Technological innovation can provide the opportunity to de-escalate treatments. Oncotype DX is considered a valid tool to promote a reduction in the use of chemotherapy in women with a score indicating intermediate-risk early breast cancer. The TAILORx randomized trial showed noninferiority in terms of long-term outcomes of hormone therapy only vs hormone- and chemotherapy (1). Mariotto et al. tested the impact of hypothetical testing of early breast cancer in the real world using SEER-Medicare–based data (2). They showed for the intermediate-risk group a reduction of the burden of chemotherapy in comparison with usual care in the United States.
This study raises two points that invite reflection. First, Oncotype DX testing of early breast cancers assumes a priori ignorance regarding the probability of recurrences (all types), an unsustainable assumption that includes women with different clinical risks. Traditional clinical parameters are relevant in the prediction of recurrences.
In the TAILORx group, in which early breast cancer is defined as hormone receptor-positive, HER2-negative, lymph node-negative, about 73% were smaller than 2 cm and 27% were at high clinical risk, defined according to tumor size and grading (1). In the comparable MINDACT trial (3), it was possible to identify women with such a low risk of recurrence that adding chemotherapy was of no benefit (ceiling effect), regardless of their genomic risk, simply on the basis of size, nodes, grading, and hormonal receptors. Also in the population included in the TAILORx trial, there must be a subgroup for whom additional information on genomic risk should not change the oncologist’s treatment decision.
In the hypothesis that women with low clinical risk cancer would not benefit from adding chemotherapy to hormone therapy, as observed in the MINDACT trial (3), we can define an alternative strategy for decision making—testing only women with high clinical risk (grade 3 or large cancer)—whereas low-risk women would not receive chemotherapy without testing. This strategy would be much more efficient than referring all women to genomic testing, as shown in Figure 1.
Figure 1.
Modeling strategies for the use of genetic testing in early breast cancer, with and without the use of clinical risk in the decision-making process. Comparison of testing and treatment costs of two strategies to decide when to add chemotherapy to hormone in women with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer. A) Genomic testing for all, as proposed by the TAILORx trial. B) Clinical classification of risk followed by genomic testing only for those at high risk (low risk defined by low grade and tumor size ≤3 cm, intermediate grade and tumor size ≤2 cm, and high grade and tumor size ≤1 cm; high risk defined as all other cases with known values for grade and tumor size, as in MINDACT) (3). Costs are based on those computed by Mariotto et al. (2). Distribution of Oncotype DX risk score by clinical risk stratum is reported in the TAILORx trial (1). HR+ = hormone receptor–positive; HT = hormone therapy.
Secondly, the estimated frequency of chemotherapy using SEER-Medicare data showed that a minority of women received chemotherapy in the pretrial scenario. This observation suggests caution when predicting how many chemotherapies could be avoided in other contexts. In fact, oncologists’ behavior differs; chemotherapy is more likely to be used in the United States than in some European countries. Based on the conclusions of the St Gallen conference, European Society Medical Oncology in 2017 stated that “multigene assay should not be the only factor considered in making a decision to proceed or to avoid chemotherapy in this type of early breast cancer” (4). Because the pretrial use of chemotherapy is the most influential parameter in Mariotto and colleagues’ cost analysis (2), it is important to replicate such studies in different countries and settings to predict the real impact on budget (and other factors) of introducing genomic testing.
Funding
PGR and EP received no funding for this paper.
Notes
PGR and EP have no conflicts of interest to declare.
References
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