| 1. |
- Look, M, et al.
(författare)
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Pooled analysis of prognostic impact of uPA and PAI-I in breast cancer patients
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 90:3, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-I for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-I survival analyses, reflecting the interaction between nodal status and uPA/PAI-I. The estimates for uPA and PAI-I were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-I were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-I are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.
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| 2. |
- 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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| 3. |
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| 4. |
- 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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| 5. |
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| 6. |
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| 7. |
- Alkner, S., et al.
(författare)
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Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer : the Danish cohort of BIG 1-98
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 166, s. 481-490
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. Method: AIB1 was analyzed with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group’s trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). Results: Forty-six percent of the tumors had a high AIB1 expression. In line with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1 also correlated to higher estrogen receptor expression (80–100 vs. 1–79%), and ductal histological type. High AIB1 expression was associated with a poor disease-free survival (univariable: hazard ratio 1.35, 95% confidence interval 1.12–1.63. Multivariable: hazard ratio 1.29, 95% confidence interval 1.06–1.58) and overall survival (univariable: hazard ratio 1.34, 95% confidence interval 1.07–1.68. Multivariable: hazard ratio 1.25, 95% confidence interval 0.99–1.60). HER2 did not seem to modify the prognostic effect of AIB1. No difference in treatment effect between tamoxifen and letrozole in relation to AIB1 was found. Conclusions: In a subset of the large international randomized trial BIG 1-98, we confirm AIB1 to be a strong prognostic factor in early breast cancer. Hence, although tumor AIB1 expression does not seem to be useful for the choice of tamoxifen versus an aromatase inhibitor in postmenopausal endocrine-responsive breast cancer, AIB1 is an interesting target for new anti-cancer therapies and further investigations of this biomarker is warranted.
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| 8. |
- Andersson, C., et al.
(författare)
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Immunocytochemical demonstration of oestrogen receptor beta in blood vessels of the female rat
- 2001
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 169:2, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- The role of oestrogen receptor (ER) beta in vascular function remains unclear. With the use of a specific ERbeta antibody we have now, using immunocytochemistry, visualized ERbeta in different parts of the vascular tree. In about 70% of medial smooth muscle cells of female rat aorta, tail artery and uterine artery, nuclear immunoreactivity to ERbeta was observed. In these vessels endothelial cells also expressed ERbeta. Vascular expression of the ERalpha subtype was lower than that of ERbeta. In aorta and tail artery, no immunoreactivity towards ERalpha was observed, while in uterine vessels occasional medial smooth muscle and endothelial cells expressed this ER subtype. ERbeta and alpha expression in uterine vessels was independent of the stage of the oestrous cycle, suggesting that variations in uterine blood flow occurring during the cycle are independent of ER density. The regional distribution of ERalpha, as determined by immunocytochemistry, was supported by measurements of ERalpha levels by enzyme immunoassay. In the uterine artery, the level of ERalpha was several times higher (P<0.001) than that of aorta and tail artery (10.1+/-1.7 fmol/mg protein in the uterine artery vs 3.3+/-1.0 and 0.5+/-0.5 fmol/mg protein in aorta and tail artery respectively). Thus, a prominent nuclear expression of ERbeta was observed in the vascular wall of several parts of the vascular tree, while ERalpha predominantly was expressed in uterine vessels, suggesting that ERbeta and alpha may have different roles in vascular function.
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| 9. |
- Borg, A, et al.
(författare)
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HER-2/neu amplification predicts poor survival in node-positive breast cancer
- 1990
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Ingår i: Cancer Research. - 0008-5472. ; 50:14, s. 7-4332
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Tidskriftsartikel (refereegranskat)abstract
- HER-2/neu protooncogene amplification and protein expression were analyzed with slot blot and Western blot techniques, respectively, in more than 300 invasive primary breast tumors of all stages. Amplification (2- greater than 30 copies) was found in 17% of these tumors and high expression was seen in 19%. There was a striking coincidence between gene amplification and high expression. Tumors associated with many involved axillary lymph nodes or with Stage IV disease were more often HER-2/neu amplified or overexpressed. Furthermore, gene alteration was strongly correlated with the absence of steroid receptors and with larger tumor size. High expression without gene amplification was seen in a minor subset of tumors of less aggressive character. Neither amplification nor overexpression was correlated with disease outcome for patients with negative axillary lymph nodes. For node-positive patients, however, HER-2/neu amplification was a significant predictor of early relapse and death (median follow-up = 45 months), and a similar trend, although not significant, existed for high gene expression. Multivariate analyses indicated that HER-2/neu alterations were not independent predictors of patient outcome.
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| 10. |
- Borg, A, et al.
(författare)
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Prognostic significance of p53 overexpression in primary breast cancer : a novel luminometric immunoassay applicable on steroid receptor cytosols.
- 1995
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 71:5, s. 1013-1017
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Tidskriftsartikel (refereegranskat)abstract
- A novel quantitative luminometric immunoassay (LIA) has been developed for the measurement of wild-type and mutant p53 protein in extracts from breast tumour tissue. The LIA was found to yield reliable estimates of p53 expression in cytosol samples routinely prepared for steroid receptor analysis as compared with results obtained with immunohistochemical analysis. The LIA was evaluated on 205 primary breast tumour cytosols prepared for steroid receptor analysis and stored frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the samples (range 0.01-23 ng mg-1 protein). Using an arbitrary cut-off value of 0.15 ng mg-1 protein, 30% of the tumours were classified as manifesting p53 overexpression. Significant and independent correlations were found to exist between p53 overexpression and shorter disease-free (P < 0.001) and overall survival (P = 0.039) at a median duration of follow-up of 50 months. p53 overexpression was related to low oestrogen receptor content and high proliferation rate (S-phase fraction). No relationship was found to tumour size or the presence of lymph node metastasis. Three tumours possessed an extremely high p53 content (> 10 ng mg-1 protein), all of which were of medullary or high-grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid, had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.
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| 11. |
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| 12. |
- Ekholm, M., et al.
(författare)
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Effects of adjuvant tamoxifen over three decades on breast cancer–free and distant recurrence–free interval among premenopausal women with oestrogen receptor–positive breast cancer randomised in the Swedish SBII:2pre trial
- 2019
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 110, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The primary aim was to compare 2 years of adjuvant tamoxifen versus no systemic treatment in premenopausal patients with oestrogen receptor (ER)–positive tumours, regarding breast cancer–free interval (BCFi) and distant recurrence–free interval (D-RFi), with 30 years of follow-up and for specified intervals. Moreover, we aimed to investigate the effects of adjuvant tamoxifen on the incidence of secondary malignancies and survival after distant recurrence. Methods: Premenopausal patients with primary breast cancer were randomised to 2 years of tamoxifen (n = 277) or no systemic treatment (n = 287), irrespective of ER status. Information regarding events was collected by a review of medical records and from national registers. Results: The median follow-up for all patients without events was 28 years, and only four of the patients alive had a follow-up of <20 years. With 30 years of follow-up, tamoxifen prolonged BCFi in the intention-to-treat population (hazard ratio [HR] = 0.76, 95% confidence interval (CI) 0.61–0.94, p = 0.011) compared with no treatment. In patients with ER-positive tumours (n = 362), tamoxifen prolonged BCFi (HR = 0.62, 95% CI 0.47–0.82, p = 0.001) and D-RFi (HR = 0.73, 95% CI 0.54–0.99, p = 0.043). The positive effect on BCFi was significant also for the interval >15–30 years (HR = 0.53, 95% CI 0.28–0.98, p = 0.042). For patients with ER-positive tumours who were diagnosed with distant recurrence (n = 165), survival after distant recurrence was shorter among tamoxifen-treated patients (median, 29 months versus 43 months). The incidence of contralateral breast cancer was 42% lower in the tamoxifen group (HR = 0.58, 95% CI 0.35–0.96, p = 0.035), whereas no differences were observed regarding other secondary malignancies. Conclusions: With three decades of follow-up, 2 years of adjuvant tamoxifen reduced the incidence of breast cancer–related events and distant recurrence, and the carryover effect seems to extend beyond 15 years. Moreover, adjuvant tamoxifen seems to be associated with shorter survival after diagnosis of distant recurrence.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Tanner, M M, et al.
(författare)
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Genetic aberrations in hypodiploid breast cancer: frequent loss of chromosome 4 and amplification of cyclin D1 oncogene
- 1998
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Ingår i: American Journal of Pathology. - 1525-2191. ; 153:1, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of somatic genetic aberrations in breast cancer has remained poorly understood. The most common chromosomal abnormality is hyperdiploidy, which is thought to arise via a transient hypodiploid state. However, hypodiploidy persists in 1 to 2% of breast tumors, which are characterized by a poor prognosis. We studied the genetic aberrations in 15 flow cytometrically hypodiploid breast cancers by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). Surprisingly, numerous copy number gains were detected in addition to the copy number losses. The number of gains per tumor was 4.3 +/- 3.2 and that of losses was 4.5 +/- 3.3 (mean +/- SD), which is similar to that previously observed in hyperdiploid breast cancers. Gains at chromosomes or chromosomal regions at 11q13, 1q, 19, and 16p and losses of 2q, 4, 6q, 9p, 13, and 18 were most commonly observed. Compared with unselected breast carcinomas, hypodiploid tumors showed certain differences. Loss of chromosome 4 (53%) and gain of 11q13 (60%) were significantly more common in hypodiploid tumors. The gain at 11q13 was found by FISH to harbor amplification of the Cyclin D1 oncogene, which is therefore three to four times more common in hypodiploid than in unselected breast cancers (15 to 20%). Structural chromosomal aberrations (such as Cyclin D1 amplification) were present both in diploid and hypodiploid tumor cell populations, as assessed by FISH and CGH after flow cytometric sorting. Together these results indicate that hypodiploid tumors form a distinct genetic entity of invasive breast cancer, although they probably share a common genetic evolution pathway where structural chromosomal aberrations precede gross DNA ploidy changes.
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| 18. |
- Tobin, N. P., et al.
(författare)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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| 19. |
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| 20. |
- Carlsson, Michael, et al.
(författare)
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Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.
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| 21. |
- Domanski, A M., et al.
(författare)
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Comparison of the oestrogen and progesterone receptor status in primary breast carcinomas as evaluated by immunohistochemistry and immunocytochemistry: a consecutive series of 267 patients
- 2013
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Ingår i: Cytopathology. - : Blackwell Publishing. - 0956-5507 .- 1365-2303. ; 24:1, s. 21-25
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Tidskriftsartikel (refereegranskat)abstract
- A.M. Domanski, N. Monsef, H.A. Domanski, D. Grabau and M. Ferno Comparison of the oestrogen and progesterone receptor status in primary breast carcinomas as evaluated by immunohistochemistry and immunocytochemistry: a consecutive series of 267 patients Objective: The use of cytological specimens to evaluate tumour biomarkers in metastatic breast cancer lesions has attracted increased interest because of the considerable number of reports that have shown discordance between the primary tumour and metastatic lesion. Oestrogen receptor (ER) and progesterone receptor (PgR) assays are crucial for the management of patients with breast cancer, in both adjuvant and palliative settings. The aim of this study was to compare the ER and PgR immunocytochemical analysis of fine needle aspiration (FNA) samples with the immunohistochemistry (IHC) of surgical specimens and core biopsies from primary breast cancers. Methods: The FNA specimens were prepared as cell blocks (n = 25) or ThinPreps (n = 258) for the immunocytochemistry (IC) ER and PgR analyses. Sixteen patients were excluded because of lack of follow-up (n = 1), neoadjuvant therapy (n = 3) or cell counts in their fine needle aspirates that were too low (n = 12). The results of IC on 25 cell blocks and 242 ThinPreps were compared with IHC on the corresponding core needle biopsies (n = 16) or excised tumours (n = 251). The ER and PgR status was defined as negative (when less than 10% of the nuclei were stained) or positive (when equal or more than 10% of the nuclei were stained). Kappa statistics were used to evaluate the concordance. Results: The ER concordance was 98% with ThinPrep (kappa = 0.93) and 92% with cell block (kappa = 0.82). The corresponding values for PgR were 96% (kappa = 0.91) and 96% (kappa = 0.92). Conclusions: Our results confirm that, in cases in which biopsies or surgical specimens are not available, IC (with either cell block or ThinPrep techniques) is a reliable method for the determination of the ER and PgR status performed under strict conditions using primary breast carcinomas, and is therefore potentially useful in metastatic settings.
