In situ levels of oestrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients

Licznerska, Barbara; Wegman, Pia; Nordenskjöld, Bo; Wingren, Sten

doi:10.1007/s10549-007-9819-x

Cited by 12 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to evaluate whether there was a relationship between nuclear and cytoplasmic FOXL2 expression, we performed a correlation test, and the results demonstrated no significant correlation (RR=1.07, 95% CI=0.94-1.22, P=0.31). In addition, the present patient cohort was previously immunohistochemically stained for aromatase (3) and cases with a tumour expressing nuclear FOXL2 were more likely to have a concomitant expression of aromatase in the stroma and/or in the cytoplasm of cancer epithelial cells (Or=2.54, 95% CI=1.06-6.09, P=0.034; Or=3.03, 95% CI=1.31-7.02, P=0.008, respectively) ( Table I). Using mCF7 cells, we performed Western blot analysis in order to examine the specificity of the antibody as well as the basal level of FOXL2.…”

Section: Resultsmentioning

confidence: 95%

See 1 more Smart Citation

Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen

Wegman

Eremo²,

Lindlöf³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract.Aromatase is an important enzyme in the local synthesis of oestrogens and its expression has been shown to be increased in breast cancer through the activation of multiple promoters. However, the mechanisms behind this are not yet fully understood. A novel candidate in this context is the transcription factor forkhead box L2 (FOXL2), which has been recognised to be co-expressed with aromatase and transcriptionally active promoter II in developing goat and chicken ovaries. We propose that FOXL2 could be involved in the increased expression of aromatase in breast cancer. We examined FOXL2 and its relation to aromatase in 132 postmenopausal breast cancer patients by immunohistochemistry. Using in silico analysis, we further searched for FOXL2 binding-elements in the aromatase gene promoters. The results demonstrate that FOXL2 is expressed in breast cancer and influences clinical outcome with improved recurrence-free survival in cases with nuclear expression. In a multivariate Cox model, nuclear FOXL2 was a significant prognostic factor in ER-positive patients treated with tamoxifen (HR=0.18, 95% confidence interval (CI)=0.04-0.81, P=0.03). Tumours expressing nuclear FOXL2 were also more likely positive for stromal and/or cytoplasmic aromatase (P=0.03 and P=0.008, respectively). In silico analyses revealed binding elements of FOXL2 in promoters I.3, II and I.7 of the aromatase gene of which promoter I.7 was most significant. In conclusion, this is the first study to report that FOXL2 is expressed in breast cancer and correlates with aromatase as well as with clinical outcome. The results further strengthen a possible binding of FOXL2 to aromatase promoter I.7. Nevertheless, whether FOXL2 is a direct activator of aromatase requires further investigation.

show abstract

Section: Resultsmentioning

confidence: 95%

“…There have been many studies on the prognostic significance of aromatase in breast cancer, although no conclusive results have been reached (1,2). We have previously found that aromatase is a significant prognostic factor in post-menopausal breast cancer patients, with an improved relapse-free survival in cases with stromal expression (3).…”

Section: Introductionmentioning

confidence: 96%

Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen

Wegman

Eremo²,

Lindlöf³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…The increase in breast fat is also likely to have an adverse impact on the breast cancer pathogenesis. It has been known for at least two decades that breast stroma, in particular, breast fat, actively produces estrogens [4][5][6][7][19][20][21][22][23][24][25]. The following is an overview of some of these studies and reviews.…”

Section: The Impact Of Menopause and Hrt On Breast Cancer Riskmentioning

confidence: 99%

Menopausal status, adipose tissue, and breast cancer risk: impact of estrogen replacement therapy

Eden¹

2013

Hormone Molecular Biology and Clinical Investigation

View full text Add to dashboard Cite

The seeds of breast cancer are likely sown in the first two or three decades of life. Rapid weight gain and height in infancy predict breast cancer risk in later life. The age at first pregnancy is also a strong predictor for breast cancer; the earlier the first full-term pregnancy, then the lower the risk of breast cancer in later life. It has been postulated that the breast stem cell number may be the factor linking these observations together. Menopause, per se, is associated with an increase in central adiposity, which is reversed by hormone replacement usage. Breast and nonbreast fat both produce estrogens and cytokines that may promote the growth of small breast cancers making them appear earlier. Obesity also is associated with metabolic syndrome, which is a risk factor for breast cancer. The breast cancer stem cells make up only around 1%-2% of the tumor mass and, yet, are the likely driver for much of a breast cancer's behavior. Future research into breast cancer biology, especially into the cancer stem cells is likely to translate into novel methods of treatment and prevention of this common cancer.

show abstract

“…Over the last 2 decades, it has become abundantly clear that the normal and malignant breast has all the enzymes necessary to produce oestrogens locally, within the breast itself. This intracrine and paracrine process has been recently reviewed by several authors [36][37][38][39][40][41]. Breast tissue levels of oestrogens are much higher than serum, both before and after menopause [36][37][38][39][40][41].…”

Section: Local Breast Production Of Oestrogen Is Far More Important Tmentioning

confidence: 99%

“…Most breast malignancies are surrounded by tissues (fat, stroma and sometimes malignant epithelial cells) with enhanced aromatase activity -even compared with aromatase activity within other areas of the same breast [36,37,40]. Professor Pasqualini's group have shown that the sulphatase enzyme pathway which converts oestrone sulphate (the most abundant oestrogen in serum) into oestrone, is 100-500 times more active in human breast cancer tissue than aromatase [37].…”

Section: Local Breast Production Of Oestrogen Is Far More Important Tmentioning

confidence: 99%

Why does oestrogen-only hormone therapy have such a small impact on breast cancer risk? A hypothesis

Eden

2010

Gynecological Endocrinology

View full text Add to dashboard Cite

There seems to be irrefutable evidence that oestrogen is involved in the pathogenesis of breast cancer. The disease mostly affects women and the epidemiology of breast cancer relates to reproductive markers such as pregnancy, age at menarche and age of menopause. Most breast cancers elaborate oestrogen receptors (ER) and in such cases endocrine therapies such as tamoxifen and aromatase-inhibitors (AIs) are effective adjuvant treatments. However, high-quality randomised controlled trials (RCTs) (such as the WHI study) have shown that oestrogen-only hormone therapy (ET) does not increase breast cancer risk at all. This would seem to be a remarkable paradox. There appears to be at least two reasons for this apparent contradiction. First, it has been known for two decades that the breast itself produces oestrogens locally and the microenvironment around a breast cancer is more important that the impact of systemic-oestrogens. Second, breast cancer stem cells (breast CSC) have been identified and it seems likely that these long-lived, multipotential cells are responsible for the genesis of many breast cancers, as well as their malignant behaviour. Breast CSC usually do not contain sex-hormone receptors, but their offspring often elaborate ER and progesterone receptor (PR). Thus, it appears unlikely that oestrogen per se initiates breast cancer, but rather might stimulate an existing tumour.

show abstract

In situ levels of oestrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients

Abstract: Protein expression of stromal aromatase may serve as a significant prognostic marker in ER-positive patients.

Cited by 12 publications

References 45 publications

Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen

Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen

Menopausal status, adipose tissue, and breast cancer risk: impact of estrogen replacement therapy

Why does oestrogen-only hormone therapy have such a small impact on breast cancer risk? A hypothesis

Contact Info

Product

Resources

About