Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer.
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Date
2019-09-01ICR Author
Author
Abubakar, M
Figueroa, J
Ali, HR
Blows, F
Lissowska, J
Caldas, C
Easton, DF
Sherman, ME
Garcia-Closas, M
Dowsett, M
Pharoah, PD
Type
Journal Article
Metadata
Show full item recordAbstract
Although most women with luminal breast cancer do well on endocrine therapy alone, some will develop fatal recurrence thereby necessitating the need to prospectively determine those for whom additional cytotoxic therapy will be beneficial. Categorical combinations of immunohistochemical measures of ER, PR, HER2, and KI67 are traditionally used to classify patients into luminal A-like and B-like subtypes for chemotherapeutic reasons, but this may lead to the loss of prognostically relevant information. Here, we compared the prognostic value of quantitative measures of these markers, combined in the IHC4-score, to categorical combinations in subtypes. Using image analysis-based scores for all four markers, we computed the IHC4-score for 2498 patients with luminal breast cancer from two European study populations. We defined subtypes (A-like (ER + and PR + : and HER2- and low KI67) and B-like (ER + and/or PR + : and HER2 + or high KI67)) by combining binary categories of these markers. Hazard ratios and 95% confidence intervals for associations with 10-year breast cancer-specific survival were estimated in Cox proportional-hazard models. We accounted for clinical prognostic factors, including grade, tumor size, lymph-nodal involvement, and age, by using the PREDICT-score. Overall, Subtypes [hazard ratio (95% confidence interval) B-like vs. A-like = 1.64 (1.25-2.14); P-value < 0.001] and IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.32 (1.20-1.44); P-value < 0.001] were prognostic in univariable models. However, IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.24 (1.11-1.37); P-value < 0.001; likelihood ratio chi-square (LRχ2) = 12.5] provided more prognostic information than Subtype [hazard ratio (95% confidence interval) B-like vs. A-like = 1.38 (1.02-1.88); P-value = 0.04; LRχ2 = 4.3] in multivariable models. Further, higher values of the IHC4-score were associated with worse prognosis, regardless of subtype (P-heterogeneity = 0.97). These findings enhance the value of the IHC4-score as an adjunct to clinical prognostication tools for aiding chemotherapy decision-making in luminal breast cancer patients, irrespective of subtype.
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Subject
Humans
Breast Neoplasms
Receptor, erbB-2
Ki-67 Antigen
Receptors, Estrogen
Receptors, Progesterone
Prognosis
Adult
Aged
Middle Aged
Female
Biomarkers, Tumor
Research team
Endocrinology
Language
eng
Date accepted
2019-03-12
License start date
2019-09
Citation
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019, 32 (9), pp. 1244 - 1256
Publisher
NATURE PUBLISHING GROUP