Joseph A. Sparano, MD
Detection of positive circulating tumor cells (CTCs) in the blood 5 years after a breast cancer diagnosis was associated with an increased risk for late recurrence in women with hormone receptor (HR)–positive, HER2-negative breast cancer, the results of a prospective clinical trial showed. These patients had a 21.7-fold increased risk of breast cancer recurrence compared with those who had a negative CTC result, Joseph A. Sparano, MD, explained during a press conference at the 2017 San Antonio Breast Cancer Symposium.1
“[These findings] provide level 1 evidence supporting circulating tumor cells as a biomarker prognostically for late recurrence in this specific subgroup of patients with HR-positive, HER2-negative early breast cancer, which accounts of about two-thirds of all breast cancers,” said Sparano, associate director for clinical research at the Montefiore Einstein Center for Cancer Care, Albert Einstein Cancer Center in New York. “[The results also] demonstrate a very high level of risk stratification, a 20-fold higher risk, which far surpasses other biomarkers that are currently available.”
Late recurrences occurring ≥5 years after diagnosis account for approximately 50% of recurrences in women with estrogen receptor (ER)–positive breast cancer, he said. In a meta-analysis from the EBCTCG group, the 10-year risk of recurrence after 5 years of endocrine therapy was found to be 5% in patients with 0 positive lymph nodes, 10% for patients with 1 to 3 positive lymph nodes, and 22% in patients with 4 to 9 positive lymph nodes.2
“Late recurrence in estrogen receptor–positive breast cancer is a huge clinical problem, and some experts in the field have dubbed this to be the next frontier for research,” Sparano said.
Patients enrolled in the study had previously been enrolled in the phase III ECOG-ACRIN E5103 clinical trial (NCT00433511) and were asked to provide blood samples for the prospective study if they showed no clinical evidence of recurrence at baseline.1
The ECOG-ACRIN E5103 trial had been looking at the addition of adjuvant bevacizumab (Avastin) to chemotherapy in patients with lymph node–positive or high-risk, lymph node–negative breast cancer. Nine percent of patients (n = 547) from the E5103 study enrolled in the prospective study.
More than half of the patients (56%) were ≥50 years, 59% had a tumor ≥2 cm, 73% had lymph node–positive disease, 65% had HR-positive disease, 55% had high-grade tumors, and 88% were receiving endocrine therapy.
Of the 353 patients with HR-positive disease, 14 (4%; 95% CI, 3.0%-7.9%) had a recurrence and only 1 patient (0.5%; 95% CI, 0%-2.9%) with HR-negative disease had a local recurrence.
Overall, 4.8% (95% CI, 3.1%-6.9%) of patients had a positive CTC result, amounting to ≥1 cell/7.5 mL in the blood. CTCs were tested using the CellSearch CTC assay, which has been cleared by the FDA as an aid in monitoring patients with metastatic breast cancer. In the HR-positive group of patients, 5.1% (95% CI, 3.0%-7.9%) had a positive CTC result, and 4.1% (95% CI, 1.8%-9.0%) had positive CTCs in the HR-negative subgroup.
Sparano focused on the HR-positive group in his presentation. This patient population demonstrated a median time to recurrence of 1.6 years (range, 0.5-2.8). The hazard ratio for patients with CTC negative results compared with CTC positive results was 21.7 (95% CI, 7.0-67.8; P
<.001). Multivariate analysis showed a hazard ratio of 18.1 (95% CI, 5.0-65.3).
Positive CTC results led to a predictive value for recurrence of 35% at 2 years in the HR-positive population, while negative results had a predictive value of 98% for this group. The recurrence rate per person-year was 24.7% for patients who had positive CTCs and 1.5% for patients with negative CTCs.
“I think, very importantly, it supports the concept of perhaps a new paradigm, and that is to have a second decision point to tailor therapy for individual patients based on a biomarker that is attained not at the time of diagnosis,” Sparano said.
Instead of making all decisions at the time of diagnosis, he said, clinicians could identify a second decision point 5 years after diagnosis that would be “based not only on the patient’s tolerance to prior therapy and their risk of subsequent recurrence based on clinical pathologic features, but also integrating a biomarker to assist in making decisions.”