Photo Credit: Hernan Caputo
Routinely assessing molecular residual disease (MRD) may offer an opportunity to intervene earlier in patients with inflammatory breast cancer at high risk for recurrence, according to an abstract presented at the 2024 San Antonio Breast Cancer Symposium.
“Early detection of MRD correlates with disease recurrence and survival outcomes in patients with inflammatory breast cancer,” wrote Jennifer Chen, MD, and colleagues. “We sought to determine the lead time of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection prior to radiographic confirmation of disease relapse in stage 3 inflammatory breast cancer.”
Study Design & Patient Demographics
The researchers enrolled 92 patients with stage 3 inflammatory breast cancer from a prospective registry from 2015 to 2022. The participants underwent serial blood draws at the start of the study, throughout neoadjuvant treatment, and at 6 and 12 months after surgery.
The patients were an average 51 years of age (IQR, 17.8), had a mean BMI of 28.9 kg/m2 (IQR, 11.5), and were mostly White (72.9%).
“Patients had predominantly node-positive (n=87, 94.6%), high-grade (n=64, 66.7%), ductal (n=83, 86.5%) disease. Almost all patients received trimodality therapy—neoadjuvant systemic therapy (100%), modified radical mastectomy (100%), and adjuvant radiotherapy (n=88, 95.7%),” the researchers reported.
The authors defined MRD as at least one CTC or ctDNA variant detected any time after surgery. To calculate the lead time in patients who experienced recurrence, the researchers used the date of the first positive CTC and/or ctDNA variant and the date when disease relapse was first confirmed via imaging. In patients with no detectable MRD, the lead time began from the date of the first negative CTC and/or ctDNA variant post-surgery.
“Per standard of care guidelines, surveillance imaging was obtained based on patient symptoms and physical exam findings,” Dr. Chen and colleagues noted.
MRD Detected Approximately Six Months Earlier
At baseline, 60.7% of patients tested positive for CTCs, and 65.6% for ctDNA. Postoperatively, the MRD detection rate ranged between 34.5% and 39.4% at 6 and 12 months, respectively.
At a median follow-up of 7.1 years, 37% of patients experienced recurrence. Among these, 80% had detectable MRD following surgery, with a median lead time of 5.8 months prior to radiographic confirmation of disease relapse. Patients without MRD had a longer median time to recurrence, approximately 12.5 months.
Patients with negative CTC and ctDNA assessments had significantly longer time to recurrence compared with those who had positive MRD. Specifically, the estimated 6-year time to recurrence was 93.3% for MRD-negative patients versus 58.3% for MRD-positive patients (P=0.027).
The researchers conducted multivariable Cox regression analysis and found that CTC positivity was significantly associated with shorter time to recurrence (HR, 3.8; 95% CI, 1.8-7.9; P<0.001).
While demographic and tumor characteristics, such as age, race/ethnicity, receptor subtype, and histology, did not differ significantly by recurrence status, patients with recurrence had a higher median number of positive lymph nodes at resection (5 vs 0; P<0.001) and were more likely to have detectable CTCs post-surgery (71.4% vs 43.9%; P=0.01) than patients without recurrence.
“MRD was detected with a median lead time of approximately 6 months prior to radiographic confirmation of disease recurrence. Incorporation of serial assessments of MRD may offer the opportunity for early systemic treatment intervention in [patients with inflammatory breast cancer] with high risk of relapse,” Dr. Chen and colleagues concluded.
