Study finds circulating tumor DNA levels after treatment could guide therapy decisions in HER2-positive breast cancer patients.
Circulating tumor DNA (ctDNA) levels in patients with HER2-positive breast cancer after neoadjuvant treatment and surgery predicted worse outcomes than in patients without ctDNA, even among those with a pathologic complete response (pCR), according to a study published in Cancer Research Communications.
The findings suggest ctDNA testing could serve as a more accurate predictor of disease recurrence than pCR, the current surrogate marker for outcomes in this patient population.
“Patients with HER2-positive early breast cancer have a high recurrence rate. After these patients receive neoadjuvant systemic therapy, pCR has been a surrogate marker of outcomes, but some patients with pCR still experience recurrence or distant metastasis,” says lead author Chiun-Sheng Huang, MD, PhD, MPH, professor of surgery and director of the Breast Care Center at National Taiwan University Hospital in Taipei, Taiwan, in a release. “This highlights the need for a better biomarker to identify which patients may experience disease recurrence.”
HER2-positive breast cancer accounts for about 13% of breast cancer cases in the US. The study involved a retrospective analysis of 117 patients with HER2-positive early-stage breast cancer who received neoadjuvant therapy in the form of chemotherapy with single or dual anti-HER2 antibodies.
ctDNA Status Outperformed pCR as Predictor
Researchers collected blood samples from patients before starting neoadjuvant therapy and after surgery. Of the 117 patients, 79 (67.5%) tested positive for ctDNA before treatment, and 32 of those 79 (40.5%) remained ctDNA-positive after treatment.
Overall, 25 patients (21.4%) achieved pCR after neoadjuvant therapy. Among these patients with pCR, six (24%) tested positive for ctDNA after treatment. In the 92 patients who did not experience pCR, ctDNA was detected after treatment in 26 (28%) patients.
Among 99 patients not treated with trastuzumab emtansine (T-DM1), those who were ctDNA-positive after neoadjuvant therapy were 5.5 times more likely to experience disease recurrence than ctDNA-negative patients within the median 4.02 years of follow-up, regardless of pCR status.
Recurrence-free survival was not statistically different between ctDNA-negative patients with pCR and ctDNA-negative patients without pCR, nor between ctDNA-positive patients with and without pCR.
Implications for T-DM1 Therapy
The researchers also investigated ctDNA’s potential to guide use of adjuvant T-DM1 therapy, which is currently recommended for patients without pCR. Among patients not receiving T-DM1, those with ctDNA clearance after neoadjuvant therapy experienced significantly better recurrence-free survival than patients with persistent ctDNA.
Eighteen patients without pCR received adjuvant T-DM1 therapy. During serial testing, adjuvant T-DM1 led to significantly higher ctDNA clearance rates (8/8) than non-T-DM1 therapy (7/12) in patients who were ctDNA-positive after neoadjuvant therapy.
When researchers compared recurrence-free survival among four patient groups, only the ctDNA-positive patients who did not receive T-DM1 experienced significantly worse three-year recurrence-free survival than the others.
“Our findings indicate that ctDNA could be a better prognostic factor than pCR in patients with HER2-positive early breast cancer after they’ve received neoadjuvant therapy,” says Huang in a release. “We believe that this knowledge could be effectively used to guide escalation or de-escalation of adjuvant therapy.”
The results suggest adjuvant T-DM1 could benefit patients who test positive for ctDNA after neoadjuvant therapy and surgery, potentially independent of pCR status. Conversely, patients who test negative for ctDNA may not experience added benefit from adjuvant T-DM1.
The study’s limitations include its retrospective design, limited sample size, and the possibility of confounded ctDNA reads due to sequencing methods used. The researchers note that the implications need verification through larger studies or randomized trials.
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