Survival Benefit In Breast Cancer Research Articles

Cost-Outcome of Radiotherapy for Local Control and Overall Survival Benefits in Breast Cancer

PurposeRadiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. Methods and MaterialsAll RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. Results481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages.The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively.266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592–3864 AUD (£1350–2012 GBP) per patient was estimated had these patients been treated with the protocol. ConclusionsThe cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol.

Interactions of EGFR/PTEN/mTOR-Pathway Activation and Estrogen Receptor Expression in Cervical Cancer.

(1) Objective: Late-line chemotherapy rechallenge in recurrent cervical cancer is associated with modest therapy response but significant side effects. As mTOR pathways modulate cellular growth via estrogen receptor (ER) signaling and combined mTOR and ER inhibition previously demonstrated survival benefits in breast cancer, this exploratory study evaluates mTOR pathway and ER expression interactions in a preclinical cervical cancer model. (2) Methods: Immunostaining of a 126-tumor core tissue microarray was performed to assess phosphorylated-mTOR and ER expression. To identify tumor subsets with different clinical behavior, expression results were matched with clinicopathologic patient characteristics, and both univariate and multivariable survival statistics were performed. (3) Results: phosphorylated-mTOR correlates with ER (r = 0.309, p < 0.001) and loss of PTEN expression (r = -2.09, p = 0.022) in tumor samples across stages but not in matched negative controls. Positive ER expression is observed significantly more often in phosphorylated-mTOR positive samples (30.0% vs. 6.3%, p = 0.001). In the subgroup of phosphorylated-mTOR positive tumors (n = 60), ER expression is associated with improved survival (p = 0.040). (4) Conclusion: ER expression appears closely intertwined with EGFR/PTEN/mTOR-pathway activation and seems to define a subgroup with clinically distinct behavior. Considering limited therapeutic options in recurrent cervical cancer, further validation of combined mTOR and ER inhibition in selected patients could appear promising.

Abstract P2-23-13: Highly proliferative estrogen receptor-positive breast cancer is associated with better response to neoadjuvant chemotherapy but worse clinical outcome

Abstract Introduction: Highly proliferative cancers are known to respond better to neoadjuvant chemotherapy (NAC), and pathological complete response (pCR) is a surrogate for survival benefit in breast cancer. Ki67 is the most commonly used cell proliferation marker; however, conventional immunostaining is subjected to variability by the assessor and the institution including the antibody used. To this end, we used the Ki67 gene expression to identify highly proliferative breast cancer and investigated whether it is associated with better response to NAC and survival by intrinsic subtype. Materials and Methods: Total of 6623 breast cancer patients from 11 independent cohorts with full transcriptome and clinical data were analyzed. The top 20% of Ki67 gene expression in each cohort were defined as highly proliferative group based on previous studies using immuno-staining. Results: Highly proliferative breast cancer was associated with high proliferation score, and all five cell proliferation-related gene sets in the Hallmark collection; E2F Targets, G2M Checkpoint, Mitotic Spindle, and Myc Targets v1 and v2 were enriched by gene set enrichment analysis in multiple cohorts regardless of subtype. MKI67 gene expression increased with higher grade in both ER-positive breast cancer and TNBC in multiple cohorts, but no clear association with staging was observed. Highly proliferative ER-positive breast cancer was significantly associated with worse disease-free, disease-specific, and overall survival consistently in METABRIC and GSE96058 cohorts, and showed a trend toward worse overall survival in TCGA; however, this was not the case in TNBC. Further, we found that highly proliferative tumor was significantly associated with better pathologic complete response (pCR) rate in six of the eight neoadjuvant chemotherapy cohorts of ER-positive breast cancer, but only two for TNBC. We also found that highly proliferative ER-positive breast cancer was associated with abundant silent and non-silent mutations, increased intra-tumoral heterogeneity, and homologous recombination defect scores when compared to lower proliferation groups, and this was not seen in TNBC in TCGA cohort. Although DNA repair gene set was enriched in the highly proliferative ER-positive breast cancer, it was also associated with higher neoantigen activity, higher infiltration of tumor infiltrating lymphocytes including Th1 cells, Th2 cells, regulatory T cells, and M1 macrophages, as well as with enrichment of Interferon-gamma response gene set consistently in 3 large cohorts. In contrast, several stromal cell fractions were decreased in this group. Conclusions: Highly proliferative ER-positive breast cancer is significantly associated with pCR after NAC with increased tumor infiltrating lymphocytes, but is not a surrogate for survival, which are not the case in TNBC. Citation Format: Rongrong Wu, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li yan, Takashi Ishikawa, Kazuaki Takabe. Highly proliferative estrogen receptor-positive breast cancer is associated with better response to neoadjuvant chemotherapy but worse clinical outcome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-13.

An 11-Gene Signature Based on Treatment Responsiveness Predicts Radiation Therapy Survival Benefit Among Breast Cancer Patients.

PurposeWe developed a strategy of building prognosis gene signature based on clinical treatment responsiveness to predict radiotherapy survival benefit in breast cancer patients.Methods and MaterialsAnalyzed data came from the public database. PFS was used as an indicator of clinical treatment responsiveness. WGCNA was used to identify the most relevant modules to radiotherapy response. Based on the module genes, Cox regression model was used to build survival prognosis signature to distinguish the benefit group of radiotherapy. An external validation was also performed.ResultsIn the developed dataset, MEbrown module with 534 genes was identified by WGCNA, which was most correlated to the radiotherapy response of patients. A number of 11 hub genes were selected to build the survival prognosis signature. Patients that were divided into radio-sensitivity group and radio-resistant group based on the signature risk score had varied survival benefit. In developed dataset, the 3-, 5-, and 10-year AUC of the signature were 0.814 (CI95%: 0.742–0.905), 0.781 (CI95%: 0.682–0.880), and 0.762 (CI95%: 0.626–0.897), respectively. In validation dataset, the 3- and 5-year AUC of the signature were 0.706 (CI95%: 0.523–0.889) and 0.743 (CI95%: 0.595–0.891). The signature had higher predictive power than clinical factors alone and had more clinical prognosis efficiency. Functional enrichment analysis revealed that the identified genes were mainly enriched in immune-related processes. Further immune estimated analysis showed the difference in distribution of immune micro-environment between radio-sensitivity group and radio-resistant group.ConclusionsThe 11-gene signature may reflect differences in tumor immune micro-environment that underlie the differential response to radiation therapy and could guide clinical-decision making related to radiation in breast cancer patients.

Abstract 2486: APOBEC3B and APOBEC3C-H have opposite associations with DNA instability and immune cell infiltration in breast cancer tumors

Abstract Introduction: APOBEC3 enzymes are strong mutagenic factors because of their cytidine deamination activity. In particular, the detrimentally of tumoral APOBEC3B (A3B) expression to clinical outcomes has been well established for breast cancer. We have previously demonstrated that high tumoral expression of many other APOBEC3s (A3C-H) confers better T cell anti-cancer immunity and survival benefit in breast cancer, an interesting finding given that these enzymes are DNA mutators. To this end, we hypothesized that each APOBEC3 has different activity on genomic instability and anti-cancer immunity in breast cancer tumors. Methods: Transcriptomic and clinical data for primary tumors were obtained from The Cancer Genome Atlas (TCGA). Patients were divided into thirds by gene expression and highest and lowest expressors were compared. Measurements of genomic or molecular features such as tumor mutation burden, neoantigen load, aneuploidy, homologous recombinant deficiency (HRD), intra-tumor heterogeneity (ITH), B and T cell receptor (BCR and TCR) diversity hypervariable complementarity- determining region 3 (CDR3) which are critical component of B cell immunoglobulin heavy chain were calculated using the datasets from previous publications. Results: As expected, tumor with high expression of A3B, DNA mutagenesis enzyme, were strongly associated with genome instability. Compared to tumors with low A3B expression, those with high expression had significantly greater mutation burden (1.9x for median value) and neoantigen load (1.8x), as well as scores for aneuploidy (1.7x), HRD (2.5x), and ITH (2.5x; all p values &amp;lt; 0.01).In contrast to A3B, we found that A3C, A3D, A3G and A3H are predominantly expressed in immune cells. Tumor with high expression of A3C demonstrated lower tumor mutation burden (0.9x) and aneuploidy (0.7x). Neoantigen load, HRD and ITH were significantly decreased (0.7 - 0.9x, all p&amp;lt; 0.001) in high A3D expressors. Although infiltrating leukocytes and their CD8 T cell subset were both decreased in tumors with high A3B expression, interestingly, they were increased 1.5-1.8-fold in tumors with high A3G or A3H expression. We also found that A3G and A3H expression had positive correlation with not only TCR diversity (2.0x and 2.1x for A3G and A3H respectively) and immune cytolytic activity (6.4x and 6.5x), but also both BCR diversity (2.6x and 2.1x) and number of unique CDR3s (6.4x and 4.8x) with all p &amp;lt; 0.001 significances. Conclusion: Our data suggests that APOBEC3B and APOBEC3C, 3D, 3G and 3H demonstrate opposite phenotype regarding DNA instability and immune cell infiltration in breast cancer. Citation Format: Mariko Asaoka, Santosh K. Patnaik, Takashi Ishikawa, Kazuaki Takabe. APOBEC3B and APOBEC3C-H have opposite associations with DNA instability and immune cell infiltration in breast cancer tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2486.

