| 1. |
- Gentile, Massimiliano, et al.
(författare)
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Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer
- 2001
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 92:2, s. 208-213
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Tidskriftsartikel (refereegranskat)abstract
- Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes.
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| 2. |
- Sundquist, Marie, et al.
(författare)
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Incidence and prognosis in early onset breast cancer
- 2002
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Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 11:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the incidence and prognosis in early onset breast cancer. Age-adjusted incidence and death rate for the 5394 Swedish women diagnosed with breast cancer under the age of 40 between 1960 and 1996 was studied using data from the Swedish Cancer Registry and Swedish Death Cause Registry. A total of 107 consecutive young patients with invasive breast cancer undergoing surgery during 1980–1993 in the Southeast Swedish health care region were retrospectively followed up and their cancers reviewed and graded blindly. The median follow-up time was 11.2 years. The applicability of the Nottingham Prognostic Index (NPI) as a prognostic tool was investigated. Grade, age, node status, tumour size, S-phase fraction and steroid receptor content were related to survival univariately and multivariately in a Cox proportional hazard analysis.The incidence of early onset breast cancer has increased moderately and the survival rate has not improved during the last 35 years. When young women are diagnosed with breast cancer their tumours are larger, their lymph nodes more often involved, and the median grade higher than in older with 64% having grade 3 tumours. Lymph node status was the strongest sole prognostic indicator but the use of NPI gave more accurate prognostic information than node status alone.
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| 3. |
- Arlehag, L, et al.
(författare)
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ATM expression in rectal cancers with or without preoperative radiotherapy
- 2005
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 14:2, s. 313-317
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Tidskriftsartikel (refereegranskat)abstract
- Patients with ATM (Ataxia-Telangiectasia mutated) mutation show increased sensitivity to radiation and have a higher risk of developing malignancies. The present study aimed to investigate whether ATM expression was related to radiotherapy, and clinicopathological and biological variables in rectal cancers. ATM expression was immunohistochemically examined in 78 rectal cancers from patients who participated in a Swedish rectal cancer trial of preoperative radiotherapy. Of 78 patients, 44 underwent surgery alone, and 34 underwent both preoperative radiotherapy and surgery. Fifty-eight cases had normal rectal mucosa adjacent to the tumour. The results showed that, compared to normal mucosa, tumours had less nuclear (p=0.03) but more cytoplasmic expression of ATM (p=0.004). In tumours, less expression of ATM, either in the nucleus (p=0.07) or in the cytoplasm (p=0.02 for staining intensity, and p=0.07 for staining percentage), tended to be correlated with male patients. Also, ATM expression was not related to radiotherapy or other clinicopathological and biological variables (p > 0.05). In conclusion, the pattern of ATM expression was changed from normal mucosa to tumour. Less expression of ATM may be related to males.
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| 4. |
- Lundström, Claes, 1973-, et al.
(författare)
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Summary of 2nd Nordic symposium on digital pathology
- 2015
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Ingår i: Journal of Pathology Informatics. - : Medknow Publications. - 2229-5089 .- 2153-3539. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Techniques for digital pathology are envisioned to provide great benefits in clinical practice, but experiences also show that solutions must be carefully crafted. The Nordic countries are far along the path toward the use of whole-slide imaging in clinical routine. The Nordic Symposium on Digital Pathology (NDP) was created to promote knowledge exchange in this area, between stakeholders in health care, industry, and academia. This article is a summary of the NDP 2014 symposium, including conclusions from a workshop on clinical adoption of digital pathology among the 144 attendees.
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| 5. |
- Lööf-Johansson, Margareta, et al.
(författare)
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Breastfeeding and prognostic markers in breast cancer
- 2011
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Ingår i: BREAST. - : CHURCHILL LIVINGSTONE, JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND. - 0960-9776. ; 20:2, s. 170-175
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies suggest that total breastfeeding time reduces breast cancer risk. The underlying mechanisms are unclear. Whether breastfeeding also affects the prognosis is not yet investigated. A number of tumour characteristics, i.e. histological type of cancer, grade, tumour size, Nottingham prognostic index, vascular invasion and DNA-ploidy, have been demonstrated to be of prognostic value. Methods: We have searched for a possible link between these prognostic markers and breastfeeding time, age at first child and number of children. 250 women treated for breast cancer have answered a questionnaire. Results: No significant interactions were found possibly with one exception, LVI vs. age at first child. We found, significant correlations between lobular cancer, and thereby also DNA-ploidy, and age at first childbirth. Conclusions: We have found that lobular cancer (and thereby also diploid tumours) are connected, independently, to age at first childbirth and possibly also to number of children but no other correlations between reproductive data, breastfeeding included, and prognostic markers used in this study were found.
