General Session 3

In this video, Prof Dr François Duhoux comments on the data of some interesting studies presented during General Session 3 at SABCS 2024. 

The ZEST trial explored minimal residual disease (MRD) detection in breast cancer using circulating tumour DNA (ctDNA). This phase 3 study included 1,900 patients treated with curative intent for either triple-negative breast cancer or HR+/ HER2- breast cancer with BRCA mutations. The study used a bespoke assay that identified 16 mutations per patient to detect ctDNA. Findings showed that 8% of patients were ctDNA-positive, with 50% of these already exhibiting radiographic progression at the time of ctDNA detection. ctDNA was more commonly found in higher-stage disease: 13.7% in stage 3, compared to only 2.3% in stage 1. After neoadjuvant therapy, ctDNA detection was less common in patients achieving pCR, observed in only 2%, compared to 14% in those without pCR. Of the ctDNA-positive patients without radiographic recurrence, 40 were randomised to receive niraparib, a PARP inhibitor, or observation. Niraparib significantly extended median relapse-free survival (11.4 months vs. 5.4 months in the observation arm). The study highlighted that ctDNA detection tends to occur early in follow-up, particularly in the triple-negative breast cancer cohort, with 60% of cases detected within the first six months. The results demonstrated the potential of ctDNA as an early marker of recurrence and the efficacy of MRD-guided interventions like niraparib. However, the overall low recurrence rates and frequent overlap of ctDNA detection with radiographic progression illustrate the challenges in deploying MRD-based strategies in clinical practice.

The role of anthracyclines in HR+/ HER2- breast cancer was examined in a secondary analysis of data from the TAILORx study. This analysis included patients with stage 1 and 2 node-negative breast cancer who all had a recurrence score (RS) above 11. While chemotherapy regimens were not randomised, patients who received anthracyclines were generally younger, premenopausal, had higher stage and grade tumours, were more often PR-negative, and had higher RS. Among patients with RS ≥31, anthracyclines were associated with a five-year relapse-free survival rate of 95.4%, compared to 90% for those treated with taxanes alone, an absolute improvement of 5.4%. The benefit of anthracyclines was more pronounced in tumours larger than 2 cm and in patients with progressively higher recurrence scores. However, the study acknowledged that late toxicities of anthracyclines, such as leukaemia and chronic heart failure, must be carefully considered when selecting patients for this treatment approach.

Two trials examined immune checkpoint inhibitors in triple-negative breast cancer. The NSABP-B59 trial, a large study including 1,550 patients with stage 2 and 3 triple-negative breast cancer, investigated the addition of atezolizumab, a PD-L1 inhibitor, to standard chemotherapy. Patients were randomised to receive weekly paclitaxel and carboplatin, followed by AC or EC chemotherapy, with or without one year of atezolizumab. The trial did not meet statistical significance for its primary endpoint. At 46.9 months of median follow-up, four-year EFS was 85% in the atezolizumab arm versus 82% in the placebo arm, a 3% absolute improvement. pCR rates were also higher with atezolizumab (63% vs. 57%), but overall survival showed no significant difference. The subgroup analysis suggested that patients with larger tumours, node-positive disease, or lower tumour-infiltrating lymphocytes (TILs) may derive more benefit. However, the overall results were inconclusive, and the treatment was associated with more immune-related adverse events.

In contrast, a smaller Chinese trial investigated camrelizumab, a PD-1 inhibitor, in combination with chemotherapy in a similar triple-negative breast cancer population. This study randomized 441 patients to receive dose-dense EC chemotherapy preceded by weekly nab-paclitaxel and carboplatin, with or without camrelizumab. The primary endpoint of pCR showed a significant 12% improvement with camrelizumab (57% vs. 45%), especially in node-positive patients, where the pCR rate was 57% compared to 42% without the PD-1 inhibitor. Trends favouring improved EFS and overall survival were observed, but definitive conclusions could not be made due to the study’s limited size and scope.

These studies reflect ongoing efforts to refine breast cancer treatment by leveraging new biomarkers like ctDNA for minimal residual disease detection, reconsidering the role of traditional therapies like anthracyclines, and exploring immunotherapy in high-risk triple-negative breast cancer patients. While some findings suggest practice-changing potential, others underscore the need for further investigation and validation in larger trials.