We want to announce a substudy proposal!
REtrospective Study to Evaluate the Molecular Differences Between PET-POsitive and PET-Negative Tumor Samples from HER2-Positive Breast Cancer Patients within the PHERGain Trial (The RESPONSE Study).
About 14,69% of patients screened for PHERGain study had failed to enter because of non-measurable disease by Positron Emission Tomography (PET) criteria (PERCIST). Early PET-SCAN evaluation has shown to be a strong predictor of pathological Complete Response (pCR) to neoadyuvant chemotherapy in early breast cancer.
As initial estimations on screening failures by PET were underestimated, we need to explore the clinical, pathological and molecular characteristics of these screening failures in order to manage a more adequate patient selection. Several hypotheses can be suggested, from the high heterogeneity in term of molecular signatures and metabolic pathways, to a strong relationship between smaller or more indolent tumors and molecular or pathological characteristics.
In order to prove our hypothesis, firstly we will review retrospectively all clinical, radiological and pathological characteristics of the first 60 patients with a screening failure by PET criteria. This revision will include: i) a centralized and independent imaging analysis for Magnetic Resonance Imaging (MRI) (in order to confirm the tumor size ≥1.5 centimeter) and PET (Standardized Uptake Value maximum [SUVmax] value detected); ii) collection of data about Estrogen Receptor (ER) and Progesterone Receptor (PgR) status, Ki67 proliferation marker and fluorescence in situ hybridization (FISH)-HER2 status. Then, on the basis of clinicopathological characteristics we will match the first 60 screening failures to the first 200 patients included in order to identify potential markers of screening failure by PET.
Secondly, if consistency data is not obtained, we will analyze the molecular and metabolic profiles of those tumors from both cohorts of patients. Considering the clinically and biologically heterogeneous status of HER2-positive disease, the characterization of the metabolome, which constitutes the downstream products of cellular functions, together with the genotype and phenotype can provide a better understanding of which subgroup of patients might not need chemotherapy if treated with dual HER2 blockade, and endocrine therapy if necessary.