| 1. |
- Andersson, Lisa, et al.
(author)
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The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations
- 2012
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In: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 64:3, s. 201-208
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Journal article (peer-reviewed)abstract
- Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (p(raw)=2.34x10(-5)), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p=0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations.
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| 2. |
- Ellegård, Sander, et al.
(author)
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ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2-positive metastatic breast cancer treated with trastuzumab
- 2019
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In: Oncology Letters. - Athens, Greece : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:3, s. 3371-3381
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Journal article (peer-reviewed)abstract
- Trastuzumab has markedly improved the treatment and long-term prognosis of patients with HER2-positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2-associated PI3K/Akt signalling pathway were explored. The first 46 consecutive patients treated at the Department of Oncology, Linkoping University Hospital between 2000 and 2007 with trastuzumab for HER2-positive metastatic breast cancer were retrospectively included. The gene copy number variation and protein expression of several components of the PI3K/Akt pathway were assessed in the tumour tissue and biopsy samples using droplet digital polymerase chain reaction and immunohistochemistry. Patients with tumours displaying a high-grade ERBB2 (HER2) amplification level of amp;gt;= 6 copies had a significantly improved overall survival hazard ratio [(HR)=0.4; 95%, confidence interval (CI): 0.2-0.9] and progression-free survival (HR=0.3; 95% CI: 0.1-0.7) compared with patients with tumours harbouring fewer ERBB2 copies. High-grade ERBB2 amplification was significantly associated with the development of central nervous system metastases during palliative treatment. Copy gain (amp;gt;= 3 copies) of the gene encoding the tyrosine phosphatase PTPN2 was associated with a shorter overall survival (HR=2.0; 95% CI: 1.0-4.0) and shorter progression-free survival (HR=2.1; 95% CI: 1.0-4.1). In conclusion, high ERBB2 amplification level is a potential positive prognostic factor in trastuzumab-treated HER2-positive metastatic breast cancer, whereas PTPN2 gain is a potential negative prognostic factor. Further studies are warranted on the role of PTPN2 in HER2 signalling.
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| 3. |
- Janeva, Slavica, et al.
(author)
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Clinical relevance of biomarker discordance between primary breast cancers and synchronous axillary lymph node metastases.
- 2023
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In: Clinical & experimental metastasis. - 0262-0898 .- 1573-7276. ; 40:4, s. 299-308
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Journal article (peer-reviewed)abstract
- Clinical decision-making for patients with breast cancer (BC) is still primarily based on biomarker characteristics of the primary tumor, together with the evaluation of synchronous axillary lymph node metastasis (LNM). In this study, we investigated the prevalence of discordance in the biomarkers and surrogate subtyping between the primary BC and the LNM, and whether subsequent changes would have altered clinical treatment recommendations. In this retrospective study, 94 patients treated for unifocal primary BC and synchronous LNM at Sahlgrenska UniversityHospital during 2018 were included. Estrogen (ER) and progesterone (PR) receptor, Ki67, and HER2 status were assessed in the primary tumor and LNM using immunohistochemistry. Discordances between the primary tumor and the LNM were analyzed for each individual biomarker and surrogate subtyping. The concordance between the primary tumor and the LNM for ER, PR, Ki67, and HER2 status was 98.9%, 89.4%, 72.3%, and 95.8%, respectively. Discordance in surrogate subtyping was found in 28.7% of the tumors and matched LNMs, the majority (81.5%) of which changed to a more favorable subtype in the LNM; most commonly from Luminal B to Luminal A (48.6%). No changes in surrogate subtyping were detected where ER or HER2 status changed from negativity in the BC to positivity in the LNM, thereby showing no additional value in performing immunohistochemistry on the LNM from a treatment decision-making perspective. However, large studies need to be performed that test both the primary BCs and synchronous LNMs for more accurate diagnostics.
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| 4. |
- Lööf-Johansson, Margareta, et al.
(author)
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Breastfeeding and prognostic markers in breast cancer
- 2011
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In: 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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Journal article (peer-reviewed)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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| 5. |
- Lööf-Johansson, Margareta, et al.
(author)
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Breastfeeding Associated with Reduced Mortality in Women with Breast Cancer
- 2016
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In: Breastfeeding Medicine. - : MARY ANN LIEBERT, INC. - 1556-8253 .- 1556-8342. ; 11:6, s. 321-327
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Journal article (peer-reviewed)abstract
- Objective: To study whether breastfeeding affects survival from breast cancer. Background: There are few studies on the relationship between breastfeeding, reproductive health, and breast cancer survival. This study is a follow-up of an earlier study showing no convincing associations between breastfeeding and breast cancer prognostic parameters. Methods: From a cohort of 629 women with primary breast cancer having undergone surgery between 1988 and 1992, 341 were traced and consequently studied 20 years later regarding breastfeeding and reproductive variables, as well as for prognostic parameters such as the Nottingham histological grade, tumor size, lymph node status, and vascular invasion (VI). Multivariate Cox regression analyses were used. Results: Increased breast cancer mortality was associated with the Nottingham prognostic index (hazard rate ratio (HR) 4.47; 95% confidence interval (CI) 2.04-9.79), VI (HR 3.44; CI 2.03-5.82), fewer pregnancies (three categories; amp;gt;2, 1-2, 0) (HR per category 2.04; CI 1.34-3.11), and breastfeeding amp;lt;= 6 months (HR 2.74; CI 1.41-5.35). The HRs for overall mortality were, as expected, lower for the Nottingham prognostic index (HR 1.28; CI 0.89-1.85) and VI (HR 2.09; CI 1.38-3.17), and they were slightly lower for the number of pregnancies (HR 1.61; CI 1.48-4.59), but notably similar for breastfeeding (HR 3.01; CI 1.92-4.73). Conclusion: A total breastfeeding history amp;gt;6 months and pregnancy are associated with both greater overall and breast cancer-specific survival for women diagnosed with breast cancer, having lived long enough for other causes of death to contribute substantially to mortality.
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| 6. |
- Razavi, Amir Reza, et al.
(author)
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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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In: BMC Medical Informatics and Decision Making. - : Springer Science and Business Media LLC. - 1472-6947. ; 5:29, s. 29-35
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Journal article (peer-reviewed)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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| 7. |
- Sundquist, Marie, et al.
(author)
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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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In: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 63:1, s. 11-15
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Journal article (peer-reviewed)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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| 8. |
- Sundquist, Marie, et al.
(author)
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Applying the Nottingham Prognostic Index to a Swedish breast cancer population
- 1999
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In: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 53:1, s. 1-8
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Journal article (peer-reviewed)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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| 9. |
- Sundquist, Marie, et al.
(author)
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Disease free interval and survival after dissemination of breast cancer
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Other publication (other academic/artistic)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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| 10. |
- Sundquist, Marie, et al.
(author)
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Incidence and prognosis in early onset breast cancer
- 2002
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In: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 11:1, s. 30-35
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Journal article (peer-reviewed)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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