Jan 20, 2015 - Than Anthracyclines Plus. Cyclophosphamide for Lower-Risk. Patients With Early-Stage. Breast Cancer? TO THE EDITOR: The report of the ...
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article.1 If the advantage of AC over T is mainly confined to HER2positive tumors, then there would be a rationale for reconsidering the less toxic regimen with single-agent T as a possible option for HER2negative patients, which should be tested in a future prospective randomized trial.
Should Adjuvant Weekly Paclitaxel Be Considered Less Efficacious Than Anthracyclines Plus Cyclophosphamide for Lower-Risk Patients With Early-Stage Breast Cancer?
Vito Amoroso University of Brescia at Spedali Civili Hospital, Brescia, Italy
Rebecca Pedersini Spedali Civili Hospital, Brescia, Italy
TO THE EDITOR: The report of the Cancer and Leukemia Group B (CALGB) 40101 trial1 has shown that doxorubicin plus cyclophosphamide (AC) is potentially superior to weekly paclitaxel (T) suggesting that anthracyclines should not be abandoned in the management of early-stage breast cancer, even in subsets with a low/moderate risk of relapse as seen in those included in this study. Besides the methodological issues of all trials with a factorial design discussed in the accompanying editorial,2 we have noticed that patients with either human epidermal growth factor receptor 2 (HER2) -positive or HER2-negative breast cancer were recruited in the CALGB 40101 trial without prior stratification. In our opinion, HER2 status may be a potential confounder in the analysis testing the noninferiority of T compared with AC. The prognosis of HER2-positive breast cancers in the absence of trastuzumab is notoriously worse compared with HER2-negative tumors, but HER2 positivity may also have a predictive value of efficacy of anthracyclines.3 A published meta-analysis of adjuvant trials with individual patient data demonstrated a quantitative interaction between anthracycline activity and HER2 status.4 Furthermore, in relation to taxanes, a retrospective analysis of the CALGB 9344/INT0148 trial showed a significant benefit with the addition of paclitaxel after adjuvant therapy with doxorubicin and cyclophosphamide only in patients with tumors that had HER2 overexpression or amplification.5 To our knowledge, no data on the relative efficacy of anthracyclines over paclitaxel according to HER2 status are available up to now. The CALGB 40101 trial initiated in the early 2000s, and at that time HER2 status was not considered a stratification variable. As a consequence, only 48% of the 3,871 patients enrolled onto this study had their HER2 status available. This limitation notwithstanding, we believe that it would be clinically relevant to explore the hypothesis that the relative efficacy of AC compared with T might be different according to HER2 status in the CALGB 40101 data set. This single subgroup-specific analysis would involve approximately 1,800 women and might potentially have adequate statistical power.6 Treatment-associated toxicities are an important concern, particularly when adjuvant therapy is prescribed in a patient with breast cancer with low risk of relapse, as Shulman et al pointed out in their
Phoebe Sharratt Barts and The London School of Medicine and Dentistry, London, United Kingdom
Lucia Vassalli Spedali Civili Hospital, Brescia, Italy
Laura Ferrari University of Brescia at Spedali Civili Hospital, Brescia, Italy
Sandra Sigala University of Brescia, Brescia, Italy
Edda Simoncini Spedali Civili Hospital, Brescia, Italy
Alfredo Berruti University of Brescia at Spedali Civili Hospital, Brescia, Italy
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Shulman LN, Berry DA, Cirrincione CT, et al: Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol 32:2311-2317, 2014 2. Goodwin PJ, Ballman KV, Levine M: Twenty-twenty hindsight: An adjuvant breast cancer trial through the retrospectoscope. J Clin Oncol 32:2284-2286, 2014 3. Pritchard KI, Shepherd LE, O’Malley FP, et al: HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 354:2103-2111, 2006 4. Di Leo A, Desmedt C, Bartlett JM, et al: HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: A meta-analysis of individual patient data. Lancet Oncol 12:1134-1142, 2011 5. Hayes DF, Thor AD, Dressler LG, et al: HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496-1506, 2007 6. Peto R: Current misconception 3: That subgroup-specific trial mortality results often provide a good basis for individualising patient care. Br J Cancer 104:1057-1058, 2011
DOI: 10.1200/JCO.2014.58.7923; published online ahead of print at www.jco.org on December 15, 2014
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© 2014 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 3 (January 20), 2015: pp 290-
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Correspondence
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Should Adjuvant Weekly Paclitaxel Be Considered Less Efficacious Than Anthracyclines Plus Cyclophosphamide for Lower-Risk Patients With Early-Stage Breast Cancer? The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Vito Amoroso No relationship to disclose
Laura Ferrari No relationship to disclose
Rebecca Pedersini No relationship to disclose
Sandra Sigala No relationship to disclose
Phoebe Sharratt No relationship to disclose
Edda Simoncini No relationship to disclose
Lucia Vassalli No relationship to disclose
Alfredo Berruti No relationship to disclose
www.jco.org
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 1, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
