Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer.
BACKGROUND
Studies have shown that Ki-67 response after short-term neoadjuvant aromatase inhibitors may predict recurrence in postmenopausal breast cancer, whereas its prognostic effect in premenopausal women is unknown.


METHODS
We compared the prognostic and predictive value of baseline and post-treatment Ki-67 in 120 pre- and postmenopausal women with early-stage estrogen receptor-positive breast cancer who participated in a 4-week presurgical trial of tamoxifen.


RESULTS
After 7.2 years of follow-up, women with post-treatment Ki-67 in the second (14%-19%), third (20%-29%) and top (≥30%) quartiles had a recurrence hazard ratio of 2.92 [95% confidence interval (CI) 0.95-8.96], 4.37 (1.56-12.25) and 6.05 (2.07-17.65), respectively, as compared with those in the bottom quartile (<14%) (P-trend = 0.001). The risk of invasive disease recurrence was 2.2% (95% CI 0.9-5.0) per point increase in baseline Ki-67 (P-trend = 0.076) and 5.0% (95% CI 2.3-7.7) per point increase in post-tamoxifen Ki-67 (P-trend < 0.001). The risk of death was 5.5 (95% CI 1.26-23.16) times higher in patients with post-drug Ki-67 ≥20% than in those with Ki-67 <20% (P-trend = 0.006).


CONCLUSIONS
Ki-67 response after short-term neoadjuvant tamoxifen is a good predictor of recurrence-free survival and overall survival, further supporting its use as surrogate biomarker to personalize adjuvant treatment and to screen novel drugs cost-effectively.
DeCensi
A
A
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan; Medical Oncology Unit, E.O. Ospedali Galliera, Genoa. Electronic address: andrea.decensi@galliera.it.
Guerrieri-Gonzaga
A
A
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan.
Gandini
S
S
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
Serrano
D
D
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan.
Cazzaniga
M
M
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan.
Mora
S
S
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan.
Johansson
H
H
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan.
Lien
E A
EA
Hormone Laboratory, Haukeland University Hospital; Section for Endocrinology, Institute of Medicine, University of Bergen, Bergen, Norway.
Pruneri
G
G
Division of Pathology, European Institute of Oncology; University of Milan School of Medicine, Milan, Italy.
Viale
G
G
Division of Pathology, European Institute of Oncology; University of Milan School of Medicine, Milan, Italy.
Bonanni
B
B
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan.
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D013194:Staining and Labeling; D013629:Tamoxifen / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C508053:ERBB2 protein, human