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| 6. |
- Nilsson, Cecilia, et al.
(författare)
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High proliferation is associated with inferior Outcome in male breast cancer patients
- 2013
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 26:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. Modern Pathology (2013) 26, 87-94; doi:10.1038/modpathol.2012.145; published online 24 August 2012
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| 7. |
- Nilsson, Cecilia, et al.
(författare)
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Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:1, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Background. Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters. Material and methods. In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. Results. Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size andgt;20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. Conclusion. MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.
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| 8. |
- Razavi, Amir Reza, et al.
(författare)
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Exploring cancer register data to find risk factors for recurrence of breast cancer : Application of Canonical Correlation Analysis
- 2005
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Ingår i: BMC Medical Informatics and Decision Making. - : Springer Science and Business Media LLC. - 1472-6947. ; 5:29, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Background A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time. One essential outcome after breast cancer treatment is recurrence of the disease. It is important to understand the relationship between different predictors and recurrence, including the time interval until recurrence. This study describes the application of CCA to find important predictors for two different outcomes for breast cancer patients, loco-regional recurrence and occurrence of distant metastasis and to decrease the number of variables in the sets of predictors and outcomes without decreasing the predictive strength of the model. Methods Data for 637 malignant breast cancer patients admitted in the south-east region of Sweden were analyzed. By using CCA and looking at the structure coefficients (loadings), relationships between tumor specifications and the two outcomes during different time intervals were analyzed and a correlation model was built. Results The analysis successfully detected known predictors for breast cancer recurrence during the first two years and distant metastasis 2–4 years after diagnosis. Nottingham Histologic Grading (NHG) was the most important predictor, while age of the patient at the time of diagnosis was not an important predictor. Conclusion In cancer registers with high dimensionality, CCA can be used for identifying the importance of risk factors for breast cancer recurrence. This technique can result in a model ready for further processing by data mining methods through reducing the number of variables to important ones.
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| 9. |
- Rydén, Lisa, et al.
(författare)
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Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor receptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer
- 2005
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 23:21, s. 4695-4704
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance.Patients and Methods Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors.Results VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER–positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor–positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status.Conclusion Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor–positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.
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| 10. |
- Rydén, Lisa, et al.
(författare)
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Two years of adjuvant tamoxifen in premenopausal patients with breast cancer : a randomised, controlled trial with long-term follow-up
- 2005
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 41:2, s. 256-264
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant tamoxifen treatment increases recurrence-free survival (RFS) and overall survival (OS) in early breast cancer, although in premenopausal patients the number of studies comparing tamoxifen vs no treatment are limited. We report herein the effect on RFS of adjuvant tamoxifen treatment in a multicentre trial of premenopausal patients with stage II breast cancer patients randomised between 1986 and 1991 to 2 years of tamoxifen treatment (n = 276) or no treatment (n = 288). The receptor status of the tumour was known for 541 (96%) of the patients included. Tamoxifen treatment significantly increased RFS in patients with hormone receptor-positive (oestrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)) tumours (Relative Risk (RR) 0.65; 95% Confidence Interval (CI): 0.48–0.89, P = 0.006), and the beneficial effect of tamoxifen was extended to patients with indicators of poor prognosis, such as young age and nodal-positivity. PR status was a significant predictor of response to tamoxifen in multivariate models with testing of interactions of hormone receptor status and adjuvant therapy.
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| 11. |
- Sundquist, Marie, et al.
(författare)
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A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 63:1, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
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| 12. |
- Sundquist, Marie, et al.
(författare)
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Applying the Nottingham Prognostic Index to a Swedish breast cancer population
- 1999
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 53:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.
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| 13. |
- Sundquist, Marie, et al.
(författare)
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Disease free interval and survival after dissemination of breast cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Tumour and patients characteristics were analysed and correlated to disease development in 184 women who were consecutively diagnosed with systemic breast cancer. Nottingham histologic grade (NHG) and steroid receptor content were significantly associated with disease-free interval and survival after dissemination. In the multiple regression analysis, NHG was the strongest predictor. Patients with tumours of grade 1 had median disease-free interval of 8,9 years; tumours of grade 2 4,4 years and patients with grade 3 tumours 1,8 years. Grade 2 patients had a median survival after dissemination of 2,6 years and patients with grade 3 tumours 1,2 years. Only 1 of the 12 grade 1 patients are so far diseased. 85 patients participated in a prospective trial assessing the value of serum cerbb-2 as prognostic indicator. Patients with high serum-cerbb-2 levels when distant disease was diagnosed had a more rapid disease development.Tumour grade was associated with disease-free interval and post-recurrence survival. Follow up progranunes could be differentiated according to tumour grade.
