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Nordenskjöld, Bo
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Publications (10 of 91) Show all publications
Hilborn, E., Gacic, J., Fornander, T., Nordenskjöld, B., Stål, O. & Jansson, A. (2016). Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer. British Journal of Cancer, 114(3), 248-255
Open this publication in new window or tab >>Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer
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2016 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 3, p. 248-255Article in journal (Refereed) Published
Abstract [en]

Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P < 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
Keywords
Androgen receptor; breast cancer; tamoxifen; oestrogen receptor; triple-negative breast cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-125675 (URN)10.1038/bjc.2015.464 (DOI)000369223600003 ()26742006 (PubMedID)
Note

Funding Agencies|Swedish research council [A0346701]; Swedish cancer foundation [13 0435]

Available from: 2016-03-02 Created: 2016-02-29 Last updated: 2017-05-03
Manna, S., Bostner, J., Sun, Y., Miller, L. D., Alayev, A., Schwartz, N. S., . . . Holz, M. K. (2016). ERRα Is a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer.. Clinical Cancer Research, 22(6), 1421-1431
Open this publication in new window or tab >>ERRα Is a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer.
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2016 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 6, p. 1421-1431Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Estrogen-related receptor alpha (ERRα) signaling has recently been implicated in breast cancer. We investigated the clinical value of ERRα in randomized cohorts of tamoxifen-treated and adjuvant-untreated patients.

EXPERIMENTAL DESIGN: Cox proportional hazards regression was used to evaluate the significance of associations between ERRα gene expression levels and patient DMFS in a previously published microarray dataset representing 2,000 breast tumor cases derived from multiple medical centers worldwide. The 912 tumors used for immunostaining were from a tamoxifen-randomized primary breast cancer trial conducted in Stockholm, Sweden, during 1976-1990. Mouse model was used to study the effect of tamoxifen treatment on lung colonization of MDA-MB-231 control cells and MDA-MB-231 cells with stable knockdown of ERRα. The phenotypic effects associated with ERRα modulation were studied using immunoblotting analyses and wound-healing assay.

RESULTS: We found that in ER-negative and triple-negative breast cancer (TNBC) adjuvant-untreated patients, ERRα expression indicated worse prognosis and correlated with poor outcome predictors. However, in tamoxifen-treated patients, an improved outcome was observed with high ERRα gene and protein expression. Reduced ERRα expression was oncogenic in the presence of tamoxifen, measured by in vitro proliferation and migration assays and in vivo metastasis studies.

CONCLUSION: Taken together, these data show that ERRα expression predicts response to tamoxifen treatment, and ERRα could be a biomarker of tamoxifen sensitivity and a prognostic factor in TNBC. Clin Cancer Res; 1-11. ©2015 AACR.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH, 2016
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-125928 (URN)10.1158/1078-0432.CCR-15-0857 (DOI)000373358900018 ()26542058 (PubMedID)
Note

Funding agencies:  NIH [CA151112, HL098216]; Atol Charitable Trust; American Cancer Society [RSG-13-287-01-TBE]; National Cancer Center; Yeshiva University; Swedish Cancer Society

Available from: 2016-03-09 Created: 2016-03-09 Last updated: 2018-03-21
Veenstra, C., Perez-Tenorio, G., Stelling, A., Karlsson, E., Mirwani Mirwani, S., Nordenskjöld, B., . . . Stål, O. (2016). Met and its ligand HGF are associated with clinical outcome in breast cancer. OncoTarget, 7(24), 37145-37159
Open this publication in new window or tab >>Met and its ligand HGF are associated with clinical outcome in breast cancer
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 24, p. 37145-37159Article in journal (Refereed) Published
Abstract [en]

Few biomarkers exist to predict radiotherapy response in breast cancer. In vitro studies suggest a role for Met and its ligand HGF. To study this suggested role, MET and HGF gene copy numbers were determined by droplet digital PCR in tumours from 205 pre-menopausal and 184 post-menopausal patients, both cohorts randomised to receive either chemo-or radiotherapy. MET amplification was found in 8% of the patients in both cohorts and HGF amplification in 7% and 6% of the patients in the pre-and post-menopausal cohort, respectively. Met, phosphorylated Met (pMet), and HGF protein expression was determined by immunohistochemistry in the premenopausal cohort. Met, pMet, and HGF was expressed in 33%, 53%, and 49% of the tumours, respectively. MET amplification was associated with increased risk of distant recurrence for patients receiving chemotherapy. For the pre-menopausal patients, expression of cytoplasmic pMet and HGF significantly predicted benefit from radiotherapy in terms of loco-regional recurrence. Similar trends were seen for MET and HGF copy gain. In the post-menopausal cohort, no significant association of benefit from radiotherapy with neither genes nor proteins was found. The present results do not support that inhibition of Met prior to radiotherapy would be favourable for pre-menopausal breast cancer, as previously suggested.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2016
Keywords
radiation; copy number variation; droplet digital PCR; triple-negative breast cancer; radiotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-130130 (URN)10.18632/oncotarget.9268 (DOI)000377756800127 ()27175600 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society; Swedish Research Council; LiU Cancer Foundation

