This phase II trial studies how well letrozole, anastrozole, or fulvestrant work when given together with ribociclib, palbociclib, and/or abemaciclib in treating patients with hormone receptor (HR) positive breast cancer that has spread to other places in the body (metastatic) and has an ERS1 activating mutation. Letrozole, anastrozole, ribociclib, palbociclib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known if giving letrozole, anastrozole, or fulvestrant with ribociclib, palbociclib, and/or abemaciclib will work better in treating patients with breast cancer.
Name: Abemaciclib
Name: Anastrozole
Name: Fulvestrant
Name: Letrozole
Name: Palbociclib
Name: Ribociclib
Description: Survival curves for PFS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.
Measure: Progression-free survival (PFS) Time: Up to 30 daysDescription: Graphical analysis, such as scatter plots with Lowess smoothers, will be used to assess the correlative structure of outcomes and compare MAF between fulvestrant and aromatase inhibitor-treated groups. The Pearson correlation, or its non-parametric analogue, the Spearman correlation, will be used to estimate the linear correlation among variables.
Measure: Circulating tumor deoxyribonucleic acid (ctDNA) ESR1 mutant allele fraction (MAF) and kinetics Time: Up to 30 daysDescription: Will be assessed by the secondary resistance of endocrine therapy.
Measure: Prevalence of Emergence of Estrogen Receptor 1 (ESR1) mutations Time: Up to 30 daysDescription: Will correlate ctDNA with CA 15-3 tumor marker changes.
Measure: Changes in cancer antigens (CA) 15-3 tumor marker Time: Up to 30 daysDescription: Survival curves for OS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.
Measure: Overall survival (OS) Time: Up to 30 daysDescription: Will be assessed on next line of therapy after progression.
Measure: Time to next treatment Time: Up to 30 daysAllocation: Randomized
Parallel Assignment
There are 3 SNPs
D538G, Y537S/N, S463P) identified on ctDNA. --- D538G ---
D538G, Y537S/N, S463P) identified on ctDNA. --- D538G --- --- Y537S --- --- S463P ---
D538G, Y537S/N, S463P) identified on ctDNA. --- D538G --- --- Y537S ---