Anthracyclines in the treatment of patients with early breast cancer

Abstract

In the past decades, systemic treatment for early-stage breast cancer (EBC) patients has undergone a profound evolution, driven by the progressively improving knowledge and understanding of breast tumor biology, with consequent outcome improvement. In this context, chemotherapy still represents a cornerstone of EBC treatment across different breast cancer (BC) subtypes. Once chemotherapy is considered, the next step is a careful risk–benefit balance aiming at choosing which specific regimen to offer. Within this framework, although anthracyclines have long been one of the mainstays of the cytotoxic therapy, in the last years their role has been challenged. Indeed, alongside with the concerns regarding anthracycline-related toxicity, the emergence of alternative active cytotoxic agents as well as targeted strategies to be combined with has progressively fueled the debate about de-escalating anthracyclines. In order to properly and critically address this high-priority clinical issue, the following questions need to be answered: Are the data supporting the use of anthracyclines no longer appropriate in the contemporary landscape of EBC treatment? Are the data supporting chemotherapy de-escalation solid enough to enable us to safely withhold anthracyclines? Are concerns regarding anthracycline long-term safety justified with cumulative doses reached with contemporary regimens? The answers are no. The 2012 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) individual patient meta-analysis1Peto R. Davies C. Godwin J. et al.Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials.Lancet. 2012; 379: 432-444Abstract Full Text Full Text PDF PubMed Scopus (1382) Google Scholar has demonstrated that: (i) anthracycline-based regimens are superior to no adjuvant chemotherapy; (ii) anthracycline-based regimens are superior to chemotherapy regimens that contain neither anthracycline nor taxane; (iii) anthracycline–taxane combination is superior to anthracycline-based chemotherapy. The proportional risk reductions are little affected by age, nodal status, and estrogen receptor (ER) status. These data cannot be questioned; however, the past decades have been marked by the questioning of the actual indispensability of anthracyclines. One of the first pieces of evidence in this regard comes from the US-Oncology-9735 trial demonstrating survival benefit with docetaxel-based (TCx4) over anthracycline-based chemotherapy (ACx4) in unselected EBC patients.2Jones S. Holmes F.A. O’Shaughnessy J. et al.Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735.J Clin Oncol. 2009; 27: 1177-1183Crossref PubMed Scopus (460) Google Scholar However, the US-Oncology-9735 population was enriched for lower-risk patients. Even when restricting the field to the human epidermal growth factor receptor 2 (HER2)-negative subgroup, available data do not support taxane-only as an equally effective alternative to anthracycline–taxane chemotherapy. The joint efficacy analysis of Anthracyclines in early Breast Cancer (ABC) trials failed to formally demonstrate the non-inferiority of six courses of taxane-based chemotherapy over anthracycline–taxane combination. Rather, an improvement of invasive disease-free survival (IDFS) was demonstrated for the anthracycline-based combination.3Blum J.L. Flynn P.J. Yothers G. et al.Anthracyclines in early breast cancer: the ABC trials - USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology).J Clin Oncol. 2017; 35: 2647-2655Crossref PubMed Scopus (141) Google Scholar Similarly, a pooled analysis of ABC, West German Study Plan B (WSG Plan B) and Hellenic Oncology Research Group (HORG) trials was not able to prove the non-inferiority of taxanes versus anthra-taxanes.4Ntellas P. Spathas N. Agelaki S. Zintzaras E. Saloustros E. Taxane & cyclophosphamide vs anthracycline & taxane-based chemotherapy as adjuvant treatment for breast cancer: a pooled analysis of randomized controlled trials by the Hellenic Academy of Oncology.Oncotarget. 2019; 10: 1209-1216Crossref Google Scholar Closing credits, the most recent update of the EBCTCG meta-analysis demonstrated a 15% proportional reduction and a 2.5% absolute reduction at 10 years in the risk of invasive recurrence for anthracycline–taxane combinations versus taxane-based regimen, independently of ER and nodal status.5Braybrooke J, Bradley R, Gray R, et al. Taxane with anthracycline versus taxane without anthracycline: an individual patient-level meta-analysis of 16,500 women with early-stage breast cancer in 13 randomised trials. Cancer Res. 2022;82(4_suppl):GS2-06.Google Scholar HER2-positive EBC deserves a separate discussion. First-generation adjuvant trials establishing trastuzumab as the standard of care mostly included anthracycline–taxane chemotherapy backbone.6Moja L. Tagliabue L. Balduzzi S. et al.Trastuzumab containing regimens for early breast cancer.Cochrane Database Syst Rev. 2012; 2012CD006243Google Scholar The Breast Cancer International Research Group 006 (BCIRG-006) trial provided the first assumption