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Daniel Flora, MD, PharmD's avatar

Great article! More and more patients are asking about ctDNA testing, and it’s on us to help them understand both the benefits and the limitations. I’ve started incorporating it into my practice, sometimes a bit earlier than guidelines might suggest, because in certain cases, that extra piece of information can completely change the course of treatment. Like any new technology, it’s not just about having the tool—it’s about using it wisely and working with our patients to navigate these complex decisions together.

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Rice Mark's avatar

Recently, my wife was diagnosed with stage IB triple-negative breast cancer (TNBC), invasive ductal carcinoma, grade 3/3. She has just started the ACT regimen with Keytruda. Her oncologist explained that imaging will be used to determine if her 2 cm tumor has begun to shrink. Despite having undergone five mammograms, including screening, diagnostic, and 3D tomography, none of them detected the tumor. However, both ultrasound and MRI revealed the tumor, with slight discrepancies in size between the two technologies. There is no indication of metastasis or lymph node involvement.

We have expressed interest in circulating tumor DNA (ctDNA) testing even if it is considered experimental, but the oncologist stated that imaging is the standard protocol. While I understand the importance of following protocol, I struggle to comprehend why an additional method of observation would not be encouraged—especially since we have repeatedly offered to pay out of pocket. Wouldn’t ctDNA testing provide a complementary way to monitor progress during and after treatment, particularly given the neoadjuvant approach?

We are strongly advocating for ctDNA testing, as well as Galectin-3 (Gal-3) staining of the remaining biopsy samples, to better monitor circulating tumor load. Could ctDNA testing potentially show a reduction in tumor burden before changes become visible on imaging? Additionally, the Gal-3 test, while based on research from smaller studies, might offer insights into the efficacy of Keytruda. This science suggests that Gal-3 staining could guide the selection of immunotherapy drugs, should adjustments become necessary. The data surrounding Gal-3 staining is compelling and indicates it could help refine treatment decisions.

I believe these two additional metrics—ctDNA and Gal-3 staining—could play a critical role in preventing micro-metastases and potential tumor seeding. By providing the oncology team with more detailed tools, they could adjust the treatment plan, potentially incorporating another platinum-class immunosuppressant if needed.

As an aside, I do trust our oncology team. However, I feel there are additional avenues worth exploring to ensure the best possible treatment regimen.

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