Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline

Visvanathan, Kala; Hurley, Patricia A.; Bantug, Elissa; Brown, Powel H.; Col, Nananda F.; Cuzick, Jack; Davidson, Nancy E.; DeCensi, Andrea; Fabian, Carol J.; Ford, Leslie G.; Garber, Judy E.; Katapodi, Maria C.; Kramer, Barnett S.; Morrow, Monica; Parker, Barbara A.; Runowicz, Carolyn D.; Vogel, Victor G.; Wade, James L.; Lippman, Scott M.

doi:10.1200/jco.2013.49.3122

Cited by 279 publications

(191 citation statements)

References 60 publications

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“…13 Anti-estrogen therapies such as the selective estrogen receptor modulator (SERM) including tamoxifen or aromatase inhibitors (AI) have been shown to reduce the risk of breast cancer. 24 The effects on mammographic density between these therapies are, however, somewhat different; tamoxifen seems to reduce mammographic density, whereas AI have lesser effect. [25][26][27][28] Anti-estrogen therapies are associated with severe side-effects and decreased quality of life and the adherence of these therapeutics is very low.…”

Section: Introductionmentioning

confidence: 99%

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo

et al. 2016

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Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n D 20, or entirely fatty breasts (nondense), n D 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1b was decreased in dense breasts. No differences were found in levels of IL1b, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

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Section: Introductionmentioning

confidence: 99%

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo

et al. 2016

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“…MCF7 control cells (MCF7-CTRL) were cultured in RPMI 1640 medium supplemented with 5% FBS and 0.1% ethanol as vehicle. In order to label cells with stable isotopic amino acids, MCF7-CTRL and MCF7-TamR cells were propagated in RPMI 1640 SILAC media (Thermo Fisher Scientific, Waltham, MA) with 5% FBS supplemented with light lysine (K) and arginine (R) for light and 13 C 6 15 N 2 -K and 13 C 6 15 N 4 -R for heavy state labeling (Cambridge Isotope Laboratories, Tewksbury, MA). The labeling efficiency was confirmed by mass spectrometry analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Tamoxifen, a selective ER modulator (SERM), competes with E2 binding on ER and induces conformational changes leading to inactivation of ER (3,4). Tamoxifen has been used for the treatment and prevention of breast cancer for more than three decades (5,6). However, up to 40% of patients receiving tamoxifen adjuvant therapy develop recurrent disease within 5 years (7,8).…”

mentioning

confidence: 99%

Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer

Zahari

Renuse

et al. 2015

Molecular & Cellular Proteomics

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Tamoxifen, an estrogen receptor-␣ (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally upregulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers. Molecular & Cellular

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“…Yet clinical trials for prevention of cancer have been less successful as they require large enrolment and the studies are cost prohibitive (Steward and Brown, 2010). Despite that, many clinical trials have been completed with some success (Visvanathan et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Current paradigms of cancer chemoprevention

Mehta¹

2014

Turk J Biol

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Cancer chemoprevention has been continually evolving ever since the term was coined in the 70s. From the original approaches of identifying chemopreventive agents from the dietary constituents based on the epidemiological data to the current status of adapting them from the molecular targets, significant understanding of cancer as a disease and its possible prevention has been achieved. The identification of the chemopreventive agent from a complex mixture of natural product extracts involves numerous steps including bioassay guided fractionation; evaluation of the extracts, fractions and isolated new chemicals selectively using in vitro and in vivo experimental models; and understanding the mechanism of their action. This in turn provides identification of the molecular target for the parent drug and a basis for the synthesis of more effective, nontoxic analogs. A chemopreventive agent by definition needs to be nontoxic, since it is expected to be consumed by healthy people that may be at a higher risk of developing cancer. This makes a case for these agents to be evaluated as possible adjuvant chemotherapeutic agents. It is expected that more selective delivery methods to the target organs to eliminate toxicity and use of chemopreventive agents as adjuvant chemotherapeutic agent using personalized approaches will be the next steps for chemoprevention.

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Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline

Cited by 279 publications

References 60 publications

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo

Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer

Current paradigms of cancer chemoprevention

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