Result card

  • ORG9: How are the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) accepted by healthcare professionals and other staff?

How are the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) accepted by healthcare professionals and other staff?

Authors: Jennifer Butt, Marco Marchetti, Angelica Carletto, Americo Cicchetti, Chiara Filippi

Internal reviewers: Paolo Giorgi Rossi, Claudia Wild, Anne Lee, Antonio Migliore, Stefan Mathis-Endenhofer, Cari Almazan

Analysis of selected studies extracted from the basic literature search and data from electronic clinician survey. Seven articles were found to be relevant to this question.

The Clinical Effectiveness domain of this HTA has analysed the impact of use of the tests on clinicians’ decision-making. Here we consider only data about acceptance of the tests by clinicians.

All of the literature refers to the generic uPA/PAI-1 test rather than to the brand FEMTELLE.

The currently available literature suggests that risk stratification in breast cancer patients has not improved considerably over the past years. Clinicians still use tumour size, grade, and age, with the addition of biomarkers such as uPA/PAI-1, Oncotype DX or MammaPrint in some centres, to determine recurrence risk. Meanwhile, clinicians are eager to implement new techniques, including uPA/PAI-1 assessment, to better refine treatment decisions {4} but they tend to look for more confirmative data concerning the validity of the tests before implementing them in routine clinical practice. During a conference about the regular use of genetic assays in clinical practice in San Francisco in 2009, the audience members voted 50% in favour of regular use of multigene assays in low-risk, node-positive patients and 50% against. After the debate, the audience vote shifted away from regular use, with 33% in favour and 67% against {27}.

Results from the electronic survey show that clinicians and nursing staff have a good acceptance of the tests. (Seven out of eight respondents (88%) reported that both clinicians and nurses accepted or readily accepted the tests.) Nevertheless there was some resistance. Possible reasons for resistance were given by individual survey respondents as follows: lack of confidence in cost effectiveness; the fact the patient has to pay the cost of the test; lack of availability of patients (many are already involved in ongoing clinical trials on adjuvant therapy which do not use these tests); the desire to wait for published data from clinical trials (TailoRX, MINDACT) to define the role and necessity of these tests in therapeutic decision making. Some resistance comes also from administrative staff or nursing staff: some reported anxiety about offering a test to the patient that they would need to pay for or fear of an immediate cost increase due to a lack of confidence in the cost effectiveness of the tests. (See {COL-3} for the full survey results.)

Moreover, the uPA/PAI-1 assay and, until recently, MammaPrint require a fresh-frozen tissue sample, and there is some reluctance to adopt the tests in countries in which fresh-frozen tissue is not readily available after surgery. Core biopsy specimens are now more common and researchers are therefore trying to demonstrate that assays from core biopsies are reliable{4}.

Li et al. (2008) suggest that national or regional healthcare systems should develop supporting information systems that offer educational and consultation programmes for physicians and other healthcare providers, as well as for the general population, to guide the adoption and use of these tests {15}.


A survey performed in 15 community hospitals (Retèl et al. 2009) showed that all the physicians interviewed expected that the MammaPrint signature will eventually become part of future regular diagnostics. Some expected the signature to be performed in all patients; others considered it as a complementary parameter especially in difficult cases. In general, the physicians rated the addition of the 70-gene signature as beneficial for patient management; however, several medical oncologists tended to look for more confirmative data concerning the validity of the signature {10}.

Oncotype DX

Some studies reported that the Oncotype DX Recurrence Score (RS) increased medical oncologists’ confidence in their treatment recommendation:

  • Henry et al. (2009) investigated the impact of the assay on a panel of five breast oncology experts. RS results increased panel consensus by 10% but did not appear to increase the reported strength of panellists’ recommendations {28}.
  • Lo et al. (2010) investigated physician satisfaction about the 21-gene RS assay through a prospective observational study. Results showed increased confidence of medical oncologists in their treatment recommendation in 68 cases (76%). When asked whether they would order the RS assay again, medical oncologists stated they would order it again in 97% of cases {29}.
  • Oratz R et al. (2011) carried out a web-based survey, in the USA, of medical oncologists who ordered the 21-gene RS assay. The response rate was low (16%). Of the 160 respondents, 112 (70%) reported being mostly or completely satisfied with the data supporting the use of the 21-gene RS assay in postmenopausal patients with LN+, ER+ disease, and 75 (47%) reported the same level of satisfaction with the data regarding its use in premenopausal patients with LN+,ER+ disease {30}.

The quality of studies available is poor and the reliability of results, weak. Indeed, data on acceptance come from observational studies, surveys and expert opinions. Moreover, healthcare professionals who responded to the surveys may have had a systematically different impression of the clinical utility of the tests compared with non-respondents, so that acceptance results could be overestimates.

Butt J et al. Result Card ORG9 In: Butt J et al. Organisational aspects 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 (, Italy ; 2013. [cited 2 December 2022]. Available from: