A generalizable relationship between mortality and time-to-death among breast cancer patients can be explained by tumour dormancy

BACKGROUND: Women with ER-positive breast cancer may recur as late as 20 years post-diagnosis. The reason for this delayed recurrence is unknown. We studied survival patterns, including time-to-death in 123,705 women with stage I to III invasive breast cancer, enrolled in the SEER database. Among these 76.8% were ER-positive and 23.2% were ER-negative. METHODS: We divided the cohort into ten classes with varying risks of death from breast cancer. The 20-year mortality for women in the highest risk decile 10 was 69% versus 5% for women in the lowest decile 1. The difference in the time-to-death by decile could be explained by a variable α which represents the annual rate of reactivation from tumour dormancy. RESULTS: The duration of tumour dormancy was much longer, on average, for ER-positive breast cancers than for ER-negative breast cancers. Reactivation from tumour dormancy appears to occur at random and may explain the very long time to cancer recurrence in women with small node-negative ER-positive breast cancers. CONCLUSION: The clinical course of women with low-risk ER-positive breast cancer is inherently unpredictable and consequently death is equally as likely to occur at year 3 than at year 20. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-019-05334-5) contains supplementary material, which is available to authorized users.