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52. The Risk of QTc-Interval Prolongation in Breast Cancer Patients Treated with Tamoxifen in Combination with Serotonin Reuptake Inhibitors

Author

Roelof W.F. van Leeuwen, Florine A. Berger, Robbert J. van Alphen, Esther Oomen-de Hoop, Teun van Gelder, Natasja M.S. de Groot, Lisette Binkhorst, Ron H.J. Mathijssen, Koen G. A. M. Hussaarts, Daniëlle Mathijssen van Stein, Medical Oncology, Pharmacy, and Cardiology

Subjects
Oncology, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Pharmaceutical Science, Venlafaxine, Breast Neoplasms, 030204 cardiovascular system & hematology, Citalopram, electrocardiogram, QT interval, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Medicine, Escitalopram, Humans, Pharmacology (medical), cardiovascular diseases, QTc-interval, Aged, Pharmacology, business.industry, serotonin reuptake inhibitors, Organic Chemistry, Middle Aged, medicine.disease, Paroxetine, Tamoxifen, Long QT Syndrome, 030220 oncology & carcinogenesis, Concomitant, cardiovascular system, Molecular Medicine, Antidepressive Agents, Second-Generation, Female, business, drug-drug interaction, Selective Serotonin Reuptake Inhibitors, Biotechnology, medicine.drug, Research Paper
Abstract

Purpose Antidepressants like the serotonin reuptake inhibitors (SRIs) are often used concomitantly with tamoxifen (e.g. for treatment of depression). This may lead to an additional prolongation of the QTc-interval, with an increased risk of cardiac side effects. Therefore we investigated whether there is a drug-drug interaction between tamoxifen and SRIs resulting in a prolonged QTc-interval. Methods Electrocardiograms (ECGs) of 100 patients were collected at steady state tamoxifen treatment, with or without concomitant SRI co-medication. QTc-interval was manually measured and calculated using the Fridericia formula. Primary outcome was difference in QTc-interval between tamoxifen monotherapy and tamoxifen concomitantly with an SRI. Results The mean QTc-interval was 12.4 ms longer when tamoxifen was given concomitantly with an SRI (95% CI:1.8–23.1 ms; P = 0.023). Prolongation of the QTc-interval was particularly pronounced for paroxetine (17.2 ms; 95%CI:1.4–33.0 ms; P = 0.04), escitalopram (12.5 ms; 95%CI:4.4–20.6 ms; P P = 0.047), where other agents like venlafaxine did not seem to prolong the QTc-interval. None of the patients had a QTc-interval of >500 ms. Conclusions Concomitant use of tamoxifen and SRIs resulted in a significantly higher mean QTc-interval, which was especially the case for paroxetine, escitalopram and citalopram. When concomitant administration with an SRI is warranted venlafaxine is preferred.

Published
2019

59. MicroRNA Profiling of Salivary Duct Carcinoma Versus Her2/Neu Overexpressing Breast Carcinoma Identify miR-10a as a Putative Breast Related Oncogene

Author

Luciano Cascione, Kati Maharry, Steve Oghumu, Carlo M. Croce, Paolo Fadda, O. Hans Iwenofu, Veronica Balatti, Arianna Bottoni, and Anil V. Parwani

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Receptor, ErbB-2, Breast Neoplasms, HER2/neu, Pathology and Forensic Medicine, Salivary duct carcinoma, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, microRNA, Medicine, Humans, skin and connective tissue diseases, Original Paper, Oncogene, Salivary gland, biology, business.industry, Gene Expression Profiling, medicine.disease, Salivary Gland Neoplasms, Ductal Breast Carcinoma, Carcinoma, Ductal, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Oncology, Otorhinolaryngology, 030220 oncology & carcinogenesis, biology.protein, Female, Breast carcinoma, business
Abstract

Salivary duct carcinomas (SDC) and Her2/Neu3-overexpressing invasive breast carcinomas (HNPIBC/IBC) are histologically indistinguishable. We investigated whether common histopathologic and immunophenotypic features of SDC and IBC are mirrored by a similar microRNA (miRNA) profile. MiRNA profiling of 5 SDCs, 6 IBCs Her2/Neu3+, and 5 high-grade ductal breast carcinoma in situ (DCIS) was performed by NanoString platform. Selected miRNAs and HOXA1 gene were validated by RT-PCR. We observed similar miRNA expression profiles between IBC and SDC with the exception of 2 miRNAs, miR-10a and miR-142-3p, which were higher in IBC tumors. DCIS tumors displayed increased expression of miR-10a, miR-99a, miR-331-3p and miR-335, and decreased expression of miR-15a, miR-16 and miR-19b compared to SDC. The normal salivary gland and breast tissues also showed similar expression profiles. Interestingly, miR-10a was selectively increased in both IBC and normal breast tissue compared to SDC and normal salivary gland tissue. Moreover, our NanoString and RT-PCR data confirmed that miR-10a was upregulated in IBC and DCIS compared to SDC. Finally, we show downregulation of HOXA1, a miR-10 target, in IBC tumors compared to normal breast tissue. Taken together, our data demonstrates that, based on miRNA profiling, SDC is closely related to HNPIBC. Our results also suggest that miR-10a is differentially expressed in IBC compared to SDC and may have potential utility as a diagnostic biomarker in synchronous or metachronous malignant epithelial malignancies involving both organs. In addition, miR-10a could be playing an important role as a mammary-specific oncogene, involved in breast cancer initiation (DCIS) and progression (IBC), through mechanisms that include modulation of HOXA1 gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12105-018-0971-x) contains supplementary material, which is available to authorized users.

Published
2018

81. Ovarian Suppression: Early Menopause and Late Effects

Author

Molinelli, Chiara, Jacobs, Flavia, Nader-Marta, Guilherme, Borea, Roberto, Scavone, Graziana, Ottonello, Silvia, Fregatti, Piero, Villarreal-Garza, Cynthia, Bajpai, Jyoti, Kim, Hee Jeong, Puglisi, Silvia, de Azambuja, Evandro, and Lambertini, Matteo

Published
2024
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