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OncoTargets and Therapy 2019To evaluate efficacy and safety of lapatinib or trastuzumab alone or both plus chemotherapy for the treatment of breast cancer patients with positive HER-2 expression.
AIM
To evaluate efficacy and safety of lapatinib or trastuzumab alone or both plus chemotherapy for the treatment of breast cancer patients with positive HER-2 expression.
METHODS
Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, OVID, Embase, Chinese Biomedical Literature Database, and China Academic Journals Database were searched from 1994 through December 2017 using the keywords "breast cancer", "preoperative", "neo-adjuvant", "lapatinib", "pertuzumab", "Herceptin", and "trastuzumab".
RESULTS
Meta-analysis found that pathological complete response (PCR; risk ratio [RR]=0.82, 95% CI: 0.72-0.93) and tall PCR (tPCR; RR=0.77, 95% CI: 0.67-0.88) of chemotherapy plus lapatinib were significantly less effective or safe compared to that of chemotherapy plus trastuzumab (<0.05). PCR (RR=1.30, 95% CI: 1.15-1.47) and tPCR (RR=1.32, 95% CI: 1.16-1.50) of chemotherapy plus both lapatinib and trastuzumab were significantly superior to that of chemotherapy plus trastuzumab alone (<0.05). However, there was no significant difference in breast reservation rate between chemotherapy plus lapatinib vs chemotherapy plus trastuzumab (RR=0.91, 95% CI: 0.72-1.16) or chemotherapy plus both lapatinib and trastuzumab (RR=1.11, 95% CI: 0.73-1.68, >0.05). Incidence of diarrhea, hepatic toxicity, and skin rash in the groups of chemotherapy plus lapatinib or chemotherapy plus both lapatinib and trastuzumab was significantly higher than that in chemotherapy plus trastuzumab (<0.05).
CONCLUSION
Efficacy of lapatinib was less than that of trastuzumab, but incidence of adverse effect of lapatinib was higher than that of trastuzumab. Combination of chemotherapy plus both lapatinib and trastuzumab could significantly increase PCR and tPCR in breast cancer patients, but rate of breast conservation, event-free survival, and overall survival was not significantly improved. Incidence of diarrhea, hepatic toxicity, and skin rash was significantly increased in the groups using lapatinib.
PubMed: 30655674
DOI: 10.2147/OTT.S183304 -
BMC Cancer Aug 2014Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a... (Comparative Study)
Comparative Study Review
Effect and safety of dual anti-human epidermal growth factor receptor 2 therapy compared to monotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer: a systematic review.
BACKGROUND
Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies.
METHODS
We identified randomized control trials that compared dual anti-HER2 therapy and anti-HER2 monotherapy in patients with HER2-positive breast cancer. Outcomes included pathologic complete response (pCR), overall survival (OS), progression-free survival (PFS), and adverse events. Included in the analysis were seven trials that recruited 2,609 patients.
RESULTS
In the neoadjuvant setting, the pooled pCR rate in the dual anti-HER2 therapy and monotherapy groups in combination with chemotherapy was 54.8% and 36%, respectively. This difference was statistically significant (relative risk, 1.56; 95% confidence interval (CI), 1.23-1.97; p < 0.001). In the metastatic setting, dual anti-HER2 therapy demonstrated significant benefits in both PFS (hazard ratio (HR), 0.71; 95% CI, 0.62-0.81; p < 0.001) and OS (HR, 0.68; 95% CI, 0.57-0.82; p < 0.001). Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant settings. However, in the metastatic setting, similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy. Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy, but no statistical differences were observed in cardiac toxicity.
CONCLUSIONS
This systematic review provides a summary of all the data currently available, and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Lapatinib; Middle Aged; Neoplasm Metastasis; Quinazolines; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Trastuzumab; Treatment Outcome
PubMed: 25164542
DOI: 10.1186/1471-2407-14-625 -
Medicine Sep 2019This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with...
BACKGROUND
This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with HER2-positive breast cancer (HER2-PBC).
METHODS
A comprehensive literature search for this study will consist of 2 parts: electronic database records and gray literature. The electronic database literatures are searched from PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be searched from inception up to the present. In addition, gray literatures, such as dissertations, ongoing trials, and so on, will also be searched. Two authors will independently read the records, extract data collection, and evaluate the risk of bias. RevMan V.5.3 software will be applied for statistical analysis.
RESULTS
This study will summarize up-to-date evidence of PTD for patients with HER2-PBC via overall survival, complete response, cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities.
CONCLUSION
This study will provide efficacy and safety of PTD for HER2-PBC.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Female; Genes, erbB-2; Humans; Receptor, ErbB-2; Trastuzumab; Treatment Outcome
PubMed: 31568001
DOI: 10.1097/MD.0000000000017262 -
The Cochrane Database of Systematic... Oct 2018This is an update of a previously published version of the review (Issue 10, 2011).Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an update of a previously published version of the review (Issue 10, 2011).Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among women worldwide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy. Between 55% and 75% of women who respond to first-line therapy experience relapse within two years. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Improved understanding about the molecular basis of EOC has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and anti-EGFR antibodies.
OBJECTIVES
To compare the effectiveness and harmful effects of interventions that target the epidermal growth factor receptor in the treatment of epithelial ovarian cancer (EOC).
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2010, Issue 4), MEDLINE, and Embase up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field. This update includes further searches up to September 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven EOC.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data, assessed risk of bias, and performed GRADE assessment.
MAIN RESULTS
From 6105 references obtained through the literature search and an additional 15 references derived from grey literature searches, we identified seven RCTs that met our inclusion criteria and included 1725 participants. Trial results show that after first-line chemotherapy is provided, maintenance treatment with erlotinib (EGFR tyrosine kinase inhibitor (TKI)) probably makes little or no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.81 to 1.20; one study; 835 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 1.05, 95% CI 0.90 to 1.23; one study; 835 participants; very low-certainty evidence). Less than 50% of participants provided quality of life data, and study authors reported these results incompletely. The certainty of evidence is very low, but treatment may reduce quality of life compared to observation.Treatment with an EGFR TKI (vandetanib) for women with relapsed EOC may make little or no difference in overall survival (HR 1.25, 95% CI 0.80 to 1.95; one study; 129 participants; low-certainty evidence) and may make little or no difference in progression-free survival (HR 0.99, 95% CI 0.69 to 1.42; one study; 129 participants; very low-certainty evidence). In treating patients with relapse, giving EGFR TKI may slightly increase some toxicities, such as severe rash (risk ratio (RR) 13.63, 95% CI 0.78 to 236.87; one study; 125 participants; very low-certainty evidence). Quality of life data were not available for meta-analysis.Anti-EGFR antibody treatment in relapsed EOC may or may not make a difference to overall survival (HR 0.93, 95% CI 0.74 to 1.18; four studies; 658 participants; moderate-certainty evidence) and may or may not have any effect on progression-free survival (HR 0.90, 95% CI 0.70 to 1.16; four studies; 658 participants; low-certainty evidence). Anti-EGFR antibody treatment may or may not increase side effects, including severe nausea and/or vomiting (RR 1.27, 95% CI 0.56 to 2.89; three studies; 503 participants; low-certainty evidence), severe fatigue (RR 1.06, 95% CI 0.66 to 1.73; I² = 0%; four studies; 652 participants; low-certainty evidence), and hypokalaemia (RR 2.01, 95% CI 0.80 to 5.06; I² = 0%; three studies; 522 participants; low-certainty evidence). Severe diarrhoea rates were heterogeneous across studies (RR 2.87, 95% CI 0.59 to 13.89; four studies; 652 participants; low-certainty evidence), and subgroup analysis revealed that severe diarrhoea was more likely with pertuzumab (RR 6.37, 95% CI 1.89 to 21.45; I² = 0%; three studies; 432 participants; low-certainty evidence) than with seribantumab treatment (RR 0.38, 95% CI 0.07 to 2.23; I² = 0%; one study; 220 participants; very low-certainty evidence). Quality of life data were incompletely reported, and we were unable to combine them in a meta-analysis.
