BACKGROUND: Breast cancer cells can develop resistance to standard hormonal treatment and chemotherapy with the activation of the mTOR pathway; this is supported by results of preclinical and clinical studies. In clinical trials, the addition of everolimus to hormonal treatment or anti-HER2 treatment improved the outcomes of breast cancer patients. The aim of this review is to discuss the efficacy and safety data of everolimus in all categories of breast cancer in recent published studies. SCOPE: Everolimus showed positive results in clinical studies. A literature search was made from PubMed, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts by using the following search key words: 'everolimus', 'RAD001', 'mTOR inhibitor', 'breast cancer' 'endocrine therapy resistance' and 'HER-2 targeted therapies'. The last search was on June 10, 2013. The most important limitation of our review is that most of the data on everolimus rely on phase I and II trials. FINDINGS: Preclinical studies showed that mTOR activation can be the responsible mechanism in all subgroups of breast cancer. Results of both the TAMRAD and BOLERO-2 studies have showed that mTOR inhibition in combination with endocrine therapy can be a new treatment strategy for MBC patients who are resistant to aromatase inhibitors. In the BOLERO-2 study, time to deterioration in health-related quality of life was also significantly higher in the everolimus and exemestane arm compared to the exemestane plus placebo arm. The recently completed BOLERO-3 study showed that mTOR inhibition in combination with trastuzumab plus vinorelbine treatment significantly improved PFS compared to trastuzumab plus vinorelbine alone in trastuzumab-resistant MBC patients. CONCLUSION: Recent trials have shown that everolimus has produced promising anti-tumor activity in combination with trastuzumab in HER2-positive metastatic breast cancer and in combination with exemestane in patients with hormone-receptor-positive metastatic breast cancer who had recurrence or progression while receiving a nonsteroidal aromatase inhibitor. Results of ongoing studies with everolimus show evidence that using everolimus in earlier stages of the disease, namely in the adjuvant and neoadjuvant settings, could be benefical.
BACKGROUND:Breast cancer cells can develop resistance to standard hormonal treatment and chemotherapy with the activation of the mTOR pathway; this is supported by results of preclinical and clinical studies. In clinical trials, the addition of everolimus to hormonal treatment or anti-HER2 treatment improved the outcomes of breast cancerpatients. The aim of this review is to discuss the efficacy and safety data of everolimus in all categories of breast cancer in recent published studies. SCOPE: Everolimus showed positive results in clinical studies. A literature search was made from PubMed, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts by using the following search key words: 'everolimus', 'RAD001', 'mTOR inhibitor', 'breast cancer' 'endocrine therapy resistance' and 'HER-2 targeted therapies'. The last search was on June 10, 2013. The most important limitation of our review is that most of the data on everolimus rely on phase I and II trials. FINDINGS: Preclinical studies showed that mTOR activation can be the responsible mechanism in all subgroups of breast cancer. Results of both the TAMRAD and BOLERO-2 studies have showed that mTOR inhibition in combination with endocrine therapy can be a new treatment strategy for MBCpatients who are resistant to aromatase inhibitors. In the BOLERO-2 study, time to deterioration in health-related quality of life was also significantly higher in the everolimus and exemestane arm compared to the exemestane plus placebo arm. The recently completed BOLERO-3 study showed that mTOR inhibition in combination with trastuzumab plus vinorelbine treatment significantly improved PFS compared to trastuzumab plus vinorelbine alone in trastuzumab-resistant MBCpatients. CONCLUSION: Recent trials have shown that everolimus has produced promising anti-tumor activity in combination with trastuzumab in HER2-positive metastatic breast cancer and in combination with exemestane in patients with hormone-receptor-positive metastatic breast cancer who had recurrence or progression while receiving a nonsteroidal aromatase inhibitor. Results of ongoing studies with everolimus show evidence that using everolimus in earlier stages of the disease, namely in the adjuvant and neoadjuvant settings, could be benefical.
Authors: Nicole M Davis; Melissa Sokolosky; Kristin Stadelman; Steve L Abrams; Massimo Libra; Saverio Candido; Ferdinando Nicoletti; Jerry Polesel; Roberta Maestro; Antonino D'Assoro; Lyudmyla Drobot; Dariusz Rakus; Agnieszka Gizak; Piotr Laidler; Joanna Dulińska-Litewka; Joerg Basecke; Sanja Mijatovic; Danijela Maksimovic-Ivanic; Giuseppe Montalto; Melchiorre Cervello; Timothy L Fitzgerald; Zoya Demidenko; Alberto M Martelli; Lucio Cocco; Linda S Steelman; James A McCubrey Journal: Oncotarget Date: 2014-07-15
Authors: Xīn Gào; Yan Zhang; Barbara Burwinkel; Yang Xuan; Bernd Holleczek; Hermann Brenner; Ben Schöttker Journal: Clin Epigenetics Date: 2019-01-24 Impact factor: 6.551