p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.
BACKGROUND
Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer.


METHODS
Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients.


RESULTS
p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2.


CONCLUSIONS
We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.
Ravaioli
A
A
Department of Oncology, Ospedale Infermi, Rimini and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (FC) Italy. aravaiol@auslrn.net
Monti
F
F
Regan
M M
MM
Maffini
F
F
Mastropasqua
M G
MG
Spataro
V
V
Castiglione-Gertsch
M
M
Panzini
I
I
Gianni
L
L
Goldhirsch
A
A
Coates
A
A
Price
K N
KN
Gusterson
B A
BA
Viale
G
G
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis*; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen; D013629:Tamoxifen; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate