The German Institute for Quality and Efficiency in Health Care (IQWiG) re-examined the benefits of biomarker tests to support a decision for or against adjuvant systemic chemotherapy in selected patients with breast cancer, that is, women with primary hormone receptor-positive, HER2 / neu- negative cancer breast, and from 0 to 3 involved lymph nodes.
When the Institute, presented his final report on the matter at the end of 2016, the evidence was insufficient to assess the benefits of such tests. The only useful data at the time were MINDACT studies that examined the effect of the lack of chemotherapy on the basis of favorable results MammaPrint test in the first five years. As important results of a large study TAILORx were published in the spring of 2018, the Federal Joint Committee (G-BA) commissioned IQWiG to assess these results in the addendum to the final report.
IQWiG concluded that the Oncotype DX test can identify women who may refuse chemotherapy. However, only women participate without the study of affected lymph nodes. It is unclear whether women with lymph nodes to take advantage of this test. It is also unclear whether the clinical assessment of compliance risk, which was surprisingly unreliable in TAILORx study corresponded to everyday medicine in Germany. In addition, the results do not apply to the strategy of decision-making on the basis of biomarkers as a whole, as only one test is carried out in the study.
Not all tests are equal
Available tests biomarkers are intended to assess whether or not a woman has produced a relapse if it does not tolerate chemotherapy in addition to hormonal therapy, ie if it is breast cancer coming back. In each test group is analyzed the expression of other genes.
It is therefore possible that some tests are better predict the risk of relapse than a clinician who looks at factors such as tumor size and type of the tumor tissue, while other tests do not. Therefore, the result IQWiG assessment - a reference to the added benefit - can not simply be transferred to other biomarker tests.
One of the issues examined by the study TAILORx, was whether women with intermediate risk indicator onkotipa (11 to 25) relapses were significantly more frequent without additional chemotherapy than with chemotherapy. For all participants in general was not a statistically significant difference. Age women, apparently, had a value, however: for patients over 50 years of age or after menopause recurrence rate was about the same with or without chemotherapy; so this group has benefited from the solutions, based on tests against chemotherapy. Participants under the age of 50 years or until the menopause, on the contrary, the chemotherapy had significant advantages.
Women with a risk score below 11 and above 25 were not randomized in the study. Instead, the low scores not received chemotherapy, whereas participants with high risk indicators received such treatment. However, the likely assumption can be made on the basis of further research and analysis of data subgroups with values 11-15, 16-20 and 21-25. Under these assumptions elderly women with a risk score of between 0 and 25, and young women with a risk score of 0 to 10 without affected lymph nodes may omit chemotherapy , without increasing the risk of relapse. Naturally, the woman for whom a decision for or against chemotherapy, it is clear from other factors, are exempt from this recommendation.
Clinical evaluation of the risk
Stefan Lange, Deputy Director of IQWiG, said: "Comparison with other studies shows two things: firstly, the incidence rates of 15 to 17 percent were significantly higher than, for example, in MINDACT study. This means that, in particular, more women had recurrences. In principle, it was to be expected, since the observation period to nine years was more than research data available so far. The final report, we noted that breast cancer often returns only after many years, so the five-year data are not suitable for reliable conclusions. Chemotherapy is generally did not reduce the risk of recurrence in older study participants. "
Secondly, TAILORx data showed that the risk of relapse, defined clinically, was very fragile: in study participants with low and high risk was about the same chance of remaining disease-free at the end of the observation period. "It is possible, however, that further factors influence the clinical evaluation in the German health care or that they are weighted differently," - says Stefan Lange. "It would be too early to declare useless assessment of clinical risk based on a single study, and replace it with biomarker tests."