Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial

Earl, Helena; Hiller, Louise; Howard, Helen; Dunn, Janet A.; Young, Jennie; Bowden, Sarah; McDermaid, M; Waterhouse, Anna; Wilson, Gregory; Agrawal, Rajiv; O’Reilly, Susan; Bowman, A.; Ritchie, Diana; Goodman, Andrew; Hickish, Tamas; McAdam, Karen; Cameron, David; Rea, Daniel; Caldas, Carlos; Provenzano, Elena; Abraham, Jean; Canney, Peter; Crown, John; Kennedy, M. John; Coleman, Robert E.; Leonard, Robert; Carmichael, James; Wardley, Andrew M; Poole, Christopher

doi:10.1016/s1470-2045(17)30319-4

Cited by 15 publications

(13 citation statements)

References 31 publications

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“…Chemotherapy remains the important strategy for TNBC treatment following mastectomy, it has elevated a lot in 5 years overall survival rate since it becomes the standard adjuvant therapy for breast cancer. Epirubicin, taxol and cyclophosphamide compose the first line of chemotherapeutics recommended by the guideline [ 17 ]. Nevertheless, drug resistance in TNBC is the major obstacle to a successful outcome following chemotherapy treatment.…”

Section: Discussionmentioning

confidence: 99%

The implication from RAS/RAF/ERK signaling pathway increased activation in epirubicin treated triple negative breast cancer

et al. 2017

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BackgroundTriple negative breast cancer (TNBC) is not sensitive to RAS/RAF/ERK signaling pathway (ERK pathway) targeting therapy, due to the absence of excessive activation of ERK pathway. However, the kinase cascades might be activated after chemotherapy in TNBC. Here we aimed to predict whether ERK pathway targeting therapy could be used as an adjuvant therapy in TNBC.MethodsWithin online GEO datasets (GSE43816 and GSE54326), gene set enrichment analysis (GSEA) was performed to detect molecular changes in epirubicin treated TNBC samples and cells, ERK pathway components and regulation genes changes were included.ResultsIn epirubicin treated TNBC samples and cells, we found ERK pathway components (eg. MAPK13, MAP3K1, MAPK12, MAPK11 and MAPKAPK3) were obviously enriched, also, expression of ERK pathway positive regulation genes significantly increased (P<0.05) and negative regulation genes decreased (P<0.05) in epirubicin resistant cells. Moreover, phosphorylated ERK levels were significantly elevated in MDA-MB-231 cells after epirubicin treatment.ConclusionERK signaling pathway was more activated in epirubicin treated TNBC, possibly contributing to the epirubicin resistance in TNBC, it implicated that ERK pathway could be used as an novel candidate for targeting therapy in refractory and relapse TNBC.

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Section: Discussionmentioning

confidence: 99%

The implication from RAS/RAF/ERK signaling pathway increased activation in epirubicin treated triple negative breast cancer

et al. 2017

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“…Both regimens were found to be safe, deliverable, and tolerable based on toxicity profile, dose intensity and a detailed safety substudy. The results indicated that addition of gemcitabine to anthracycline and taxane-based adjuvant chemotherapy at the dose and schedule of the trial did not confer a therapeutic advantage in terms of disease-free survival in EBC, although it could result in increased toxicity [90].…”

Section: Therapeutic Combinations In Breast Cancermentioning

confidence: 99%

Drug Combinations in Breast Cancer Therapy

Fisusi

Akala

2019

PNT

333

163

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Breast cancer therapy involves a multidisciplinary approach comprising surgery, radiotherapy, neoadjuvant and adjuvant therapy. Effective therapy of breast cancer requires maximum therapeutic efficacy, with minimal undesirable effects to ensure a good quality of life for patients. The carefully selected combination of therapeutic interventions provides patients with the opportunity to derive maximum benefit from therapy while minimizing or eliminating recurrence, resistance and toxic effects, as well as ensuring that patients have a good quality of life. This review discusses therapeutic options for breast cancer treatments and various combinations that had been previously exploited. The review will also give an insight into the potential application of the nanotechnology platform for codelivery of therapeutics in breast cancer therapy.

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“…Trials investigating newer cytotoxic agents for breast cancer have not yet identified any classes that are clearly superior to taxanes and anthracyclines,2, 3, 4 but the optimal dosage and timing of these two drugs is still unclear. Cell biology and cytokinetic modelling suggest that increasing dose intensity (ie, the amount of drug delivered per unit time) 5 could enhance tumour cell kill, reduce tumour regrowth between cycles, and thereby further improve the likelihood of cure 6, 7.…”

Section: Introductionmentioning

confidence: 99%

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Gray¹,

Bradley²,

Braybrooke³

et al. 2019

The Lancet

Self Cite

296

121

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Summary Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrentl...

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Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial

Cited by 15 publications

References 31 publications

The implication from RAS/RAF/ERK signaling pathway increased activation in epirubicin treated triple negative breast cancer

The implication from RAS/RAF/ERK signaling pathway increased activation in epirubicin treated triple negative breast cancer

Drug Combinations in Breast Cancer Therapy

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

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