Molecular Profiling Is Rather Likely to Be Cost Effective
Authors: Valesca P. Retèl, Sabine C. Linn, Wim H. van Harten
Journal: Journal of Clinical Oncology (2015)

In a recent report, Bonastre et al 1 calculated the cost effectiveness of molecular profiling for adjuvant decision making in patients with node-negative breast cancer and concluded that, under the present circumstances in France, the 70-gene signature (MammaPrint) is unlikely to be cost effective.We believe that there are two main aspects of the article that deserve a rebuttal, especially given that one of our articles is mentioned in the discussion. 2 Bonastre et al 1 state that our group made assumptions that were in favor of the 70-gene signature. 2,3However, these assumptions were all evidence based and published in peer-reviewed journals-although, of course, they were based on the Dutch health care system.One issue in the article by Bonastre et al is that the costs of chemotherapy as shown seem low.This is probably because of the type of third-generation adjuvant chemotherapy regimen that was chosen.Although a direct comparison is lacking, the three cycles of fluorouracil-epirubicin-cyclophosphamide followed by three cycles of docetaxel (T) is likely to be the least effective third-generation regimen, albeit the cheapest.On the basis of recent evidence 4,5 and European Union recommendations 6 or US National Comprehensive Cancer Network guidelines, 7 preferable treatment regimens include doxorubicin-cyclophosphamide (AC) once every 3 weeks for four cycles, followed by T once every 3 weeks for four cycles, or TAC once every 3 weeks for six cycles, both with pegfilgrastim for four to six cycles (administered subcutaneously). 4Furthermore, AC once every 2 weeks for four cycles with pegfilgrastim, followed by paclitaxel once every 2 weeks for four cycles with pegfilgrastim, is equal to six cycles of TAC with pegfilgrastim. 5 Moreover, according to the European Union recommendations, all of these regimens, including three cycles of fluorouracil-epirubicin-cyclophosphamide/three cycles of T, require pegfilgrastim. 6This will substantially raise the total chemotherapy costs.The estimated cost of providing pegfilgrastim to every highrisk patient receiving a taxane-based regimen is 5 ϫ €1,100, 8 which amounts to €5,500 instead of the €749 reported by Bonastre et al, who estimated that pegfilgrastim would be given to 22% of the high-risk patients.Subsequently, it is known that in the node-negative breast cancer population, 10% of patients have a human epidermal growth factor receptor 2/neu-positive tumor; of this 10%, 78% are in the high-risk group. 9This means that use of trastuzumab should also be taken into account, even if for only a small percentage of patients, resulting in high costs per patient of approximately €35,000, 3 an amount that excludes additional costs for adverse events such as cardiotoxicity.In Table 1 of the article by Bonastre et al, it was unclear how many office visits were included in the chemotherapy cost calculation or exactly how the survival probabilities were estimated; therefore, it was difficult for us to reproduce the entire analysis.However, if the additional costs already discussed (a total of approximately €4,751) are added to the presented total chemotherapy price (€4,751 plus €7,486 amounts to €12,237 per patient),