Abstract P3-08-05: High APOBEC3C-H gene expression in tumor associates with better survival in breast cancer

Abstract Background APOBEC3 (A3) enzymes are strong mutagenic factors. A3B has been well described as an active mutator in breast cancer, whereas the roles of the other APOBEC3s (A3A, C-H) are unclear. While mutations may directly drive cancer progression, they can indirectly suppress cancer growth by generating neoantigens. To elucidate this, we comprehensively analyzed all APOBEC3s for their association with mutations and immune activity in breast cancer. Methods RNA seq.-based gene expression data for 1091 primary carcinomas and 113 adjacent normal tissues was from TCGA. Patients were divided into high and low groups by top and bottom gene expression tertiles. Tumor immune features like cytolytic activity, T cell receptor (TCR) diversity, and cell fractions were quantified from gene expression data. Data for some of these features, mutation-related aspects, and survival outcomes were obtained from the Pan-Cancer Atlas. Gene expression data for 55 breast cancer cell-lines was from Cancer Cell Line Encycolpedia. Cox regression and Spearman methods were respectively used for survival and correlation analyses. Welch's t test was used for group comparison. P &amp;lt;0.05 was deemed significant. Hallmark gene-sets were used for enrichment analysis with recommended 25% FDR. Results A3B and A3C together represented most (91%) of A3 gene expression in breast cancer cell-lines. In TCGA patients, expression of only A3B was increased by 4.5x in tumors compared to normal tissue, whereas levels for other A3 genes were unchanged. Surprisingly, tumor A3B or A3A levels had no significant association with overall (OS) or disease-specific survival (DSS), whereas for each of A3C-H, higher expression was significantly associated with improved OS (hazard ratios of 0.45-0.66) or DSS (0.43-0.61). The prognostic benefit of high A3C-H expression was also seen in survival analyses of two meta-datasets of microarray-based gene expression (KMPlot and SurvExpress). A3A and A3B levels correlated with both mutation burden and neoantigen load (Spearman ρ = 0.28-0.34), which respectively were 2.0-2.9x higher in high compared to low expressors. But there was no association of expression with mutation burden or neoantigen load for A3C-H. On the other hand, A3C-H levels correlated positively with tumor leukocyte fraction (ρ = 0.29-0.70) and its lymphocyte subset (ρ = 0.20-0.50), whereas the correlation was poor for A3B (ρ = 0.10 &amp; -0.01 respectively). Expression of genes of immune function like interferon response and complement activation was enriched in high A3C-H expressors. It was not so for A3B, for which enrichment was instead observed for cell proliferation. Both CD4 and CD8 T cells were significantly more (2.3-4.0x &amp; 2.1-5.4x resp.), and TCR diversity significantly higher (1.3-2.1x) in A3C-H high expressors. Concordantly, for each of A3C-H, expression correlated with tumor immune cytolytic activity (ρ = 0.31-0.79), which was increased 3.1-7.9x in high compared to low expressors. Conclusions These findings suggest that in spite of A3C-H being known as DNA mutators, an increase in their expression confers a survival benefit in breast cancer. Their increased expression likely reflects a heightened anti-cancer immune response, and may be useful for disease prognosis and monitoring immunotherapy. Citation Format: Asaoka M, Patnaik SK, Katsuta E, Kawaguchi T, Ishikawa T, Takabe K. High APOBEC3C-H gene expression in tumor associates with better survival in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-05.

