplotype G-G-G-A formed by rs3773678, rs2630349, rs2630351 and rs167771 in DRD3; haplotype of G-A formed by rs2779562 and rs2808566 in GABBR2 and haplotype of T-T-A-G-A formed by rs6832644, rs4057797, rs9764, rs4552421 and rs10033119 in NPY1R are associated with FTND (p = 3.61 × 10− 7–8.78 × 10− 6). Our results provided confirmation of the previous findings that DRD2, DRD3, DDC, CHRNB3, GABBR2 and CHRNA4 are associated with nicotine dependence. Furthermore, we for the first time report a significant association between nicotine dependence and DRD5, MAP3K4 and NPY1R. These findings need independent replication in the future studies.

Background and purpose: The aim of this randomized, double-blind, placebo-controlled, cross-over study was to test whether levetiracetam relieves the postmastectomy pain syndrome (PMPS). Methods: Postmastectomy pain syndrome was defined as pain of neuropathic character located in the area of the surgery and/or the ipsilateral arm. The inclusion criteria were: age more than 18 years, characteristic symptoms corresponding to PMPS more than 6 months after surgery for breast cancer, pain duration more than 3 months, peripheral nerve lesions confirmed by abnormal neurological and quantitative sensory tests, intensity of pain more than 4 on a numeric rating scale from 0 to 10 and pain present at least 4 days a week. Results: Forty-nine patients were screened for participation and 27 patients were included in the study. Twenty-five patients completed two treatment phases of 4 weeks duration with levetiracetam (3000 mg/day) and placebo. There was no difference in the rating of pain relief between treatment with levetiracetam (P = 0.83) and placebo nor when adjusted for possible period effect (P = 0.60). Analysis defining response as pain relief more than 4 on an eleven-point numeric rating scale showed no significant difference between treatment with levetiracetam and placebo (P = 1.00). Conclusions: Levetiracetam apparently does not relieve peripheral neuropathic pain in PMPS.

The prevalence of the postmastectomy pain syndrome (PMPS) and its clinical characteristics was assessed in a group of patients who had undergone surgery for breast cancer at the Department of Surgery, Odense University Hospital, within the period of 1 May 2003 to 30 April 2004. The study included 258 patients and a reference group of 774 women. A questionnaire was mailed to the patients 1½ year after surgery and to the women in the reference group. The PMPS was defined as pain located in the area of the surgery or ipsilateral arm, present at least 4 days per week and with an average intensity of at least 3 on a numeric rating scale from 0 to 10. The prevalence of PMPS was found to be 23.9%. The odds ratio of developing PMPS was 2.88 (95% confidence interval 1.84–4.51). Significant risk factors were as follows: having undergone breast surgery earlier (OR 8.12), tumour located in the upper lateral quarter (OR 6.48) and young age (OR 1.04). This study shows that, although recent advances in the diagnostic and surgical procedures have reduced the frequency of the more invasive surgical procedures, there still is a considerable risk of developing PMPS after treatment of breast cancer.

Background. The validation series of sentinel lymph node biopsy (SLNB) in the treatment of breast cancer have shown that 10-20% more lymph node metastases are detected. However, their impact has never been studied in populations where the method has been fully implemented. In a population-based setting, the objective of the current study was to estimate the increased risk of metastases after introduction of the sentinel lymph node biopsy technique. Methods. We identified all new breast cancer patients in three different counties in two time periods (1996-1997 and 2002-2003). The study cohort was comprised of 2 932 patients. The main outcome was the frequency of patients with metastases. The frequencies of patients with metastases were compared as well as adjusted (using a multivariate logistic regression) and unadjusted odds-ratio for detecting lymph node metastases. Results. In counties where sentinel lymph node biopsy was implemented, the frequency of patients with lymph node metastases increased significantly 7.3% (95% CI: 1.0-13.7%) and 13.3% (95% CI: 7.3-19.3%), respectively. In the county without sentinel lymph node biopsy, an insignificant increase of 6.9'% (-0.1-13.9%) in the frequency of patients with metastases was seen. The adjusted odds- ratio for detecting lymph node metastases was 1.41 (1.07-1.87) and 1.70 (1.30-2.23) in the counties with SLNB. Conclusion. The frequency of patients with metastases increased significantly in counties where sentinel lymph node biopsy was implemented.

European Journal of PainVolume 11, Issue S1 p. S131-S131 295 THE POSTMASTECTOMY PAIN SYNDROME: AN EPIDEMIOLOGICAL STUDY O.J. Vilholm, O.J. Vilholm Department of Neurology, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorS. Cold, S. Cold Department of Oncology, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorL. Rasmussen, L. Rasmussen Department of Surgery, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorS.H. Sindrup, S.H. Sindrup Department of Neurology, Odense University Hospital, Odense, DenmarkSearch for more papers by this author O.J. Vilholm, O.J. Vilholm Department of Neurology, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorS. Cold, S. Cold Department of Oncology, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorL. Rasmussen, L. Rasmussen Department of Surgery, Odense University Hospital, Odense, DenmarkSearch for more papers by this authorS.H. Sindrup, S.H. Sindrup Department of Neurology, Odense University Hospital, Odense, DenmarkSearch for more papers by this author First published: 16 January 2012 https://doi.org/10.1016/j.ejpain.2007.03.310Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume11, IssueS1June 2007Pages S131-S131 RelatedInformation

Purpose To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer. Patients and Methods Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or 100 mg/m 2 intravenously every 3 weeks. Results Five hundred twenty-seven patients were randomly assigned (intent to treat [ITT]), and 524 were assessable for toxicity. In the population assessable for efficacy (n = 407), logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate (P = .007) and improved time to progression (TTP; P = .014). In the ITT analysis, a significant dose-response relationship was observed for tumor response (P = .026) but not for TTP (P = .067). The incidences of most hematologic and nonhematologic toxicities were related to increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and 93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients administered the 60, 75, and 100 mg/m 2 doses, respectively. One death was considered treatment related. Conclusion A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m 2 every 3 weeks. Toxicities were related to increasing dose. Depending on the therapy goal, any of the doses studied may be appropriate for second-line treatment of advanced breast cancer.

