| 1. |
- Lundstedt, Dan, 1970, et al.
(författare)
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Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy.
- 2012
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 83:1, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. METHODS AND MATERIALS: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. RESULTS: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. CONCLUSIONS: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting breast pain compared to older women. Time since treatment may decrease the occurrence of pain.
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| 2. |
- Margolin, Sara, et al.
(författare)
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A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.
- 2011
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.
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| 3. |
- Kovács, Anikó, 1961, et al.
(författare)
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Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes : A Long-Term Follow-Up of the SweBCG91RT Randomized Trial
- 2019
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:14, s. 1179-87
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. METHODS: In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1,178 patients with breast cancer stage I and II were randomly assigned to breast-conserving surgery plus postoperative RT or breast-conserving surgery only and followed for a median of 15.2 years. Tumor blocks were retrieved from 1,003 patients. Stromal TILs were assessed on whole-section hematoxylin-eosin-stained slides using a dichotomized cutoff of 10%. Subtypes were scored using immunohistochemistry on tissue microarray. In total, 936 patients were evaluated. RESULTS: Altogether, 670 (71%) of patients had TILs less than 10%. In a multivariable regression analysis with IBTR as dependent variable and RT, TILs, subtype, age, and grade as independent variables, RT (hazard ratio [HR], 0.42; 95% CI, 0.29 to 0.61; P < .001), high TILs (HR, 0.61; 95% CI, 0.39 to 0.96, P = .033) grade (3 v 1; HR, 2.17; 95% CI, 1.08 to 4.34; P = .029), and age (≥ 50 v < 50 years; HR, 0.55; 95% CI, 0.38 to 0.80; P = .002) were predictive of IBTR. RT was significantly beneficial in the low TILs group (HR, 0.37; 95% CI, 0.24 to 0.58; P < .001) but not in the high TILs group (HR, 0.58; 95% CI, 0.28 to 1.19; P = .138). The test for interaction between RT and TILs was not statistically significant (P = .317). CONCLUSION: This study shows that high values of TILs in the primary tumor independently seem to reduce the risk for an IBTR. Our findings further suggest that patients with breast cancer with low TILs may derive a larger benefit from RT regarding the risk of IBTR.
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| 4. |
- Lundstedt, Dan, 1970, et al.
(författare)
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Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial
- 2010
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 97:2, s. 281-287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative radiotherapy decreases the risk for local and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy. Material and methods: Between 1997 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups. Results: Fox six symptom group (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurence after radiotherapy was observed for pain in the breast or in the skin, reported to occur "occasionally" by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p = 0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p = 0.001). Daily life and analgesic use did not differ between the groups. Conclusion: Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweight the risk for long-term symptoms for most women. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 281-287
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| 5. |
- Sjöström, Martin, et al.
(författare)
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Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer.
- 2019
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 37:35, s. 3340-3349
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT.ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit (Pinteraction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT.ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
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| 6. |
- Sjöström, Martin, et al.
(författare)
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Comprehensive transcriptomic profiling identifies breast cancer patients who may be spared adjuvant systemic therapy.
- 2020
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 26:1, s. 171-182
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Tidskriftsartikel (refereegranskat)abstract
- There is currently no molecular signature in clinical use for adjuvant endocrine therapy omission in breast cancer. Given the unique trial design of SweBCG91-RT, where adjuvant endocrine and chemotherapy were largely unadministered, we sought to evaluate the potential of transcriptomic profiling for identifying patients who may be spared adjuvant endocrine therapy.We performed a whole transcriptome analysis of SweBCG91-RT, a randomized phase III trial of +/- radiotherapy after breast-conserving surgery for node-negative stage I-IIA breast cancer. 92% of patients were untreated by both adjuvant endocrine therapy and chemotherapy. We calculated 15 transcriptomic signatures from the literature and combined them into an Average Genomic Risk, which was further used to derive a novel 141-gene signature (MET141). All signatures were then independently examined in SweBCG91-RT, and in the publicly-available METABRIC cohort.In SweBCG91-RT, 454 patients were node-negative, post-menopausal and systemically untreated with ER-positive, HER2-negative cancers, which constitutes a low-risk subgroup and potential candidates for therapy omission. Most transcriptomic signatures were highly prognostic for distant metastasis, but considerable discordance was observed on the individual patient level. Within the MET141 low-risk subgroup (lowest 25th percentile of scores), 95% of patients were free of metastasis at 15 years even in the absence of adjuvant endocrine therapy. In a clinically low-risk subgroup of the METABRIC cohort not treated with systemic therapy, no breast cancer death occurred among the MET141 low-risk patients.Transcriptomic profiling identifies patients with an excellent outcome without any systemic adjuvant therapy in clinically low-risk patients of the SweBCG91-RT and METABRIC cohorts.