AUTHORS' CONCLUSIONS
Current evidence suggests that an anti-EGFR single-agent biological treatment (EGFR TKI or anti-EGFR antibody) makes little or no difference to survival, either as maintenance treatment after first-line chemotherapy or in association with chemotherapy in recurrent cancer. Anti-EGFR therapy may increase some side effects and may or may not reduce quality of life.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Deoxycytidine; ErbB Receptors; Erlotinib Hydrochloride; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Piperidines; Progression-Free Survival; Quality of Life; Quinazolines; Randomized Controlled Trials as Topic
PubMed: 30321910
DOI: 10.1002/14651858.CD007927.pub4 -
Breast Cancer Research and Treatment Apr 2020In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously... (Meta-Analysis)
Meta-Analysis
Evaluating the clinical effectiveness and safety of various HER2-targeted regimens after prior taxane/trastuzumab in patients with previously treated, unresectable, or metastatic HER2-positive breast cancer: a systematic review and network meta-analysis.
PURPOSE
In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously treated patients with unresectable or metastatic HER2-positive breast cancer (BC).
METHODS
Systematic reviews were conducted of published controlled trials of treatments for unresectable or metastatic HER2-positive BC with early relapse (≤ 6 months) following adjuvant therapy or progression after trastuzumab (Tras) + taxane published from January 1998 to January 2018. Random-effects NMA was conducted for overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety endpoints.
RESULTS
The NMA included regimens from seven randomized controlled trials: T-DM1 and combinations of Tras, capecitabine (Cap), lapatinib (Lap), neratinib, or pertuzumab (Per; unapproved). OS results favored T-DM1 over approved comparators: hazard ratio (HR) (95% credible interval [95% CrI]) vs Cap 0.68 (0.39, 1.10), LapCap 0.76 (0.51, 1.07), TrasCap 0.78 (0.44, 1.19). PFS trends favored T-DM1 over all other treatments: HR (95% CrI) vs Cap 0.38 (0.19, 0.74), LapCap 0.65 (0.40, 1.10), TrasCap 0.62 (0.34, 1.18); ORR with T-DM1 was more favorable than with all approved treatments. In surface under cumulative ranking curve (SUCRA) analysis T-DM1 ranked highest for all efficacy outcomes. Discontinuation due to adverse events was less likely with T-DM1 than with all comparators except neratinib. In general, gastrointestinal side effects were less likely and elevated liver transaminases and thrombocytopenia more likely with T-DM1 than with comparators.
CONCLUSIONS
The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Molecular Targeted Therapy; Network Meta-Analysis; Receptor, ErbB-2; Taxoids; Trastuzumab; Treatment Outcome
PubMed: 32100144
DOI: 10.1007/s10549-020-05577-7 -
Journal of Comparative Effectiveness... May 2024This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor... (Review)
Review
This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor receptor 2 (HER2) treatments in advanced/metastatic HER2+ breast cancer. Three databases from 2016 to September 2021 were searched for clinical trials and observational studies in patients receiving first-line (1L) standard of care (SOC), second-line (2L) SOC or third-line or subsequent lines (3L+). 2692 citations were screened, and 38 studies were included. Eleven studies were randomized-controlled trials (RCTs; 5 in 1L, 6 in 3L+), 6 were single-arm trials (5 in 1L, 1 in 3L+) and 21 were observational studies (13 in 1L, 6 in 2L, 4 in 3L+ [note that studies with subgroups for 1L, 2L, 3L+ are double-counted]). Longer overall survival (OS) was associated with 1L and 2L treatment, and for 3L+ studies that included ERI, ERI or trastuzumab (Tmab) + ERI led to longer OS than treatments of physician's choice (median OS of 11, 10 and 8.9 months, respectively). Progression-free survival was 9 months in Tmab + pertuzumab (Pmab) + ERI, 4 months in Tmab + ERI and 3.3 months in ERI. Available treatments provide a wide range of efficacy. However, later lines lack standardization and conclusions on comparative effectiveness are limited by differing trial designs. Thus, the chance of prolonged survival with new agents warrants further research.
