| 1. |
- Bjohle, J, et al.
(författare)
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Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 139:3, s. 751-758
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.
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| 2. |
- Dihge, Looket, et al.
(författare)
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Epidermal growth factor receptor (EGFR) and the estrogen receptor modulator amplified in breast cancer (AIB1) for predicting clinical outcome after adjuvant tamoxifen in breast cancer.
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 109:2, s. 255-262
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Tidskriftsartikel (refereegranskat)abstract
- The epidermal growth factor receptor (EGFR) and the estrogen receptor (ER) modulator Amplified In Breast cancer-1 (AIB1) have been reported to be of importance for the prognosis of breast cancer patients. We have analyzed AIB1 and EGFR by immunohistochemistry in primary breast cancers (n = 297) arranged in a tissue microarray in order to predict outcome after adjuvant endocrine therapy with tamoxifen for two years. High expression of AIB1 was associated with DNA-nondiploidy, high S-phase fraction, HER2 amplification, and short term (≤2 years) distant disease-free survival (DDFS), independent of ER status. High expression of EGFR was strongly associated to ER negativity and also correlated with progesterone receptor negativity, high S-phase fraction, and inversely correlated with nodal metastases. In univariate analysis, high EGFR was associated with shorter DDFS (hazard ratio 2.1; P = 0.017), and reached borderline significance in a multivariate analysis, adjusting for ER, menopausal and lymph node status, tumor size, and HER2 (P = 0.057). In conclusion, both AIB1 and EGFR were associated to DDFS for breast cancer patients treated with two years of adjuvant tamoxifen; AIB1 with the development of early distant recurrences, indicating association between high AIB1 and resistance to tamoxifen during treatment, and EGFR with distant recurrences up to a follow up of five years.
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| 3. |
- Ewers, Sven-Börje, et al.
(författare)
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Prognostic significance of flow cytometric DNA analysis and estrogen receptor content in breast carcinomas--a 10 year survival study
- 1992
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 24:2, s. 115-126
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Tidskriftsartikel (refereegranskat)abstract
- The prospective prognostic significance of flow cytometry derived DNA-ploidy status, the level of the S-phase fraction (SPF), estrogen receptor (ER) content, and combinations of these factors, was evaluated with respect to overall survival (OS) in a series of 516 breast cancer patients who were without signs of residual or distant disease after primary completed treatment. The median duration of survival follow-up time was ten years (range, 95-148 months) for surviving patients. Of the single factors, ER was the only significant predictor among node-negative patients; the ten-year OS rate was 71% in cases with ER-rich tumors vs. 62% for ER-poor tumors (p = 0.03). Where tumors were both non-diploid and ER-poor, the ten-year OS rate was 58%, as compared to 75% for the remaining node-negative patients (p = 0.003), who constituted a low-risk group whose survival was comparable with that in the age-matched normal population. Among patients with 1-3 positive nodes, the ten-year OS rate was 65% in patients whose tumors had an SPF < 7.3% vs. 50% if the SPF was > or = 7.3% (p = 0.01), and 58% in cases with ER-rich tumors vs. 45% where the tumors were ER-poor (p = 0.02). In a multivariate analysis, apart from age and menopausal status the combination of ploidy status and ER content was the significant (p = 0.002) predictor of OS in node-negative patients. Thus, combining ploidy and ER status, both of which are variables easily determined, enabled the selection of a subgroup of patients at high risk of relapse and reduced survival whose prognosis should be improved by effective adjuvant systemic treatment, whereas the remaining low risk N0 patients can not be expected to derive any survival benefit from adjuvant therapy since their predicted survival is already on a par with that of the general population.
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| 4. |
- Falck, Anna-Karin, et al.
(författare)
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Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years follow-up
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 140:1, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- Molecular profiles of asynchronous breast cancer metastases are of clinical relevance to individual patients treatment, whereas the role of profiles in synchronous lymph node metastases is not defined. The present study aimed to assess individual biomarkers and molecular subtypes according to the St Gallen classification in primary breast tumours, synchronous lymph node metastases and asynchronous relapses and relate the results to 10-year breast cancer mortality (BCM). Tissue microarrays were constructed from archived tissue blocks of primary tumours (N = 524), synchronous lymph node metastases (N = 147) and asynchronous relapses (N = 36). The samples were evaluated by two independent pathologists according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. The expression of biomarkers and molecular subtypes in the primary tumour was compared with that in the synchronous lymph node metastases and relapses, and related to 10-year BCM. Discordances were found between primary tumours and relapses (ER: p = 0.006, PR: p = 0.04, Ki67: p = 0.02, HER2: p = 0.02, St Gallen subtypes: p = 0.07) but not between primary tumours and metastatic lymph node. Prognostic information was gained by the molecular subtype classification in primary tumours and nodal metastases; triple negative subtype had the highest BCM compared with the luminal A subtype (primary tumours: HR 4.0; 95 % CI 2.0-8.2, p andlt; 0.001, lymph node metastases: HR 3.5; 95 % CI 1.3-9.7, p = 0.02). When a shift in subtype inherence between primary tumour and metastatic lymph node was identified, the prognosis seemed to follow the subtype of the lymph node. Molecular profiles are not stable throughout tumour progression in breast cancer. Prognostic information for individual patients appears to be available from the analysis of biomarker expression in synchronous metastatic lymph nodes. The study supports biomarker analysis also in asynchronous relapses.