of superimposable efficacy of sequential anthracycline–taxane and taxane-only chemotherapy.7Slamon D. Eiermann W. Robert N. et al.Adjuvant trastuzumab in HER2-positive breast cancer.N Engl J Med. 2011; 365: 1273-1283Crossref PubMed Scopus (1851) Google Scholar However, the trial was not powered for a formal comparison, thus missing the opportunity to provide solid evidence supporting the use of anthracycline-free chemotherapy in combination with single HER2 blockade. Aphinity and Katherine trials set new adjuvant standards for high-risk patients: dual HER2 blockade with trastuzumab–pertuzumab in the first case, and post-operative trastuzumab emtansine (T-DM1) in patients failing to achieve a pathologic complete response (pCR) after standard neoadjuvant chemotherapy including trastuzumab in the latter case.8von Minckwitz G. Procter M. de Azambuja E. et al.Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer.N Engl J Med. 2017; 377: 122-131Crossref PubMed Scopus (745) Google Scholar,9von Minckwitz G. Huang C.S. Mano M.S. et al.Trastuzumab emtansine for residual invasive HER2-positive breast cancer.N Engl J Med. 2019; 380: 617-628Crossref PubMed Scopus (924) Google Scholar Notably, ∼77% of the patients in both trials have received anthracycline-based chemotherapy. Just to complete the scenario, the NeoSphere neoadjuvant trial, which firstly demonstrated the efficacy of pertuzumab–trastuzumab in the neoadjuvant setting, included four courses of post-operative anthracycline-based chemotherapy.10Gianni L. Pienkowski T. Im Y.H. et al.5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial.Lancet Oncol. 2016; 17: 791-800Abstract Full Text Full Text PDF PubMed Scopus (447) Google Scholar Two trials (TRAIN-2 and TRYPHAENA) specifically investigated whether the omission of anthracycline from the neoadjuvant backbone of dual HER2 blockade could provide a more favorable risk–benefit ratio, providing evidence that this de-escalated approach does not seem to jeopardize the likelihood of pCR; however, none of these trials was statistically powered to formally establish the non-inferiority of omitting anthracycline.11van Ramshorst M.S. van der Voort A. van Werkhoven E.D. et al.Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial.Lancet Oncol. 2018; 19: 1630-1640Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 12Schneeweiss A. Chia S. Hickish T. et al.Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).Ann Oncol. 2013; 24: 2278-2284Abstract Full Text Full Text PDF PubMed Scopus (690) Google Scholar, 13Schneeweiss A. Chia S. Hickish T. et al.Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.Eur J Cancer. 2018; 89: 27-35Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar In addition, in both of them, the de-escalated arm consisted of taxane + carboplatin, which is not unanimously considered a ‘standard’ de-escalation treatment; finally, the TRYPHAENA de-escalated arm, containing docetaxel, was associated with an unexpectedly high rate of non-cardiac toxicity, thus raising major concerns regarding a possible implementation of such an approach in clinical practice. Therefore, unless clinically contraindicated, anthracycline-based chemotherapy is still the standard, with the exception of very-low-risk patients. Two single-arm phase II trials independently reported excellent survival rates of low-risk HER2-positive EBC patients receiving trastuzumab + taxane as adjuvant treatment, thus fueling the enthusiasm for this de-escalated approach, enough to build it up as the new adjuvant standard in HER2-positive EBC patients with small tumors and node-negative disease.14Tolaney S.M. Barry W.T. Dang C.T. et al.Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer.N Engl J Med. 2015; 372: 134-141Crossref PubMed Scopus (465) Google Scholar,15Jones S.E. Collea R. Paul D. et al.Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study.Lancet Oncol. 2013; 14: 1121-1128Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar However, given the lack of a control standard arm, results from these trials should be considered should be for EBC patients in the neoadjuvant to the results of the trial, post-operative in patients with residual after standard neoadjuvant chemotherapy demonstrated survival a new for this N. S. et al.Adjuvant for breast cancer after Engl J Med. 2017; PubMed Scopus Google Scholar standard chemotherapy was by anthracycline–taxane combination in of the trial demonstrated a and survival with the of to standard chemotherapy over chemotherapy to the of the first in the early P. J. L. et for early breast cancer.N Engl J Med. PubMed Scopus Google Scholar the neoadjuvant chemotherapy backbone consisted of both taxane and the of such standard backbone in this clinical and clinical the use of anthracyclines in this context, to the of safety is a issue, in in a The most anthracycline-related long-term are by and the risk of both at cumulative doses however, are reached with Indeed, sequential use of anthracycline and taxane has been to be effective a of anthracyclines. The risk of and in a contemporary is thus and cardiac be by improving patient cardiac and S. S. et al.Early breast cancer: for treatment and Oncol. 2019; Full Text Full Text PDF PubMed Scopus Google Scholar the last EBCTCG meta-analysis no in without recurrence and no in from or was longer follow-up is these data are chemotherapy has been the of for patients with early the A. N. of regimens in early stage breast cancer in J Clin Oncol. 2011; Scopus Google Scholar However, evidence the use of anthracycline in the of chemotherapy and for early breast cancer recurrence and an of the randomised 365: Full Text Full Text PDF PubMed Scopus Google Scholar in the the of in is anthracycline use is associated with the risk of long-term or and or R. Davies C. Godwin J. et al.Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials.Lancet. 2012; 379: 432-444Abstract Full Text Full Text PDF PubMed Scopus (1382) Google Scholar to the of new effective and to a knowledge of with the of of patients to their risk of recurrence and the de-escalation of anthracycline-containing regimens for patients is in clinical trials. at the Breast Cancer the results of a patient-level meta-analysis taxane with anthracycline versus taxane without anthracycline In trials including a 15% proportional reduction and a 2.5% to absolute reduction at 10 years in the risk of invasive recurrence for anthracycline + taxane versus taxane chemotherapy proportional reduction in recurrence not by ER or nodal status. these it should be considered as a of in contemporary clinical has been an anthracycline-free regimens for patients. Indeed, early-stage and are to a absolute benefit from adjuvant chemotherapy compared to with or or with more biology, and at risk for a recurrence of et by tumor and treatment in women with node-negative breast cancer: a Clin Oncol. PubMed Scopus Google Scholar, L. R. P. invasive breast cancer recurrence risk in human epidermal growth factor receptor and node-negative breast cancer from to a from an care Clin Oncol. PubMed Scopus Google Scholar, G. G. et of HER2 in patients with small tumor and node-negative breast Clin Oncol. 2009; 27: PubMed Scopus Google Scholar the associated with it should be whether the use of anthracyclines in these low-risk patients could be more A. et careful of anthracycline use in breast Breast Cancer. Scopus Google Scholar study results have to the of de-escalating anthracycline-based chemotherapy in patients with early and are of and a and E. D. de Azambuja E. for patients with breast Scopus Google Scholar In the lack of more in the early setting, it to use an chemotherapy as first given as neoadjuvant S. S. et al.Early breast cancer: for treatment and Oncol. 2019; Full Text Full Text PDF PubMed Scopus Google Scholar the of and to an anthracycline–taxane regimen has to and P. J. L. et for early breast cancer.N Engl J Med. PubMed Scopus Google M. M. et neoadjuvant chemotherapy in breast cancer: a and Oncol. 2018; Full Text Full Text PDF PubMed Scopus Google M. M. et a to neoadjuvant chemotherapy for breast cancer: the of the Oncol. Full Text Full Text PDF Scopus Google Scholar this it is that anthracycline-based chemotherapy be for this patient unless are for anthracyclines. patients with HER2-positive which of have been with chemotherapy and most have the of the patients with small node-negative are with adjuvant paclitaxel for and of the long-term results of the and S.M. S. et follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor breast Clin Oncol. 2019; PubMed Scopus Google Scholar The 7-year disease-free survival was to with four 7-year overall survival was to and 7-year was to S.M. S. et follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor breast Clin Oncol. 2019; PubMed Scopus Google Scholar The trial a adjuvant regimen, of docetaxel, and trastuzumab for patients with early HER2-positive the analysis with a follow-up of and in the anthracycline and versus and rates and in and although not powered for The arm rate of cardiac versus of and of versus In of patients in the arm this compared to patients in the arm Eiermann W. Robert et follow-up of doxorubicin plus cyclophosphamide by docetaxel with doxorubicin plus cyclophosphamide by docetaxel and trastuzumab with docetaxel, and trastuzumab Res. 2016; Scholar Notably, when to the neoadjuvant setting, these In the TRYPHAENA trial, a neoadjuvant chemotherapy and rates compared with an anthracycline-based regimen, when to dual HER2 blockade with trastuzumab and A. Chia S. Hickish T. et al.Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.Eur J Cancer. 