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| 2. |
- Barnes, N. L. P., et al.
(författare)
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Cyclooxygenase-2 inhibition : effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer
- 2007
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:4, s. 575-582
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Tidskriftsartikel (refereegranskat)abstract
- Cyclooxygenase-2 (COX-2) is associated with poor-prognosis breast cancer. We used a nude mouse xenograft model to determine the effects of COX-2 inhibition in breast cancer. Oestrogen receptor (ER)-positive MCF7/HER2-18 and ER-negative MDAMB231 breast cancer cell lines were injected into nude mice and allowed to form tumours. Mice then received either chow containing Celecoxib (a COX-2 inhibitor) or control and tumour growth measured. Tumour proliferation, apoptosis, COX-2, lymphangiogenesis and angiogenesis were assessed by immunohistochemistry (IHC), Western blotting or Q-PCR. Celecoxib inhibited median tumour growth in MCF7/HER2-18 (58.7%, P=0.029) and MDAMB231 (46.3%, P=0.0002) cell lines compared to control. Cyclooxygenase-2 expression decreased following Celecoxib treatment (MCF7/HER2-18 median control 65.3% vs treated 22.5%, P=0.0001). Celecoxib increased apoptosis in MCF7/HER2-18 tumours (TUNEL 0.52% control vs 0.73% treated, P=0.0004) via inactivation of AKT (median pAKT(ser473) 57.3% control vs 35.5% treated, P=0.0001--confirmed at Western blotting). Q-PCR demonstrated decreased podoplanin RNA (lymphangiogenesis marker) in the MCF7/HER2-18 - median 2.9 copies treated vs 66.6 control (P=0.05) and MDAMB231-treated groups--median 160.7 copies vs 0.05 control copies (P=0.015), confirmed at IHC. Cyclooxygenase-2 is associated with high levels of activated AKT(ser473) and lymphangiogenesis in breast cancer. Cyclooxygenase-2 inhibition decreases tumour growth, and may potentially decrease recurrence, by inactivating AKT and decreasing lymphangiogenesis.
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| 3. |
- Bindra, Amarinder, et al.
(författare)
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Search for DNA of exogenous mouse mammary tumor virus-related virus in human breast cancer samples
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88, s. 1806-1809
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Tidskriftsartikel (refereegranskat)abstract
- Earlier reports of a human exogenous retrovirus (HMTV) related closely to mouse mammary tumor virus (MMTV) led us to search for these viral sequences in breast cancer tissues and normal tissues. A real-time PCR was developed based on MMTV and published HMTV envelope sequences. The real-time PCR method can detect one to ten copies of MMTV target DNA. Tissue samples were collected prospectively from 18 breast cancer patients and 11 non-malignant control cases, as well as peripheral blood leukocytes from the same women. Despite the high sensitivity of the real-time PCR method used, none of the samples were positive for HMTV DNA or RNA. The absence of HMTV DNA in both breast cancer samples and controls indicates either that the concentration of putative HMTV DNA in the breast cancers was too low for detection or that it did not exist there.
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- Dalberg, Kristina, et al.
(författare)
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Paget's disease of the nipple in a population based cohort
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 111:2, s. 313-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Paget's disease of the nipple is a rare form of breast cancer characterised by the presence of intraepidermal tumour cells. It is often associated with ductal carcinoma in situ (DCIS) and/or invasive cancer in the breast parenchyma. We have studied the presentation and symptoms of Paget's disease, local control and breast cancer corrected survival following breast conserving surgery or mastectomy. PATIENTS AND METHODS: The study is based on 223 women with histological verified Paget's disease of the nipple diagnosed between 1976 and 2001 at 13 Swedish hospitals. All women s charts were reviewed. All recurrences and deaths were registered. A comparison was made for differences in breast cancer-corrected survival (BCS) and disease-free survival (DFS) in univariate analyses. RESULTS: The median follow-up was 12 (4-28) years. In a vast majority (98%), the main presenting symptom was eczema or ulceration of the nipple. The diagnosis of an underlying breast malignancy was established in 79% of the women before surgery. A cone excision of the nipple-areola complex was performed in 43 women and 169 women had a mastectomy. Eleven elderly women were not operated. One hundred and seventeen women had a non-invasive Paget of which 40 had an underlying DCIS. Invasive cancer was seen in 68 women. In 38 cases the histopathological report did not state if the tumour was invasive or not. Thirty-three women died from breast cancer. In operated women BCS and DFS at 10 years were 87% and 82%, respectively. The 10-year BCS for non-operated patients (n = 11) was 34%. At 10 years, the cumulative local recurrence rate was 9%, 8% among women undergoing mastectomy and 16% among those treated with breast conserving surgery. In univariate analysis the type of surgery, cone excision or mastectomy, had no statistically significant impact on BCS or DFS. Risk factors for breast cancer death and recurrence were having an underlying invasive cancer compared with an in situ carcinoma and having a palpable tumour in the breast. CONCLUSION: The main presenting symptoms were eczema or ulceration of the nipple. Patients with non invasive Pagets disease of the nipple had an excellent cancer outcome. Selected patients with Paget's disease of the nipple were treated with breast conserving surgery with survival rates similar to those achieved with mastectomy.
