| 1. |
- Engström, Terese, et al.
(författare)
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Hormone receptor mRNA and protein levels as predictors of premenopausal tamoxifen benefit
- 2024
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Ingår i: Acta Oncologica. - : Medical Journal Sweden AB. - 0284-186X .- 1651-226X. ; 63, s. 125-136
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen. Patients and Methods: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. Results: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36–0.79]; IHC-ER+ 0.55 [0.38–0.79]; GEX-ER+ 0.54 [0.37–0.77]; cytosol-PR+ 0.49 [0.34–0.72]; IHC-PR+ 0.58 [0.40–0.85]; GEX-PR+ 0.55 [0.38–0.80]). Results were similar for OS. Interpretation: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.
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| 2. |
- Aamand Grabau, Dorthe, et al.
(författare)
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The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:8, s. 1657-1666
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Tidskriftsartikel (refereegranskat)abstract
- Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement andgt;= 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.
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| 3. |
- Boiesen, P, et al.
(författare)
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Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group
- 2000
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 39:1, s. 41-45
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Tidskriftsartikel (refereegranskat)abstract
- Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.
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| 4. |
- Chebil, G, et al.
(författare)
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Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer - Clinical associations and reasons for discrepancies
- 2003
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:7, s. 719-725
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen ( ER) and progesterone receptor (PgR) status was analysed in paraffin-embedded breast cancer material with immunohistochemical (IHC) technique and compared with corresponding analyses in cytosols ( CYT). ER showed the same status (positive/negative) with both methods in 88% of the samples (352/ 402). The concordance was also high for PgR status (81% [321/394]). Besides values near cut-off, heterogeneity in the distribution of receptor positive and negative nuclei within a tumour sample was the main reason for discordances. Histological type, presence of sclerosis, necrosis and non-invasive cells, and technical artefacts seem to be of only limited importance for explaining discordances. All patients have been treated with adjuvant tamoxifen for two years. The two subgroups, which were ERCYT+/ ERIHC+ or ERCYT-/ERIHC+, both had a significantly better progression-free survival (PFS; median follow-up: almost 6 years) than the ERCYT -/ERIHC- group (p< 0.001 and p = 0.007, respectively). The remaining group, ERCYT+/ERIHC-, had an intermediate PFS. For PgR, the associations with PFS were weaker, with significantly better PFS than the PgR(CYT)-/PgR(IHC)- group being found only for the PgR(CYT)+/PgR(IHC) - group (p = 0.03).
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| 5. |
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| 6. |
- Ehinger, Anna, et al.
(författare)
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Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013
- 2017
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 56:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Background: The St Gallen surrogate definition of the intrinsic subtypes of breast cancer consist of five subgroups based on estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2), and Ki-67. PgR and Ki-67 are used for discriminating between the Luminal A-like and Luminal B-like (HER2-negative) subtypes. Histological grade (G) has prognostic value in breast cancer; however, its relationship to the St Gallen subtypes is not clear. Based on a previous pilot study, we hypothesized that G could be a primary discriminator for ER-positive/HER2-negative breast cancers that were G1 or G3, whereas Ki-67 and PgR could provide additional prognostic information specifically for patients with G2 tumors. To test this hypothesis, a larger patient cohort was examined. Patients and methods: Six hundred seventy-one patients (amp;gt;= 35 years of age, pT1-2, pN0-1) with ER-positive/HER2-negative breast cancer and complete data for PgR, Ki-67, G, lymph node status, tumor size, age, and distant disease-free survival (DDFS; median follow-up 9.2 years) were included. Results: Luminal A-like tumors were mostly G1 or G2 (90%) whereas Luminal B-like tumors were mostly G2 or G3 (87%) and corresponded with good and poor DDFS, respectively. In Luminal B-like tumors that were G1 (n = 23), no metastasis occurred, whereas 14 of 40 Luminal A-like tumors that were G3 metastasized. In the G2 subgroup, low PgR and high Ki-67 were associated with an increased risk of distant metastases, hazard ratio (HR) and 95% confidence interval (CI) 1.8 (0.95-3.4) and 1.5 (0.80-2.8), respectively. Conclusions: Patients with ER-positive/HER2-negative/G1 breast cancer have a good prognosis, similar to that of Luminal A-like, while those with ER-positive/HER2-negative/G3 breast cancer have a worse prognosis, similar to that of Luminal B-like, when assessed independently of PgR and Ki-67. Therapy decisions based on Ki-67 and PgR might thus be restricted to the subgroup G2.
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| 7. |
- Ekholm, Maria, et al.
