Breast cancer is the most common malignancy among women in the United States. A reduction in breast cancer mortality has been observed over recent years and is in part attributable to general use of adjuvant chemotherapy and trastuzumab. Besides the addition of specific therapeutic agents, the therapy of early-stage breast cancer has benefited from dose-dense approaches, identification of molecular markers, and translational research innovations such as prognostic gene expression assays. Treatment recommendations for adjuvant breast cancer chemotherapy are traditionally guided by results from clinical studies reflecting a general population; however, molecular and genomic information can potentially enable clinicians to formulate more refined therapeutic decisions. These advances also generate further questions regarding situations where application of therapy is necessary to optimize efficacy and circumstances where sparing therapy is appropriate. Taken together, the advances made through early-stage breast cancer chemotherapy positions us closer to fulfilling the promise of personalized medicine. This article reviews the recent progress of adjuvant chemotherapy and trastuzumab in breast cancer.
American Cancer Society.Cancer Facts and Figures 2007. Available at: http://www.cancer.org/docroot/stt/stt_0.asp . Accessed November 20, 2007.
2.
Early Breast Cancer Trialists' Group.Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687-1717.
3.
National Institutes of Health consensus development conference statement: adjuvant therapy for breast cancer, November 1-3, 2000. J Natl Cancer Inst. 2001;93(13): 979-989.
4.
Goldhirsch A. , Glick JH, Gelber RD, Coates AS, Thurlimann B., Senn HJMeeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol . 2005;16(10): 1569-1583.
5.
Goldhirsch A. , Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. 2007;18(7):1133-1144.
Harris L., Fritsche H., Mennel R., et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol . 25(33):5287-5312.
8.
Paik S., Shak S., Tang G., et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 351(27):2817-2826.
9.
Paik S., Tang G., Shak S., et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-3734.
10.
Paik S.Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist. 2007; 12(6):631-635.
11.
Bonadonna G. , Brusamolino E., Valagussa P., et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294(8): 405-410.
12.
Fisher B., Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifennonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990;8(9):1483-1496.
13.
Martin M., Villar A., Sole-Calvo A., et al. Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM Group. Ann Oncol. 2003;14(6):833-842.
14.
Levine MN, Bramwell VH, Pritchard KI, et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1998;16(8):2651-2658.
15.
Poole CJ, Earl HM, Hiller L., et al. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med . 2006;355(18):1851-1862.
16.
Henderson IC , Berry DA, Demetri GD, 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(6):976-983.
17.
Martin M., Pienkowski T., Mackey J., et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352(22):2302-2313.
18.
Hupperets PS , Tjan-Heijnen VCPrimary or secondary G-CSF prophylaxis to support TAC chemotherapy in breast cancer? Ann Oncol. 2006;17(8):1181-1183.
19.
Martin M., Lluch A., Segui MA, 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(8):1205-1212.
20.
von Minckwitz G., Kummel S., du Bois A., et al. Pegfilgrastim ± ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. Ann Oncol . September 9, 2007, 2007:mdm438.
21.
Khatcheressian JL, Wolff AC, Smith TJ, et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006;24(31):5091-5097.
22.
Brain EG, Bachelot T., Serin D., et al. Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer. JAMA. 2005; 293(19):2367-2371.
23.
Seidman AD, Hudis CA, Albanel J., et al. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. 1998;16:3353-3361.
24.
Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R.Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. 2001;19:4216-4223.
25.
Seidman DB, Cirrincione C., Harris L., et al. CALGB 9840: phase III study of weekly (w) paclitaxel (p) via 1-hour(h) infusion versus standard (s) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (t) for HER2 positive MBC and randomized for t in HER2 normal MBC. Paper presented at the 40th annual meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.
26.
Green MC, Buzdar AU, Smith T., et al. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol. 2005;23(25):5983-5992.
27.
Jones SE, Erban J., Overmoyer B., et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005;23(24): 5542-5551.
28.
Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24(34): 5381-5387.
29.
