Ongoing research is focusing on refining minimally invasive procedures and tests in breast cancer treatment, potentially shifting the standard of care for patients with node-positive disease post-neoadjuvant chemotherapy. These efforts aim to reduce the extent of surgical interventions and improve disease monitoring through systemic treatment methods and biomarker analysis.
Targeted Lymph Node Dissection
The phase 3 A011202 trial (NCT01901094) is currently assessing whether radiation therapy to the undissected axilla and regional lymph nodes is non-inferior to axillary lymph node dissection with radiation therapy to the regional lymph nodes in terms of invasive breast cancer recurrence-free survival. This study involves patients with node-positive breast cancer who have undergone neoadjuvant chemotherapy followed by surgery, where 1 to 8 lymph nodes were removed. The trial seeks to determine if a less invasive approach can achieve similar outcomes, reducing potential morbidities associated with extensive surgery.
According to Dr. Yuan Yuan, Director of Breast Oncology at Cedars-Sinai Medical Center, the trend over the past 5 to 10 years has been to minimize surgery as much as possible, while maintaining patient safety. For patients who are clinically lymph node negative after neoadjuvant chemotherapy, sentinel lymph node dissection is the standard practice. However, for those with clinical N1 disease (less than 3 positive nodes), the goal is to downstage the nodes successfully with systemic therapy to minimize surgical intervention, an approach known as targeted lymph node dissection.
The Role of ctDNA Testing
The utility of circulating tumor DNA (ctDNA) testing is another area under intense investigation. The increasing adoption of ctDNA analyses in clinical trials could solidify the role of minimally invasive biomarker collection methods in breast cancer treatment. ctDNA is being explored for disease monitoring and treatment decision-making, particularly in the metastatic and neoadjuvant settings.
The ongoing phase 3 SERENA-6 trial (NCT04964934) exemplifies the ctDNA-guided approach. SERENA-6 is evaluating a CDK4/6 inhibitor combined with either camizestrant (AZD9833) or an aromatase inhibitor in patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have detectable ESR1 mutations via ctDNA testing before disease progression.
Challenges and Future Directions
Despite the promise of ctDNA, significant challenges remain. One critical issue is the management of patients who exhibit disease recurrence based on ctDNA results but show no visible disease on scans. This scenario creates uncertainty regarding treatment strategies. Should oncologists initiate chemotherapy in the absence of confirmed histological evidence, or are there more targeted approaches that could be employed?
Dr. Yuan emphasized the need for clear, delineated pathways to guide clinicians when patients have abnormal ctDNA levels. The lack of a standardized algorithm for interpreting and acting upon ctDNA results poses a significant hurdle. Furthermore, the psychological impact on patients with fluctuating ctDNA levels, who are constantly anticipating disease recurrence, needs to be addressed.
Ultimately, further research is essential to fully elucidate the role of ctDNA in breast cancer management and to develop evidence-based guidelines for its use in clinical practice.