2018; 89: 27-35Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar the study demonstrated rates and between anthracycline and regimens versus and versus However, the small and the of tumors should be The anthracycline-based arm more of from to versus Two patients with anthracyclines der Voort A. van Ramshorst M.S. van Werkhoven E.D. et follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual blockade in patients with breast cancer: a analysis of the phase 3 Oncol. Scopus Google Scholar Research are to chemotherapy in HER2-positive early In the West German Study Group - trial phase II trial, patients with receptor HER2-positive early an excellent rate of after de-escalated neoadjuvant chemotherapy with pertuzumab and and was associated with survival N. M. et neoadjuvant with or without paclitaxel in early breast cancer: and survival Clin Oncol. Google Scholar The in trial is a single-arm trial to the of de-escalated adjuvant in patients with following neoadjuvant trastuzumab and T. et The a study of chemotherapy de-escalation response to neoadjuvant in HER2-positive breast Res. Scholar data a overall rate of T. et The a study of chemotherapy de-escalation response to neoadjuvant in HER2-positive breast Res. Scholar The long-term efficacy of this approach be in the use of response to in HER2 breast cancer trial the the most recent Cancer that anthracycline-based chemotherapy from the of that this regimen could be considered in W. M. J. in Breast Scholar the of an anthracycline-containing regimen should be the and benefit for specific that benefit is in patients with tumors or which is an population in clinical trials. the of cardiac associated with the combination of chemotherapy and In which of is evidence de-escalating chemotherapy and therapy, to the of able to patients to their risk of C. C. et of in breast cancer patients: a Breast Cancer. Scopus Google Scholar In patients with to the combination has been as one of the W. M. J. in Breast Scholar However, clinical trials this combination with standard anthracycline and taxane-based sequential regimen in have results thus In a of adjuvant was to a combination of anthracyclines and taxanes in patients with J.L. Flynn P.J. Yothers G. et al.Anthracyclines in early breast cancer: the ABC trials - USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology).J Clin Oncol. 2017; 35: 2647-2655Crossref PubMed Scopus (141) Google Scholar a phase randomized trial demonstrated the non-inferiority of an anthracycline-free regimen six of to standard anthracycline and taxane-based regimen and cyclophosphamide for by paclitaxel for for patients with high-risk L. et or regimen as adjuvant chemotherapy for breast cancer: a phase randomized non-inferiority trial.Lancet West Scholar The in and to 3 study to this In a phase trial to whether patients with high clinical risk and or and risk could and between and anthracycline-based regimens versus and versus the trial was not powered to demonstrate the of a given chemotherapy S. M. E. et anthracycline versus in early high clinical risk breast cancer in the phase Clin Oncol. Scopus Google Scholar In the Trial for a randomized trial to demonstrate the non-inferiority of versus the combination of and in patients with a recurrence of a Gray et al.Adjuvant chemotherapy by a in breast cancer.N Engl J Med. 2018; 379: PubMed Scopus Google Scholar most patients randomized to the arm received and with different chemotherapy regimens and in patients receiving anthracycline without a taxane and anthracycline plus a Gray et in early breast cancer with a high recurrence of to 100 to adjuvant chemotherapy plus a analysis of the randomized clinical Oncol. PubMed Scopus Google Scholar the trial was not powered to demonstrate between chemotherapy and these data should be considered as with the available a analysis including patients with early to chemotherapy a that anthracyclines are more to with tumors and with recurrence the in clinical of the associated with anthracycline treatment in patients to J. P. anthracycline use in receptor early-stage breast Breast Cancer. 2019; 19: Full Text Full Text PDF Scopus Google Scholar In although anthracycline-based chemotherapy regimens have standard in the the use in the is to the small of benefit in and the associated risk–benefit patients with HER2-positive or to chemotherapy benefit from a The use of anthracyclines should be to patients with a high risk of recurrence or or with high are still in clinical trials. the risk of long-term and anthracyclines as standard of chemotherapy for breast cancer HER2-positive and that adjuvant paclitaxel + of trastuzumab the of the trial data be an for HER2-positive low-risk S.M. Barry W.T. Dang C.T. et al.Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer.N Engl J Med. 2015; 372: 134-141Crossref PubMed Scopus (465) Google Scholar However, is a of the of the of to be given the associated with the 7-year rate of the trial, cannot a to in the in for Breast Cancer trial, the of the trial a of the of the of when at 3 the trial reported an of these are the of single-arm trials. at a in for the anthracycline-containing arm was In the Aphinity trial, which set the combination of pertuzumab–trastuzumab as the new adjuvant standard regimen for high-risk a absolute at years was it is a of at the to the neoadjuvant setting, the that available evidence overall a possible more favorable risk–benefit in of omitting anthracycline from the neoadjuvant backbone for patients receiving dual HER2 Ramshorst M.S. van der Voort A. van Werkhoven E.D. et al.Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial.Lancet Oncol. 