Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer.
The study of changes in proliferation as a marker of treatment benefit during presurgical endocrine treatment of breast cancer has become increasingly popular, particularly using the nuclear marker Ki67, and holds the potential for prioritizing new treatments for full clinical development. There are weakly significant relationships between Ki67 change and clinical response that differ according to data handling. In the neoadjuvant Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial, suppression of Ki67 at both 2 and 12 weeks was greater with the aromatase inhibitor anastrozole than with either tamoxifen or the combination of anastrozole and tamoxifen. We report here that absolute values of Ki67 after 2 weeks were also significantly lower with anastrozole than with tamoxifen and the combination. This indicates that it may be possible to make such comparisons using surgical samples only. We argue that these changes in proliferation and concurrent changes in apoptosis may be expected to be more predictive of adjuvant benefit from endocrine therapy than clinical response.
Dowsett
Mitch
M
Academic Department of Biochemistry and Breast Unit, Royal Marsden Hospital, London SW3 6JJ, United Kingdom. mitch.dowsett@icr.ac.uk
Smith
Ian E
IE
Ebbs
Steve R
SR
Dixon
J Michael
JM
Skene
Anthony
A
Griffith
Clive
C
Boeddinghaus
Irene
I
Salter
Janine
J
Detre
Simone
S
Hills
Margaret
M
Ashley
Susan
S
Francis
Stephen
S
Walsh
Geraldine
G
A'Hern
Roger
R
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D009570:Nitriles / Q000627:therapeutic use; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole