Stage 4 breast cancer
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Stage 4 Breast Cancer: Incidence and Patient Demographics
Stage 4 breast cancer, also known as metastatic breast cancer, is diagnosed when cancer has spread beyond the breast to other parts of the body. In developed countries, about 6–10% of breast cancer patients present with stage 4 disease at diagnosis, with higher rates in other regions 31. Patients with stage 4 breast cancer tend to be older, more often of Black race, and less likely to be married compared to those with earlier-stage disease .
Tumor Subtypes and Frequency of Stage 4 Presentation
The likelihood of being diagnosed with stage 4 breast cancer varies by tumor subtype. The proportion of patients presenting with stage 4 disease is lowest in hormone receptor-positive, HER2-negative (HR+/HER2-) tumors (4.6%) and highest in HER2-negative, HER2-positive (HR-/HER2+) tumors (11.3%) . Triple-negative breast cancer (TNBC) and HR+/HER2+ subtypes also have higher rates of stage 4 presentation . Over the past decade, the proportion of stage 4 cases has increased modestly in most subtypes, except HR+/HER2+ .
Common Sites of Metastasis and Prognosis
The most frequent sites of metastasis at diagnosis are bone (about 66%), lung (30%), liver (26%), and brain (8%) . Patients with bone-only metastasis have the best survival outcomes, while those with brain metastasis have the poorest prognosis . Survival also varies by tumor subtype and metastatic site, with bone metastasis associated with longer survival and brain metastasis being the most aggressive .
Survival Outcomes and Prognostic Factors
Despite advances in treatment, stage 4 breast cancer remains associated with high mortality. Five-year breast cancer-specific survival (BCSS) rates differ by subtype: HR+/HER2- (32.5%), HR+/HER2+ (43.9%), HR-/HER2+ (37.3%), and TNBC (11%) . Ten-year survival rates are low, with about 13% of women surviving 10 years after diagnosis; younger women (under 50) have slightly better long-term survival than older women . Key prognostic factors include age, race, marital status, tumor grade, subtype, tumor size, and whether the patient received surgery, radiation, or chemotherapy 79.
Advances in Treatment and Impact on Survival
Recent years have seen significant improvements in survival for certain subtypes, especially those with HER2-positive disease. The introduction of anti-HER2 therapies, such as antibody-drug conjugates and targeted agents, has made stage 4 HER2-positive breast cancer potentially curable for some patients 126. Studies show that some patients who achieve a complete clinical response (cCR) with anti-HER2 therapy may be able to discontinue treatment after several years, especially if liquid biopsy tests confirm the absence of tumor-related genes 26. For HR+/HER2- disease, CDK 4/6 inhibitors and other targeted therapies have also improved outcomes .
Role of Surgery and Local Treatment
While systemic therapy remains the mainstay of treatment for stage 4 breast cancer, several studies suggest that surgery to remove the primary tumor, when combined with systemic therapy, can improve overall survival in selected patients 45. A randomized clinical trial showed that patients who received locoregional treatment (surgery and/or radiation) followed by systemic therapy had better 10-year survival compared to those who received systemic therapy alone .
Special Considerations: Inflammatory Breast Cancer
Patients with inflammatory breast cancer who present with distant metastasis (stage 4) have particularly poor survival, and current staging systems may not fully capture the aggressive nature of this subtype .
Treatment Goals and Quality of Life
For most patients, stage 4 breast cancer is treatable but not curable, with the primary goals being to prolong life and maintain quality of life . Treatment is tailored based on tumor subtype, metastatic sites, and patient preferences, and may include systemic therapies (endocrine, targeted, immunotherapy, chemotherapy), surgery, and radiation 110.
Conclusion
Stage 4 breast cancer remains a challenging diagnosis with significant variation in outcomes based on tumor subtype, metastatic site, and patient characteristics. Advances in targeted therapies, especially for HER2-positive disease, have improved survival and even raised the possibility of cure in select cases. However, triple-negative and brain-metastatic disease continue to have poor outcomes, highlighting the need for ongoing research and new treatment strategies 136.
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