title: St Gallen 2015 subtyping of luminal breast cancers: impact of different Ki67-based proliferation assessment methods.
abstract: Ki67 has been proposed as prognostic proliferation marker in luminal breast cancer (BC), but little is known on the influence of Ki67 assessment methods on subtyping into luminal A- and B-like tumors. Our aim was to study the influence of different Ki67-labeling index (Ki67-LI) assessment methods on the proportion of BCs classified as luminal A-like. 280 early BCs were subtyped according to the St Gallen 2015 definitions into 71 % luminal (HER2 negative), 6 % luminal B-like (HER2 positive), 13 % triple negative, 1 % HER2 positive (nonluminal), and 9 % special type. Digitized whole slides were counted manually on the screen. We used nine defined counting methods to assess the Ki67-LI (including the International Ki67 in Breast Cancer Working Group recommendations), and compared the resulting medians and the proportions of cancers classified as luminal A-like according to the formerly used cut-off <20 %. Methods assessing hot spots and tumor periphery resulted in significantly higher Ki67-LI medians than those measuring an average proliferation (27.45 % vs 16.96 %, p < 0.0001). Substantially lower median Ki67-LI were found when assessing 1020 compared to counting 100, 200, 300 cells (17.65 vs 33 %, vs 28 %, vs 24.33 %, respectively; p < 0.0001), or 510 cells (20.59 %, p = 0.019). Applying a standard Ki67-LI cut-off <20 % to define low proliferation for all methods, the proportion of luminal A-like cancers varied between 13 and 44 %. The proportion of BCs classified as luminal A-like is highly influenced by the Ki67-LI assessment method. As a consequence, the selection of a specific Ki67-LI assessment method may have a direct effect on the proportion of patients considered having low-risk disease and thus influence therapeutic decision making. This calls for a standardized assessment method.
authors: Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestrasse 30, 17036, Neubrandenburg, Germany. cornelia.focke@web.de.|Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX Utrecht, The Netherlands. cornelia.focke@web.de.
authors: Cornelia M
authors: CM
authors: Focke
authors: Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX Utrecht, The Netherlands.
authors: Paul J
authors: PJ
authors: van Diest
authors: Department of Pathology, Dietrich Bonhoeffer Medical Centre, Allendestrasse 30, 17036, Neubrandenburg, Germany.
authors: Thomas
authors: T
authors: Decker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000145:classification* / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Intrinsic subtyping; Ki67; Methodology; Proliferation; St Gallen consensus