Expression of estrogen receptors-α and -β in primary breast neoplasms and tumors exposed to neoadjuvant hormonal therapy

Bershtein, L. M.; Порошина, Т. Е.; Zimarina, T. S.; Цырлина, Е. В.; Жильцова, Е. К.; Kovalevskii, A. Yu.; Семиглазов, Владимир

doi:10.1007/s10517-005-0079-7

Cited by 4 publications

(2 citation statements)

References 8 publications

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“…Interestingly, IR expression significantly decreased upon metformin treatment, possibly in relation to the decrease in circulating insulin induced by this drug. Previously, a reduction in tumor ER expression was reported in patients with breast cancer treated with the aromatase inhibitor exemestane [ 32 ], indicative of a relationship between ligand and receptor levels.…”

Section: Discussionmentioning

confidence: 99%

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study

et al. 2015

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IntroductionThe antidiabetic drug metformin exhibits potential anticancer properties that are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin mTOR signaling, and indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling and the factors governing sensitivity in patients remain unknown.MethodsWe conducted a neoadjuvant, single-arm, “window of opportunity” trial to examine the clinical and biological effects of metformin on patients with breast cancer. Women with untreated breast cancer who did not have diabetes were given 500 mg of metformin three times daily for ≥2 weeks after diagnostic biopsy until surgery. Fasting blood and tumor samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, and immunohistochemical analysis of tumors was used to characterize cellular markers before and after treatment.ResultsLevels of IR expression decreased significantly in tumors (P = 0.04), as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2, T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P < 0.0001, P < 0.005 and P = 0.02, respectively). All tumors expressed organic cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or higher.ConclusionsReduced PKB/Akt and ERK1/2 phosphorylation, coupled with decreased insulin and IR levels, suggest insulin-dependent effects are important in the clinical setting. These results are consistent with beneficial anticancer effects of metformin and highlight key factors involved in sensitivity, which could be used to identify patients with breast cancer who may be responsive to metformin-based therapies.Trial registrationClinicalTrials.gov identifier: NCT00897884. Registered 8 May 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0540-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study

et al. 2015

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“…Despite the lack of independent effects of AI and FS on ERβ, each has been reported to affect expression of this receptor. Flaxseed lignans have been shown to down-regulate ERβ expression in estrogen-dependent MCF7 breast cancer cells (42), but conflicting effects have been reported for anastrozole (43, 44) Given the small sample size, the combination of AI and FS may have been necessary to produce the observed decreased ERβ expression.…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

McCann

Edge

Hicks

et al. 2014

Nutrition and Cancer

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Use of complementary approaches is common among breast cancer survivors. Potential interactions between aromatase inhibitors (AI) and high phytoestrogen foods, such as flaxseed (FS) are not often described. We conducted a pilot 2×2 factorial, randomized intervention study between tumor biopsy and resection, in 24 postmenopausal women with estrogen receptor positive (ER+) breast cancer, to assess the effects of flaxseed and anastrozole, and possible interactions between them, on serum steroid hormone and tumor-related characteristics associated with long-term survival (Roswell Park Cancer Institute, 2007–2010). The effect of each treatment vs placebo on outcomes was determined by linear regression adjusting for pre-treatment measure, stage, and grade. Although not statistically significant, mean ERβ expression was approximately 40% lower from pre- to post-intervention in the FS+AI group only. We observed a statistically significant negative association (β±SE −0.3±0.1; p=0.03) for androstenedione in the FS+AI group vs placebo and for DHEA with AI treatment (β±SE −1.6±0.6; p=0.009). Enterolactone excretion was much lower in the FS+AI group compared to the FS group. Our results do not support strong effects of flaxseed on AI activity for selected breast tumor characteristics or serum steroid hormone levels, but suggest AI therapy might reduce the production of circulating mammalian lignans from flaxseed.

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Phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy: A comparison with baseline rates of change

Hariri

Roma

Hasteh

et al. 2017

Annals of Diagnostic Pathology

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Expression of estrogen receptors-α and -β in primary breast neoplasms and tumors exposed to neoadjuvant hormonal therapy

Cited by 4 publications

References 8 publications

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

Phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy: A comparison with baseline rates of change

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