Selection of breast cancer subtypes to improve benefits of intensive dose‑dense chemotherapy: A systematic meta‑analysis
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- Published online on: November 7, 2023 https://doi.org/10.3892/ol.2023.14136
- Article Number: 4
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Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women worldwide (1). Although adjuvant chemotherapy confers a one-third reduction in the 10-year risk of mortality from BC (2), a large number of patients will experience recurrence and BC-associated mortality (3). To improve the prognosis and sensitivity to chemotherapy of patients with BC, a new chemotherapy interval protocol has been proposed called intensive dose-dense (DD) chemotherapy, which consists of using the same chemotherapy agents and dosing but with shorter intervals between treatment cycles (4). Generally, the usual chemotherapy once every 3 weeks is shortened to once every 2 weeks to shorten the treatment time, improve the treatment effect, prolong the survival time of patients and improve the quality of life.
To the best of our knowledge, no studies have previously investigated which pathological type of patients is more suitable for DD chemotherapy. Zhu et al (5) revealed that patients with hormone receptor (HR)-positive (HR+) BC treated with DD chemotherapy may benefit more from treatment (5). Lambertini et al showed that patients with Her2+ BC receive less benefit under DD chemotherapy (6). Furthermore, the lack of an increased risk of serious adverse events with intensive chemotherapy for DD suggests that shorter chemotherapy intervals can be considered for follow-up treatments (7). Therefore, intensive DD chemotherapy may be more suitable for some patients.
However, the most suitable pathological BC subtype, including patients with HR− or HR+ BC, that is most responsive to DD chemotherapy remains to be identified. Currently, it is unknown whether intensive DD chemotherapy is beneficial for patients with different pathological subtypes. To the best of our knowledge, no previous systematic review (8–10) has provided a comprehensive overview using pairwise and network meta-analyses to evaluate which pathological type of BC is the most responsive to DD chemotherapy regimens. The present study aimed to determine the most suitable pathological subtype of BC to benefit from intensive DD chemotherapy.
Materials and methods
Protocol registration
The present network meta-analysis was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) (11) and the Cochrane Collaboration guidelines (12). This systematic review was registered with the PROSPERO online system as no. CRD2022420351567 (13).
Search strategy and eligibility criteria
The present study searched studies registered in PubMed(ncbi.nlm.nih.gov/pubmed), Web of Science(apps.webofknowledge.com), the Cochrane Library(www.cochranelibrary.com/) and China National Knowledge Infrastructure(https://www.cnki.net/)_ from the date of database inception to October 2022, and an upgraded search was conducted on March 10, 2023. The keywords ‘breast cancer’, ‘intensive dose-dense chemotherapy’ and their MeSH terms were used (see details in Data S1). The Gene Expression Omnibus and The Cancer Genome Atlas databases do not have relevant data and were therefore not included. The studies were required to have written the inclusion and exclusion criteria distinctly and clearly based on PICOS as follows: P, patients with BC; I, intensive DD chemotherapy; C, standard chemotherapy; O, survival rate and adverse effects; and S, randomized controlled trials (RCTs) and retrospective studies. Studies that met the aforementioned PICOS criteria were included in the present meta-analysis. After selection, the present study included RCTs and retrospective studies comparing intensive DD chemotherapy with standard chemotherapy in patients with BC, and patients with available information on pathological subtype and clinical stage were included. Studies with different durations of intensive DD chemotherapy and no available survival data were excluded. For DD chemotherapy, the experimental arm was designed to narrowly deliver agents over a shorter interval in the same cycle and dosage as the conventional schedule in the control arm. Survival data were synthesized and merged for analysis. No language restrictions were set, and reference lists from previous similar systematic reviews were also identified for potentially eligible studies.
Data extraction and quality assessment
A total of two reviewers (SD and ZTQ) independently performed the selection of the title and abstract and the evaluation of the full text of potentially eligible studies. Discrepancies between the two authors were resolved through discussion and by consultation with an experienced reviewer (ZYS). Eligible studies were analyzed for first author, publication year, study type, sample size (age range, before or after surgery, pre/postmenopausal status), tumor size (≤2.0, 2.1–5.0, ≥5.1) or tumor stage (T0-1/T2/T3-4), lymph node status (pN1/pN2-3) or (cN0-1/cN2-3), tumor grade (G1/G2/G3), estrogen/progesterone receptor (ER/PR) status, HER2 status and Ki-67 positivity (20%/>20%); DD type, agents and treatment cycle were extracted as baseline characteristics. For eligible RCTs, the Cochrane tool for assessing risk of bias (RoB 2.0) (14) was used to rate RCTs as follows: All low-risk domains were considered low-risk studies, one high-risk domain was considered a high-risk study and all other studies were considered unknown-risk studies. The quality of the eligible retrospective study was assessed using the Newcastle-Ottawa Scale score (15), with a score >4 considered acceptable.
To evaluate the effects of DD chemotherapy in patients with BC, overall survival (OS), disease-free survival (DFS), event-free survival (EFS), recurrence-free survival (RFS), pathologic complete response (pCR) and objective remission rate (ORR) were analyzed. BC subgroups of overall HR+, HR−, Her2+, Her2 and triple-negative breast cancer (TNBC) were also evaluated. Luminal A and B classification could not be analyzed in subgroups due to limited data. Furthermore, the safety results related to DD chemotherapy included anemia, leukocytopenia, fatigue, diarrhea, nausea, vomiting and febrile neutropenia. The present study also used the Grading of Recommendations Assessment, Development, and Evaluation scales (16) to evaluate the quality of the outcomes from pairwise meta-analysis.
Statistical analysis
The present study performed pairwise meta-analyses for all direct comparisons with at least two different pathological types available and random effects network meta-analysis with a frequented approach to simultaneously combine direct and indirect evidence of all pathological types. For both pairwise meta-analyses and network meta-analysis, a random effects model to prevent inconsistencies was estimated. The present study assumed the variance of the heterogeneity model, which reported P<0.05 or I2>50%, indicating heterogeneity in the results (17).
For all results, the odds ratios (OR) and the hazard ratio (HR) with their corresponding 95% credible intervals (95% CI) were used to confirm significance of the meta-analysis results. Furthermore, a meta-analysis P<0.05 was used to determine whether a specific factor was the source of heterogeneity (18). Furthermore, Begg's and Egger's tests were performed to assess publication bias for available comparisons, and P<0.05 indicated the existence of publication bias.
The inconsistency between indirect sources of evidence was statistically assessed using a global (design-by-treatment inconsistency model) and a local method (back calculation) (19,20). The mean rank and relative treatment rankings were assessed for each intervention node according to the surface under the cumulative ranking curve (SUCRA) values and produced rankograms for the results of the OS and DFS analyses. The SUCRA score ranged from 0–100%, and a higher SUCRA indicated that patients with this pathological classification were more suitable for DD chemotherapy. Comparison-adjusted funnel plots were produced to explore the publication bias for network meta-analysis outcomes. All analyses were performed using StataSE version 15.1 (College Station, Texas 77845 USA).
Results
Study selection
A total of 449 publications were evaluated for eligibility after the removal of duplicates. After screening at the title and abstract level, 33 articles were left for full-text assessment. Furthermore, six records were removed based on a priori study selection criteria. A total of 27 studies (21–47) that included 27,580 patients were included in primary meta-analyses (Fig. 1). Of these, 25 studies were RCTs, including 12 that were phase III trials, and the remaining two were retrospective studies.
Study characteristics
The summarized characteristics of the studies are reported in Table I by pathological type and outcomes (see details in Table SI), with a sample size range of 43 to 3,264; of these, 17/43 included survival outcomes, such as the pathological subtype, which could provide data for the network meta-analysis (Table I). The baseline was balanced in terms of indicators before or after surgery, menopausal status, tumor size, lymph node status, ER/PR status, HER2 status and Ki-67 positivity (Table II). The worst tumor grade was determined in the DD chemotherapy group (Table II). Regarding quality assessment, all included studies achieved acceptable quality (Fig. S1; Table SII).
Evaluation of the effectiveness of DD chemotherapy from pairwise meta-analysis
All included studies included reporting of survival data for DD chemotherapy compared with standard chemotherapy. For OS, 13 studies provided HR data, and 30 of them provided OR data. Significant differences were found in the general group with low heterogeneity (HRa as in hazard ratios=0.82; 95% CI, 0.76 to 0.89; P=0.205; I2=23.6%). Furthermore, the HR+ and HR− subgroups also scored significant differences (0.75, 0.67 to 0.83; 0.77, 0.67 to 0.83). Furthermore, no significant difference in the OR results was found, with no sources of heterogeneity detected among meta-regressions that indicated low publication bias, ranging from very low to low grade (Table III).
 | Table III.Subgroup meta-analysis of summary both HRa and OR outcomes from different pathological types on the efficacy of intensive DD chemotherapy for BC. |
For DFS, significant differences could also be found in the overall sample [0.85 (95% CI, 0.79 to 0.91)] and in the HR+ [0.62 (95% CI, 0.30 to 0.95)], Her2+ [0.62 (95% CI, 0.30 to 0.95)] and Her2− [0.45 (95% CI, 0.21, 0.70)] subgroups when considering outcomes and in the OR results of the TNBC subgroup [1.58 (95% CI, 1.03 to 2.43)], which had low heterogeneity in most subgroups and a small publication bias. Furthermore, meta-regression revealed that Her2+ or HER1− status may have had a significant effect on the overall results (P=0.080). Significant differences in EFS could also be found in the overall sample [0.77 (95% CI, 0.70 to 0.84)] and for the HR− status group [0.76 (95% CI, 0.65, 0.88)] with no heterogeneity; likewise, there were significant differences in the overall RFS [0.76 (95% CI, 0.61 to 0.91)] for HRa outcomes and the ORR [1.48 (95% CI, 1.08 to 2.04)] with OR outcome (Table III).
Altogether, the present study revealed that DD chemotherapy successfully improved patient survival, especially with regard to OS and DFS. Subsequently, network meta-analysis was used to determine the most suitable pathological type of patients for DD chemotherapy. Furthermore, compared with OR, the HRa not only reflected the existence of events at the endpoint but also the time taken to reach the endpoint and the censored data. Therefore, the present study used HRa data for subsequent network meta-analysis.
Pathological subtypes of patients with BC suitable for DD chemotherapy derived from the network meta-analysis
The network graphs of direct comparisons between the 13 studies included in the network meta-analysis that provided OS data are shown in Fig. 2. Regarding the HRa outcome for OS, TNBC ranked the lowest with the lowest SUCRA score, and the second to last group was the overall patient sample. In terms of reduced survival risk, HR+ was classified first, followed by Her2−, Her2+ and HR− BC subtypes, with no significant differences. Furthermore, DFS was classified as OS, and significance was found in subgroups of HR+ [-0.85 (95% CI, −1.15 to −0.55)], Her2− [-0.94 (95% CI, −1.26 to −0.61)], Her2+ [-0.73 (95% CI, −1.06 to −0.40)], HR− [-0.51 (95% CI, −0.91 to −0.11)] and the overall sample [-0.59 (95% CI, −0.89 to −0.29)] compared with TNBC. Significant differences were also identified when comparing the overall group in terms of HR+ [-0.26 (95% CI, −0.47 to −0.05)] and Her2− [-0.35 (95% CI, −0.65 to −0.04)] status subgroups and when comparing the HR+ and Her vs. HR− status subgroups (Fig. 3). In summary, DD chemotherapy may be more effective in patients with HR+ and Her2− pathological subtypes.
Evaluation of the effectiveness of DD chemotherapy from pairwise meta-analysis
Grade 3 to 4 toxicity of DD chemotherapy compared with standard chemotherapy was reported in only 17 studies. DD chemotherapy did not increase the risk of serious leukocytopenia, fatigue, diarrhea, vomiting or febrile neutropenia. However, DD chemotherapy resulted in significant increases in the serious risk of anemia [3.024 (95% CI, 2.173 to 4.208)] and nausea [1.482 (1.096 to 2.004)], with low to substantial heterogeneity, low publication bias and low to moderate grade (Table IV).
| Table IV.Most frequent toxicities (grade III or higher) for patients treated with DD vs. standard treatment. |
Discussion
The present network meta-analysis systematically reviewed the efficacy and safety of DD chemotherapy in patients with BC and determined the most suitable pathological subtype that would benefit from DD chemotherapy. A total of 27 studies involving 27,580 patients were included and the baseline indicators were balanced, except for tumor grade. In addition, from the pairwise meta-analysis of efficacy outcomes of DD chemotherapy, significant differences were frequently found in the general, HR+ and Her2− status subgroups in terms of HRa outcome. Moreover, the meta-regression revealed stratified patients with Her2 status and the heterogeneity source. Furthermore, the network meta-analysis indicated that patients with the HR+, Her2− pathological BC subtype may be more responsive to DD chemotherapy. In addition, chemotherapy for DD can cause serious anemia and nausea. For patients with BC with HR+ and Her2− pathology, chemotherapy for DD was recommended.
This network meta-analysis adhered to the PRISMA guidelines and was registered with the PROSPERO website, which means that the review was systematic and robust. The present study concluded that patients with BC with HR+ and Her2− states were the pathological subtypes most suitable for intense DD chemotherapy. Similar conclusions were obtained by Puglisi et al, whereby DD adjuvant chemotherapy showed a consistent benefit in patients with early BC with HR+/HER2− disease, although its effects varied according to the composite measure of the risk of recurrence (48). Lambertini et al concluded that DD chemotherapy is associated with a significant improvement in survival in patients with high-risk breast cancer. Its benefit is smaller in patients with HER2+ disease who received adjuvant trastuzumab (6). In terms of safety outcomes, information regarding treatment with pertuzumab, trastuzumab and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles and pCR rates that were consistent with those from previous studies of pertuzumab (49). These studies support the present results and suggest that the safety of DD chemotherapy is acceptable.
Currently, standard chemotherapy based on anthracycline and taxane is still recommended for patients with HER2−/HR+ BC with a 21-day cycle. The present study recommended a 14-day cycle of chemotherapy without changing chemotherapy agents to achieve an improved patient benefit and acceptable safety. The mechanism of DD chemotherapy is more effective, as the DD regimen was less toxic to the immune system, presented reduced immunosuppression by the tumor microenvironment, and triggered macrophage recruitment and tumor-specific CD8+ T-cell responses to tumors as determined by IL-2 and IFN-γ secretion (50). Furthermore, other mechanisms of action may also be involved, such as induction of apoptosis or inhibition of angiogenesis (51). Furthermore, DD chemotherapy may contribute to overcoming drug resistance, giving a high response rate, although durable remissions were achieved in few patients (52). These studies indicate that it is important to investigate non-traditional chemotherapy interval options for the treatment of BC.
There are also several limitations among the studies included in the meta-analysis. First, the baseline was not balanced as an indicator of tumor grade, which may have influenced the overall outcome. Second, the present study found that significant differences in OS and DFS data often appeared in HRa but not in OR data because HRa data were more accurate. Third, the present study did not perform a subgroup analysis based on the classification of chemotherapeutic agents or on the clinical stage because the included studies did not provide enough HRa data. Fourth, the sample size of the network meta-analysis may not have been large enough to show the final conclusion. In the future, high-quality studies with larger sample sizes should be conducted in an effort to clearly report agents and clinical stages, thereby allowing network meta-analysis determination of the most suitable chemotherapeutic agents and clinical stage of patients to benefit from intensive DD chemotherapy. Finally, the present study found that repeated data were reported; for example, some data were included in both the HR+ and Her2− groups, which may have also influenced the overall results. In conclusion, patients with HR+ and Her2− BC are the most suitable pathological subtype to benefit from intense DD chemotherapy with an acceptable safety profile.
The findings of the present network meta-analysis represent studies with the best evidence base currently available and provide a guide on the choice of intense DD chemotherapy or standard chemotherapy regimens for patients. From a clinical standpoint, it is important to also consider the most suitable chemotherapy interval for different pathological subtypes in patients with BC, and it is hoped that these results will improve informed and shared decision-making processes for patients and clinicians. The present study hypothesized that intensive DD chemotherapy was most appropriate for patients with the luminal A type. Future studies should focus on the specific characteristics of patients to provide a personalized prediction of comparative effectiveness and safety with respect to the applicability of DD chemotherapy.
Supplementary Material
Supporting Data
Supporting Data
Supporting Data
Acknowledgements
Not applicable.
Funding
The present study was supported by National College Students Innovation and Entrepreneurship Training Program of Shenyang Pharmaceutical University (grant no. 202210163017), Science Foundation of Shenyang Pharmaceutical University (grant no. GGJJ2021107) and Scientific Research Fund of Liaoning Provincial Education Department (grant no. LJKQZ20222349).
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
Authors' contributions
DS, TQZ, and YSZ contributed to the study conception and design. Data collection and analysis were performed by DS, TQZ, HMH, XYS, YL and XYW. The first draft of the manuscript was written by DS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. DS and YSZ confirm the authenticity of all the raw data.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
|
Siegel RL, Miller KD, Wagle NS and Jemal A: Cancer statistics, 2023. CA Cancer J Clin. 73:17–48. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Schopper D and de Wolf C: How effective are breast cancer screening programmes by mammography? Review of the current evidence. Eur J Cancer. 45:1916–1923. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Tian Z, Tang J, Liao X, Yang Q, Wu Y and Wu G: An immune-related prognostic signature for predicting breast cancer recurrence. Cancer Med. 9:7672–7685. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Li BX, Chen XJ, Ding TJ, Liu YH, Ma TT, Zhang GL and Wang XM: Potentially overestimated efficacy of nanoparticle albumin-bound paclitaxel compared with solvent-based paclitaxel in breast cancer: A systemic review and meta-analysis. J Cancer. 12:5164–5172. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu T, Xu F, Zhang L, Zhang Y, Yang C, Cheng M, Chen F and Wang K: Measurement of molecular biomarkers that predict the tumor response in estrogen receptor-positive breast cancers after dose-dense (biweekly) paclitaxel/carboplatin neoadjuvant chemotherapy. Oncotarget. 8:101087–101094. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lambertini M, Poggio F, Bruzzone M, Conte B, Bighin C, de Azambuja E, Giuliano M, De Laurentiis M, Cognetti F, Fabi A, et al: Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial. Int J Cancer. 147:160–169. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Tomasello G, Valeri N, Ghidini M, Smyth EC, Liguigli W, Toppo L, Mattioli R, Curti A, Hahne JC, Negri FM, et al: First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: Final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study. Oncotarget. 8:111795–111806. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou W, Chen S, Xu F and Zeng X: Survival benefit of pure dose-dense chemotherapy in breast cancer: A meta-analysis of randomized controlled trials. World J Surg Oncol. 16:1442018. View Article : Google Scholar : PubMed/NCBI | |
|
Goldvaser H, Majeed H, Ribnikar D, Šeruga B, Ocaña A, Cescon DW and Amir E: Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis. Breast Cancer Res Treat. 169:413–425. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Petrelli F, Coinu A, Lonati V, Cabiddu M, Ghilardi M, Borgonovo K and Barni S: Neoadjuvant dose-dense chemotherapy for locally advanced breast cancer: A meta-analysis of published studies. Anticancer Drugs. 27:702–708. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al: The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 372:n712021. View Article : Google Scholar : PubMed/NCBI | |
|
