| 1. |
- 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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| 2. |
- 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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