Revealing clonality and subclonality of driver genes for clinical survival benefits in breast cancer.

Genomic studies have revealed that genomic aberrations play important roles in the progression of this disease. The aim of this study was to evaluate the associations between clinical survival outcomes of the clonality and subclonality status of driver genes in breast cancer. We performed an integrated analysis to infer the clonal status of 55 driver genes in breast cancer data from TCGA. We used the chi-squared test to assess the relations between clonality of driver gene mutations and clinicopathological factors. The Kaplan-Meier method was performed for the visualization and the differences between survival curves were calculated by log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to adjust for clinicopathological factors. We identified a high proportion of clonal mutations in these driver genes. Among them, there were 17 genes showing significant associations between their clonality and multiple clinicopathologic factors. Performing survival analysis on BRCA patients with clonal or subclonal driver gene mutations, we found that clonal ERBB2, FOXA1, and KMT2C mutations and subclonal GATA3 and RB1 mutations predicted shorter overall survival compared with those with wild type. Furthermore, clonal ERBB2 and FOXA1 mutations and subclonal GATA3 and RB1 mutations independently predicted for shorter overall survival after adjusting for clinicopathological factors. By longitudinal analysis, the clonality of ERBB2, FOXA1, GATA3, and RB1 significantly predicted patients' outcome within some specific BRCA tumor stages and histological subtypes. In summary, these clonal or subclonal mutations of driver genes have implications for diagnosis, prognosis, and treatment with BRCA patients.

Angiopoietin pathway gene expression associated with poor breast cancer survival.

Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a "big data" approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA). A total of 888 patients with adequate gene expression, disease-free survival (DFS), and overall survival (OS) data were selected for analysis. DFS and OS were calculated for patients with high and low expression of angiopoietin and VEGF pathway genes using TCGA data. Gene-specific thresholds to dichotomize patients into high and low expression were determined and survival plots were generated. The TCGA cohort was representative of national breast cancer patients with respect to stage, pathology, and survival. High Ang2 gene expression was associated with not only decreased DFS (p=0.05), but also decreased OS (p<0.05). High co-expression of Ang2 and its receptor Tie2 was associated with both decreased DFS and OS (p<0.05). There was strong correlation between angiopoietin and VEGF pathway genes. While high expression of VEGFA alone was not associated with survival, high co-expression with Ang2 was associated with decreased OS. This study validates TCGA as a representative database providing genomic data and survival outcomes in breast cancer. Our TCGA data support the angiopoietin pathway as a key mediator in the pathologic angiogenic switch in breast cancer.

Emerging Immunotherapy Strategies in Breast Cancer

Although immunogenicity is typically associated with renal cell carcinomas and melanoma, there are several compelling reasons why immune-based therapies should be explored in breast cancer. First, breast cancers express multiple putative tumor-associated antigens, such as HER-2 and MUC-1, which have been the successful focus of vaccine development over the past decade, translating into tumor-specific immune responses and, in some cases, clinical benefit. Second, passive immune strategies with anti-HER-2 antibodies, such as trastuzumab and pertuzumab, have led to survival benefits in breast cancer. Finally, the successes observed with novel immunotherapeutic strategies, such as immune checkpoint blockade and adoptive T-cell therapies in other malignancies, combined with a growing body of literature that supports an interplay between solid tumors and the immune system, indicate that these strategies have the potential to revolutionize the treatment of breast cancer.

