Clinical trial NCT06518382: Tumor-microenvironment Spatial Interaction to Identify Markers of Resistance to Therapy in HER2+ Breast Cancer Patients
Official 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: HER2-positive Breast Cancer
Lead sponsor: IRCCS Ospedale San Raffaele
Sponsor class: OTHER
First posted: 2024-07-24
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HER2+ Breast Cancer patients displaying residual invasive disease in the breast/lymph node at surgery after neo-adjuvant treatment \[sequential chemotherapy comprising treatment with antracyclines (AC/EC q21, 4 cycles) followed by taxanes (paclitaxel 1,8,15 q21 for 12 weeks) in combination with the anti-HER2 antibody trastuzumab\].

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: number of different cells per each phenotype
timeFrame: before and within 3 months from neo-adjuvant therapy (at surgery)
measure: density of each phenotype
timeFrame: before and within 3 months from neo-adjuvant therapy (at surgery)
measure: fraction of proliferative/active cells of each phenotype
timeFrame: before and within 3 months from neo-adjuvant therapy (at surgery)
measure: frequency of interactions
timeFrame: before and within 3 months from neo-adjuvant therapy (at surgery)
measure: frequency of functional crosstalk events
timeFrame: before and within 3 months from neo-adjuvant therapy (at surgery)
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: IRCCS San Raffaele Hospital
state: Lombardy
Study officials:
affiliation: Head Breast Cancer Group - Department of Medical Oncology - IRCCS San Raffaele Hospital
name: Giampaolo Bianchini, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang XQ, Danenberg E, Huang CS, Egle D, Callari M, Bermejo B, Dugo M, Zamagni C, Thill M, Anton A, Zambelli S, Russo S, Ciruelos EM, Greil R, Gyorffy B, Semiglazov V, Colleoni M, Kelly CM, Mariani G, Del Mastro L, Biasi O, Seitz RS, Valagussa P, Viale G, Gianni L, Bianchini G, Ali HR. Spatial predictors of immunotherapy response in triple-negative breast cancer. Nature. 2023 Sep;621(7980):868-876. doi: 10.1038/s41586-023-06498-3. Epub 2023 Sep 6.