Adjuvant Dose-Dense Chemotherapy in Breast Cancer: Standard of Care in High-Risk Patients

Overview

Journal Breast Care (Basel)

Publisher Karger

Date 2016 Apr 7

PMID 27051389

Citations 11

Authors

Volker Mobus

Affiliations

Soon will be listed here.

Abstract

Meta-analyses persistently confirm the superiority of dose-dense chemotherapy in comparison with standard chemotherapy. In contrast, individual studies have shown conflicting results. These may be explained by different risk profiles of the treated patient populations. Some trials show a significant advantage in disease-free survival (DFS) and overall survival (OS) in the estrogen receptor (ER)-negative population only, whereas trials with high-risk populations like GIM-2 (Gruppo Italiano Mammella) and AGO-iddETC (Arbeitsgemeinschaft Gynäkologische Onkologie, intense dose-dense epirubicin, paclitaxel, and cyclophosphamide) show a significant superiority in DFS and OS for both, ER-negative and ER-positive patients even after 7 and 10 years, respectively, of follow-up. In contrast, the 10-year follow-up data of the E1199/Intergroup trial no longer showed any superiority of weekly paclitaxel for ER-positive/HER2-negative patients; superiority was observed in the triple-negative subgroup only. Although a direct head-to-head comparison is missing, iddETC or 4 cycles each of dose-dense epirubicin/cyclophosphamide followed by paclitaxel are the preferred adjuvant regimens for patients at risk. Patients with ≥ 4 positive lymph nodes should preferentially be treated with iddETC.

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References

Swain S, Tang G, Geyer Jr C, Rastogi P, Atkins J, Donnellan P . 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. 2013; 31(26):3197-204. PMC: 3757290. DOI: 10.1200/JCO.2012.48.1275. View

Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G . 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. 2015; 385(9980):1863-72. DOI: 10.1016/S0140-6736(14)62048-1. View

Levine M, Pritchard K, Bramwell V, Shepherd L, Tu D, Paul N . Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials.... J Clin Oncol. 2005; 23(22):5166-70. DOI: 10.1200/JCO.2005.09.423. View

Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer S . Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst. 2010; 102(24):1845-54. PMC: 3001963. DOI: 10.1093/jnci/djq409. View

Venturini M, Del Mastro L, Aitini E, Baldini E, Caroti C, Contu A . Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst. 2005; 97(23):1724-33. DOI: 10.1093/jnci/dji398. View

Budd G, Barlow W, Moore H, Hobday T, Stewart J, Isaacs C . SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2014; 33(1):58-64. PMC: 4268253. DOI: 10.1200/JCO.2014.56.3296. View

Hryniuk W, Levine M . Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol. 1986; 4(8):1162-70. DOI: 10.1200/JCO.1986.4.8.1162. View

Sparano J, Zhao F, Martino S, Ligibel J, Perez E, Saphner T . Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer. J Clin Oncol. 2015; 33(21):2353-60. PMC: 4500829. DOI: 10.1200/JCO.2015.60.9271. View

Martin M, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M . Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer. J Natl Cancer Inst. 2008; 100(11):805-14. DOI: 10.1093/jnci/djn151. View

10.

Sparano J, Wang M, Martino S, Jones V, Perez E, Saphner T . Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008; 358(16):1663-71. PMC: 2743943. DOI: 10.1056/NEJMoa0707056. View

11.

Citron M, Berry D, Cirrincione C, Hudis C, Winer E, Gradishar W . 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.... J Clin Oncol. 2003; 21(8):1431-9. DOI: 10.1200/JCO.2003.09.081. View

12.

Petrelli F, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V . Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials. Breast Cancer Res Treat. 2015; 151(2):251-9. DOI: 10.1007/s10549-015-3405-4. View

13.

Moebus V, Jackisch C, Lueck H, du Bois A, Thomssen C, Kurbacher C . 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. 2010; 28(17):2874-80. DOI: 10.1200/JCO.2009.24.7643. View

14.

Burnell M, Levine M, Chapman J, Bramwell V, Gelmon K, Walley B . 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. 2009; 28(1):77-82. PMC: 2799234. DOI: 10.1200/JCO.2009.22.1077. View

15.

Martin M, Ruiz A, Borrego M, Barnadas A, Gonzalez S, Calvo L . Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013; 31(20):2593-9. DOI: 10.1200/JCO.2012.46.9841. View