Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

Wolff, Antonio C.; Lazar, Ann; Bondarenko, Igor; Garin, A.; Brincat, Stephen; Chow, Louis W.C.; Sun, Yan; Nešković-Konstantinović, Z.; Guimarães, Ricardo Queiroz; Fumoleau, P.; Chan, Arlene; Hachemi, Soulef; Strahs, Andrew; Cincotta, Maria; Berkenblit, Anna; Krygowski, Mizue; Kang, Lih Lisa; Moore, Laurence; Hayes, Daniel F.

doi:10.1200/jco.2011.38.3331

Cited by 246 publications

(170 citation statements)

References 26 publications

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“…In the everolimus trials, adverse effects (AEs) such as fatigue, stomatitis, anorexia, diarrhea, and metabolic disorders are often observed in patients but usually can be tolerated with dose reduction. Similar AEs are also noticed in the temsirolimus trials, with some milder cases of headache and fever, and severe cases of hyperglycemia, hyperlipemia, and asthenia [65,66]. Natural products such as cyclovirobuxine D (CVB-D), an alkaloid component isolated from the roots of Buxus microphylla var.…”

Section: Anticancer Therapies Correlated With Autophagymentioning

confidence: 56%

Autophagy regulation in the development and treatment of breast cancer

Zhou

2016

ABBS

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Autophagy is a major catabolic process in which intracellular membrane structures, protein complexes, and lysosomes are formed as lysoautophagosome to degrade and renew cytoplasmic components. Autophagy is physiologically a strategy and mechanism for cellular homeostasis as well as adaptation to stress, and thus alterations in the autophagy machinery may lead to diverse pathological conditions. The role of autophagy in cancer is complex, and the current literature reflects this as a 'double-edged sword'. Autophagy shows promise as a novel therapeutic target in various types of breast cancer, inhibiting or increasing treatment efficacy in a context-and cell-type-dependent manner. This review aims to summarize the recent advances in the understanding of the mechanisms by which key modulators of autophagy participate in cancer metastasis, highlight different autophagydeficient murine models for breast cancer study, and provide further impetus for the modulation of autophagy in anticancer therapy.

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Section: Anticancer Therapies Correlated With Autophagymentioning

confidence: 56%

Autophagy regulation in the development and treatment of breast cancer

Zhou

2016

ABBS

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“…As the study is ongoing, no data are available yet. Furthermore, efficacy of letrozole plus the mTOR inhibitor, temsirolimus, was investigated in another randomized phase III trial (Wolff et al 2013). In this study, the combination was administered as a first-line treatment to postmenopausal women with AI-naïve locally advanced or metastatic breast cancer.…”

Section: Perspectivesmentioning

confidence: 99%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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“…However, data were presented only in an abstract form and no statistical analyses are currently available [51]. A subsequent phase 3 study (the HORIZON study) randomized 1,112 postmenopausal women with locally advanced or metastatic breast cancer to receive letrozole alone or letrozole plus oral temsirolimus as a first-line endocrine treatment [52]. The study was terminated prematurely, as the combination yielded no clinical benefit.…”

Section: Temsirolimusmentioning

confidence: 99%

Endocrine Resistance in Breast Cancer: Focus on the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway

Hasson¹,

Rubinek²,

Ryvo³

et al. 2013

Breast Care

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Breast cancer is the most common cancer among women. Up to 75% of breast cancers express the estrogen receptor (ER)α and/or the progesterone receptor (PR). Patients with hormone receptor-positive metastatic breast cancer are typically treated with endocrine therapy. Yet, not all patients with metastatic breast cancer respond to endocrine treatments and are considered to have primary (de novo) resistance. Furthermore, all patients who initially respond to endocrine treatment will eventually develop acquired resistance. Several mechanisms have been linked to the development of endocrine resistance, including reduced expression of ERα, altered regulation of the ER pathway, and activation of various growth factor signaling pathways, among them the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. This pathway is involved in critical processes including cell survival, proliferation, and angiogenesis, and plays a central role in breast cancer development. Recent laboratory and clinical data implicate this pathway as mediating endocrine resistance, and agents directed against critical components of this pathway are either already approved for clinical use in breast cancer patients or are currently being tested in clinical trials. In this review, we describe the interaction between the PI3K/Akt/mTOR pathway and the ER cascade, its role in mediating endocrine resistance, and the clinical implications of this interaction.

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Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

Cited by 246 publications

References 26 publications

Autophagy regulation in the development and treatment of breast cancer

Autophagy regulation in the development and treatment of breast cancer

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Endocrine Resistance in Breast Cancer: Focus on the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway

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