Hayes DF, Thor AD, Dressler LG, et al. HER2 and response to paclitaxel in node-positive breast cancer . N Engl J Med. 2007;357(15):1496-1506.
30.
Olsen KE, Knudsen H., Rasmussen BB, et al. Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new fish probes. Acta Oncol . 2004;43(1):35-42.
31.
Knoop AS, Knudsen H., Balslev E., et al. Retrospective analysis of topoisomerase IIα amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol. 2005;23(30):7483-7490.
32.
Coon JS, Marcus E., Gupta-Burt S., et al. Amplification and overexpression of topoisomerase II alpha predict response to anthracycline-based therapy in locally advanced breast cancer . Clin Cancer Res. 2002;8(4):1061-1067.
33.
Di Leo A., Gancberg D., Larsimont D., et al. HER-2 amplification and topoisomerase II alpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res. 2002; 8(5):1107-1116.
34.
MacGrogan G. , Rudolph P., Mascarel Id I., et al. DNA topoisomerase II alpha expression and the response to primary chemotherapy in breast cancer . Br J Cancer. 2003;89(4):666-671.
35.
Dressler LG , Berry DA, Broadwater G., et al. Comparison of HER2 status by fluorescence in situ hybridization and immunohistochemistry to predict benefit from dose escalation of adjuvant doxorubicin-based therapy in node-positive breast cancer patients. J Clin Oncol. 2005;23(19):4287-4297.
36.
Fisher B., Anderson S., DeCillis A., et al. Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-25. J Clin Oncol. 1999;17(11):3374-3388.
37.
Moore HCF , Green SJ, Gralow JR, et al. Intensive dose-dense compared with high-dose adjuvant chemotherapy for high-risk operable breast cancer: Southwest Oncology Group/Intergroup Study 9623. J Clin Oncol. 2007;25(13):1677-1682.
38.
Rodenhuis S, Bontenbal M, Beex LVAM, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 ; 349(1):7-16.
39.
Tallman MS, Gray R., Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med. 2003; 349(1):17-26.
40.
Norton L., Simon R.The Norton-Simon hypothesis revisited. Cancer Treat Rep. 1986;70(1):163-169.
41.
Norton L.Conceptual and practical implications of breast tissue geometry: toward a more effective, less toxic therapy. Oncologist. 2005;10(6):370-381.
42.
Simon R., Norton L.The Norton-Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens. Natl Clin Pract Oncol. 2006;3(8):406-407.
43.
Citron ML, Berry DA, Cirrincione C., 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(8):1431-1439.
44.
Venturini M. , Del Mastro L., Aitini E., et al. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial . J Natl Cancer Inst. 2005; 97(23):1724-1733.
45.
Dang CT, D'Andrea GM, Moynahan ME, et al. Phase II study of feasibility of dose-dense FEC followed by alternating weekly taxanes in high-risk, four or more node-positive breast cancer. Clin Cancer Res. 2004; 10(17):5754-5761.
46.
Bardia A, Loprinzi CL, Goetz MP. Hand-foot syndrome after dose-dense adjuvant chemotherapy for breast cancer: a case series. N Engl J Med. 2006;24(13):e18-e19.
47.
Tolaney SM, Partridge AH, Sheib RG, Burstein HJ, Winer EPPneumocystis carinii pneumonia during dose-dense chemotherapy for breast cancer . J Clin Oncol. 2006;24(33):5330-5331.
48.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A., McGuire WLHuman breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177-182.
49.
Yamauchi H. , Stearns V., Hayes DFWhen is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol. 2001;19(8):2334-2356.
50.
Romond EH, Perez EA, Bryant J., et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16): 1673-1684.
51.
Piccart-Gebhart MJ, Procter M., Leyland-Jones B., et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005; 353(16):1659-1672.
52.
Joensuu H., Kellokumpu-Lehtinen PL, Bono P., et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006; 354(8):809-820.
53.
Fisher B., Anderson S., Tan-Chiu E., et al. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001;19(4):931-942.
