| 1. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 2. |
- Bergkvist, Leif, et al.
(författare)
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Axillary recurrence rate after negative sentinel node biopsy in breast cancer : three-year follow-up of the Swedish Multicenter Cohort Study
- 2008
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 247:1, s. 150-156
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sentinel lymph node biopsy is an established staging method in early breast cancer. After a negative biopsy, most institutions will not perform a completion axillary dissection. The present study reports the current axillary recurrence (AR) rate, overall and disease-free survival in the Swedish Multicenter Cohort Study.Methods: From 3534 patients with primary breast cancer ≤3 cm prospectively enrolled in the Swedish multicenter cohort study, 2246 with a negative sentinel node biopsy and no further axillary surgery were selected. Follow-up consisted of annual clinical examination and mammography. Twenty-six hospitals and 131 surgeons contributed to patient accrual.Results: After a median follow-up time of 37 months (0-75), the axilla was the sole initial site of recurrence in 13 patients (13 of 2246, 0.6%). In another 7 patients, axillary relapse occurred after or concurrently with a local recurrence in the breast, and in a further 7 cases, it coincided with distant or extra-axillary lymphatic metastases. Thus, a total of 27 ARs were identified (27 of 2246, 1.2%). The overall 5-year survival was 91.6% and disease-free survival 92.1%.Conclusions: This is the first report from a national multicenter study that covers, not only highly specialized institutions but also small community hospitals with just a few procedures per year. Despite this heterogeneous background, the results lie well within the range of AR rates published internationally (0%-3.6%). The sentinel node biopsy procedure seems to be safe in a multicenter setting. Nevertheless, long-term follow-up data should be awaited before firm conclusions are drawn.
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| 3. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
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| 4. |
- Falck, Anna-Karin, et al.
(författare)
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Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods: Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results: DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63-2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions: The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.
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| 5. |
- Hietala, Maria, et al.
(författare)
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Natural remedy use in a prospective cohort of breast cancer patients in southern Sweden.
- 2011
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50, s. 134-143
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background. Complementary and alternative medicine (CAM) use is common among breast cancer patients. Several CAM therapies may have negative side effects or interact with conventional therapies. We studied biologically based CAM use with and without vitamins/minerals in relation to patient and tumor characteristics as well as treatment in an ongoing prospective cohort of 855 primary breast cancer patients. Methods. Patients from two hospitals in southern Sweden were included. Pre-operative and follow-up questionnaires containing questions on food intake, lifestyle, and concomitant medications, including natural remedies, were completed up to five years postoperatively. Clinical information was obtained from clinical records and tumor characteristics from pathology reports. Results. CAM and/or vitamins/minerals were used by 34.2% pre-operatively and by 57.9% during at least one visit. Over 100 different preparations were reported. At least eight of the commonly used preparations may interact with conventional breast cancer therapies. CAM users more often had a BMI <25 kg/m(2) (OR 1.76; 95%CI 1.33-2.33), were more often nulliparous (OR 1.59; 1.08-2.34), alcohol (OR 2.13; 1.44-3.14), antidepressants (OR 1.48; 1.02-2.15), and hormone therapy users (OR 1.57; 1.18-2.07), less often smokers (OR 0.71; 0.50-0.99), and consumed less coffee (OR 0.88; 0.82-0.95) than non CAM users. Tumor characteristics were not associated with CAM use. CAM use was more common among tamoxifen (OR 1.32; 1.00-1.75) and less common among chemotherapy (OR 0.63; 0.42-0.92) treated patients. Vitamins/minerals use was more common in aromatase inhibitor treated patients (OR 1.84; 1.33-2.53). There was no significant association between short-term disease-free survival and CAM use. Conclusion. CAM use was common and associated with certain patient characteristics. CAM use may cause clinically significant drug interactions and it is therefore of clinical interest to identify potential CAM users.
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| 6. |
- Jernström, Helena, et al.
(författare)
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CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients
- 2009
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 101:11, s. 1817-1823
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Tidskriftsartikel (refereegranskat)abstract
- CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival. Methods: A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports. Results: Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C8*4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9*3/*1*/*2/*1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11–5.79). The effect appeared to be driven by CYP2C8*3, adjusted HR 8.56 (95%CI 1.53–51.1). Conclusion: Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients.
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| 7. |
- Malmström, Per, et al.
(författare)
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Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.
- 2003
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Ingår i: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39, s. 1690-
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Tidskriftsartikel (refereegranskat)abstract
- The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.
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| 8. |
- Olsson, H, et al.
(författare)
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Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors
- 1996
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 40:2, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.
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| 9. |
- Vidarsdottir, Linda, et al.
(författare)
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PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BRAF inhibitors (BRAFi) selectively target oncogenic BRAFV600E/K and are effective in 80% of advanced cutaneous malignant melanoma cases carrying the V600 mutation. However, the development of drug resistance limits their clinical efficacy. Better characterization of the underlying molecular processes is needed to further improve treatments. We previously demonstrated that transcription of PTEN is negatively regulated by the PTEN pseudogene antisense RNA, PTENP1-AS, and here we investigated the impact of this transcript on clinical outcome and BRAFi resistance in melanoma. We observed that increased expression levels of PTENP1-AS in BRAFi resistant cells associated with enrichment of EZH2 and H3K27me3 at the PTEN promoter, consequently reducing the expression levels of PTEN. Further, we showed that targeting of the PTENP1-AS transcript sensitized resistant cells to BRAFi treatment and that high expression of PTENP1-AS in stage III melanoma correlated with poor survival. Collectively, the data presented here show that PTENP1-AS is a promising target for re-sensitizing cells to BRAFi and also a possible prognostic marker for clinical outcome in stage III melanoma.
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