PubMed: 38808626
DOI: 10.57264/cer-2023-0153 -
Frontiers in Oncology 2021To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+)...
PURPOSE
To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.
METHODS
A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.
RESULTS
Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70-0.86), Lap-Cap (0.64, 0.59-0.69), Tra-Cap (0.63, 0.56-0.70), Cap (0.50, 0.45-0.56), Ner (0.59, 0.51-0.69), Per-Tra-Cap (0.68, 0.59-0.79), and Ner-Cap (0.72, 0.64-0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52-0.99), Cap (0.68, 0.49-0.96), and Ner (0.65, 0.45-0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22-56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%).
CONCLUSIONS
These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.
PubMed: 34012912
DOI: 10.3389/fonc.2021.608781 -
Journal of Oncology 2020Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)- positive early breast cancer (EBC), drug resistance and...
Dual HER2 Blockade versus a Single Agent in Trastuzumab-Containing Regimens for HER2-Positive Early Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
PURPOSE
Although trastuzumab is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)- positive early breast cancer (EBC), drug resistance and disease relapse occur. Therefore, we performed a meta-analysis to assess the efficacy and safety of trastuzumab-containing dual anti-HER2 therapy compared to trastuzumab alone.
METHODS
A systematic search was performed to identify eligible randomized controlled trials (RCTs). Main outcomes including event-free survival/invasive disease-free survival (EFS/iDFS), overall survival (OS), and safety were considered.
RESULTS
Ten RCTs were included (15,284 patients). Significant improvements were observed in both EFS/iDFS (HR 0.86, =0.0003) and OS (HR 0.86, =0.02) with trastuzumab-based dual anti-HER2 therapy, especially in adjuvant treatment, while in the neoadjuvant setting, dual-targeted therapy also achieved a substantial pathological complete response (pCR) benefit (HR 1.34, =0.0002). Subgroup analysis revealed that the EFS/iDFS benefit was slightly higher with trastuzumab plus pertuzumab or plus neratinib than trastuzumab plus lapatinib, while OS benefit was significant with trastuzumab plus lapatinib, but there were no subgroup differences (interaction test, =0.80 and 0.24, resp.). In addition, EFS/iDFS benefit was unrelated to hormone receptor status but pronounced in the lymph node-positive (LN+) subgroup, which should be interpreted cautiously for lacking interaction (=0.18). Besides, patients receiving dual therapy, especially with the lapatinib-containing regimen, experienced more toxicity, but no increase in cardiotoxicity.
CONCLUSIONS
Despite being associated with more toxicity, trastuzumab-containing dual anti-HER2 therapy is superior to trastuzumab single agent for HER2-positive EBC independent of hormone receptor status. The correlation between survival and LN status needs further verification. Trastuzumab plus pertuzumab or plus neratinib is the preferred regimen with substantial efficacy and lower toxicity.
PubMed: 32256583
DOI: 10.1155/2020/5169278 -
Frontiers in Oncology 2021This meta-analysis aimed to better elucidate the predictive value of human epidermal growth factor receptor 2 (HER2)-enriched subtype of pathological complete response...
BACKGROUND
This meta-analysis aimed to better elucidate the predictive value of human epidermal growth factor receptor 2 (HER2)-enriched subtype of pathological complete response (pCR) rate within HER2-positive breast cancer patients receiving neoadjuvant treatment.
