Result card

  • ETH9: What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing uPA/PAI-1, Oncotype or Mammaprint? Who will balance the risks and benefits in practice and how?
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What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing uPA/PAI-1, Oncotype or Mammaprint? Who will balance the risks and benefits in practice and how?

Authors: Dario Sacchini, Roberta Minacori, Pietro Refolo

Internal reviewers: Petra Schnell-Inderst, Mirella Marlow, Narine Sahakyan

In this context, clinical utility is the likelihood that using a gene expression profiling test to guide management in patients with diagnosed early-stage breast cancer will significantly improve health-related outcomes. Clinical utility is assessed by investigating the balance of benefits (reduced adverse events due to low-risk women avoiding chemotherapy) and harms (cancer recurrence that might have been prevented) associated with the use of the test, compared with the use of alternative management strategies.

No direct evidence links use of the MammaPrint test to clinical outcomes.

No studies evaluated the capacity of MammaPrint to predict benefit from other treatments (e.g., chemotherapy).

No studies determined whether use of MammaPrint in place of, or in addition to, current clinicopathological approaches (e.g., Adjuvant! Online, St. Gallen) changes management, and/or improves outcomes based on management with clinicopathological markers alone.

Retrospective analysis of one arm of a prospective clinical trial showed that the chemotherapy benefit in ER-positive, node-negative patients, randomised to tamoxifen or to tamoxifen plus chemotherapy, was most convincing in women in the Oncotype DX RS high-risk category (27% reduction in 10-year recurrence rate) {35}.

Many persons would likely have been offered chemotherapy without testing, but test results may influence patient–clinician decision making. This study provided the strongest evidence available addressing the clinical utility of the Oncotype DX test, but the study design was not optimal and prospective confirmation of these findings is needed. Three quarters of Oncotype DX results are in the intermediate and low risk ranges, where estimates of recurrence risk have wide and overlapping confidence intervals, and evidence of benefit provided by chemotherapy is inadequate to make decisions. The TAILORx trial will focus on these result groups, {37} but results will not be known for some time.

No direct evidence was found that links the use of the uPA/PAI-1 test to clinical outcomes.

Direct evidence was not found linking any of the three tests to improved outcomes, but there are studies about the components of clinical utility that might provide indirect evidence for clinical utility. There is encouraging indirect evidence for Oncotype DX, and plausibility for potential use of MammaPrint and, possibly, the uPA/PAI-1 test {36, 37, 38, 39, 2, 4}.

It seems plausible that more women will benefit (i.e., avoid unnecessary chemotherapy), but there is the potential for significant harms among a small number of low or intermediate risk women (who might have benefitted from chemotherapy), possibly resulting in breast cancer recurrence or death. There are currently insufficient data to confidently estimate these risks and benefits. In addition, it is difficult to determine what proportion of women with moderate to high risk based on conventional risk assessments will have a “low enough” score to affect their decision about chemotherapy.

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Sacchini D et al. Result Card ETH9 In: Sacchini D et al. Ethical analysis In: Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy ; 2013. [cited 7 February 2023]. Available from: http://corehta.info/ViewCover.aspx?id=113

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