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| 5. |
- Fernö, Mårten, et al.
(författare)
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Recurrence-free survival in breast cancer improved by adjuvant tamoxifen--especially for progesterone receptor positive tumors with a high proliferation
- 1995
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 36:1, s. 23-34
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Tidskriftsartikel (refereegranskat)abstract
- Although the beneficial effect on breast cancer of adjuvant tamoxifen (TAM) is well established, in the series studied by our group this effect seems to have been restricted to patients with steroid receptor (especially progesterone receptor (PgR)) positive tumors. However, as some patients with PgR-positive tumors manifested recurrence despite adjuvant TAM treatment, the question arose whether some other biological factor(s) could be used to identify these non-responding cases. The level of the S-phase fraction (SPF), as measured by flow cytometry, has been shown to be a useful prognostic marker, prognosis being better in cases where the SPF is low than in those where it is high. The aim of the present study was to relate the prognosis after adjuvant TAM to SPF among patients with PgR-positive tumors. In the PgR-positive group as a whole, the effect of TAM on prognosis was more pronounced in the high SPF group than in the low SPF group (p = 0.005) the respective decrease in 3 year recurrence rate was from 19 to 43% and from 17 to 9%. Multivariate analysis of the data for the TAM-treated group showed the level of PgR concentration (low positive vs. high positive), lymph node status, and tumor size to be independent predictive factors, but not the level of SPF (i.e. high vs. low). By contrast, among patients not treated with TAM, the SPF was a strong independent prognostic factor. To sum up, SPF was a strong independent predictor of outcome only for patients receiving no systemic adjuvant therapy, but not in patients receiving adjuvant TAM. Patients with PgR-positive and high S-phase tumors derived more benefit from TAM than patients with PgR-positive and low SPF tumors.
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| 6. |
- Fernö, Mårten, et al.
(författare)
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Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 59:1, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p = 0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p = 0.53 and p = 0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
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| 7. |
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| 8. |
- Hatschek, T, et al.
(författare)
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Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
- 2012
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Ingår i: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
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Tidskriftsartikel (refereegranskat)abstract
- Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
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| 9. |
- Jerevall, Piiha-Lotta, et al.
(författare)
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Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Institutionen för klinisk och experimentell medicin. - 0167-6806 .- 1573-7217. ; 107:2, s. 225-234
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Tidskriftsartikel (refereegranskat)abstract
- Background: The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systemically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power. Patients and methods: Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients. Results: A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR=0.39; p=0.030), or low expression of HOXB13 (RR=0.37; p=0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance. Conclusion: We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.
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| 10. |
- Jørgensen, Charlotte Levin Tykjær, et al.
(författare)
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Expression of epithelial-mesenchymal transition-related markers and phenotypes during breast cancer progression
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 181:2, s. 369-381
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The study aimed to investigate expression of epithelial-to-mesenchymal transition (EMT)-related proteins and phenotypes during breast cancer progression and to relate this to patient outcome. Methods: Protein expression patterns of E-cadherin, N-cadherin, twist, and vimentin were examined by immunohistochemistry on formalin-fixed paraffin-embedded samples from primary tumors (PTs) (n = 419), synchronous lymph node metastases (LNMs) (n = 131) and recurrences (n = 34) from patients included in an observational prospective primary breast cancer study. Markers were evaluated individually and combined as defined EMT phenotypes (epithelial, mesenchymal, partial EMT, and negative). EMT profiles were compared between matched tumor progression stages, and related to clinicopathological data and distant recurrence-free interval (DRFi). Results: N-cadherin-positivity, vimentin-positivity, mesenchymal and partial EMT phenotypes were associated with more aggressive tumor characteristics such as triple-negative subtype. Single EMT markers and phenotype discordance rates between paired tumor samples were observed in the range of 2–35%. Non-epithelial phenotypes were more frequently identified in recurrences compared to PTs, however, no skewness of expression or phenotype was detected between PTs and matched LNMs or between PTs and matched recurrences (Exact McNemar test). Interestingly, patients with a twist positive PT had shorter DRFi, compared to patients with a twist negative PT (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.2–5.1, P = 0.02). Essentially, the same effect was seen in multivariable analysis (HR 2.5, 95% CI 0.97–6.6, P = 0.06). Conclusion: The epithelial phenotype was indicated to be lost between PTs and recurrences as a reflection of tumor progression. Twist status of the PT was related to long-term prognosis warranting further investigation in larger cohorts.
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