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.

Inclusion Criteria:

1. Participant is willing and able to give informed consent for participation in the study.
2. 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.
3. Specimen collected at surgery display residual invasive disease in the breast/lymph node.

Exclusion Criteria:

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

HER2+ Breast Cancer patients displaying residual invasive disease in the breast/lymph node at surgery after neo-adjuvant treatment [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].