Annals of Oncology Advance Access originally published online on August 5, 2008
Annals of Oncology 2008 19(10):1811-1812; doi:10.1093/annonc/mdn547
letters to the editor |
The anthracyclines and the clinical practice: do all breast cancer patients benefit? Results from the NORA study
Recent data seem to indicate that only some groups of early breast cancer patients benefit from an adjuvant treatment with anthracyclines [1]. In particular, in HER2-positive disease, anthracyclines are reported to be superior to nonanthracycline regimens in terms of disease-free survival (DFS) and overall survival, independently of the method by which the overexpression or amplification was determined.Few data are available at the moment about a possible benefit of anthracyclines in particular groups of HER2– patients, such as those with lack of hormone receptor expression (basal like) or undifferentiated tumours (G3).
The National Oncological Research survey on Adjuvant therapy in breast cancer (NORA) survey is a longitudinal, prospective cohort study which monitored 3515 early breast cancer patients who underwent adjuvant treatment in 77 oncological centres in Italy in the period 2000–2003 [2]. The median age of the patients was 58 years (range 25–92), 43.5% were N+, HER2 status was known in 1621 patients (46.1%), HR status in 3382 (96.2%) and grading in 3171 (90.2%). Adjuvant medical treatment was administered in 97.8% of the cases; 1310 patients received an anthracycline-based regimen as sole therapy or as part of a sequential treatment with hormones.
We conducted a retrospective analysis to verify if there is an interaction between HER2 status and the benefit determined by the use of anthracycline-based regimens in terms of DFS; a second analysis was conducted to establish if there are some groups of HER2– patients that can derive a benefit from the use of anthracyclines.
We considered HER2+ those patients classified as 3+ by immunoistochemistry (IHC) or those with FISH+ results; on the other hand, HER2– patients were identified as those with 0/1+ at IHC determination or FISH–.
Cox proportional hazards model was used to estimate and test clinical–biological features for their effect on DFS and to test the interaction with the presence/absence of anthracycline treatment.
HER2+ patients, for whom a FISH test was not available (200, 18.1%), were excluded from analysis. We identified 250 HER2+ patients, of whom 174 (69.6%) were treated with anthracyclines and 649 HER2– ones, 370 (57.0%) treated with different regimens.
Furthermore, we classified 138 as basal-like patients (HER2–/ER–/PgR–) and identified 1092 patients with poorly differentiated (G3) tumours, of whom 235 (21.5%) did neither express nor amplify HER2 receptor. Eighty-six patients (62.3%) in the former group and 157 (66.8%) in the second one were treated with anthracyclines.
No significant interaction with the presence/absence of anthracycline treatment has been found for all the comparisons carried out. Having HER2+ group as comparator, basal-like patients had a similar DFS (HR = 1.24, P = 0.41), while HER2–/ER+ and/or PgR+ showed a better DFS than HER2+ patients (HR = 0.46, P = 0.04) as well with basal-like patients (HR = 0.39, P = 0.04) (Figure 1).
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Patients with HER2–/undifferentiated tumours (G3) had a DFS similar to HER2+ ones (HR = 0.97, P = 0.91), but worse than HER2–/G1, G2 ones (HR = 3.34, P < 0.0001).
Our data lacked to demonstrate an interaction between the usefulness of anthracyclines and the HER2 status. This result could be due to a true absence of interaction, thus being not able to confirm the data published by Gennari et al., or to the high percentage of missing determinations, that could have generated bias in the analysis.
As pointed out by other authors [3, 4], basal-like subtypes as well HER2+ tumours are more sensitive to chemotherapy. Our data, even if retrospective and extrapolated by a cohort study, demonstrated that DFS rates were similar in HER2–/ER–/PgR– (basal-like) tumours as well in HER2+ ones, suggesting that the former ones can derive a benefit of the same magnitude from an anthracycline treatment and that have to be considered as aggressive as HER2+ groups.
Similarly to what observed for the lack of hormone receptor expression in HER2– tumours, DFS in HER2–/G3 cancers did not significantly differ from what reported in HER2+ ones, suggesting another time that the presence of a low grading could identify a subgroup of HER2– tumours that could have a clinical benefit from aggressive treatment.
According to our data, in HER2– patients, grading and hormone receptor expression are two prognostic variables we have to consider in choosing the most appropriate adjuvant treatment.
1 Department of Medical Oncology, San Gerardo Hospital, Monza
2 Department of Medical Oncology, IST, Genoa
3 Department of Medical Oncology, University of Trieste, Trieste
4 Department of Medical Oncology C, Istituto Pascale, Naples
5 Department of Medical Oncology, Ospedale Careggi, Florence
6 Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
* (E-mail: oncologia{at}tin.it)
References
1. 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.
2. Cazzaniga ME, Mustacchi G, Pronzato P, et al. Adjuvant systemic treatment of early breast cancer: the NORA study. Ann Oncol (2006) 17:1386–1392.
3. Carey LA, Dees EC, Sawyer L, et al. The basal like paradox: primary tumour chemosensitivity of breast cancer subtypes. Clin Cancer Res (2007) 13(8):2329–2334.
4. Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res (2005) 11(16):5678–5685.
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