(författare)
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Highly reproducible results of breast cancer biomarkers when analysed in accordance with national guidelines - a Swedish survey with central re-assessment
- 2015
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Ingår i: Acta Oncologica. - : TAYLOR and FRANCIS LTD. - 0284-186X .- 1651-226X. ; 54:7, s. 1040-1048
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Tidskriftsartikel (refereegranskat)abstract
- Background. Biomarkers are crucial for decisions regarding adjuvant therapy in primary breast cancer, and their correct assessment is therefore of the utmost importance. Aims. To investigate the concordance between Swedish pathology departments and a reference laboratory, for routine analysis of oestrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2), alone, and in combination (St Gallen subtypes). Methods. This survey included 27 of the 28 pathology laboratories in Sweden, covering 98% of cases of primary breast cancer surgery in Sweden. Paraffin-embedded tumour blocks (n = 270) were collected and sent to the central reference laboratory, together with the originally stained slides, for re-analysis. The primary evaluations were previously performed according to national Swedish guidelines, without any knowledge of the subsequent central assessment. Results. The agreement for ER, PR, and Ki67 was 99% [kappa value (kappa) = 0.95], 95% (kappa = 0.85), and 85% (kappa = 0.70), respectively. The agreement for HER2 (0/1 + vs. 2+/3+) was 85% (kappa = 0.64), but when equivocal tumours were further analysed with in situ hybridisation, only one discrepancy was observed. Discrepancies between results for ER and PR seem to be explained by analytical differences, whereas the interpretation of staining seems to be more critical for Ki67 and HER2 immunohistochemistry. The agreement between the results from the Swedish laboratories and the reference laboratory, based on the St Gallen subtypes, was 88% (kappa = 0.81). Conclusions. When applying national guidelines, highly reproducible results were obtained in routine assessment of breast cancer biomarkers, and the results of this study confirm the clinical utility of these markers for decisions regarding the treatment of primary breast cancer.
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| 8. |
- Ewers, Sven-Börje, et al.
(författare)
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Flow cytometry DNA analysis and prediction of loco-regional recurrences after mastectomy in breast cancer
- 1992
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 31:7, s. 733-740
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Tidskriftsartikel (refereegranskat)abstract
- The study concerns whether DNA flow cytometry and estrogen receptor analysis might help predict which breast cancer patients, particularly node-positive ones, were at the greatest risk of developing loco-regional recurrence (LRR). Such patients would best benefit from postoperative radiotherapy following modified radical mastectomy and axillary lymph node dissection. After this type of surgery, 506 patients were followed up for a median time of nearly 5 years. Among the 235 patients given postoperative radiotherapy, the loco-regional control rate was 100% in N0 cases (n = 93), 94% in cases with 1-3 positive nodes (n = 90), 93% in cases with 4-9 positive nodes (n = 43), and 67% in cases with 10 or more positive nodes (n = 9). Among the 271 non-irradiated patients, the corresponding figures for loco-regional control were 91% in N0 cases (n = 141), 71% in cases with 1-3 positive nodes (n = 84), 65% in cases with 4-9 positive nodes (n = 31), and 67% in cases with 10 or more positive nodes (n = 15). Ploidy status, level of S-phase fraction, estrogen receptor content, and primary tumor size did not, in the present material, yield significant additional information with regard to the risk of LRR in the different nodal subgroups, a finding confirmed in multivariate analysis where the only significant predictor of LRR was the number of positive nodes (p = 0.01). Adjuvant tamoxifen treatment could not replace postoperative radiotherapy for achieving loco-regional tumor control, the overall rate of which was 81% among patients treated with tamoxifen only (n = 117), as compared with 98% among those also treated with radiotherapy (n = 54) (p = 0.003).
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| 9. |
- Fernö, Mårten, et al.
(författare)
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Flow cytometric DNA index and S-phase fraction in breast cancer in relation to other prognostic variables and to clinical outcome
- 1992
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 31:2, s. 157-165
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Tidskriftsartikel (refereegranskat)abstract
- One frequently used classification of flow cytometric DNA ploidy status (diploid versus nondiploid) was compared with a division into seven ploidy classes based on DNA index (DI) and number of cell populations (hypodiploid, diploid, near-hyperdiploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid). The latter ploidy classification showed a better correlation with prognosis and other prognostic factors (i.e., lymph node involvement, estrogen and progesterone receptor status, and S-phase fraction). The improvement in correlation was mainly due to the identification of near-hyperdiploid cases (DI 1.00-1.14) which could be combined with the diploid cases to form a group with favourable prognosis. In contrast to cases with a small increase in DNA content (near-hyperdiploid), those with a small decrease of DNA content (hypodiploid) manifested a more aggressive disease. In multivariate analysis, S-phase fraction (SPF) was a more important prognostic factor than both the improved or the conventional ploidy classification.
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| 10. |
- Fernö, Mårten, et al.
(författare)
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Intra- and inter-laboratory reproducibility of estrogen and progesterone receptor enzyme immunoassay in breast cancer cytosol samples--a Swedish multicenter study. Swedish Society of Cancer Study Group
- 1997
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:8, s. 793-798
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen and progesterone receptor analysis results were compared within and between six laboratories in Sweden using frozen breast cancer cytosol samples, and the same technique (enzyme immunoassay, Abbott Laboratories). The concordance in receptor status (positive vs. negative) was excellent (98.4% (571/580)). The discordant results were attributable to values near cut-off (n = 4) or outliers (n = 5), the latter probably being due to analytical errors. One laboratory reported significantly higher ER concentrations than the others; thus caution should be observed when comparing absolute values from different centers. For PgR there were similar differences between the laboratories. However, the intra- and inter-laboratory differences were small compared with the overall variability in ER and PgR content between different samples in a large database. The range of the median intra-laboratory coefficient of variation was 11-23% for ER and 12-19% for PgR, indicating that there is room for improvement in the quality of assay performance.
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