The natural history of breast cancer: a chronological analysis of breast cancer progression using data from the SEER database.

Background: Numerous mathematical models and retrospective analyses have been conducted to explore the natural progression of breast cancer, but there is no precise timeline as to how long it takes breast cancer to progress from stages 0 to IV. Studying the natural history of breast cancer requires the follow-up of a large cohort of patients who received no treatment following diagnosis for a long period, but this has become unpractical in the modern era. In this study, we quantified the natural progression of breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database which was collected the clinical-pathological characteristics and survival data of untreated breast cancer patients.

Methods: We included 12,687 female patients who did not receive surgical treatment, radiotherapy, or chemotherapy, had complete information on tumor staging, and had only 1 primary tumor in their lifetime in our study as the untreated group. Overall survival (OS) was calculated from the date of the latest diagnosis of breast cancer to the date of death. Medium survival time (MST) was defined as the time at which 50% of the patients reached the endpoint. The medium survival time (MST) was calculated for each stage. The progression time was calculated by subtracting the MST of a higher stage from that of a lower stage, which also indicated "life loss". Estrogen receptor (ER) negative and positive patients were analyzed as two separate groups.

Results: For the ER positive patients, the median progression times from stages 0 to I, I to II, II to III, and III to IV were 5.2±1.2, 4.2±0.5, 2±0.3, and 0.9±0.2 years, respectively, which were similar to those of the ER negative patients of 5.4±2.9, 4.7±1.3, 2.5±0.7, and 1.1±0.4 years (P=0.49). The survival of stage IV patients was longer in ER positive patients than ER negative patients (2.7±0.1 0.9±0.2 year, P<0.001).

Conclusions: ER negative patients appear to have the same progression time as that of ER positive patients in the primary site, but had a much worse process in the metastasis site.