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| 22. |
- Fernö, M., et al.
(författare)
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Estrogen and progesterone receptor analyses in more than 4000 human breast cancer samples : A study with special reference to age at diagnosis and stability of analyses
- 1990
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 29:2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen (ER) and progesterone receptors (PgR) were measured in the same laboratory in more than 4000 breast cancer biopsy samples obtained from 15 different hospitals during ten years. ER was measured with isoelectric focusing and PgR with the dextran-coated charcoal method and Scatchard analysis. The distribution pattern for both ER and PgR was during this time period and for the different hospitals rather similar indicating a good stability of the analytical methods. ER concentration was positively correlated with patient age, with a higher percentage of positive samples and higher concentrations in patients ≥50 years of age compared with patients <50 years. PgR concentration increased with age for patients under 50 years, but a considerable reduction of PgR concentration and of the proportion of positive samples was seen in patients between 50 and 59 years of age. Above this age the PgR concentration again increased with increasing age. The PgR/ER ratio and the proportion of ER- PgR+ samples were higher in patients under 50 years compared to older patients. ER and PgR values decreased during tamoxifen treatment, during pregnancy and after preoperative radiotherapy. Wet weight, DNA and protein were compared as reference parameters for the expression of ER and PgR concentrations. Strong correlations were obtained suggesting that similar information can be obtained with either of these reference parameters.
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| 23. |
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| 24. |
- Fredstorp-Lidebring, M, et al.
(författare)
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Urokinase plasminogen activator and its inhibitor, PAI-1, in association with progression-free survival in early stage endometrial cancer
- 2001
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Ingår i: European Journal of Cancer. - 1879-0852. ; 37:18, s. 2339-2348
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Tidskriftsartikel (refereegranskat)abstract
- Components of the urokinase plasminogen activator (u-PA) system are involved in the metastatic process, and have accordingly been associated with clinical outcome in a variety of malignant tumours. We investigated the prognostic importance of u-PA and plasminogen activator inhibitor type 1 (PAI-1) in endometrial cancer, analysed with luminometric immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Two different cut-off levels were used: the median and the 80th percentile-the latter because of the low progression rate for patients with early stage (I-II) endometrial cancer. After a median follow-up time of 6.8 years, univariate analysis of patients with stage I-II disease (n=188) showed that high u-PA and high PAI-1 content was associated with a shorter progression-free survival (PFS), but at different cut-off levels, uPA at the median (P=0.003), and PAI-1 at the 80th percentile (P<0.001). Among the other factors, DNA ploidy status was most strongly correlated to PFS, followed by age (continuous), International Federation of Gynaecology and Obstetrics (FIGO) grade of differentiation, S-phase fraction and progesterone receptor (PgR) status. Bivariate analyses, including ploidy and one of the factors u-PA or PAI-1, showed that both add significant prognostic information. We conclude that u-PA and PAI-1 are promising prognostic factors in early stage endometrial cancer.
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| 25. |
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| 26. |
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| 27. |
- Klintman, Marie, et al.
(författare)
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The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off >= 10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95% CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95% CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95% CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95% CI: 1.1-6.7), and cyclin A (HR=2.7, 95% CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.
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| 28. |
- Lindahl, B, et al.
(författare)
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Correlation between estradiol-17 beta and progesterone cytosol receptor concentration, histologic differentiation and 3H-thymidine incorporation in endometrial carcinoma
- 1982
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Ingår i: Anticancer research. - 0250-7005. ; 2:4, s. 7-203
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Tidskriftsartikel (refereegranskat)abstract
- Women treated with estrogen exhibit a higher risk of developing endometrial cancer. steroid hormones exert their effects on target tissue through specific cytosol receptor protein. Knowledge of this steroid receptor concentration in endometrial carcinoma might facilitate the treatment of recurrences. We have compared the concentrations of endometrial estrogen and progesterone cytosol receptors with the histologic grade of endometrial carcinoma as well as the rate of 3H-thymidine incorporation. We found a significant difference in receptor concentration between well-moderately differentiated tumours and poorly differentiated ones. No correlation was found between 3H-thymidine incorporation rate and differentiation. A positive correlation between thymidine incorporation rate and progesterone receptor concentration was noticed. The concentration of receptors varies within a wide range of each group of differentiation; thus 23% and 4% of the poorly differentiated tumours had higher concentration of estradiol and progesterone receptors respectively than the median values for well differentiated tumours.