van Tulder M, Furlan A, Bombardier C and Bouter L; Editorial Board of the Cochrane Collaboration Back Review Group, : Updated method guidelines for systematic reviews in the cochrane collaboration back review group. Spine (Phila Pa 1976). 28:1290–1299. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Jinatongthai P, Kongwatcharapong J, Foo CY, Phrommintikul A, Nathisuwan S, Thakkinstian A, Reid CM and Chaiyakunapruk N: Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with ST-segment elevation myocardial infarction: A systematic review and network meta-analysis. Lancet. 390:747–759. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, et al: RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 366:l48982019. View Article : Google Scholar : PubMed/NCBI | |
|
Wells G: The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. Symposium on Systematic Reviews: Beyond the Basics. 2014. | |
|
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P and Schünemann HJ; GRADE Working Group, : GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 336:924–926. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Yang C, Xu C, Li X and Zhang Y, Zhang S, Zhang T and Zhang Y: Could camrelizumab plus chemotherapy improve clinical outcomes in advanced malignancy? A systematic review and network meta-analysis. Front Oncol. 11:7001652021. View Article : Google Scholar : PubMed/NCBI | |
|
Feng F, Jiang Q, Jia H, Sun H, Chai Y, Li X, Rong G, Zhang Y and Li Z: Which is the best combination of TACE and Sorafenib for advanced hepatocellular carcinoma treatment? A systematic review and network meta-analysis. Pharmacol Res. 135:89–101. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Higgins JPT, Jackson D, Barrett JK, Lu G, Ades AE and White IR: Consistency and inconsistency in network meta-analysis: Concepts and models for multi-arm studies. Res Synth Methods. 3:98–110. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
König J, Krahn U and Binder H: Visualizing the flow of evidence in network meta-analysis and characterizing mixed treatment comparisons. Stat Med. 32:5414–5429. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Schneeweiss A, Michel LL, Möbus V, Tesch H, Klare P, Hahnen E, Denkert C, Kast K, Pohl-Rescigno E, Hanusch C, et al: Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer. Eur J Cancer. 160:100–111. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Y: Efficacy and long-term survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer. PhD Thesis. Chin Acad Med Sci. 2021.(In Chinese). | |
|
Blondeaux E, Lambertini M, Michelotti A, Conte B, Benasso M, Dellepiane C, Bighin C, Pastorino S, Levaggi A, Alonzo A, et al: Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-Year results of the phase 3 Mammella InterGruppo (MIG)-1 study. Br J Cancer. 122:1611–1617. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
He J: Application of Dose-dense Chemotherapy in Neoadjuvant Therapy for Breast Cancer. PhD Thesis. Hebei Med Univ. 2020.(In Chinese). | |
|
Schneeweiss A, Möbus V, Tesch H, Hanusch C, Denkert C, Lübbe K, Huober J, Klare P, Kümmel S, Untch M, et al: Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer. 106:181–192. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Möbus V, Jackisch C, Lück HJ, du Bois A, Thomssen C, Kuhn W, Nitz U, Schneeweiss A, Huober J, Harbeck N, et al: Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: Final results of AGO phase III iddEPC trial. Ann Oncol. 29:178–185. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
van Rossum AGJ, Kok M, van Werkhoven E, Opdam M, Mandjes IAM, van Leeuwen-Stok AE, van Tinteren H, Imholz ALT, Portielje JEA, Bos MMEM, et al: Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: First results of the randomised MATADOR trial (BOOG 2004–04). Eur J Cancer. 102:40–48. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, et al: Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): A multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 18:929–945. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lambertini M, Ceppi M, Cognetti F, Cavazzini G, De Laurentiis M, De Placido S, Michelotti A, Bisagni G, Durando A, Valle E, et al: Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies. Eur J Cancer. 71:34–42. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Bao Z, Chen Y, Ren H, Jiang Y, Yang J and Li S: Clinical observation of dose-dense chemotherapy in the postoperative treatment of triple-negative breast cancer. J Mod Oncol. 24:2221–2224. 2016.(In Chinese). | |
|
Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, et al: Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: A randomized clinical trial. JAMA. 316:1888–1896. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, et al: Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 385:1863–1872. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Y: Clinical study of postoperative intensive chemotherapy with pirarubicin for triple negative breast cancer. J Clin Med. 2:6059–6062. 2015.(In Chinese). | |