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| 7. |
- Sjöström, Martin, et al.
(författare)
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Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer.
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:8, s. 1533-1540
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach.We analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132).Patients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P = .81, and HR, 1.5 [0.14 to 16], P = .74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P = .0055, and HR, 0.25 [0.07 to 0.92], P = .038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P = .066).The novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.
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| 8. |
- Sjöström, Martin, et al.
(författare)
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Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast-conserving surgery : a long-term follow-up of the SweBCG91-RT randomised trial
- 2020
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 14:11, s. 2713-2726
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies suggest that hepatocyte growth factor (HGF) and its transmembrane tyrosine kinase receptor, Met, in part also relying on Akt kinase activity, mediate radioresistance. We investigated the importance of these biomarkers for the risk of ipsilateral breast tumour recurrence (IBTR) after adjuvant radiotherapy (RT) in primary breast cancer. HGF, phosphorylated Met (pMet) and phosphorylated Akt (pAkt) were evaluated immunohistochemically on tissue microarrays from 1004 patients in the SweBCG91-RT trial, which randomly assigned patients to breast-conserving therapy, with or without adjuvant RT. HGF was evaluated in the stroma (HGFstr); pMet in the membrane (pMetmem); HGF, pMet and pAkt in the cytoplasm (HGFcyt, pMetcyt, pAktcyt); and pAkt in the nucleus (pAktnuc). The prognostic and treatment predictive effects were evaluated to primary endpoint IBTR as first event during the first 5 years. Patients with tumours expressing low levels of HGFcyt and pMetcyt and high levels of pAktnuc derived a larger benefit from RT [hazard ratio (HR): 0.11 (0.037–0.30), 0.066 (0.016–0.28) and 0.094 (0.028–0.31), respectively] compared to patients with high expression of HGFcyt and pMetcyt, and low pAktnuc [HR: 0.36 (0.19–0.67), 0.35 (0.20–0.64) and 0.47 (0.32–0.71), respectively; interaction analyses: P = 0.052, 0.035 and 0.013, respectively]. These differences remained in multivariable analysis when adjusting for patient age, tumour size, histological grade, St Gallen subtype and systemic treatment (interaction analysis, P-values: 0.085, 0.027, and 0.023, respectively). This study suggests that patients with immunohistochemically low HGFcyt, low pMetcyt and high pAktnuc may derive an increased benefit from RT after breast-conserving surgery concerning the risk of developing IBTR.
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| 9. |
- Sjöström, Martin, et al.
(författare)
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Reply to V. Nardone et al.
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:23, s. 3959-3960
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Sjöström, Martin, et al.
(författare)
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Response to Radiotherapy After Breast-Conserving Surgery in Different Breast Cancer Subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized Clinical Trial.
- 2017
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 35:28, s. 3222-3229
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was collected from 1,003 patients with node-negative, stage I and II breast cancer who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy trial between 1991 and 1997 to breast conservation surgery with or without RT. Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with immunohistochemistry and in situ hybridization on tissue microarrays for 958 tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) as a first event within 10 years for luminal A-like tumors (19% v 9%; P = .001), luminal B-like tumors (24% v 8%; P < .001), and triple-negative tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2-positive (luminal and nonluminal) tumors (15% v 19%; P = .6); however, evidence of an overall difference in RT effect between subtypes was weak ( P = .21). RT reduced the rate of death from breast cancer (BCD) for triple-negative tumors (hazard ratio, 0.35; P = .06), but not for other subtypes. Death from any cause was not improved by RT in any subtype. A hypothesized clinical low-risk group did not have a low risk of IBTR without RT, and RT reduced the rate of IBTR as a first event after 10 years (20% v 6%; P = .008), but had no effect on BCD or death from any cause. Conclusion Subtype was not predictive of response to RT, although, in our study, human epidermal growth factor receptor 2-positive tumors seemed to be most radioresistant, whereas triple-negative tumors had the largest effect on BCD. The effect of RT in the presumed low-risk luminal A-like tumors was excellent.
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