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| 29. |
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| 30. |
- Look, MP, et al.
(författare)
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Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients
- 2002
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 94:2, s. 116-128
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Tidskriftsartikel (refereegranskat)abstract
- Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph nodenegative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.
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| 31. |
- Narbe, U., et al.
(författare)
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St Gallen 2019 guidelines understage the axilla in lobular breast cancer : a population-based study
- 2021
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:12, s. 1465-1473
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The St Gallen 2019 guidelines for primary therapy of early breast cancer recommend omission of completion axillary lymph node dissection (cALND), regardless of histological type, in patients with one or two sentinel lymph node (SLN) metastases. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with four or more axillary lymph node (ALN) metastases. The aim of this study was to estimate the proportion of patients with invasive lobular cancer (ILC) versus invasive ductal cancer of no special type (NST) with one or two SLN metastases for whom cALND would have led to a recommendation for adjuvant chemotherapy. METHODS: Patients with ILC and NST who had surgery between 2014 and 2017 were identified in the National Breast Cancer Register of Sweden. After exclusion of patients with incongruent or missing data, those who fulfilled the St Gallen 2019 criteria for cALND omission were included in the population-based study cohort. RESULTS: Some 1886 patients in total were included in the study, 329 with ILC and 1507 with NST. Patients with ILC had a higher metastatic nodal burden and were more likely to have a luminal A-like subtype than those with NST. The prevalence of at least four ALN metastases was higher in ILC (31.0 per cent) than NST (14.9 per cent), corresponding to an adjusted odds ratio of 2.26 (95 per cent c.i. 1.59 to 3.21). Luminal A-like breast cancers with four or more ALN metastases were over-represented in ILC compared with NST, 52 of 281 (18.5 per cent) versus 43 of 1299 (3.3 per cent) (P < 0.001). CONCLUSION: Patients with ILC more often have luminal A-like breast cancer with at least four nodal metastases. Omission of cALND in patients with luminal A-like invasive lobular cancer and one or two SLN metastases warrants future attention as there is a risk of nodal understaging and undertreatment in one-fifth of patients.
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| 32. |
- Narbe, Ulrik, et al.
(författare)
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The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast
- 2019
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 175:2, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC). Methods: Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets. Results: AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not. Conclusions: AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.
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| 33. |
- Olsson, H., et al.
(författare)
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A biological marker, strongly associated with early oral contraceptive use, for the selection of a high risk group for premenopausal breast cancer
- 1986
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Ingår i: Medical Oncology and Tumor Pharmacotherapy. - 0736-0118. ; 3:2, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based group of women, consecutively diagnosed, with premenopausal breast cancer there was a significant correlation between tumour size and plasma prolactin (r=0.30;P<0.004). The concentration of estrogen receptor was negatively correlated to tumour size (r=-0.17;P<0.09). There were no substantial correlations between tumour size and progesterone receptor, plasma progesterone or estradiol. Adjustments for menstrual cycle day and age did not alter the above findings. The ratio of plasma prolactin and estrogen receptor was significantly greater (P<0.037) for the group of the patients that had started using oral contraceptives before the age of 20 as compared with the other patients. Consequently, the tumour size was significantly greater in the group of early users (P<0.003). The findings indicate that breast tumours developing in previous early users of oral contraceptives have a low estrogen receptor concentration, while these patients have plasma prolactin. The tumour size is greater in early users indicating a poorer prognosis than other women with breast cancer. As early use of oral contraceptives increases, breast cancer risk and a high ratio of plasma prolactin and estrogen receptor concentration of the primary tumour characterize early oral contraceptive users the ratio may be a valuable marker for the breast cancer risk.
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| 34. |
- Olsson, H., et al.
