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NCT Number: NCT06518382

Tumor-microenvironment Spatial Interaction to Identify Markers of Resistance to Therapy in HER2+ Breast Cancer Patients

This retrospective observational study aims at the comparison of the tumour-microenvironment tissue architecture before and after neo-adjuvant therapy in samples from HER2-positive (HER2+) breast cancer (BrCa) patients that display residual invasive disease in the breast/lymph node at surgery after standard-of-care combined chemotherapy and trastuzumab treatment.

The working hypothesis of the investigators is that:

Therapy imposes a selective pressure on tumour-microenvironment features promoting resistance to treatment.

Participant that have already undergone neo-adjuvant treatment as part of their regular medical care for HER2-positive breast cancer will provide access to formalin-fixed paraffin-embedded (FFPE) samples taken before and after therapy.

Tumoral, peri-tumoral and stromal regions of each specimen will be analyzed with the ultimate goal to identify new biomarkers (and putative targets) of resistance to therapy.

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Key information

Conditions

HER2-positive Breast Cancer

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

IRCCS San Raffaele Hospital

Milan, Lombardy, 20132, Italy

Location status: Recruiting

Location contact

Giampaolo Bianchini, MD

CONTACT

[email protected]

+39 02 2643 6530

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant is willing and able to give informed consent for participation in the study.
  • Patient underwent the following procedure before surgery: biopsy, sequential chemotherapy comprising treatment with antracyclines (AC/EC q21, 4 cycles) followed by taxanes (paclitaxel 1,8,15 q21 for 12 weeks) in combination with the anti-HER2 antibody trastuzumab.
  • Specimen collected at surgery display residual invasive disease in the breast/lymph node.

Exclusion criteria

  • pre-existing conditions or concurrent diagnoses;
  • concomitant use of other medications during neo-adjuvant treatment;
  • quality of stored specimen does not meet the standard for Imaging Mass Cytometry analysis.

Treatment and study plan

Primary outcomes

  1. number of different cells per each phenotype

    Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)

    Cell types will be classified based on the expression of specific lineage/phenotype markers.

  2. density of each phenotype

    Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)

    Cell phenotype densities will be calculated by dividing the number of total cells counted by the total area of the tissue acquired.

  3. fraction of proliferative/active cells of each phenotype

    Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)

    The proportion of cells positive for the proliferation marker Ki67 will be assessed per cell phenotype. To assess the proportion of active immune cells, we will quantify the expression level of activation markers.

  4. frequency of interactions

    Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)

    Cells will be defined as partaking in an interaction if their whole-cell profiles are in direct contact (contiguous pixels). Cell phenotypes will be mapped to cell-cell interaction masks, and for each specimen proximity events (cell-cell interactions) will be classified as homotypic or heterotypic proximity events

  5. frequency of functional crosstalk events

    Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)

    Cells will be defined as participating in a functional crosstalk event if the proximal (contiguous pixels) cells express functional pairs (receptor/ligand) of markers (e.g. PD1/PDL1).

    The frequency of functional crosstalk events will be computed as the number of interactions between cells expressing functional pairs divided by the total number of cells expressing one of the markers (receptor, e.g. PD1) in the specimen.

Study contacts

Contact information is provided by the study sponsor or research team.

Tiziana Daniele, PhD

CONTACT

[email protected]

+39 02 2643 6381

Sponsors and collaborators

Lead sponsor

Giampaolo Bianchini

Other

Registry information

Official study title

A Retrospective Observational Study Characterizing Tumour-microenvironment Spatial Interaction Aimed at the Identification of New Markers of Resistance to Therapy in HER2-positive Breast Cancer Patients

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Jul 24, 2024
Registry last updated
Apr 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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