A new study shows that cases of stage IV breast cancer are increasing both in incidence and as a proportion of all breast cancer diagnoses. According to the findings, published by Avila et al in JAMA Network Open, the incidence rate of stage IV breast cancer has increased significantly from 9.5 cases per 100,000 women in 2010 to 11.2 cases per 100,000 women in 2021.
“Early detection of breast cancer is critically important,” said José P. Leone, MD, a medical oncologist at Dana-Farber Cancer Institute and senior study author. “By understanding population-based outcomes, which this study provides, there is an opportunity to create the most impact to the population.”
Breast cancer incidence rates for all types of the disease have risen 1% annually from 2012 to 2021. Despite these trending increases in the disease, historically, stage IV diagnoses have been a smaller proportion of all breast cancer cases. Dr. Leone and colleagues evaluated incidence, proportion, and overall survival of individuals with de novo stage IV breast cancer diagnosed from 2010 through 2021 in a population-based database from the Surveillance Epidemiology, and End Results (SEER) Program.
The investigators analyzed 761,471 breast cancer diagnoses, 98.8% of which occurred in females. Median age at diagnosis was 63 years. Increases across stage I to III breast cancers were observed across all tumor subtypes, including hormone receptor (HR)-positive/HER2-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative disease.
The researchers found that the incidence of stage IV breast cancer increased by an average of 1.2% annually across age groups, racial groups, and tumor subtypes, compared with an annual increase of 1.0% for breast cancer overall. Over the same period, the proportion of breast cancers diagnosed at stage IV increased modestly, from 5.6% in 2010 to 6.0% in 2021. From 2010 to 2021, overall survival among patients diagnosed with stage IV breast cancer also improved over time among those with HR-positive/HER2-negative, HR-negative/HER2-positive, and HR-positive/HER2-positive disease.
Interestingly, whereas less than 1% of breast cancer diagnoses occur in men, the incidence rate in men represented a 3.7% increase per year—higher than that seen in women.
"When we think about incidence, we think may think of risk factors such as hormone replacement therapy or factors that apply more specifically for women,” Dr. Leone said. “But the fact that the increase in incidence is overall in all groups of interest suggests that the underlying factors may be affecting everyone.”
Dr. Leone added that the study underscores the importance of determining which factors contribute to these increases and the need to identify breast cancer earlier, before patients present with stage IV disease. Whereas overall survival improved due to greatly improved therapeutics, research is needed to determine factors contributing to increased incidence, potential changes in natural history of breast cancer, disease screening, and incidence of other conditions and related mortality .
“This study raises concern because we don’t have good answers as to why we are seeing an increase in de novo metastatic breast cancer, regardless of breast cancer subtype.” Dr. Leone said. “While our medicines for treating metastatic breast cancer have improved dramatically in recent years, earlier-stage breast cancer is often curable, and our study highlights the need to identify the factors driving increasing incidence of advanced disease.”
DISCLOSURE: For full disclosures of the study authors, visit jamanetwork.com.