(författare)
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Early oral contraceptive use and premenopausal breast cancer--a review of studies performed in southern Sweden.
- 1991
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Ingår i: Cancer Detection and Prevention. - 0361-090X. ; 15:4, s. 265-271
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Tidskriftsartikel (refereegranskat)abstract
- In southern Sweden, extensive oral contraceptive use (OC use) among young women was a reality during the 1960s, thus making our region especially suited for studies investigating the hypothesis that early OC use is associated with the development of premenopausal breast cancer after a possible latency time between the exposure and the disease. The results of this study revealed that the risk of developing premenopausal breast cancer in women, who during the 1960s used the pill as teenagers, is five times greater than nonusers. The risk for early users is further modified by the duration of use at an early age, implying a dose-response relationship. Later use of OCs is not associated with an increased risk for the disease. Women with breast cancer, who at an early age have used the pill, have larger breast tumors, lower estrogen receptor concentrations of their primary tumor, and a worse prognosis compared with later and nonusers with breast cancer. The incidence of breast cancer in Sweden rapidly increased in women 25 to 40 years of age between 1970 and 1984. Conventional risk factors or a change in diagnostic activities of breast cancer cannot explain the increase in incidence which could be due to the OC exposure. Studies on the risk with modern OCs must wait another 20 years because of a too short latency time.
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| 35. |
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| 36. |
- Olsson, Niclas, et al.
(författare)
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Grading breast cancer tissues using molecular portraits.
- 2013
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 12:12, s. 3612-3623
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Tidskriftsartikel (refereegranskat)abstract
- Tumor progression and prognosis of breast cancer patients is difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessment of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with histological grades of breast cancer, using a novel affinity proteomics approach. We profiled 52 breast cancer tissue samples, by combining nine antibodies and label-free LC-MS/MS, which generated detailed quantified proteomic maps representing 1,388 proteins. The results showed that we could define in-depth molecular portraits of histologically graded breast cancer tumors. Consequently, a 49-plex candidate tissue protein signature was defined that discriminated between histological grade 1, 2, and 3 of breast cancer tumors with high accuracy. Highly biologically relevant proteins were identified, and the differentially expressed proteins indicated further support for the current hypothesis regarding remodeling of tumor microenvironment during tumor progression. The protein signature was corroborated using meta-analysis of transcriptional profiling data from an independent patient cohort. In addition, the potential for using the markers to estimate the risk of distant metastasis free survival was also indicated. Taken together, these molecular portraits could pave the way for improved classification and prognostication of breast cancer.
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| 37. |
- Rudolph, P, et al.
(författare)
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Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas : prognostic implications
- 1999
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Ingår i: Journal of Pathology. - 0022-3417. ; 187:2, s. 16-207
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Tidskriftsartikel (refereegranskat)abstract
- Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size, DNA aneuploidy, lack of steroid hormone receptors, young age, and increased topoisomerase II alpha and Ki-67 expression levels. The correlation of p53 and c-erbB-2 was not significant. Topoisomerase II alpha and Ki-67 scores closely paralleled each other, indicating that both reflect the proliferative activity of tumour cells. A univariate analysis of overall (OS), specific (SS), and disease-free survival (DFS) revealed all the above-mentioned parameters to be statistically significant except patient age, which was relevant only to overall survival. Multivariate analysis with inclusion of all covariates selected tumour size and proliferation (topoisomerase II alpha and Ki-67) indices as independent predictors of survival in all three models. No additional information was gained by p53 or c-erbB-2. It is concluded that the proliferative activity, as assessed by topoisomerase II alpha or Ki-67 immunostaining, is the most useful indicator of breast cancer prognosis, except for tumour size.
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| 38. |
- Rudolph, P, et al.
(författare)
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Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer
- 1999
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 91:3, s. 8-271
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis.METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size.RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold.CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.
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| 39. |
- Sigurdsson, H, et al.
(författare)
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Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels
- 1990
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Ingår i: British Journal of Cancer. - 1532-1827. ; 62:5, s. 786-790
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Tidskriftsartikel (refereegranskat)abstract
- The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
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| 40. |
- Sigurdsson, H, et al.
