Browsing by Author "Ciruelos, E"

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Combined Label-Free Quantitative Proteomics and microRNA Expression Analysis of Breast Cancer Unravel Molecular Differences with Clinical Implications
(American Association for Cancer Research Inc., 2015) Gámez-Pozo, A; ABerges-Soria, J; Arevalillo, JM; Nanni, P; López-Vacas, R; Navarro, H; Grossmann, J; Castaneda, CA; Main, P; Díaz-Almirón, M; Espinosa, E; Ciruelos, E; Fresno Vara, Á
Better knowledge of the biology of breast cancer has allowed the use of new targeted therapies, leading to improved outcome. High-throughput technologies allow deepening into the molecular architecture of breast cancer, integrating different levels of information, which is important if it helps in making clinical decisions. microRNA (miRNA) and protein expression profiles were obtained from 71 estrogen receptor-positive (ER(+)) and 25 triple-negative breast cancer (TNBC) samples. RNA and proteins obtained from formalin-fixed, paraffin-embedded tumors were analyzed by RT-qPCR and LC/MS-MS, respectively. We applied probabilistic graphical models representing complex biologic systems as networks, confirming that ER(+) and TNBC subtypes are distinct biologic entities. The integration of miRNA and protein expression data unravels molecular processes that can be related to differences in the genesis and clinical evolution of these types of breast cancer. Our results confirm that TNBC has a unique metabolic profile that may be exploited for therapeutic intervention.
Implication of miRNA in the diagnosis and treatment of breast cancer
(Taylor and Francis Ltd., 2011) Castañeda, CA; Agullo-Ortuño, MT; Fresno Vara, JA; Cortes-Funes, H; Gomez, HL; Ciruelos, E
Breast cancer (BC) comprises a group of different diseases characterized by changes in tissue structure and gene expression. Recent advances in molecular biology have shed new light on the participation of genes and their products in the biology of BC. MicroRNAs (miRNAs) are small noncoding endogenous RNA molecules that appear to modulate the expression of more than a third of human genes, and their implications in cancer have grasped the attention of the scientific community. Recently, several studies have described the association between miRNA expression profiles and pathological and clinical BC features. Moreover, these molecules represent a new type of molecular marker that can identify prognosis and guide the management of BC patients. With the increasing understanding of miRNA networks and their impact in the biology of BC, as well as the development of viable strategies to modulate specific miRNAs, we could improve the treatment of this disease.
Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer
(N Engl J Med. 2018 Jul 12;379(2):122-137., 2018) Francis, PA; Pagani, O; Fleming, GF; Walley, BA; Colleoni, M; Láng, I; Gómez, HL; Tondini, C; Ciruelos, E; Burstein, HJ; Bonnefoi, HR; Bellet, M; Martino, S; Geyer, CE; Goetz, MP; Stearns, V; Pinotti, G; Puglisi, F; Spazzapan, S; Climent, MA; Pavesi, L; Ruhstaller, T; Davidson, NE; Coleman, R; Debled, M; Buchholz, S; Ingle, JN; Winer, EP; Maibach, R; Rabaglio-Poretti, M; Ruepp, B; Di Leo, A; Coates, AS; Gelber, RD; Goldhirsch, A; Regan, MM; SOFT and TEXT Investigators and the International Breast Cancer Study Group.
Background: In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. Methods: Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. Results: In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. Conclusions: Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).