Ki67 and breast cancer mortality in women with invasive breast cancer.

BACKGROUND: The percentage of cells staining positive for Ki67 is sometimes used for decision-making in early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut-points and the influence of inter-laboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for inter-laboratory variability and eight patient and tumor characteristics. METHODS: A multicentre cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until 31st December 2020. RESULTS: Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)-positive, HER2-negative early IBC (ptrend<0.001). This relationship remained strong after adjustment for patient and tumor characteristics (ptrend <0.001). Standardization for inter-laboratory variability did little to alter these results. For women with Ki67 scores of 0 to 5%, 6-10%, 11-19% and 20-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (2.8-4.0), 3.7% (3.0 to 4.4), 3.4% (2.8-4.1), and 3.4% (2.8-4.1), whereas for women with Ki67 scores 30-39% and 40-100%, these risks were higher, at 5.1% (4.3 to 6.2) and 7.7% (6.6 to 9.1) (ptrend<0.001). Similar results were obtained when the adjusted analysis was repeated omitting pathological information about tumor size and nodal involvement, which would not be available pre-operatively for patients being considered for neoadjuvant therapy. CONCLUSION: Our findings confirm the prognostic value of Ki67 scores ≥30% in women with ER-positive, HER2-negative early IBC, irrespective of inter-laboratory variability. They also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting.