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PPS38. Circulating tumor DNA dynamics in neoadjuvant therapy response: a prospective study in inflammatory breast cancer patients

Friday, March 6, 2026
3:40 PM - 4:10 PM MST
Location: HUB Poster Park - West Hall 1-3

    Primary Author(s)

  • Megan McClanahan, MD (she/her/hers)

    T32 Research Fellow
    MD Anderson Cancer Center
    Houston, Texas, United States

    • Co-Author(s)

  • SM

    Salyna Meas, MS

    Research Assistant
    Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center
    Houston, Texas, United States

  • VS

    Vanessa N. Sarli, n/a

    Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center
    Houston, Texas, United States

  • JC

    Jennifer H. Chen, MD

    Resident Physician
    Baylor College of Medicine
    Houston, Texas, United States

  • JU

    Joshua Upshaw, n/a

    Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center
    Houston, Texas, United States

  • BL

    Bora Lim, MD

    Associate Professor
    Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center Morgan Welch Inflammatory Breast Cancer Clinic and Research Program
    Houston, Texas, United States

  • VV

    Vicente Valero, MD

    Deputy Chairman, Professor
    Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center Morgan Welch Inflammatory Breast Cancer Clinic and Research Program
    Houston, Texas, United States

  • Wendy Woodward, MD, PhD (she/her/hers)

    Chair, ad interim, Professor
    Department of Breast Radiation Oncology, University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center Morgan Welch Inflammatory Breast Cancer Clinic and Research Program
    Houston, Texas, United States

  • Anthony Lucci, Jr., MD

    Professor
    Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center Morgan Welch Inflammatory Breast Cancer Clinic and Research Program
    Houston, Texas, United States

    • Poster Presenter(s)

  • Megan McClanahan, MD (she/her/hers)

    T32 Research Fellow
    MD Anderson Cancer Center
    Houston, Texas, United States

Introduction: Inflammatory breast cancer (IBC) is an aggressive disease with high tumor burden and poor prognosis. We examined the dynamics of serial circulating tumor DNA (ctDNA) measurements and their associations with pathologic complete response (pCR) in IBC patients receiving neoadjuvant systemic therapy (NST).  


Methods: This was a prospective study of IBC patients receiving NST prior to surgery. Serial plasma samples were collected at baseline and throughout NST (range: q3 weeks-3 months). ctDNA was quantified using a tumor-informed ctDNA assay (Signatera) as mean tumor molecules per milliliter (MTM/ml). Analysis was performed using RStudio.


Results:

In total, 34 IBC patients with ctDNA measurements at baseline, during NST, and pre-surgery timepoints, and available pathologic response data were included. Median age was 46 years (IQR 38-59). 65% had clinical stage III (17/34 50% IIIB, 5/34 15% IIIC) and 35% (12/34) had stage IV disease. Receptor subtype consisted of 29% (10/34) ER+,PR+,HER2-, 21% (7/34) ER-,PR-,HER2+, 21% (7/34) triple negative, 15% (5/34) ER+, PR+, HER2+, 12% (4/34) ER+,PR-,HER2+, and 2.9% (1/34) ER+,PR-,HER2-. Among 34 patients with baseline ctDNA assessments, 73.5% (25/34) cleared their ctDNA prior to surgery. pCR rate was 38% (13/34). Likelihood of pCR was greater in patients who cleared their ctDNA (12/25, 48%) compared to patients who did not clear their ctDNA prior to surgery (1/8, 12.5%) OR: 6.46 [CI 0.63 - 314.4], p = 0.108. Patients who achieved pCR cleared their ctDNA at a median of 84 days compared to 117 days for those who did not achieve pCR (p = 0.039). Table 1 shows the distribution of pCR according to age, race/ethnicity, stage, grade, and receptor subtype. Notably, the HER2+/HR- was associated with higher pCR, while HR+/HER2- was associated with lower pCR (p = 0.024). At a median post-surgery follow-up of 3.5 months two patients have had relapse, and neither of them cleared their ctDNA pre-surgery. Seven patients had progression of disease while on NST. Twenty-three patients are currently pending surgery with pathologic assessment.


Conclusions: Half of the IBC patients who cleared their ctDNA prior to surgery had pCR compared to 12% of those who did not clear ctDNA, though this did not reach statistical significance. Patients who cleared their ctDNA earlier were significantly more likely to achieve pCR. Timing of ctDNA clearance in the neoadjuvant setting might be useful for identifying pCR and warrants further study.  

Learning Objectives:

  • Understand the association between ctDNA clearance during neoadjuvant systemic therapy and achieving pathologic complete response in patients with inflammatory breast cancer.
  • Understand how factors such as clearance timing, and receptor sub-type are correlated to pathologic complete response in patients with inflammatory breast cancer.