Available from: 2016-07-12 Created: 2016-07-11 Last updated: 2018-03-23
Ekholm, M., Bendahl, P.-O., Ferno, M., Nordenskjöld, B., Stål, O. & Ryden, L. (2016). Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial. Journal of Clinical Oncology, 34(19), 2232-+
Open this publication in new window or tab >>Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial
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2016 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 19, p. 2232-+Article in journal (Refereed) Published
Abstract [en]

Purpose The aim of this study was to evaluate the long-term effect of 2 years of adjuvant tamoxifen compared with no systemic treatment (control) in premenopausal patients with breast cancer over different time periods through long-term (amp;gt; 25 years) follow-up. Patients and Methods Premenopausal patients with primary breast cancer (N = 564) were randomly assigned to 2 years of tamoxifen (n = 276) or no systemic treatment (n = 288). Data regarding date and cause of death were obtained from the Swedish Cause of Death Register. End points were cumulative mortality (CM) and cumulative breast cancer-related mortality (CBCM). The median follow-up for the 250 patients still alive in April 2014 was 26.3 years (range, 22.7 to 29.7 years). Results In patients with estrogen receptor-positive tumors (n = 362), tamoxifen was associated with a marginal reduction in CM (hazard ratio [HR], 0.77; 95% CI, 0.58 to 1.03; P = .075) and a significant reduction in CBCM (HR, 0.73; 95% CI, 0.53 to 0.99; P = .046). The effect seemed to vary over time (CM years 0 to 5: HR, 1.05; 95% CI, 0.64 to 1.73; years amp;gt;5 to 15: HR, 0.58; 95% CI, 0.37 to 0.91; and after 15 years: HR, 0.82; 95% CI, 0.48 to 1.42; CBCM years 0 to 5: HR, 1.09; 95% CI, 0.65 to 1.82; years amp;gt;5 to 15: HR, 0.53; 95% CI, 0.33 to 0.86; and after 15 years: HR, 0.72; 95% CI, 0.36 to 1.44). Conclusion Two years of adjuvant tamoxifen resulted in a long-term survival benefit in premenopausal patients with estrogen receptor-positive primary breast cancer. (C) 2016 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Place, publisher, year, edition, pages
AMER SOC CLINICAL ONCOLOGY, 2016
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-130273 (URN)10.1200/JCO.2015.65.6272 (DOI)000378647000006 ()27161974 (PubMedID)
Available from: 2016-08-01 Created: 2016-07-28 Last updated: 2017-11-28
Sonnenblick, A., Francis, P. A., Azim, H. A. J., de Azambuja, E., Nordenskjöld, B., Gutierez, J., . . . Crown, J. (2015). Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer. European Journal of Cancer, 51(12), 1481-1489
Open this publication in new window or tab >>Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer
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2015 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no 12, p. 1481-1489Article in journal (Refereed) Published
Abstract [en]

Aim: Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials. Patients and methods: 2887 patients were randomly assigned in a 2 x 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. Results: After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81-1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76-1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.721.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 greater than= 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63-1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57-1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01). Conclusion: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Ki67; Adjuvant taxanes; ER positive; Breast cancer; Pooled analysis
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120332 (URN)10.1016/j.ejca.2015.03.018 (DOI)000357658900001 ()26074397 (PubMedID)
Note

Funding Agencies|Sanofi Aventis; Associazione Italiana Ricerca Cancro (AIRC), Milan, Italy

Available from: 2015-07-31 Created: 2015-07-31 Last updated: 2017-12-04
Karlsson, E., Veenstra, C., Emin, S., Dutta, C., Perez-Tenorio, G., Nordenskjöld, B., . . . Stål, O. (2015). Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer. Breast Cancer Research and Treatment, 153(1), 31-40
Open this publication in new window or tab >>Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer
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2015 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 153, no 1, p. 31-40Article in journal (Refereed) Published
Abstract [en]

Breast cancer is a heterogeneous disease and new clinical markers are needed to individualise disease management and therapy further. Alterations in the PI3K/AKT pathway, mainly PIK3CA mutations, have been shown frequently especially in the luminal breast cancer subtypes, suggesting a cross-talk between ER and PI3K/AKT. Aberrant PI3K/AKT signalling has been connected to poor response to anti-oestrogen therapies. In vitro studies have shown protein tyrosine phosphatase, non-receptor type 2 (PTPN2) as a previously unknown negative regulator of the PI3K/AKT pathway. Here, we evaluate possible genomic alterations in the PTPN2 gene and its potential as a new prognostic and treatment predictive marker for endocrine therapy benefit in breast cancer. PTPN2 gene copy number was assessed by real-time PCR in 215 tumour samples from a treatment randomised study consisting of postmenopausal patients diagnosed with stage II breast cancer 1976-1990. Corresponding mRNA expression levels of PTPN2 were evaluated in 86 available samples by the same methodology. Gene copy loss of PTPN2 was detected in 16 % (34/215) of the tumours and this was significantly correlated with lower levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a significant predictive marker of poor benefit from tamoxifen treatment. In conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical marker of endocrine treatment benefit which could guide further individualised therapies in breast cancer.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
Keywords
18p; AKT; Breast cancer; Endocrine resistance; Phosphatases; PTPN2
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-121133 (URN)10.1007/s10549-015-3516-y (DOI)000359775100005 ()26208487 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society [13 0435]; Swedish Research Council [A0346701]

