Result card

  • ORG1: What work flow and patient flow processes are needed to use the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) on women with invasive breast cancer?

What work flow and patient flow processes are needed to use the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) on women with invasive breast cancer?

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

The domain methodology was used for this question (analysis of selected studies extracted from the basic literature search). Three articles were found to be relevant to this question. Information provided by the manufacturers to the HTA was also reviewed.


For the purposes of this HTA, the uPA/PAI-1 test may be analysed in three ways:

  1. The FEMTELLE test may be analysed in a laboratory recommended by the manufacturer.
  2. The FEMTELLE test may be analysed in a laboratory that meets the quality standards recommended by the manufacturer.
  3. A generic (“home brew”) uPA/PAI-1 test may be developed and analysed in a laboratory to its own standards.

All of the literature refers to the generic uPA/PAI-1 test rather than to the brand FEMTELLE. Unless specified otherwise, the information which follows therefore relates to the generic uPA/PAI-1 test and may not apply to FEMTELLE. It may also not apply consistently to the uPA/PAI-1 test since processes may differ from one laboratory to another.

Obtaining tissue samples

Tissue may be obtained from surgical specimens or from core needle biopsies for Oncotype DX® {1}, MammaPrint® {2} and uPA/PAI-1{3}. It is possible that the uPA/PAI-1 test can only reliably be carried out on tissue from surgery rather than core biopsy tissue {4}. Care must be taken in obtaining the samples in accordance with the manufacturer’s instructions (see RC-TEC13 for more details).

Preserving tissue samples

MammaPrint uses fresh-frozen tissue, tissue preserved in an RNA preservative solution, or formalin- fixed paraffin-embedded (FFPE) tissue. Oncotype DX uses FFPE  breast cancer tumour tissue. The uPA/PAI-1 test, including FEMTELLE, requires fresh-frozen tissue. {RC-TEC2, RC-TEC3, RC-TEC4}

If one particular tissue collection and preservation system is normally used in the clinical setting, use of a test that requires a different system will have an impact on work flows.

Impact on clinical communication and cooperation

Use of these tests may require some additional forms of communication and cooperation between hospital units, outpatient services and hospital structures. There is more detail on this in question ORG3 below.

Impact on patient flow

Tissue samples for Oncotype DX and MammaPrint must be sent to a central laboratory for processing. This may have implications for patient flow as the results are received in 10–14 days (Oncotype DX) or 7–10 days (MammaPrint). If the FEMTELLE test is analysed in house according to the manufacturer’s instructions, this takes two days. If it is sent to a designated laboratory for processing the results should be received in 3–4 days {COL-2}. There is no information in the literature about the time taken to process generic uPA/PAI-1 tests, but reasonably this could be variable.

There is more detail in question RC-ORG3 below about the impact on patient communication of introducing the tests.

The literature contains little information on the work flow and patient flow impact of using these tests. Some points that were made in the literature are summarised above. However, since quality criteria have not been applied to these studies (see domain methodology), the real impact of these points on work and patient flows is unknown.

Butt J et al. Result Card ORG1 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 7 February 2023]. Available from: