RNA Expression and Molecular Subtype Analysis to Optimize Novel Therapy for Metastatic Breast Cancer, HARMONY Study

PRIMARY OBJECTIVES:

Ia. To determine if the clinical:molecular primary tumor subtype incongruent rate in metastatic breast cancer is greater than 15%.

Ib. To determine whether the results of a clinical RNA-based molecular subtyping assay alters treatment plans as perceived by the treating physician in at least 10% of metastatic breast cancer patients.

SECONDARY OBJECTIVES:

I. To compare intra-patient progression free survival (PFS) ratios in congruent versus incongruent tumors among patients receiving molecularly-concordant therapy compared with PFS during clinically-concordant therapy.

II. To estimate PFS and intra-patient PFS ratios on molecularly- and clinically-concordant therapy separately for hormone receptor (HR)+/HER2-, HR-/HER2+, HR+/HER2+ and HR-/HER2- subsets in both congruent and incongruent tumors and each line of therapy.

III. To determine if PFS on endocrine therapy (ET) in congruent HR+/HER2- tumors is greater than PFS for patients on chemotherapy.

IV To determine if PFS on chemotherapy in incongruent tumors is greater than PFS on ET at the first line of therapy.

V. To describe practice patterns regarding timing and use of chemotherapy and ET in HR+/HER2- metastatic breast cancer (MBC).

VI. To measure the rate of molecular subtype discordance between the primary tumor and metastatic tissue among patients able to provide a biopsy of the metastatic site.

VII. To determine if PFS for patients receiving clinically-concordant therapy is greater than PFS for patients receiving clinically-discordant therapy in congruent tumors (where clinically-directed treatment [RxC] = molecularly-directed treatment [RxM]).

EXPLORATORY OBJECTIVE:

I. To explore other genes and signatures using the Nanostring 360 770-gene panel, RNA and deoxyribonucleic acid (DNA) sequencing, including RNA signatures representing pathways of clinical interest such as androgen receptor (AR) and immune activation.

OUTLINE:

Patients undergo collection of tissue via biopsy (if no archived tissue is available) and blood samples for analysis via RNA-based molecular subtyping assay during standard of care treatment. Patients' clinical data is also reviewed for up to 10 years.