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

Официальное название

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

Обзор

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.

Первичные конечные точки

• number of different cells per each phenotype [Срок оценки: before and within 3 months from neo-adjuvant therapy (at surgery)]
• density of each phenotype [Срок оценки: before and within 3 months from neo-adjuvant therapy (at surgery)]
• fraction of proliferative/active cells of each phenotype [Срок оценки: before and within 3 months from neo-adjuvant therapy (at surgery)]
• frequency of interactions [Срок оценки: before and within 3 months from neo-adjuvant therapy (at surgery)]
• frequency of functional crosstalk events [Срок оценки: before and within 3 months from neo-adjuvant therapy (at surgery)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• IRCCS San Raffaele Hospital — Milan

Публикации

• 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. PMID 37674077

Идентификаторы

NCT: NCT06518382 · TaME-HER2BrCa

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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