Fig. 4: Tumor Response by RECIST Criteria and Biomarker Analysis of Ki67, Rb, Cyclin E, p62, and LAMP1 in Patients Treated with HCQ + Palbociclib + Letrozole.

A Waterfall plot depicting the best percentage change in the sums of the diameters of target lesions per RECIST 1.1 in patients with measurable disease. B Tumor Response Over Time by RECIST Criteria in Patients on Treatment. percentage change from baseline in tumor size over time (days on treatment) for individual patients treated with a combination of HCQ, palbociclib, and letrozole. Each patient’s response is color-coded to indicate their response category according to RECIST criteria: progressive disease (PD), stable disease (SD), or partial response (PR). Patients 10 and 12 are labeled as “No QIAC,” indicating they were on treatment but lacked quantifiable imaging data to determine their exact response. C Immunohistochemistry (IHC) staining on biopsy from patient 5 (Pt. 5) with PD after treatment (post-Rx) indicates increased proliferation (Ki67), lack of RB expression in tumor (arrow indicates positive RB expression in stromal cells), and cyclin E levels. IHC for Ki67, RB, and cyclin E was performed on biopsies obtained from Pt. 4 with PR and Pt 13 SD prior to treatment (baseline). D Pt. 3 had two biopsies: baseline and on treatment (On-Rx), and each was stained with Ki67, Rb, and cyclin E as well as two autophagy markers, p62 and LAMP1. E Quantification of Ki67 in C at baseline for Pt 13, Pt 3, and Pt 4. F Quantification of Ki67, p62, and LAMP1 in matched biopsies from Pt.3. There is a 10% reduction in Ki67 and a 25% and 35%% increase in p62 and LAMP1, respectively, while on treatment from baseline. PD progressive disease, SD stable disease, PR partial response.