Journal of the National Cancer Institute Advance Access originally published online on April 29, 2008
JNCI Journal of the National Cancer Institute 2008 100(9):680-681; doi:10.1093/jnci/djn108
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© The Author 2008. Published by Oxford University Press.
CORRESPONDENCE |
Response:Re: HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials
Affiliations of authors: Department of Clinical Epidemiology and Medical Oncology, National Cancer Research Institute, Genoa, Italy (AG, PP, PB); Department of Health Sciences, University of Genoa, Italy (AG, MPS)
Correspondence to: Alessandra Gennari, MD, PhD, National Cancer Research Institute, Largo Rosanna Benzi, 10 16132 Genoa, Italy (e-mail: alessandra.gennari{at}istge.it).
Dr Mehta correctly points out that there may be subgroups of HER2-negative patients who would benefit from the use of anthracycline-containing adjuvant chemotherapy, and she suggests that some anthracycline-containing regimens (especially the dose-dense ones) may be more effective than others. With regard to the first issue, individual patient data were not available for all studies in our meta-analysis, which was conducted on published data; as a consequence, the subgroup analyses she advocates are not possible. However, two points must be stressed. First, this hypothetical subgroup of anthracycline-sensitive patients, if it does indeed exist, is likely to be quite small; otherwise, to explain the lack of any effect in the overall group of HER2-negative patients observed in our analysis (hazard ratio for disease-free survival = 1.00; 95% confidence interval [CI] = 0.90 to 1.11; P = .75, hazard ratio for overall survival = 1.03; 95% CI = 0.92 to 1.16; P = .60), it would be necessary to assume that anthracyclines are detrimental in the remaining hypothetically unsensitive patients, a rather implausible hypothesis. Second, the high sensitivity to chemotherapy of high-grade breast tumors mentioned by Dr Mehta, per se, does not indicate that these tumors are more sensitive to anthracycline-containing regimens than to other regimens: to our knowledge, there are no reports linking higher grade to increased sensitivity to anthracyclines. As far as dose intensity is concerned, three studies (1–3) have indicated that dose-dense anthracycline-based regimes are more effective than standard density regimens in HER2-positive patients but not in HER2-negative patients, indirectly supporting our conclusions and confirming that the differential sensitivity to anthracyclines, according to HER2 status, may have a molecular basis. Finally, we agree with Dr Mehta that choosing the appropriate adjuvant therapy for triple negative (ie, HER2-, estrogen receptor–, and progesterone receptor–negative) patients is challenging and that new studies or meta-analyses of previous studies that are based on individual patient and tumor data are needed to answer this question.
REFERENCES
1. 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(4):1107–1116.
2. Del Mastro L, Bruzzi P, Nicolo G, et al. HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. Br J Cancer (2005) 93(1):7–14.[CrossRef][Web of Science][Medline]
3. 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(18):1260–1266.
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J Natl Cancer Inst 2008 100: 680.
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