Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists.
OBJECTIVE
To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy.


METHODS
The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment.


RESULTS
52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks.


CONCLUSIONS
These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.
Dowsett
Mitch
M
Academic Department of Biochemistry and the Breast Unit, Royal Marsden Hospital, London SW3 6JJ, UK. mitch.dowsett@icr.ac.uk
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
Smith
Ian E
IE
D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles