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| 2. |
- Rydén, Lisa, et al.
(författare)
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Assessment of microvessel density in core needle biopsy specimen in breast cancer
- 2004
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Ingår i: Anticancer research. - 1791-7530. ; 24:1, s. 371-375
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Estimation of microvessel density (MVD) in primary breast cancer in core needle biopsies (CNB) may predict response to systemic therapy. The aim of the present study was to explore the accuracy of assessment of MVD in CNB related to MVD in excised tumours. MATERIAL AND METHODS: MVD was estimated in core biopsies and subsequently excised tumours in 54 consecutive patients with breast cancer without pre-operative treatment. RESULTS: The correlation between MVD in CNB and excised tumours was non-significant. However, in tumours larger than 20 mm (r=0.56, p=0.005) and in lobular carcinomas (r=0.55, p=0.014) a significant correlation was observed. CONCLUSION: The overall accuracy between estimation of MVD on CNB and excised breast tumours was non-significant. The usefulness of MVD in CNB as a marker of response to systemic therapy should be further validated before it can be used in clinical practice.
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| 3. |
- Rydén, Lisa, et al.
(författare)
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Decreased angiogenic activity in breast cancer in ever-users of oral contraceptive therapy--preliminary report
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:3C, s. 2875-2878
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiogenic activity defined by microvessel density or measurement of vascular endothelial growth factor is a key process under physiological and malignant conditions in steroid hormone responding organs. The aim of this study was to relate microvessel density (MVD) in primary breast cancer to reproductive data and use of exogenous hormones. MATERIAL AND METHODS: MVD was calculated retrospectively in forty-two consecutive tumours and related to clinical, histopathological and gynecological data. RESULTS: Tumours in ever-users of oral contraceptive therapy (OC) had lower MVD (p = 0.002), a finding not explained by smaller tumour size or lower histological grade. There was no influence on MVD by other reproductive data. CONCLUSION: These preliminary data on a supposed interaction between the use of OC and angiogenesis in breast cancer indicate that biological properties in breast tumours may be altered by ever-use of OC, but have to be further explored in an extended number of patients.
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| 4. |
- Rydén, Lisa
(författare)
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Tamoxifen response in primary breast cancer with special reference to tumour-specific VEGF-A and VEGFR2
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Treatment of primary breast cancer is individualised and adjuvant systemic treatment is delivered to most patients after surgery. Oestrogen receptor (ER) status and progesterone receptor status (PR) can define patients who would benefit from adjuvant endocrine therapy with tamoxifen (TAM) alone or as chemo-endocrine therapy. In spite of adjuvant treatment with TAM, some patients with hormone-responsive tumours relapse and eventually die from recurrent disease and new predictive markers are therefore continously being assessed . Purpose: To relate response to adjuvant TAM to established predictive markers (hormone receptor status) and investigational predictive markers such as HER2 status, HER2 gene amplification, vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2). Furthermore, microvessel density (MVD) and VEGF-A in core biopsy specimens were assessed. Patients: Two randomised trials of two years of adjuvant TAM versus no adjuvant treatments containing postmenopausal patients (n=251) and premenopausal patients (n=564) with long-term follow-up were included. Additionally, 102 non-randomised patients were included in a feasibility study of the investigational markersand 54 consecutive patients were analysed, assessing the accuracy in core biopsy specimens. Methods: In the premenopausal trial, hormone receptor status was determined prospectively by cytosol-based methods and retrospectively by immunohistochemistry (IHC)in a tissue microarray (TMA). In the postmenopausal trial, hormone receptor status was determined by IHC in TMA. Investigational predictive markers were evaluated in TMA by IHC including HER2 status, VEGF-A and VEGFR2 and by FISH for HER2 gene amplification.HER2 status and HER2 amplification were restricted to premenopausal patients. Microvessel density and VEGF-A by IHC were evaluated in pairs of whole tumour sections and core biopsy specimens. Results: Two years of adjuvant TAM significantly increased reccurence-free survival (RFS) in all subgroups of premenopausal patients with hormone receptor positive tumours (Paper II). Progesterone receptor status was superior to ER as a predictive marker in this group of patients. The beneficial effect of two years of adjuvant TAM was extended to patients at high risk of recurrence (Paper II). Expression of VEGF-A and HER2 status in tumour cells and HER2 amplification were not significant predictors of response to adjuvant TAM in premenopausal patients with hormone receptor positive tumours, whereas tumour-cell specific expression of VEGFR2 was a significant predictor of response (Paper IV). In postmenopausal node-positive patients with ER positive disease adjuvant TAM increased both disease-free (DFS) and overall survival (OS) (Paper III). Tumour-cell specific expression of VEGF-A and VEGFR2 were predictors of response to adjuvant TAM in ER positive disease (Paper III). Angiogenic markers assessed in core biopsy specimens had in general low accuracy (Paper V). Conclusion: Two years of adjuvant TAM increases RFS in premenopausal patients with hormone-responsive tumours and the beneficial effect is extended to patients at high risk of recurrence. Progesterone receptor is a strong predictive marker for response to adjuvant TAM in premenopausal patients and tumour-cell specific VEGFR2 is a predicitve marker in addition to hormone receptor status. For postmenopausal patients tumour-cell specific VEGF-A and VEGFR2 were predictors of response to adjuvant TAM in ER positive disease.
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| 5. |
- Stendahl, Maria, et al.
(författare)
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Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients
- 2004
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 90:10, s. 1942-1948
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Tidskriftsartikel (refereegranskat)abstract
- Antioestrogen treatment by tamoxifen is a well-established adjuvant therapy for oestrogen receptor-alpha (ER) positive breast cancer. Despite ER expression some tumours do not respond to tamoxifen and we therefore delineated the potential link between the cell cycle regulator and ERco-factor, cyclin D1, and tamoxifen response in a material of 167 postmenopausal breast cancers arranged in a tissue array. The patients had been randomised to 2 years of tamoxifen treatment or no treatment and the median follow-up time was 18 years. Interestingly in the 55 strongly ERpositive samples with moderate or low cyclin D1 levels, patients responded to tamoxifen treatment whereas the 46 patients with highly ER positive and cyclin D1 overexpressing tumours did not show any difference in survival between tamoxifen and no treatment. Survival in untreated patients with cyclin D1 high tumours was slightly better than for patients with cyclin D1 low/moderate tumours. However, there was a clearly increased risk of death in the cyclin D1 high group compared to an age-matched control population. Our results suggest that cyclin D1 overexpression predicts for tamoxifen treatment resistance in breast cancer, which is line with recent experimental data using breast cancer cell lines and overexpression systems.
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