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| 5. |
- Månsson, Emeli, et al.
(författare)
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Mammographic casting-type calcifications is not a prognostic factor in unifocal small invasive breast cancer : a population-based retrospective cohort study
- 2009
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Ingår i: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 100:8, s. 670-674
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: The role of mammographic casting-type microcalcifications as a prognostic factor in breast cancer has been debated. We studied the relation between mammographic features and prognosis in a population-based cohort. METHODS: In 515 women with 1-15 mm invasive breast cancer mammograms were re-classified according to Tabar et al. The relation to breast cancer death was studied. RESULTS: During the follow-up (median 155 months) 44 of 515 women died from breast cancer. Twenty-nine of 515 presented with casting-type calcifications and three of these died from breast cancer. The adjusted odds ratio for breast cancer death was 1.6 (0.5-5.8) for patients presenting with casting-type calcifications and 4.8 (1.8-12.7) for crushed stone-like (pleomorphic) calcifications using stellate tumors as a reference group. CONCLUSIONS: Except for patients with crushed stone-like microcalcifications breast cancer survival was excellent, 87-95% after 15 years. Casting-type calcifications were not a statistically significant prognostic factor. Tumors with casting-type calcifications were more often of high grade, hormone receptor negative, and HER2 positive but this was not statistically significant either. However, microcalcifications may be more prevalent in tumors with extensive ductal cancer in situ (DCIS) containing multiple foci of invasive cancer and in this study we only included unifocal cancer.
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| 6. |
- Smeds, Johanna, et al.
(författare)
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Ductal carcinoma in situ of the breast with different histopathological grades and corresponding new breast tumour events : analysis of loss of heterozygosity
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:1, s. 41-9
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Tidskriftsartikel (refereegranskat)abstract
- To compare chromosomal alterations in ductal carcinoma in situ (DCIS) of different histopathological grades and to study aberrations between primary DCIS and corresponding ipsi- or contralateral new in situ or invasive tumours, a study was undertaken of the pattern of loss of heterozygosity (LOH) at chromosomal regions in which LOH has previously been described in invasive breast cancer. LOH was analysed using 19 microsatellite markers located on chromosomes 3p, 6q, 8p, 8q, 9p, 11p, 11q, 16q, 17p, and 17q in 30 women with a primary DCIS. Eleven women with DCIS of grade 1 and 19 with grade 3 according to the EORTC classification system were included. In six patients LOH was also analysed in a subsequent new breast cancer. Fractional allelic loss (FAL, the ratio of chromosomal arms where allelic loss was detected divided by the total number of chromosomal arms with informative markers) was statistically significantly higher in grade 1 DCIS compared with grade 3 (p=0.02) for the 19 loci, indicating that the amount of allelic loss does not correlate with increasing aggressiveness of the studied tumours. Also observed was a complete heterogeneity of LOH in the primary DCIS and their corresponding new events, suggesting that these events probably developed from genetically divergent clones.
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| 7. |
- Wärnberg, Fredrik, et al.
(författare)
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Quality aspects of the tissue microarray technique in a population-based cohort with ductal carcinoma in situ of the breast
- 2008
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 53:6, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Tissue microarray (TMA) is an efficient technique for analysis of molecular markers. Prospectively collected samples have been reported to give excellent concordance between TMA data and corresponding whole-sections. The aim was to evaluate the usefulness of TMA in a population-based cohort of 213 women with ductal carcinoma in situ of the breast (DCIS). METHODS AND RESULTS: We studied immunohistochemical HER2, oestrogen (ER) and progesterone (PR) receptor status. The prognostic impact was similar for all markers comparing whole sections and TMAs. The proportion of positive tumours was similar regarding HER2 and ER, whereas PR tumours were more frequently positive in the TMAs (P = 0.007). The concordance was 80% (kappa value 0.63) between original sections and TMAs. The proportion of successfully analysed tumours was 70%. Smaller tumours had a lower ratio (P < 0.0001) and a larger proportion of mismatched results (P = 0.05). CONCLUSIONS: Retrospective analyses of tumours from cohorts with long-term follow-up are indispensable. We have shown that the TMA technique is a useful tool for high-throughput analysis of DCIS. However, our study has pinpointed some technical hazards within a population-based cohort, including many small lesions and the poor condition of some donor blocks. Mismatched results may be due to tumour heterogeneity.
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| 8. |
- Zhou, Wenjing, et al.
(författare)
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Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution
- 2009
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 3:3, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- In breast cancer, previous studies have suggested that somatic TP53 mutations are likely to be an early event. However, there are controversies regarding the cellular origin and linear course of breast cancer. The purpose of this study was to investigate tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. The entire coding sequence of TP53 was sequenced in a cohort of pure ductal carcinoma in situ (DCIS), pure invasive cancer (
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