Valorar la utilidad de la biopsia selectiva del ganglio centinela (BGC) después de la quimioterapia neoadyuvante (QTN) en pacientes con cáncer de mama operable y axila positiva al diagnóstico.Estudio prospectivo entre enero de 2008 y diciembre de 2012 en 52 pacientes, con una edad media de 50,7 años y con cáncer de mama infiltrante T1-3, N1, M0 (uno bilateral, 7 multifocales), tratadas con epirrubicina/ciclofosfamida, docetaxel y trastuzumab en HER-2/neu positivas. El estatus axilar se estableció por la exploración física, la ecografía axilar y la punción ecoguiada de ganglios sospechosos. El día antes de la cirugía se inyectó periareolarmente 74-111 MBq de 99mTc-nanocoloide de albúmina. En todas se realizó una cirugía mamaria, una BGC y una linfadenectomía axilar. El GC se analizó por cortes de congelación, hematoxilina-eosina, inmunohistoquímica u OSNA.Tamaño medio del tumor: 3,5 cm. Tipo histológico: 81,1% carcinoma ductal infiltrante. Respuesta completa al tumor primario: clínica 43,4%, patológica 41,5%. Ninguna de las pacientes presentó adenopatías axilares palpables después del tratamiento. Respuesta completa patológica axilar: 42,2%.El porcentaje de identificación del GC fue de 84,9%. En 6 de las 8 pacientes sin migración del nanocoloide la axila resultó positiva en el estudio anatomopatológico. En el 95,5% de los casos el GC determinó correctamente el estatus axilar. La tasa de falsos negativos fue de 8,3%. En el 68,2% de los casos el GC fue el único afectado de la axila. El número medio de GC identificados fue de 1,9 y el de ganglios axilares extirpados fue de 13,2.La BGC post-QTN es una técnica segura y factible en pacientes con cáncer de mama operable T1-3, N1 y axila clínicamente negativa después del tratamiento.To evaluate the utility of the sentinel lymph node biopsy (SLNB) in patients with operable breast cancer and positive axillary nodes at initial diagnosis treated with neoadjuvant chemotherapy (NAC).A prospective study was performed from January 2008 to December 2012 in 52 women, mean age 50.7 years, with infiltrating breast carcinoma T1-3, N1, M0 (1 bilateral, 7 multifocal) treated with epirubicin/cyclophosphamide, docetaxel and trastuzumab in Her2/neu-positive patients. Axillary evaluation included physical examination, axillary ultrasound, and ultrasound-guided core needle biopsy of any suspicious lymph node. The day before surgery, 74-111 MBq of 99mTc-albumin nanocolloid was injected periareolarly. All patients underwent breast surgery, with SLNB and complete axillary lymph node dissection (ALND). The SLNs were examined by frozen sections, hematoxylin-eosin staining, immunohistochemical analysis or one-step nucleic acid amplification assay (OSNA).Mean tumor size: 3.5 cm. Histologic type: 81.1% invasive ductal carcinoma. Complete response of primary tumor was clinical 43.4%, pathological 41.5%. All patients were clinically node-negative after NAC. Pathological complete response of axillary node was 42.2%.SLN identification rate was 84.9%. Axilla was positive in the pathology study in 6 of 8 patients without nanocolloid migration. SLN accurately represented the axillary status in 95.5%. False negative rate was 8.3%. SLN was the only positive node in 68.2% of patients. Mean number of SLN removed was 1.9 and of nodes resected from the ALND 13.2.SLN biopsy after NAC is a feasible and accurate tool in patients with operable breast cancer T1-3, N1 and clinically node-negative after therapy.

The purpose of this study was to examine the effect on survival of delaying the start of adjuvant chemotherapy for early breast cancer for up to 3 months after surgery. In the nation-wide clinical trials of the Danish Breast Cancer Cooperative Group, 7501 breast cancer patients received chemotherapy within 3 months of surgery between 1977 and 1999: 352 with classical cyclofosfamide, metotrexate and 5-fluorouracil (CMF); 6065 with CMF i.v. and 1084 with cyclofosfamide, epirubicin and 5-fluorouracil. For the analysis, the time between surgery and the start of chemotherapy was divided into four strata (1–3, 4, 5 and 6–13 weeks). The results show that within the three groups of chemotherapy, there was an even distribution of known prognostic factors across the four strata of initiation of chemotherapy. There was no pattern indicating a benefit from early start of chemotherapy. No significant interactions were found for subgroups of patients with a poorer prognosis (many involved lymph nodes, high-grade malignancies or hormone receptor negative disease). In conclusion, we have found no evidence for a survival benefit due to early initiation of adjuvant chemotherapy within the first 2–3 months after surgery.