Available from: 2015-09-08 Created: 2015-09-08 Last updated: 2017-12-04
Nordenskjold, A. E., Fohlin, H., Albertsson, P., Arnesson, L.-G., Chamalidou, C., Einbeigi, Z., . . . Karlsson, P. (2015). No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study. Annals of Oncology, 26(6), 1149-1154
Open this publication in new window or tab >>No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study
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2015 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 6, p. 1149-1154Article in journal (Refereed) Published
Abstract [en]

Background: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. Patients and methods: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, post-mastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. Results: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. Conclusion: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.

Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy B - Oxford Open Option F, 2015
Keywords
postoperative radiotherapy; breast cancer; positive nodes
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-120464 (URN)10.1093/annonc/mdv159 (DOI)000357997500016 ()25839671 (PubMedID)
Available from: 2015-08-12 Created: 2015-08-11 Last updated: 2017-12-04
Bostner, J., Karlsson, E., Bivik Eding, C., Perez-Tenorio, G., Franzén, H., Konstantinell, A., . . . Stål, O. (2015). S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts. Endocrine-Related Cancer, 22(3), 331-343
Open this publication in new window or tab >>S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts
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2015 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, no 3, p. 331-343Article in journal (Refereed) Published
Abstract [en]

Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, Pless than0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.

Place, publisher, year, edition, pages
BioScientifica, 2015
Keywords
pS6K; S6K1; S6K2; mTOR; AKT; estrogen receptor; endocrine treatment
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120883 (URN)10.1530/ERC-14-0513 (DOI)000359003500016 ()25972244 (PubMedID)
Note

Funding Agencies|Swedish Cancer Society; Swedish Research Council; Ostergotland County Council; Lions Research Fund

Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2017-12-04
Hilborn, E., Sivik, T., Fornander, T., Stål, O., Nordenskjöld, B. & Jansson, A. (2014). C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients. Breast Cancer Research and Treatment, 145(1), 73-82
Open this publication in new window or tab >>C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients
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2014 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 145, no 1, p. 73-82Article in journal (Refereed) Published
Abstract [en]

To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25-0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19-0.62, P less than 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38-4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2014
Keywords
CXCL10; CXCR3; Endocrine treatment; Prognosis; Tamoxifen
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106833 (URN)10.1007/s10549-014-2933-7 (DOI)000334519400007 ()
Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2017-12-05Bibliographically approved
Rosell, J., Nordenskjöld, B., Bengtsson, N.-O., Fornander, T., Hatschek, T., Lindman, H., . . . Carstensen, J. (2014). Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer: results from a randomized trial with long term follow-up.
Open this publication in new window or tab >>Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer: results from a randomized trial with long term follow-up
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND

Tamoxifen is a well-established endocrine treatment for breast cancer. We here present results with respect to second primary cancer from a large randomized trial of 5 and 2 years of adjuvant tamoxifen. Breast cancer distant recurrence and mortality are also reported.

METHODS

Our study included 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after 2 years of tamoxifen therapy. They were randomized to receive three more years of therapy or stop tamoxifen. In the comparison of 5 years versus 2 years of postoperative tamoxifen treatment hazard ratios were estimated using Cox regression for different follow-up periods defined as: During treatment (2-5 years) and after treatment (5-10 years, 10-15 years, > 5 years, > 10 years and > 15 years).

RESULTS

In the five years group the incidence of lung cancer was halved (hazard ratio [HR], 0.45, 95% confidence interval [95% CI], 0.27-0.77 [P = .0038]), and lung cancer mortality was decreased. An increased risk was observed for endometrial cancer (HR, 1.83; 95% CI, 1.19-2.81 [P = .0059]), but this risk appeared to decrease over time. The risk of contralateral breast cancer was decreased (HR, 0.73; 95% CI, 0.56-0.96 [P = .022]), also in the period after treatment stopped. In the five years group, the risk of distant recurrence was decreased, and statistically significant reductions were observed both during treatment and in the five year period after treatment stopped. The breast cancer mortality was reduced, especially during the post-treatment phase.

CONCLUSIONS

In this randomized study, tamoxifen substantially reduces the risk of new cancer both in contralateral breast and in lung up to 10 years after treatment stopped.

Keywords
breast cancer, tamoxifen, adjuvant treatment, second primary cancer, lung cancer
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-112285 (URN)
Available from: 2014-11-21 Created: 2014-11-21 Last updated: 2015-03-31Bibliographically approved
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