De Novo Stage IV Breast Cancer: A New Look at Treatment Options
"Exploring the role of intensified locoregional treatment in the early stages of de novo Stage IV breast cancer and its potential benefits for survival and quality of life."
Traditionally, the primary goal of surgery for metastatic breast cancer (BC) has been to manage symptoms in specific areas. However, recent research, including institutional and population-based studies and meta-analyses, suggests that incorporating locoregional treatment (LRT) alongside systemic therapy (ST) may extend overall survival and significantly reduce locoregional progression in de novo Stage IV BC.
Several theories aim to explain how removing the primary tumor could improve survival. These include reducing the overall tumor load, decreasing the number of circulating tumor cells, enhancing the body's immune response, improving the effectiveness of systemic treatments, targeting breast cancer stem cells, preventing the spread of new metastases, and minimizing the development of treatment-resistant cancer cells.
While these studies may have inherent biases due to their retrospective design, tumor removal has shown to improve survival in other metastatic cancers. Furthermore, some institutional studies indicate that early intervention on primary tumors may improve survival in patients treated with systemic therapy who show no evidence of disease progression.
MF07-01 Trial: A Randomized Study
The MF07-01 trial was a phase III, multi-center, randomized controlled clinical trial. It compared locoregional treatment (LRT) at the time of diagnosis with primary systemic therapy (ST) in patients newly diagnosed with Stage IV breast cancer (de novo). The results align with existing literature. The risk of death was 34% lower in the LRT group compared to the ST group.
- Benefit: 34% lower risk of death with LRT.
- Survival: 41.6% alive after 5 years in LRT group vs. 24.4% in ST group.
- Factors: Solitary bone metastasis, younger age, ER/PR-positive tumors benefit more from LRT.
- Risk: Multiple liver/lung metastases had worse outcomes with initial surgery.
- Safety: No increase in 30-day mortality with primary tumor resection.
The Future of Stage IV Breast Cancer Treatment
While a single study cannot provide all the answers, the MF07-01 trial offers a valuable option to discuss in tumor boards and with patients who meet the study criteria. It's important to recognize that not all metastatic breast cancers are the same. There appears to be a subgroup of patients who experience longer survival with intensified locoregional treatment early in the course of de novo Stage IV BC.
Intensifying LRT in the early treatment of de novo Stage IV BC is a reasonable approach for selected patients. Factors such as patient age, performance status, other health conditions, tumor type, and extent of metastasis should be carefully considered to determine the most appropriate treatment strategy.
Further research is needed to address remaining questions, such as the optimal approach to treating the primary tumor and axilla (surgery vs. radiation therapy), the best timing for surgery after systemic therapy, whether to include patients who don't respond to systemic therapy in randomization, the most effective systemic therapy regimens, interventions for specific metastatic sites, and whether solitary bone metastasis should be considered a distinct category from other de novo Stage IV BC. Ongoing studies evaluating primary breast surgery after patients respond to systemic therapy may provide answers to some of these questions.