EJC Supplements
Volume 9, Issue 2 , Pages 5-10, October 2011

Anthracyclines in the adjuvant treatment of breast cancer: state of the art

  • Monica N. Fornier

      Affiliations

    • Corresponding Author InformationCorrespondence: Monica N. Fornier, Evelyn H. Lauder Breast Center, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA. Tel.: +1 646 888 4563; fax: +1 646 888 4555

Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, USA

Article Outline

Abstract 

Anthracycline-based regimens form a cornerstone of the adjuvant and neoadjuvant treatment of breast cancer. Extensive data from clinical trials with long-term follow-up have shown that such regimens significantly prolong overall and disease-free survival, compared with non-anthracycline-based regimens. In recent years, however, the proven benefits of anthracyclines have been challenged because of concerns over toxicity, and evidence that the benefits may be confined to certain patient subgroups, such as those with over-expression of the HER2 or TOP2A genes. Nevertheless, the available evidence suggests that it is premature to consider discarding anthracycline therapy. Although cardiotoxicity is a recognised limitation of long-term anthracycline treatment, clinically overt heart failure is uncommon and associated mortality is low. Similarly, the risk of acute myeloid leukaemia or myelodysplastic syndrome is low during anthracycline treatment. Although there are some data to suggest that the efficacy of anthracyclines may vary between patient subgroups, reliable prospective data to support this are sparse. Future prospective studies, and advances in the identification and validation of potential tumour biomarkers, can be expected to facilitate the targeting of anthracycline therapy to patients who are most likely to benefit.

Keywords:  Adjuvant , Anthracyclines , Breast cancer , Chemotherapy , HER2 , Neoadjuvant , Topoisomerase II alpha

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References 

  1. Early Breast Cancer Trialists' Collaborative Group . Polychemotherapy for early breast cancer: an overview of the randomised trials . Lancet . 1998;352:930–942
  2. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) . Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials . Lancet . 2005;365:1687–1717
  3. Gianni L , Norton L , Wolmark N , Suter TM , Bonadonna G , Hortobagyi GN . Role of anthracyclines in the treatment of early breast cancer . J Clin Oncol . 2009;27:4798–4808
  4. Pinder MC , Duan Z , Goodwin JS , Hortobagyi GN , Giordano SH . Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer . J Clin Oncol . 2007;25:3808–3815
  5. Muss HB , Berry DA , Cirrincione C , et al.   Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience . J Clin Oncol . 2007;25:3699–3704
  6. 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 tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15 . J Clin Oncol . 1990;8:1483–1496
  7. 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;16:2651–2658
  8. Jones S , Holmes FA , O'Shaughnessy J , 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
  9. Muss HB , Thor AD , Berry DA , et al.   c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer . N Engl J Med . 1994;330:1260–1266
  10. Paik S , Bryant J , Park C , et al.   erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer . J Natl Cancer Inst . 1998;90:1361–1370
  11. Pritchard KI , Shepherd LE , O'Malley FP , et al.   HER2 and responsiveness of breast cancer to adjuvant chemotherapy . N Engl J Med . 2006;354:2103–2111
  12. Gennari A , Sormani MP , Pronzato P , et al.   HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials . J Natl Cancer Inst . 2008;100:14–20
  13. Oakman C , Moretti E , Di Leo A . Re-searching anthracycline therapy . Breast Cancer Res Treat . 2010;123:171–175
  14. Slamon D , Eiermann W , Robert N , et al.   Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study . Breast Cancer Res Treat . 2005;94(Suppl 1):S5
  15. Slamon D , Eiermann W , Robert N , et al.   BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients . Breast Cancer Res Treat . 2006;100(Suppl 1): abs 52.
  16. O'Malley FP , Chia S , Tu D , et al.   Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy . J Natl Cancer Inst . 2009;101:644–650
  17. McArthur HL , Tan LK , Patil S , et al.   High resolution representational oligonucleotide microarray analysis (ROMA) suggests that TOP2A and HER2 coamplification is uncommon in human breast cancer . Cancer Res . 2009;69(Meeting Abstract Supplement): abs 2023.
  18. Di Leo A , Isola J , Piette F , et al.   A meta-analysis of phase III trials evaluating the predictive value of HER2 and topoisomerase II alpha in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy . Breast Cancer Res Treat . 2008;107(Suppl):705
  19. Desmedt C , Di Leo A , de Azambuja E , et al.   Multifactorial approach to predicting resistance to anthracyclines . J Clin Oncol . 2011;29:1578–1586
  20. Rouzier R , Pérou CM , Symmans WF , et al.   Breast cancer molecular subtypes respond differently to preoperative chemotherapy . Clin Cancer Res . 2005;11:5678–5685
  21. Cheang M , Chia SK , Tu S , et al.   Anthracyclines in basal breast cancer: the NCIC-CTG trial MA5 comparing adjuvant CMF to CEE . J Clin Oncol . 2009;27(Suppl 15S):519

PII: S1359-6349(11)70003-9

doi:10.1016/S1359-6349(11)70003-9

EJC Supplements
Volume 9, Issue 2 , Pages 5-10, October 2011