Aggressiveness features and outcomes of true interval cancers

The question of whether screen detection confers an additional survival benefit in breast cancer is unclear and subject to several biases. Our aim was to examine the role of the diagnostic method (screen-detected, symptom-detected, and true interval cancers) and the clinical-pathological features in relapse-free survival and overall survival in breast cancer patients. We included 228 invasive breast cancers diagnosed in Barcelona from 1996 to 2008 among women aged 50-69 years. Ninety-seven patients were screen detected within the screening, 34 truly arose between 2-year screening mammograms (true interval cancers), and 97 were symptom detected outside the screening. The clinical-pathological features at diagnosis were compared. The overall and disease-free survival probabilities were computed using the Kaplan-Meier method. Cox proportional hazard models were applied, with adjustment by clinical-pathological variables. At diagnosis, symptom-detected and true interval cancers were in more advanced stages and were less differentiated. The highest proportion of triple-negative cancers was detected among true interval cancers (P=0.002). At 5 years of follow-up, the disease-free survival rates for screen-detected, true interval, and symptom-detected cancers were 87.5% (95% confidence interval, 80.5-95.2%), 64.1% (46.4-88.5%), and 79.4% (71.0-88.8%), respectively, and the overall survival rates were 94.5% (89.3-99.9%), 65.5% (47.1-91.2%), and 85.6% (78.3-93.6%), respectively. True interval cancers had the highest hazard ratio for relapse prediction (1.89; 0.67-5.31) and a hazard ratio of death of 5.55 (1.61-19.15) after adjustment for tumor-node-metastasis stage and phenotype. Clinically detected tumors, especially true interval cancers, more frequently showed biological features related to worse prognosis and were associated with poorer survival even after adjustment for clinical-pathological characteristics.

Phase II study of capecitabine (X) plus reirradiation in patients (pts) with recurrent squamous cell carcinoma of the head and neck (SCCHN)

15504 Background: X has shown substantial activity in SCCHN [Pivot et al. 2004] and is replacing 5-FU as the backbone of chemotherapy in a wide range of solid tumors, particularly colorectal cancer. In addition, X has a unique survival benefit in breast cancer. There is substantial data to support using X in chemoradiation [Dunst et al. 2004]. We evaluated the therapeutic impact and safety profile of X plus reirradiation in SCCHN. Methods: Pts with locally advanced unresectable SCCHN who had prior radiotherapy (RT, with or without chemotherapy) received X 450 mg/m2 twice daily, 7 days a week. RT was delivered as a standard fractionated regimen (2 Gy/day, 5 fractions/week) up to a total dose of 50–70 Gy. The cumulative (life-time) dose within overlapping fields was not to exceed 120–130 Gy. Results: Currently, 20 male pts have completed treatment. Baseline characteristics were: median age 57 (42–72), ECOG PS 0/1 5/15. Six pts had previous chemoradiation followed by radical resection; 4 had surgery and postoperative RT; 10 had concomitant chemoradiation (accelerated and hyperfractionated). Twelve pts experienced locoregional recurrences, 4 developed secondary primaries, and 4 had a regional lymph node relapse. The median time since prior radiation therapy was 16 (8–244) months. Efficacy (as evaluated by WHO criteria): 7 pts (35%) had a complete (2) or partial (5) response; stable disease was observed in 11 pts, and tumor progression immediately after therapy was observed in 2 pts. Median duration of local control and median survival will be presented at the meeting. The most frequently observed toxicity was mucositis, which was grade 3 in only 2 pts; grade 1 or 2 skin reaction was seen in 9 pts. There was no evidence of systemic toxicity or myelosuppression, probably due to the very low dose of X. RT was completed without delay in all pts, and X was interrupted prematurely in 2 pts due to grade 3 mucositis. Conclusions: Our preliminary data suggest that X chemoradiation is a well-tolerated and effective treatment modality for previously irradiated pts with SCCHN. Based on available data, a higher dose of X should be feasible and potentially more effective. Earlier use of X in SCCHN could also be evaluated. [Table: see text]

