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- Kimbung, Siker, et al.
(författare)
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Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:32, s. 33306-18
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Tidskriftsartikel (refereegranskat)abstract
- The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse.
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- Kovács, Anikó, 1961, et al.
(författare)
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Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes : A Long-Term Follow-Up of the SweBCG91RT Randomized Trial
- 2019
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:14, s. 1179-87
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. METHODS: In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1,178 patients with breast cancer stage I and II were randomly assigned to breast-conserving surgery plus postoperative RT or breast-conserving surgery only and followed for a median of 15.2 years. Tumor blocks were retrieved from 1,003 patients. Stromal TILs were assessed on whole-section hematoxylin-eosin-stained slides using a dichotomized cutoff of 10%. Subtypes were scored using immunohistochemistry on tissue microarray. In total, 936 patients were evaluated. RESULTS: Altogether, 670 (71%) of patients had TILs less than 10%. In a multivariable regression analysis with IBTR as dependent variable and RT, TILs, subtype, age, and grade as independent variables, RT (hazard ratio [HR], 0.42; 95% CI, 0.29 to 0.61; P < .001), high TILs (HR, 0.61; 95% CI, 0.39 to 0.96, P = .033) grade (3 v 1; HR, 2.17; 95% CI, 1.08 to 4.34; P = .029), and age (≥ 50 v < 50 years; HR, 0.55; 95% CI, 0.38 to 0.80; P = .002) were predictive of IBTR. RT was significantly beneficial in the low TILs group (HR, 0.37; 95% CI, 0.24 to 0.58; P < .001) but not in the high TILs group (HR, 0.58; 95% CI, 0.28 to 1.19; P = .138). The test for interaction between RT and TILs was not statistically significant (P = .317). CONCLUSION: This study shows that high values of TILs in the primary tumor independently seem to reduce the risk for an IBTR. Our findings further suggest that patients with breast cancer with low TILs may derive a larger benefit from RT regarding the risk of IBTR.
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- Nilsson, Jeanette, 1962, et al.
(författare)
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Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing Forkhead box F1.
- 2010
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Ingår i: Cancer research. - 1538-7445. ; 70:5, s. 2020-2029
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Tidskriftsartikel (refereegranskat)abstract
- Progression to metastasis is the proximal cause of most cancer-related mortality. Yet much remains to be understood about what determines the spread of tumor cells. This paper describes a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with opposite effects on these processes. We show that NF1-C2 is lost during mammary tumor progression and is almost invariably absent from lymph node metastases. NF1-C2 levels in primary tumors correlate with better patient survival. Manipulation of NF1-C2 levels by expression of a stabilized version or using small interfering RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth. FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal phenotype, increased invasiveness in vitro, and enhanced growth of breast carcinoma xenografts in nude mice. The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis.
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- Rydén, Lisa, et al.
(författare)
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Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer: a national survey performed at pathology departments in Sweden.
- 2009
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:6, s. 860-6
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Tidskriftsartikel (refereegranskat)abstract
- HER2 is a treatment predictive factor for the effect of trastuzumab and associated with poor prognosis in breast cancer. The analysis of HER2 must be performed with good quality, with regard to both the immunohistochemical (IHC) and in situ hybridization (ISH) analysis.A tissue microarray (TMA) including 11 breast cancer samples was sent twice (once in 2005 and again in 2006) to 24 pathology departments in Sweden. A questionnaire was also sent to the departments in 2006.With IHC, all departments reported the same results (0/1+ vs. 2+ vs. 3 + ) for three (2005) and six samples (2006). The mean kappa-value increased from 0.67 to 0.77, indicating a good reproducibility at both occasions. With fluorescence-ISH (FISH), the 11 departments using this technique reported the same results (amplified vs. normal) for nine (2005) and ten samples (2006). The mean kappa-value showed very good reproducibility both 2005 and 2006 (0.92 and 0.96, respectively). Based on the answers from the participating departments, the questionnaire revealed that 31% of primary breast cancer diagnosed in 2006 (n = 5 043) were 2 + /3+. FISH analysis of 2+ confirmed 12% of the samples to be amplified. The corresponding figure for 3 + was 90%. In total, 14.3% of the samples were HER2 positive (2+ and amplified, or 3 + ).The results obtained in this study indicate that the reproducibility for HER2 analysis is good (IHC) and very good (FISH) between the pathology departments in Sweden using TMA-based tumor samples. In 2006, 14.3% of invasive breast cancers were HER2 positive.
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| 6. |
- Sjöström, Martin, et al.
(författare)
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Response to Radiotherapy After Breast-Conserving Surgery in Different Breast Cancer Subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized Clinical Trial.
- 2017
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 35:28, s. 3222-3229
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was collected from 1,003 patients with node-negative, stage I and II breast cancer who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy trial between 1991 and 1997 to breast conservation surgery with or without RT. Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with immunohistochemistry and in situ hybridization on tissue microarrays for 958 tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) as a first event within 10 years for luminal A-like tumors (19% v 9%; P = .001), luminal B-like tumors (24% v 8%; P < .001), and triple-negative tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2-positive (luminal and nonluminal) tumors (15% v 19%; P = .6); however, evidence of an overall difference in RT effect between subtypes was weak ( P = .21). RT reduced the rate of death from breast cancer (BCD) for triple-negative tumors (hazard ratio, 0.35; P = .06), but not for other subtypes. Death from any cause was not improved by RT in any subtype. A hypothesized clinical low-risk group did not have a low risk of IBTR without RT, and RT reduced the rate of IBTR as a first event after 10 years (20% v 6%; P = .008), but had no effect on BCD or death from any cause. Conclusion Subtype was not predictive of response to RT, although, in our study, human epidermal growth factor receptor 2-positive tumors seemed to be most radioresistant, whereas triple-negative tumors had the largest effect on BCD. The effect of RT in the presumed low-risk luminal A-like tumors was excellent.
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