(författare)
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Indicators of prognosis in node-negative breast cancer
- 1990
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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| 41. |
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| 42. |
- Stål, Olle, 1952-, et al.
(författare)
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ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer
- 2000
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Ingår i: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 11:12, s. 1545-1550
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Tidskriftsartikel (refereegranskat)abstract
- Aim:We aimed to study the importance of erbB2 status in early stage postmenopausal breast cancer for patients who participated in a trial of five vs. two years of adjuvant tamoxifen.Patients and methods: We analysed the erbB2 status of the tumours from 577 patients participating in the trial, either by a DNA amplification assay (n=181) or by measurement of the protein level with flow cytometry (n=396).Results: ErbB2 was overexpressed or gene amplified in 102 of the patients (18%). Overall, erbB2-positive patients had a significantly lower recurrence-free probability than others, 62% at five years as compared to 83%, and showed a significantly decreased breast cancer survival rate (P=0.0007). ErbB2 status was significantly associated with recurrence and death in Cox multivariate analysis, adjusting for nodal status, tumour size and estrogen receptor status. The relative risk of recurrence (RR) for five vs. two years of tamoxifen was analysed in relation to erbB2 status for patients still disease-free two years after surgery. Whereas erbB2-negative patients showed significant benefit from prolonged treatment (RR=0.62, 95% confidence interval (95% CI): 0.42–0.93), no benefit was evident for erbB2-positive patients (RR=1.1, 95% CI: 0.41–3.2). When the same analysis was restricted to ER-positive patients a similar difference in relative hazard was obtained but the difference was not strictly significant (P=0.065).Conclusions: For early stage breast cancer patients treated with adjuvant tamoxifen, overexpression of erbB2 is an independent marker of poor prognosis. The results suggest that overexpression decreases the benefit from prolonged tamoxifen treatment.
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| 43. |
- Tobin, Nicholas P., et al.
(författare)
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PAM50 provides prognostic information when applied to the lymph node metastases of advanced breast cancer patients
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:23, s. 7225-7231
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting. Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable locoregional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan–Meier and/or multivariate Cox regression analyses. Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan–Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer–specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance. Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients.
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| 44. |
- Tutzauer, Julia, et al.
(författare)
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Breast cancer hypoxia in relation to prognosis and benefit from radiotherapy after breast-conserving surgery in a large, randomised trial with long-term follow-up
- 2022
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 126:8, s. 1145-1156
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast-conserving surgery followed by radiotherapy is part of standard treatment for early-stage breast cancer. Hypoxia is common in cancer and may affect the benefit of radiotherapy. Cells adapt to hypoxic stress largely via the transcriptional activity of hypoxia-inducible factor (HIF)-1α. Here, we aim to determine whether tumour HIF-1α-positivity and hypoxic gene-expression signatures associated with the benefit of radiotherapy, and outcome.METHODS: Tumour HIF-1α-status and expression of hypoxic gene signatures were retrospectively analysed in a clinical trial where 1178 women with primary T1-2N0M0 breast cancer were randomised to receive postoperative radiotherapy or not and followed 15 years for recurrence and 20 years for breast cancer death.RESULTS: The benefit from radiotherapy was similar in patients with HIF-1α-positive and -negative primary tumours. Both ipsilateral and any breast cancer recurrence were more frequent in women with HIF-1α-positive primary tumours (hazard ratio, HR0-5 yrs1.9 [1.3-2.9], p = 0.003 and HR0-5 yrs = 2.0 [1.5-2.8], p < 0.0001). Tumour HIF-1α-positivity is also associated with increased breast cancer death (HR0-10 years 1.9 [1.2-2.9], p = 0.004). Ten of the 11 investigated hypoxic gene signatures correlated positively to HIF-1α-positivity, and 5 to increased rate/risk of recurrence.CONCLUSIONS: The benefit of postoperative radiotherapy persisted in patients with hypoxic primary tumours. Patients with hypoxic primary breast tumours had an increased risk of recurrence and breast cancer death.
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| 45. |
- Tutzauer, Julia, et al.
(författare)
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Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Background G protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance. Methods Total GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point. Results GPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment. Conclusion PM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.
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| 46. |
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