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| 14. |
- Sundquist, Marie, et al.
(författare)
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Indicators of loco-regional recurrence in breast cancer
- 2000
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 26:4, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the investigation was to contribute to the identification of patients who have increased or decreased risk of loco-regional recurrence.Methods: Six hundred and twenty-nine consecutive patients with primary breast cancer diagnosed between 1988 and 1990 were studied. Two-thirds of the patients underwent mastectomy. Radiotherapy was administered if patients were node positive or breast conserved. The Nottingham histological grading protocol was used and presence of lymphovascular invasion was assessed. Investigated parameters were: age, size, grade, steroid receptor content, surgical radicality, vascular invasion and nodal status. Statistically significant risk factors for loco-regional recurrence using univariate or Cox proportional hazard analysis were grade and lymphovascular invasion.Results: Women with grade 1-2, node-negative tumours without vascular invasion had a very low loco-regional recurrence rate - 3.1%. Seventeen percent of patients with grade 3 tumours and vessel invasion had loco-regional recurrence.Conclusions: Our findings, and those of others, indicate that the use of adjuvant radiotherapy should be influenced to a greater extent by grade and lymphovascular invasion.
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| 15. |
- Thorstenson, Andreas, et al.
(författare)
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Gender-related differences in urothelial carcinoma of the bladder : a population-based study from the Swedish National Registry of Urinary Bladder Cancer
- 2016
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Ingår i: Scandinavian journal of urology. - : Informa UK Limited. - 2168-1805 .- 2168-1813. ; 50:4, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this investigation was to describe tumour characteristics, treatments and survival in patients with urinary bladder cancer (UBC) in a national population-based cohort, with special reference to gender-related differences. Material and methods: All primary UBC patients with urothelial pathology reported to the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) from 1997 to 2011 were included in the study. Groups were compared regarding tumour, node, metastasis classification, primary treatment and survival. Results: In total, 30,310 patients (74.9% male, 25.1% female) with UBC were analysed. A larger proportion of women than men had stage T2-T4 (p<0.001), and women also had more G1 tumours (p<0.001). However, compared to women, a larger proportion of men with carcinoma in situ or T1G3 received intravesical treatment with bacillus Calmette-Guerin or intravesical chemotherapy, and a larger proportion of men with stage T2-T4 underwent radical cystectomy (38% men vs 33% women, p<0.0001). The cancer-specific survival at 5 years was 77% for men and 72% for women (p<0.001), and the relative survival at 5 years was 72% for men and 69% for women (p<0.001). Conclusions: In this population-based cohort comprising virtually all patients diagnosed with UBC in Sweden between 1997 and 2011, female gender was associated with inferior cancer-specific and relative survival. Although women had a higher rate of aggressive tumours, a smaller proportion of women than men received optimal treatment.
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| 16. |
- Thorstenson, Sten, et al.
(författare)
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Implementation of large‑scale routine diagnostics using whole slide imaging in Sweden: Digital pathology experiences 2006-2013
- 2014
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Ingår i: Journal of Pathology Informatics. - : Elsevier BV. - 2229-5089 .- 2153-3539. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- Recent technological advances have improved the whole slide imaging (WSI) scanner quality and reduced the cost of storage, thereby enabling the deployment of digital pathology for routine diagnostics. In this paper we present the experiences from two Swedish sites having deployed routine large-scale WSI for primary review. At Kalmar County Hospital, the digitization process started in 2006 to reduce the time spent at the microscope in order to improve the ergonomics. Since 2008, more than 500,000 glass slides have been scanned in the routine operations of Kalmar and the neighboring Linköping University Hospital. All glass slides are digitally scanned yet they are also physically delivered to the consulting pathologist who can choose to review the slides on screen, in the microscope, or both. The digital operations include regular remote case reporting by a few hospital pathologists, as well as around 150 cases per week where primary review is outsourced to a private clinic. To investigate how the pathologists choose to use the digital slides, a web-based questionnaire was designed and sent out to the pathologists in Kalmar and Linköping. The responses showed that almost all pathologists think that ergonomics have improved and that image quality was sufficient for most histopathologic diagnostic work. 38 ± 28% of the cases were diagnosed digitally, but the survey also revealed that the pathologists commonly switch back and forth between digital and conventional microscopy within the same case. The fact that two full-scale digital systems have been implemented and that a large portion of the primary reporting is voluntarily performed digitally shows that large-scale digitization is possible today.
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