The efficacy of chemotherapy depends on the level of risk of the individual patient. Because of this, careful estimation of the risk level is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures might be useful in selected patients if all other criteria are inconclusive for therapeutic decision-making. If indicated, chemotherapy can be used either after surgery (adjuvant) or before surgery (neoadjuvant). Both approaches lead to comparable long-term survival. The neoadjuvant setting offers the additional opportunity for elaborate translational studies to develop and validate predictive biomarkers and to discover mechanisms of resistance to therapy. If possible, chemotherapy regimens should include both anthracyclines and taxanes. Docetaxel should be used every 3 weeks; better tolerability with equivalent efficacy favors the concurrent over the sequential approach. Paclitaxel, on the other hand, should be administered sequentially, either weekly or every 2 weeks. Especially, intense dose-dense sequential chemotherapy with granulocyte colony-stimulating factor support is very effective in high-risk breast cancer patients. In order to decrease toxicities, anthracycline-free regimens or a shortening of the duration of adjuvant chemotherapy are potential options that should be further explored.

1.
Peto R, Davies C, Godwin J, Gray R, Pan HC, et al.: 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; 379:432-444.
2.
Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, et al.: Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013;24:2206-2223.
3.
Simon RM, Paik S, Hayes DF: Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446-1452.
4.
Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, et al.: American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007;25: 5287-5312.
5.
Paik S, Shak S, Tang G, Kim C, Baker J, et al.: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817-2826.
6.
Paik S, Tang G, Shak S, Kim C, Baker J, et al.: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:3726-3734.
7.
Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, et al.: Prognostic and predictive value of the 21-gene recurrence score assay in post-menopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:55-65.
8.
Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, et al.: A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 2011;17:6012-6020.
9.
Dubsky P, Filipits M, Jakesz R, Rudas M, Singer CF, et al.: EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer. Ann Oncol 2013;24:640-647.
10.
van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AAM, et al.: Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002;415:530-536.
11.
Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, et al.: Molecular portraits of human breast tumours. Nature 2000;406:747-752.
12.
Parker JS, Mullins M, Cheang MCU, Leung S, Voduc D, et al.: Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009;27:1160-1167.
13.
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, et al.: Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014, doi: 10.1016/S0140-6736(13)62422-8 [Epub ahead of print].
14.
Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, et al.: Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol 2012;19:1508-1516.
15.
von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, et al.: Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2013;31:3623-3630.
16.
von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, et al.: Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014, doi: 10.1016/S1470-2045(14)70160-3 [Epub ahead of print].
17.
Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, et al.: Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 1976;294:405-410.
18.
Levine MN, Pritchard KI, Bramwell VHC, Shepherd LE, Tu D, et al.: 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 Group Trial MA5. J Clin Oncol 2005;23:5166-5170.
19.
Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, et al.: Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 2003;21:976-983.
20.
Roché H, Fumoleau P, Spielmann M, Canon J, Delozier T, et al.: Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 2006;24:5664-5671.
21.
Martín M, Lluch A, Seguí MA, Ruiz A, Ramos M, et al.: Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol 2006;17:1205-1212.
22.
Mackey JR, Martin M, Pienkowski T, Rolski J, Guastalla J, et al.: Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol 2013; 14:72-80.
23.
Schmidt M, Victor A, Bratzel D, Boehm D, Cotarelo C, et al.: Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer - comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial. Ann Oncol 2009;20:258-264.
24.
Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, et al.: Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med 2010;363: 2200-2210.
25.
Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin M, et al.: Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol 2011;29:3877-3884.
26.
Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, 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 2003;21:1431-1439.
27.
Moebus V, Jackisch C, Lueck H, Du Bois A, Thomssen C, 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 2010;28:2874-2880.
28.
Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, et al.: Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 2010;102:1845-1854.
29.
Sparano JA, Wang M, Martino S, Jones V, Perez EA, et al.: Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358:1663-1671.
30.
Swain SM, Tang G, Geyer CE, Rastogi P, Atkins JN, 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 2013;31:3197-3204.
31.
Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, et al.: Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol 2012;30:4071-4076.
32.
Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, 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;27:1177-1183.
33.
Giordano SH, Lin Y, Kuo YF, Hortobagyi GN, Goodwin JS: Decline in the use of anthracyclines for breast cancer. J Clin Oncol 2012;30:2232-2239.
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