METHODS
We identified prospective trials that evaluated the correlation between an HER2-enriched subtype and pCR rate in HER2-positive breast cancer. Pooled odds ratio (OR) values with 95% confidence intervals (CIs) were computed.
RESULTS
Fifteen studies comprising 2,190 patients met the inclusion criteria. The HER2-enriched subtype was associated with increased odds of achieving a pCR (OR = 4.12, 95% CI = 3.38 to 5.03, < 0.001) in patients overall. Moreover, it was correlated with improved pCR when single or dual HER2-targeted agent-based therapy was employed (OR = 3.36, 95% CI = 2.25 to 5.02, < 0.001; OR = 4.66, 95% CI = 3.56 to 6.10, < 0.001, respectively), but not when HER2-targeted agent-free chemotherapy was used (OR = 2.52, 95% CI = 0.98 to 6.49, P = 0.05). Moreover, an HER2-enriched subtype predicted higher pCR rates irrespective of HER2-targeted agents (trastuzumab, lapatinib, pertuzumab, or T-DM1); chemotherapy agents (taxane-based, or anthracyclines plus taxane-based); endocrine therapy and hormone receptor [all the differences were statistically significant ( all ≤ 0.001)].
CONCLUSIONS
The HER2-enriched subtype can more effectively and specifically predict pCR for HER2-targeted agent-based neoadjuvant treatment, irrespective of the number (single or dual) or category of HER2-targeted agent, including chemotherapy and endocrine therapy, or hormone receptor in cases of HER2-positive breast cancer.
PubMed: 34367947
DOI: 10.3389/fonc.2021.632357 -
Breast Cancer Research : BCR Nov 2015This study aimed at evaluating the overall survival (OS) gain associated with human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with...
INTRODUCTION
This study aimed at evaluating the overall survival (OS) gain associated with human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with metastatic breast cancer (mBC).
METHODS
A bibliographic search was conducted in PubMed and Cochrane databases. Only phase III randomized controlled trials (RCTs) including HER2-positive (HER2+) mBC patients were included in this review. OS was defined as time from randomization until the occurrence of death from any cause. Studies have been grouped according to the line of treatment, i.e., first-line or second-line or beyond.
RESULTS
Nineteen RCTs were eligible for inclusion, of which 12 assessed therapies targeting HER2+ mBC in the first-line setting. OS improved from 20.3 months in the first RCT (standard chemotherapy; Slamon et al. (N Engl J Med 344:783-92, 2001)) evaluating HER2-targeting therapies to 48 months in the study of Swain et al. (Lancet Oncol 14:461-71, 2013), with triple combination of pertuzumab, trastuzumab and docetaxel. Seven RCTs evaluated the OS of HER2-targeting therapies in the second-line setting and beyond. The OS in second-line setting improved from 15.3 months (capecitabine; Cameron et al. (Breast Cancer Res Treat 112:533-43, 2008)) to 30.7 months (trastuzumab emtansine; Verma et al. (N Engl J Med 367:1783-91, 2012)). In the third-line setting, the association of lapatinib and trastuzumab has demonstrated to improve OS to 4.5 months compared with lapatinib alone (14 months vs. 9.5 months; Blackwell et al. (J Clin Oncol 30:2585-92, 2012)).
CONCLUSIONS
HER2-directed therapies had an undeniable beneficial impact on the OS of patients with HER2+ mBC. The triple combination of docetaxel, pertuzumab and trastuzumab is associated with a survival extent of more than 4.5 years, compared with a life expectancy of 1.5 years achieved 14 years ago.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials, Phase III as Topic; Disease-Free Survival; Docetaxel; Female; Humans; Lapatinib; Molecular Targeted Therapy; Quinazolines; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Taxoids; Trastuzumab
PubMed: 26578067
DOI: 10.1186/s13058-015-0648-2