Timing of radiotherapy and survival benefit in breast cancer

To look at the optimum timing of radiotherapy in breast-conserving therapy (BCT) in relation to outcome in breast cancer. We analyzed 1473 BCT on 1446 breast cancer patients from our prospective cohort, stage I or II, node-negative, and without adjuvant systemic therapy. Timing was defined as time from lumpectomy till radiotherapy. Patients were categorized into three timing tertiles: 1-36 days, 37-53 days, and 54-112 days. The 10-year local relapse-free survival rates did not show significant differences between the three groups. The 10-year Distant Metastasis-Free Survival (DMFS) was 78.9% for the first tertile, versus 86.1% (HR 0.6; P = 0.009) for the second, and 90.7% (HR 0.3; P < 0.001) for the third. The 10-year Disease-specific Survival (DSS) was 83.8% for the first tertile, versus 90.6% (HR 0.5; P = 0.007) for the second, and 97.2% (HR 02; P < 0.001) for the third. Also in multivariate Cox regression analysis the second (HR 0.6; P = 0.053) and the third tertile (HR 0.3; P = 0.002) had significantly better DSS. Timing of radiotherapy in BCT for breast cancer seems to be highly important in relation to survival. This study shows a 40-70% relative survival benefit with timing after 36 days.

Three-weekly docetaxel (T) plus capecitabine (X) in 1st and 2nd line metastatic esophageal cancer (MEC): Final Results of the phase II DACAPO Trial

4142 Background: Both X and T have single agent activity in upper gastrointestinal tumors, and have together demonstrated preclinical synergy and a survival benefit in breast cancer. Phase II trials of XT have shown response rates of 40–53% and good tolerability in 1st-line metastatic gastric cancer (ASCO 04, abstracts 4051 and 4057). This trial assessed the efficacy and feasibility of XT combination in patients (pts) with MEC. Methods: Pts received T 75mg/m2 day 1 plus oral X 1000mg/m2 twice a day d1–14 every 3 weeks. The primary endpoint was response according to RECIST. Toxicity was reported according to NCI.CTCAE v3.0. Median follow up is 16.5 (7.9–21.4) months. Results: From 02/03 until 04/04 we included 24 pts in one center: 21 men, 3 women; median age 61.5 years, range 49–72; 17 had squamous cell and 7 adenocarcinomas. All pts had metastatic disease. 16 pts were treated in 1st-line, 8 in 2nd-line. Pts received a median of 4 (0–6) cycles. Dose reductions of one or both agents (to <80% of initial doses) were reported in 41% of pts. 2/24 (8.3%) pts died within 60 days after inclusion: one rapid tumor progression with upper gastrointestinal bleeding, one esophageal stent dislocation with subsequent mediastinitis. Severe adverse events (grade 3/4) reported were: neutropenia 10 (42%), febrile neutropenia 2 (8%), diarrhea 3 (13%), sensory neuropathy 3 (13%), fatigue 2 (8%), hand-foot syndrome 7 (29%). Grade1/2 sensory neuropathy was reported in 7 pts (29%) and hand-foot syndrome in 7 pts (29%). Intent-to-treat efficacy analysis showed a 46% response rate including 1 CR, 17% SD, 29% PD and 8% NE. Of the 11 responses, 9/16 (56%) were in 1st-line pts and 2/8 (25%) in 2nd-line therapy. Median survival is 16.0 months (95%CI 7.9–24.2). Median time to progression is 6.2 months (95%CI 4.6–7.8). Conclusions: Docetaxel plus capecitabine has a manageable toxicity profile and very promising activity in MEC, at least comparable to other doublet regimens. The combination merits further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis, Roche

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m−2 twice daily on days 1–14) plus intravenous docetaxel (75 mg m−2 on day 1) every 3 weeks as first- (n=16) or second-line (n=8) therapy. Patients received a median of four cycles of treatment (range, 0–6). The median follow-up is 16.5 months (range, 7.9–21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5–7.7 months). The meian survival was 15.8 months (95% CI, 7.8–23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.

Adjuvant radiotherapy confers survival benefit in breast cancer

Adjuvant radiotherapy confers survival benefit in breast cancer