2018; 19: 1630-1640Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 12Schneeweiss A. Chia S. Hickish T. et al.Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).Ann Oncol. 2013; 24: 2278-2284Abstract Full Text Full Text PDF PubMed Scopus (690) Google Scholar, 13Schneeweiss A. Chia S. Hickish T. et al.Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.Eur J Cancer. 2018; 89: 27-35Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar However, (i) these trials not formally demonstrate the non-inferiority of such de-escalated (ii) + paclitaxel does not an unanimously standard (iii) in anthracycline-containing rate of was the rates of non-cardiac the taxane-based with these de-escalating anthracyclines in at the the is more Indeed, lack solid evidence that could in the of patients for anthracycline be safely In this context, as phase randomized clinical trials demonstrating the clinical of patients to for chemotherapy be Gray et al.Adjuvant chemotherapy by a in breast cancer.N Engl J Med. 2018; 379: PubMed Scopus Google et to chemotherapy benefit in breast cancer.N Engl J Med. PubMed Scopus Google Scholar, J. et as an to treatment in early-stage breast cancer.N Engl J Med. 2016; PubMed Scopus Google Scholar, M. C. et as an for treatment in early breast cancer: results of the phase 3 randomised trial with an analysis by Oncol. Full Text Full Text PDF PubMed Scopus Google Scholar provided us with the role of anthracycline in this clinical However, none of trials was powered to formally across different available evidence still anthracycline + taxane-based chemotherapy as the standard, and chemotherapy is to a patient with should not the an anthracycline-containing is in the data the efficacy of chemotherapy in patients with early a have to be of the from randomized phase trials. However, in HER2-positive a phase non-inferiority S.M. Barry W.T. Dang C.T. et al.Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer.N Engl J Med. 2015; 372: 134-141Crossref PubMed Scopus (465) Google S.M. S. et follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor breast Clin Oncol. 2019; PubMed Scopus Google Scholar was able to in patients with small node-negative HER2-positive early and of paclitaxel + of trastuzumab for these patients. was a of phase II non-inferiority study demonstrated that could be in small node-negative HER2-positive S.M. N. Dang C. et al.Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage HER2-positive breast cancer a randomized clinical Clin Oncol. PubMed Scopus Google Scholar thus de-escalating anthracyclines. However, this approach is considered in non-inferiority trials not the as was the for of trastuzumab in the early P. A. G. et versus adjuvant trastuzumab in combination with results of the phase randomized Oncol. 2018; Full Text Full Text PDF PubMed Scopus Google Scholar, G. M. et versus of adjuvant trastuzumab in early breast cancer analysis of a multicentre, open-label, phase 3 randomised 2019; Full Text Full Text PDF PubMed Scopus Google Scholar, J. et of adjuvant trastuzumab for a of vs with chemotherapy for early human epidermal growth factor receptor breast cancer: the randomized clinical Oncol. 2018; PubMed Scopus Google Scholar, L. et versus of adjuvant trastuzumab for HER2-positive early breast cancer disease-free survival results of a randomised phase 3 non-inferiority 2019; Full Text Full Text PDF PubMed Scopus Google recent pooled analysis of Plan B and trials containing patients that anthracycline not be in most of the patients with or high-risk early in or with the exception of or In addition, with anthracycline-based regimens versus A. W. et of anthracyclines in and high-risk early breast pooled analysis of the randomised clinical trials and J Cancer. Scopus Google recent and including patients years with node-negative compared patients receiving taxane-based versus chemotherapy and and survival for anthracycline–taxane chemotherapy. The use of chemotherapy in and However, the was with taxane compared to for Similarly, was for taxane and for anthracycline–taxane chemotherapy J. M. et anthracycline + taxane versus taxane-based chemotherapy in women with node-negative breast cancer: a Cancer Scopus Google Scholar do with that most patients with to anthracycline-based chemotherapy. However, such as HER2-positive or not an anthracycline-based for with an tumor In HER2-positive anthracyclines are no longer the regimen in W. M. J. in Breast Scholar In taxane-based chemotherapy is one of the regimens as well and a for patients. In of among adjuvant chemotherapy was associated with a small in the risk of and with regimens that included anthracyclines rates for and for the safety of taxane-based regimen in of longer follow-up is J. et and after adjuvant a study among breast cancer 2018; PubMed Scopus Google Scholar cardiac anthracycline-based chemotherapy more cardiac compared to patients with taxane-based of PubMed Scopus Google Scholar anthracycline-based chemotherapy still has for patients with not for patients. The of of chemotherapy should the risk of risk and de Azambuja Research at at of

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