Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer.
BACKGROUND
Although the prognostic significance of proliferation in early invasive breast cancer has been recognized for a long time, recent gene-expression profiling studies have reemphasized its biologic and prognostic value and the potential application of its assessment in routine practice, particularly to define prognostic subgroups of luminal/hormone receptor-positive (HR+) tumors. This study aimed to assess the prognostic value of a proliferation assay by using Ki-67 immunohistochemistry as compared with mitotic count scores.


METHODS
Proliferation was assessed by using Ki-67 labeling index (Ki-67LI) and mitotic scores in a large (n = 1,550) and well-characterized series of clinically annotated primary operable invasive breast cancer with long-term follow-up. Tumors were phenotyped based on their IHC profiles into luminal/HR+, HER2+, and triple-negative (TN) classes. We used a split-sample development and validation approach to determine the optimal Ki-67LI cut-offs.


RESULTS
The optimal cut-points of Ki-67LI were 10% and 50% for the luminal class. Both Ki7LI and MS were able to split luminal tumors into subgroups with significantly variable outcomes, independent of other variables. Neither mitotic count scores nor Ki-67LI was associated with outcome in the HER2+ or the TN classes.


CONCLUSIONS
Assessment of proliferation by using Ki-67LI and MS can distinguish subgroups of patients within luminal/hormone receptor-positive breast cancer significantly different in clinical outcomes. Overall, both Ki-67 LI and mitotic-count scores showed comparable results. The method described could provide a cost-effective method for prognostic subclassification of luminal/hormone receptor-positive breast cancer in routine clinical practice.
Department of Histopathology, School of Molecular Medical Sciences, Queens Medical Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK.
Mohammed A
MA
Aleskandarany
Andrew R
AR
Green
Ahmed A
AA
Benhasouna
Fabricio F
FF
Barros
Keith
K
Neal
Jorge S
JS
Reis-Filho
Ian O
IO
Ellis
Emad A
EA
Rakha
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000145:classification / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D008940:Mitotic Index; D008954:Models, Biological; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000145:classification / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human