A new study has reported that current prognostic indicators such as hormone receptor status and proliferation index predict only early risk of recurrence (i.e., within the first few years after diagnosis). Breast cancer has a long natural history and can recur many years after initial diagnosis and treatment. Early recurrence is most likely with aggressive forms of breast cancer such as triple negative (ER-/PR-/HER2-) and HER2 overexpressing (HER2+) disease. However, hormone receptor positive breast cancer with low aggressiveness is more likely to recur many years after diagnosis than triple negative or HER2+ disease.

The study included 346 breast cancer cases with at least 23 years of follow up. All of the women had undergone breast cancer surgery at a London hospital to remove their tumors before receiving any chemotherapy or other systemic treatment. Stored tissue was used to reassess hormone receptor status, HER2 expression and tumor grade.

Breast cancer outcome was found to be influenced primarily by receptor status and tumor grade rather than tumor size. Hormone receptor positive (defined as ER+/PR+/HER2- in the study) recurrence risk was linked to tumor grade. Low grade cases were found to have very low risk of early recurrence (within the first three years) but breast cancer-specific survival had declined 20% by 10 or more years after diagnosis. Higher grade hormone receptor positive cases had recurrence risk for more than 20 years. Among triple negative (ER-/PR-/HER2-) and HER2 positive (HER2+) cases, breast cancer-specific recurrence or death occurred primarily within the first five years after diagnosis. Among lymph node positive cases, only low grade tumors appeared to confer late risk, suggesting that measures of proliferation are important for predicting early but not late recurrence. To validate insights from this study, an additional analysis was performed for 683 breast cancer cases (all lymph node negative) to evaluate the ability of proliferative potential and hormone receptor status to predict early versus late metastatic risk. To perform this analysis, the authors used data combined from four publicly available data sets. Tumor proliferative capacity was found to predict early but not late metastatic risk for hormone receptor positive cases. Immune function and hormone receptor negative-specific signatures predicted only early metastatic risk in triple negative and HER2+ cases. The authors conclude that breast cancer prognostic measures need to inform both risk and timing of metastatic events and may best be applied within breast cancer subtypes. Current measures predict outcome risk within five years of diagnosis. Predictors of late risk for hormone receptor positive breast cancer are needed.