|
Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, et al: Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: The NSABP B-38 trial. J Clin Oncol. 31:3197–3204. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu X, Qin Q, Wei C, Zhu F, Mo G and Lian B: Clinical effect analysis of intensive chemotherapy and conventional adjuvant chemotherapy in patients with advanced breast cancer. Pract Geriatr. 27:157–173. 2013.(In Chinese). | |
|
Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D, et al: Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-Year results of the Hellenic cooperative oncology group HE 10/00 phase III trial. Breast Cancer Res Treat. 132:609–619. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Jin C, Zhang Y, Ma L, Zhou Y, Wei Y and Li H and Li H: Clinical analysis of intensive chemotherapy with perarubicin after high risk breast cancer surgery. Guide China Med. 10:558–559. 2012.(In Chinese). | |
|
Arun BK, Dhinghra K, Valero V, Kau SW, Broglio K, Booser D, Guerra L, Yin G, Walters R, Sahin A, et al: Phase III randomized trial of dose intensive neoadjuvant chemotherapy with or without G-CSF in locally advanced breast cancer: Long-term results. Oncologist. 16:1527–1534. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Untch M, Fasching PA, Konecny GE, von Koch F, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, et al: PREPARE trial: A randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer-results at the time of surgery. Ann Oncol. 22:1988–1998. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, et al: PREPARE trial: A randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer-outcome on prognosis. Ann Oncol. 22:1999–2006. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, et al: Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol. 28:77–82. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Moebus V, Jackisch C, Lueck HJ, du Bois A, Thomssen C, Kurbacher C, Kuhn W, Nitz U, Schneeweiss A, Huober J, et al: Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: Mature results of an AGO phase III study. J Clin Oncol. 28:2874–2880. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Untch M, Möbus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I, Harbeck N, Werner C, Lebeau A, Schneeweiss A, et al: Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 27:2938–2945. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Venturini M, Del Mastro L, Aitini E, Baldini E, Caroti C, Contu A, Testore F, Brema F, Pronzato P, Cavazzini G, et al: Dose-dense adjuvant chemotherapy in early breast cancer patients: Results from a randomized trial. J Natl Cancer Inst. 97:1724–1733. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Baldini E, Gardin G, Giannessi PG, Evangelista G, Roncella M, Prochilo T, Collecchi P, Rosso R, Lionetto R, Bruzzi P, et al: Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: A randomized phase III trial in locally advanced breast cancer. Ann Oncol. 14:227–232. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of intergroup trial C9741/cancer and leukemia group B trial 9741. J Clin Oncol. 21:1431–1439. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Therasse P, Mauriac L, Welnicka-Jaskiewicz M, Bruning P, Cufer T, Bonnefoi H, Tomiak E, Pritchard KI, Hamilton A and Piccart MJ; EORTC: Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: An EORTC-NCIC-SAKK multicenter study. J Clin Oncol. 21:843–850. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Puglisi F, Gerratana L, Lambertini M, Ceppi M, Boni L, Montemurro F, Russo S, Bighin C, De Laurentiis M, Giuliano M, et al: Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer. NPJ Breast Cancer. 7:822021. View Article : Google Scholar : PubMed/NCBI | |
|
Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, et al: Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): A phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 29:646–653. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chang CL, Hsu YT, Wu CC, Lai YZ, Wang C, Yang YC, Wu TC and Hung CF: Dose-dense chemotherapy improves mechanisms of antitumor immune response. Cancer Res. 73:119–127. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kumar A, Hoskins PJ and Tinker AV: Dose-dense paclitaxel in advanced ovarian cancer. Clin Oncol (R Coll Radiol). 27:40–47. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Crout CA, Koh LP, Gockerman JP, Moore JO, Decastro C, Long GD, Diehl L, Gasparetto C, Niedzwiecki D, Edwards J, et al: Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy. Cancer Invest. 28:654–660. 2010. View Article : Google Scholar : PubMed/NCBI |
