Could Hydroxychloroquine Enhance Breast Cancer Treatment?

Written By Nathan Goodyear

The New Phase 1 Study Says Yes!

Hydroxychloroquine (HCQ) has been making waves in cancer research, and a new Phase 1 clinical trial has added more fuel to the fire. This study investigated HCQ’s potential role in metastatic breast cancer (MBC) when combined with palbociclib (Ibrance) and letrozole, two standard treatments for estrogen receptor-positive, HER2-negative (ER+/HER2−) breast cancer.

Why Hydroxychloroquine?

Originally developed as an antimalarial drug, HCQ has also been used for autoimmune diseases like lupus and rheumatoid arthritis. But in cancer research, it has another intriguing effect: it inhibits autophagy—a process that cancer cells exploit to survive under treatment stress.

By adding HCQ to palbociclib and letrozole, researchers hoped to disrupt cancer cells' ability to resist treatment, making them more vulnerable to therapy.

If you're in the USA and looking to explore hydroxychloroquine as part of your treatment plan, click "Book Now" to set up a consultation with a trusted physician and get a personalized prescription through Off-ScriptRX.com.

Study Overview

Objectives

Primary Goals:

  • Assess the safety and tolerability of combining HCQ with continuous low-dose palbociclib and letrozole.

  • Determine the optimal Phase 2 dose (RP2D) of HCQ in this combination.

Secondary Goals:

  • Evaluate tumor response to the new regimen.

  • Analyze biomarkers to understand how the treatment affects cancer at a molecular level.

How Was the Study Conducted?

Trial Design: Phase I, dose-escalation study (3+3 design).
Participants: 14 patients with ER+/HER2− metastatic breast cancer (MBC).

Treatment Plan:
✅ Palbociclib (Ibrance): 75 mg/day continuously (unlike standard pulsed dosing).
✅ Letrozole: 2.5 mg/day.
✅ Hydroxychloroquine: Administered in escalating doses:

  • 400 mg/day (4 patients)

  • 600 mg/day (4 patients)

  • 800 mg/day (6 patients)

What Did They Find?

✔️ Safety & Tolerability:

  • No serious adverse events reported (Grade 1–3 only).

  • Most common side effects (Grade 3):

    • Hematologic issues (3 patients at 800 mg).

    • Skin rash (2 patients at 600 mg).

    • Mild anorexia (1 patient at 400 mg).

✔️ Tumor Response:

  • Partial response (PR): 2 patients (tumor shrinkage between 30% and 55%).

  • Stable disease (SD): 11 patients.

  • Progressive disease (PD): 1 patient.

  • Overall tumor size changes:

    • Reductions ranged from 11% to 30% in most patients.

    • One patient had an increase of 55% in tumor size.

Notably, the two patients who had a partial response maintained tumor reductions for nearly 300 days!

How Did It Work?

Biomarker Analysis Revealed Key Changes in Responders:

  • ↓ Decrease in Ki67, Rb, and nuclear cyclin E (markers linked to aggressive tumor growth).

  • ↑ Increase in p62 and LAMP1 (indicators of disrupted autophagy).

What Does This Mean?
These findings suggest that HCQ successfully altered cancer cell behavior, potentially enhancing the effectiveness of palbociclib and letrozole.

What’s Next?

✅ Recommended Phase 2 Dose (RP2D): 800 mg/day of HCQ was found to be safe and tolerable.
✅ Next Steps: Larger, randomized studies are needed to confirm whether adding HCQ improves patient survival and delays disease progression.

How Can You Learn More?

Explore More on Repurposed Medications: Off-ScriptRX.com
Listen to Expert Discussions: Pre-Scribed Podcast on YouTube & Spotify
Interested in Innovative Cancer Care? Schedule a FREE consultation if you have cancer with Williams Cancer Institute to explore advanced treatment options.

Final Thoughts

This study represents an exciting step in integrative oncology. While more research is needed, the safety profile, tumor responses, and biomarker shifts suggest that hydroxychloroquine could be an effective add-on therapy for ER+/HER2− metastatic breast cancer.

Could HCQ be the missing piece in enhancing standard breast cancer treatment? The next phase of research will tell us more—but the early signs are promising!

Stay informed, stay empowered, and explore all your options in cancer care.

If you're in the USA and looking to explore hydroxychloroquine as part of your treatment plan, click "Book Now" to set up a consultation with a trusted physician and get a personalized prescription through Off-ScriptRX.com.

Reference:

  • Raghavendra AS, Kettner NM, Kwiatkowski D, et al. Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2- breast cancer. NPJ Breast Cancer. 2025 Jan 26;11(1):7. doi: 10.1038/s41523-025-00722-1

  • Study showing autophagy inhibition and HCQ’s role: https://link.springer.com/article/10.1007/s12094-017-1764-5

Nathan Goodyear
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