Why Has Breast Cancer Screening Failed to Decrease the Incidence of de Novo Stage IV Disease?

Abstract

: Background: Despite screening mammography, the incidence of Stage IV breast cancer (BC) at diagnosis has not decreased over the past four decades. We previously found that many BCs are small due to favorable biology rather than early detection. This study compared the biology of Stage IV cancers with that of small cancers typically found by screening. Methods: Trends in the incidence of localized, regional, and distant female BC were compared using SEER*Stat. The National Cancer Database (NCDB) was then queried for invasive cancers from 2010 to 2015, and patient/disease variables were compared across stages. Biological variables including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), grade, and lymphovascular invasion were sorted into 48 combinations, from which three biological subtypes emerged: indolent, intermediate, and aggressive. The distributions of the subtypes were compared across disease stages. Multivariable regression assessed the association between Stage IV disease and biology. Results: SEER*Stat confirmed that the incidence of distant BC increased between 1973 and 2015 (annual percent change [APC] = 0.46). NCDB data on roughly 993,000 individuals showed that Stage IV disease at presentation is more common in young, black, uninsured women with low income/education and large, biologically aggressive tumors. The distribution of tumor biology varied by stage, with Stage IV disease including 37.6% aggressive and 6.0% indolent tumors, versus sub-centimeter Stage I disease that included 5.1% aggressive and 40.6% indolent tumors (p < 0.001). The odds of Stage IV disease presentation more than tripled for patients with aggressive tumors (OR3.2, 95% CI 3.0–3.5). Conclusions: Stage I and Stage IV breast cancers represent very different populations of biologic tumor types. This may explain why the incidence of Stage IV cancer has not decreased with screening.

Development of an Individualized Prediction Calculator for the Benefit of Postoperative Radiotherapy in Patients with Surgically Resected De Novo Stage IV Breast Cancer

“…Breast cancer is the most common tumors in women and is also a leading cause of cancer-related death worldwide [ 1 ]. About 5–10% of patients with breast cancer are diagnosed with de novo stage IV cancer [ 2 ]. The traditional treatment strategy for these patients is usually based on systemic therapy alone, such as chemotherapy (CTx), hormonal therapy, and/or targeted therapy, while surgery or radiotherapy (RT) are used to palliate the symptoms [ 3 ].…”

Breast Cancer Stage at Presentation in Ohio: The Effect of Medicaid Expansion and the Affordable Care Act

“…One recent study notes that, despite improvements in screening, the nationwide incidence of stage IV breast cancer has not decreased over the last 40 years. 15 This study demonstrates that impoverished, young, and black patients are more likely to present with stage IV breast cancer, often as a consequence of aggressive tumor biology. 15 Moreover, they point out that biologically aggressive tumors demonstrate different growth patterns and physical characteristics, which may complicate their diagnosis.…”

“…15 This study demonstrates that impoverished, young, and black patients are more likely to present with stage IV breast cancer, often as a consequence of aggressive tumor biology. 15 Moreover, they point out that biologically aggressive tumors demonstrate different growth patterns and physical characteristics, which may complicate their diagnosis. 15 Significantly, the Ohio Medicaid data 16 demonstrate that many of the patients newly covered under Medicaid expansion are those who carry a disproportionately high risk of presenting with stage IV breast cancer.…”

“…15 Moreover, they point out that biologically aggressive tumors demonstrate different growth patterns and physical characteristics, which may complicate their diagnosis. 15 Significantly, the Ohio Medicaid data 16 demonstrate that many of the patients newly covered under Medicaid expansion are those who carry a disproportionately high risk of presenting with stage IV breast cancer. As such, this study's data may simply be identifying a national trend (no change in the percentage of patients presenting with advanced cancer) in a local population.…”

Treatment Strategies and Survival Outcomes in Breast Cancer

“…There are two studies on screening. Heller looked at approximately 993,000 individuals using a national database, aiming to see why screening did not appear to decrease the incidence of stage IV breast cancer [3]. They found that among those diagnosed up front with stage IV disease, 37.6% had aggressive tumours as compared to 5.1% in those with stage 1 disease, suggesting that the two groups are from different populations with different tumour phenotypes.…”