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.
Study Type
OBSERVATIONAL
Enrollment
10
IRCCS San Raffaele Hospital
Milan, Lombardy, Italy
RECRUITINGnumber of different cells per each phenotype
Cell types will be classified based on the expression of specific lineage/phenotype markers.
Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)
density of each phenotype
Cell phenotype densities will be calculated by dividing the number of total cells counted by the total area of the tissue acquired.
Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)
fraction of proliferative/active cells of each phenotype
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.
Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)
frequency of interactions
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
Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)
frequency of functional crosstalk events
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.
Time frame: before and within 3 months from neo-adjuvant therapy (at surgery)
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