A ground breaking staging system for de novo metastatic breast cancer has been validated in an international cohort, perhaps paving the way for more personalized care and improved outcomes for patients diagnosed with this challenging disease.

The staging system, developed by surgical oncologist Jennifer K. Plichta, MD, MS, of Duke University School of Medicine, stratifies patients into four distinct prognostic groups based on factors such as tumor biology and extent of disease. The final validation cohort, presented during the Society of Surgical Oncology 2024 Annual Meeting, demonstrated a consistent decrease in overall survival rates with increasing stage group.¹

Jennifer K. Plichta, MD, MS

“The validation of this staging system marks a significant step forward in our understanding and management of de novo metastatic breast cancer,” Dr. Plichta told The ASCO Post. “The goal is to provide a robust and clinically relevant tool that can guide treatment decisions and improve outcomes for patients with this disease. This work is meant to be a foundation, and I hope people continue to build on it.”

Background

As Dr. Plichta explained, patients with metastatic disease at the time of initial presentation generally have a poor prognosis. However, most prognostic tools and clinical trials involving patients with metastatic disease do not discriminate between patients with de novo metastatic breast cancer and those who develop subsequent metachronous metastases.

“For decades, breast cancer staging was based solely on anatomic information until the 2016 revision of the American Joint Committee on Cancer [AJCC], which included histologic grade, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2],” said Dr. Plichta. “However, these changes applied only to nonmetastatic breast cancer; patients who were diagnosed with de novo metastatic breast cancer remained stage IV regardless of histopathologic factors.”

The Plichta staging system, first published in the Annals of Surgery in 2020, originally proposed three prognostic groups (A, B, and C).² Following discussions with the AJCC breast panel, however, the model was refined to include four groups (IVA, IVB, IVC, and IVD). This updated version was published in the Journal of Clinical Oncology in May 2023.³

Study Details and Results

To provide external validation for the staging system, Dr. Plichta and her team collaborated with researchers from five different countries, analyzing data from the Netherlands Cancer Registry, Epidemiological Strategy and Medical Economics (France), British Columbia Cancer, Instituto Nacional de Cancerologia (Mexico), and Grupo Español de Investigación en Cáncer de Mama (Spain). The validation cohort included 11,199 patients diagnosed between 2002 and 2021.

The study found that the staging system performed well in each individual country, despite variations in sample sizes and data collection methods. When the data were combined, the 3-year overall survival rates consistently decreased with increasing stage group (IVA > IVB > IVC > IVD), aligning with the expected outcomes. The association between stage group and survival remained statistically significant even after adjusting for age and treatment in a subgroup analysis.

According to Dr. Plichta, the staging system for de novo metastatic breast cancer should be implemented in the same way early-stage breast cancer staging criteria are—to improve patient-provider discussions regarding therapy and goals of care. The staging system could also help researchers identify populations for whom more work is needed.

Clinical Implications

Although the current system is not perfect, said Dr. Plichta, it serves as a foundation for future refinements. Dr. Plichta and colleagues are already exploring the incorporation of genomic assays, biomarkers, and imaging techniques to further improve prognostic estimates.

One intriguing finding from the study is the potential overlap between some stage IV subgroups and stage III disease, which could raise important questions about the current treatment paradigms. “Some patients with stage IV are doing very well,” she noted, suggesting that a more nuanced approach might be needed. “Maybe our treatment for this population should not be purely palliative anymore.”

“Conversely, there is a cohort of patients with stage III disease who may not have a great chance for cure,” Dr. Plichta continued. “I hope this staging system stimulates discussions and encourages researchers and clinicians to take a closer look at how we’re treating these patients.” 

DISCLOSURE: Dr. Plichta reported no conflicts of interest.

REFERENCES

1. Plichta JK, Thomas SM, Siesling S, et al: International validation of a staging model for de novo metastatic breast cancer. Society of Surgical Oncology 2024 Annual Meeting. Abstract 4. Presented March 22, 2024.

2. Plichta JK, Ren Y, Thomas SM, et al: Implications for breast cancer restaging based on the 8th Edition AJCC Staging Manual. Ann Surg 271:169-176, 2020.

3. Plichta JK, Thomas SM, Hayes DF, et al: Novel prognostic staging system for patients with de novo metastatic breast cancer. J Clin Oncol 41:2546-2560, 2023.

EXPERT POINT OF VIEW

Julie A. Margenthaler, MD, FACS, Professor of Surgery at Washington University School of Medicine, St. Louis, underscored the importance of a validated stratification system for patients with de novo metastatic breast cancer given the variance in outcomes.

Julie A. Margenthaler, MD, FACS

“As targeted therapies have emerged, we recognize that the life expectancy for patients with stage IV disease can vary widely,” Dr. Margenthaler told The ASCO Post. “The biology of the original primary tumor, as well as the sites of metastases, can greatly affect overall survival. Therefore, a stratification system for patients with stage IV breast cancer is very helpful, so physicians can discuss expectations of treatment with patients and provide a framework for their specific metastatic pattern,” she concluded. 

DISCLOSURE: Dr. Margenthaler reported no conflicts of interest.