High prevalence of retinoblastoma protein loss in triple-negative breast cancers and its association with a good prognosis in patients treated with adjuvant chemotherapy

• Published in: Annals of oncology Vol. 20; no. 11; pp. 1818 - 1823
• Main Authors: Treré, D., Brighenti, E., Donati, G., Ceccarelli, C., Santini, D., Taffurelli, M., Montanaro, L., Derenzini, M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2009
• Subjects: Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; chemotherapy; Chemotherapy, Adjuvant; Cyclophosphamide - administration & dosage; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Fluorouracil - administration & dosage; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Neoplasm Staging; p53; Pharmacology. Drug treatments; pRb; Prevalence; Prognosis; Receptor, ErbB-2 - biosynthesis; Receptors, Estrogen - biosynthesis; Receptors, Progesterone - biosynthesis; Retinoblastoma Protein - biosynthesis; triple-negative breast cancer; Tumors; pRb; triple-negative breast cancer; chemotherapy; prognosis; p53; Human; Rb protein; Breast disease; Prognosis; Prevalence; Adjuvant treatment; Retinoblastoma protein; Patient; Breast cancer; Malignant tumor; Epidemiology; Mammary gland diseases; Chemotherapy; Treatment; TP53 Gene; Cancer; Tumor suppressor gene
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdp209

Background: Triple-negative breast cancer (TNBC) is an aggressive disease, nevertheless exhibiting a high response rate to chemotherapy. Since the retinoblastoma protein (pRb) loss confers a high sensitivity to chemotherapy regimens, we evaluated the prevalence of pRb loss in TNBCs and its relevance on the clinical outcome of patients treated with adjuvant chemotherapy. Patients and methods: pRb status was prospectively evaluated by immunocytochemistry in 518 consecutive patients with complete receptor information. The predictive value of pRb status in TNBCs was determined according to the adjuvant therapeutic treatments. Results: Fifty-three tumors were identified as TNBCs. The prevalence of pRb loss was significantly higher in TNBCs than in the other cancer subtypes. All patients with TNBCs lacking pRb and treated with systemic chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) were disease free at a medium follow-up time of 109 months, whereas the clinical outcome of those expressing pRb was significantly poorer (P = 0.008). Analysis of disease-free survival including the established anatomo-clinical prognostic parameters indicated pRb loss as the only significant predictive factor. Conclusions: pRb loss is much more frequent in TNBCs than in the other breast cancer subtypes. Patients with TNBCs lacking pRb had a very favorable clinical outcome if treated with conventional adjuvant chemotherapy.