Combination therapy with aromatase inhibitors: the next era of breast cancer treatment?

Leary, Alexandra; Dowsett, Mitch

doi:10.1038/sj.bjc.6603316

Cited by 42 publications

(29 citation statements)

References 21 publications

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“…Preclinical studies in breast cancer have suggested that rapamycin may enhance chemotherapy-induced apoptosis acting in synergisms when combined with standard agents such as paclitaxel, carboplatin, and vinorelbine [106]. The combination of temsirolimus with the aromatase inhibitor letrozole showed some biological and clinical activity in a phase II clinical trial in breast cancer; however, the phase III trial was terminated because of lack of efficacy [107]. Rapa-mycin analogs temsirolimus (CCI-779) and everolimus (RAD-001) are being used for metastatic breast cancer in combinations with drugs such as capecitabine and exemestane.…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Targeting the Phosphatidylinositol 3-Kinase Signaling Pathway in Breast Cancer

2011

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After completing this course, the reader will be able to:1. Describe how PTEN loss, PIK3CA mutations, and AKT dysregulation affect the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling network in human breast cancer.2. Review the current state of AKT and mTOR inhibitor development, and describe its potential for clinical applications.This article is available for continuing medical education credit at CME.TheOncologist.com. The Oncologist CME Program is located online at http://cme.theoncologist.com/. To take the CME activity related to this article, you must be a registered user. CME CME ABSTRACT Breast CancerThe

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Section: Mtor Inhibitorsmentioning

confidence: 99%

Targeting the Phosphatidylinositol 3-Kinase Signaling Pathway in Breast Cancer

2011

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“…Current studies on synthetic AIs generally focus on combination treatment [56][57][58], resistance mechanisms [59][60][61][62][63][64], and/or improving their safety profile by reducing side effects [55,[65][66][67].…”

Section: Aromatase Inhibition and Breast Cancermentioning

confidence: 99%

Natural Products as Aromatase Inhibitors

Balunas¹,

Su²,

Brueggemeier³

et al. 2008

ACAMC

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With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating also the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein. Keywordsaromatase inhibitors; natural products; breast cancer; botanical dietary supplements BREAST CANCERWorldwide breast cancer estimates included over one million incident cases and almost 400,000 deaths in the year 2000 [1,2]. In the United States, over 178,000 women were expected to be diagnosed with breast cancer in 2007 with over 40,000 deaths occurring from the disease [3]. In developed countries, mortality from breast cancer has recently begun to decline, primarily due to earlier detection and improved treatments [4,5]. Breast cancer is thought to be a result of inherited genetic predisposition (e.g., mutations in genes such as BRCA-1, p53, PTEN/MMAC1, and/or ATM) and/or environmental factors (e.g., radiation exposure, dietary factors, alcohol consumption, hormonal exposure) [2,6,7]. Numerous genetic mutations are necessary for breast cancer development and progression including the acquisition of the capabilities for self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis, known collectively as the "hallmarks of cancer" [8].Numerous molecular targets have been identified as playing a significant role in breast cancer development and progression. Estrogens and the estrogen receptors (ERs) are widely NIH Public Access Author ManuscriptAnticancer Agents Med Chem. Author manuscript; available in PMC 2011 April 12.Published in final edited form as:Anticancer Agents Med Chem. 2008 August ; 8(6): 646-682. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript recognized to play an important role in the development and progression of breast cancer, making estrogens and the ERs widely studied molecular targets [9][10][11][12]. Two of the endogenous estrogens found in humans include estradiol and estrone. In pre-menopausal women, estrogens are produced primarily through conversion of androgens in the ovaries while estrogen production in postmenopausal women occurs in only peripheral tissues [13,14]. Estrogens have various effects throughout the body, including positive effects on the brain, bone, heart, liver, and vagina, with negative effects such as increased risk...

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“…The results also suggest that the combination of an aromatase inhibitor and fulvestrant may be an optimal second-line therapy for patients with tumors progressing on a therapeutically effective dose of aromatase inhibitor by preventing activation of growth factor pathways (HER2 or IGF-IR) and a possible cross talk between these pathways and ER. Several clinical trials such as SOFEA, FACT, SWOG-S0226, FIRST, and D6997C00057 (36) are ongoing and will contribute further information about the benefits of combining anastrozole and fulvestrant in patients. Delay in the use of chemotherapy by a sequential use of endocrine therapies offers significant quality-of-life advantages due to good tolerability of the agents, especially in elderly patients or those with advanced disease.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports suggest that resistance to hormonal therapy may involve estrogen hypersensitivity, up-regulation of signal transduction pathways such as the ones triggered by HER family members and IGF-IR, and cross talk between signal transduction pathways and ER pathway (34)(35)(36)(37). Therefore, sensitivity to endocrine therapy may be restored by interrupting this cross-talk with an ER down-regulator such as fulvestrant (38).…”

Section: Discussionmentioning

confidence: 99%