| 1. |
- Baumgart, Juliane, et al.
(författare)
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Urogenital disorders in women with adjuvant endocrine therapy after early breast cancer
- 2011
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 204:1, s. 26.e1-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the prevalence of urogenital symptoms and vaginal atrophy in postmenopausal breast cancer patients on adjuvant endocrine therapy. STUDY DESIGN: A population-based, cross-sectional study on postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched control subjects. Vaginal atrophy was assessed by gynecologic examination and atrophy-related symptoms by validated questionnaires. RESULTS: In all, 57.6% of aromatase inhibitor-treated and 32.4% of tamoxifen-treated breast cancer patients rated at least 1 vaginal atrophy symptom as moderate/severe, which was significantly more common than in control subjects (P < .01). Aromatase inhibitor-treated patients more often had moderate or severe vaginal atrophy (P < .05), a more atrophic cytohormonal evaluation, and significantly higher vaginal pH (P < .05) than all control subjects, irrespective of hormonal use. CONCLUSION: Our findings indicate that the frequency of vaginal atrophy symptoms, particularly in aromatase inhibitor-treated women, might have been underestimated in previous clinical trials.
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| 2. |
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| 3. |
- Carlsson, Jörgen, et al.
(författare)
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HER2 expression in breast cancer primary tumours and corresponding metastases : Original data and literature review
- 2004
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 90:12, s. 2344-2348
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.
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| 4. |
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| 5. |
- Joensuu, Heikki, et al.
(författare)
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Adjuvant Capecitabine, Docetaxel, Cyclophosphamide, and Epirubicin for Early Breast Cancer : Final Analysis of the Randomized FinXX Trial
- 2012
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer.Patients and Methods: Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS).Results: During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity. Conclusion: Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine. J Clin Oncol 30:11-18. (c) 2011 by American Society of Clinical Oncology
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| 6. |
- Joensuu, Heikki, et al.
(författare)
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Adjuvant Capecitabine for Early Breast Cancer : 15-Year Overall Survival Results From a Randomized Trial
- 2022
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 40:10, s. 1051-1058
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer.METHODS: The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients.RESULTS: The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor-negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF.CONCLUSION: Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.
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| 7. |
- Joensuu, Heikki, et al.
(författare)
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Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer : an open-label, randomised controlled trial
- 2009
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:12, s. 1145-1151
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Tidskriftsartikel (refereegranskat)abstract
- Background Standard adjuvant chemotherapy regimens for patients with moderate-to-high-risk early breast cancer typically contain a taxane, an anthracycline, and cyclophosphamide. We aimed to investigate whether integration of capecitabine into such a regimen enhances outcome. Methods In this open-label trial, we randomly assigned (centrally by computer; stratified by node status, HER2 status, and centre) 1500 women with axillary node-positive or high-risk node-negative breast cancer to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival. A planned interim analysis was done after 3 years' median follow-tip. Efficacy analyses were by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT00114816. Findings Two patients in each group were excluded from efficacy analyses because of wthdrawal of consent or distant metastases. After a median follow-up of 35 months (IQR 25.5-43-6), recurrence-free survival at 3 years was better with the capecitabine regimen than with control (93% vs 89%; hazard ratio 0.66, 95% CI 0.47-0-94; p=0.020). The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhoea (46/740 [6%] vs 25/741 [3%]) and hand-foot syndrome (83/741 [11%] vs 2/741 [<1%]) and the control regimen with more occurrences of grade 3 or 4 neutropenia (368/375 198%] vs 325/378 186%]) and febrile neutropenia (65/741[9%] vs 33/742 [4%]). More patients discontinued planned treatment in the capecitabine group than in the control group (178/744 [24%] vs 23/741 [3%]). Four patients in the capecitabine group and two in the control group died from potentially treatment-related causes. Interpretation The capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents. Capecitabine administration was frequently discontinued because of adverse effects. Funding Roche, Sanofi-Aventis, AstraZeneca, Cancer Society of Finland.
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| 8. |
- Joensuu, Heikki, et al.
(författare)
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Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer : The Randomized Clinical FinXX Trial
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 3:6, s. 793-800
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC).OBJECTIVE To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2).DESIGN, SETTING, AND PARTICIPANTS This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015.MAIN OUTCOMES AND MEASURES Recurrence-free survival (RFS).RESULTS Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively).CONCLUSIONS AND RELEVANCE Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis.
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| 9. |
- Joensuu, Heikki, et al.
(författare)
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Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial
- 2018
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Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 4:9, s. 1199-1206
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear.Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab.Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries.Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year.Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease–free survival, overall survival, cardiac DFS, and safety.Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease–free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group.Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Trial Registration: ClinicalTrials.gov Identifier: NCT00593697
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| 10. |
- Joensuu, Heikki, et al.
(författare)
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Outcome of patients with HER2-positive breast cancer treated with or without adjuvant trastuzumab in the Finland Capecitabine Trial (FinXX)
- 2014
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:2, s. 186-194
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLittle information is available about survival outcomes of patients with HER2-positive early breast cancer treated with adjuvant capecitabine-containing chemotherapy with or without trastuzumab.Patients and methodsOne thousand and five hundred patients with early breast cancer were entered to the Finland Capecitabine trial (FinXX) between January 2004 and May 2007, and were randomly assigned to receive either three cycles of adjuvant TX (docetaxel, capecitabine) followed by three cycles of CEX (cyclophosphamide, epirubicin, capecitabine; TX-CEX) or three cycles of docetaxel followed by three cycles of CEF (cyclophosphamide, epirubicin, fluorouracil; T-CEF). The primary endpoint was recurrence-free survival (RFS). The study protocol was amended in May 2005 while study accrual was ongoing to allow adjuvant trastuzumab for patients with HER2-positive cancer. Of the 284 patients with HER2-positive cancer accrued to FinXX, 176 (62.0%) received trastuzumab after amending the study protocol, 131 for 12 months and 45 for nine weeks. The median follow-up time was 6.7 years.ResultsPatients with HER2-positive cancer who received trastuzumab had better RFS than those who did not (five-year RFS 89.2% vs. 75.9%; HR 0.41, 95% CI 0.23 -0.72; p = 0.001). Patients treated with trastuzumab for 12 months or nine weeks had similar RFS. There was no significant interaction between trastuzumab administration and the type of chemotherapy. Four (2.3%) patients treated with trastuzumab had heart failure or left ventricular dysfunction, three of these received capecitabine.ConclusionAdjuvant trastuzumab improves RFS of patients treated with TX-CEX or T-CEF. Few patients had cardiac failure.
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| 11. |
- Jonsson, Gabriel, et al.
(författare)
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Upfront Radiotherapy in Patients With Asymptomatic Incurable Rectal Cancer : A Retrospective Cohort Study
- 2020
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 40:10, s. 5853-5860
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: The optimal treatment sequencing for asymptomatic de novo metastatic rectal cancer is unclear. The aim of this study was to investigate the role of upfront radiotherapy, with or without chemotherapy on risk for local complications, in patients with asymptomatic advanced metastatic rectal cancer treated with palliative intention.PATIENTS AND METHODS: All patients with de novo metastatic rectal cancer diagnosed between January 2008 and December 2017 in two healthcare regions in Sweden (Örebro län, Sörmland) were identified and data were extracted from electronic medical records. Patients were divided into 3 groups based on treatment sequence: upfront radiotherapy, upfront chemotherapy, and only palliative surgery.RESULTS: In total, 102 patients were included in the study cohort, 30 patients in upfront radiotherapy group, 54 in upfront chemotherapy, and 18 in only palliative surgery group. Patients with only upfront CT [odds ratio (OR)= 5.10; 95% confidence interval (CI)=1.24-20.91, p=0.024] had a higher risk to suffer from a local complication compared to those who received upfront radiotherapy. Cause-specific Cox regression analysis among patients who received oncological therapy revealed that female patients [cause-specific hazard ratio (csHR)=3.61; 95% confidence interval (CI)=1.67-7.81] and upfront chemotherapy [csHR=1.85; 95% CI=1.11-3.77] were associated with increased cumulative incidence of local complication over time, whereas primary surgery with ostomy or stent with lower risk [csHR=0.45; 95% CI=0.21-0.99].CONCLUSION: Patients who received upfront radiotherapy, with or without chemotherapy, had fewer local complications due to primary tumor compared to patients who only received chemotherapy. This could indicate that radiotherapy to the primary tumor could be discussed with the patients as a first treatment option for asymptomatic metastatic rectal cancer to prevent local complications later during the disease.
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| 12. |
- Lindman, Henrik, et al.
(författare)
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Individually tailored toxicity-based 5-fluorouracil, epirubicin and cyclophosphamide (FEC) therapy of metastatic breast cancer
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:2, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy dosing only based on body surface area (BSA) results in marked pharmacokinetic and toxicity variations, which may result in an inferior outcome for some patients. A toxicity-based dosing schedule for individually tailored treatment with granulocyte colony-stimulating factor (G-CSF) supported 5-fluorouracil (F), epirubicin (E) and cyclophosphamide (C) (dFEC) was developed and studied in patients with metastatic breast cancer with the purpose to determine its efficiency and toxicity. Twenty-six women, median age 48 years, were included and the individual E and C doses were tailored stepwise based on the recorded hematological toxicity. Twenty-one patients (81%; 95% confidence interval (CI), 66% to 96%) had an objective response, including six complete responses (23%; CI, 7%-39%). At median follow-up of 113 months, the median time to progression and median overall survival were 14 and 36 months, respectively. The delivered dose intensity was high but varied substantially between patients (ranges F 126-202, E 14.4-36.0, C 160-510 mg/m2/w). The dominating grade III/IV toxicity was nausea (12% of patients) and febrile neutropenia (31% of patients). The tailored and dose-escalated FEC was highly active and feasible in metastatic breast cancer and may provide a pragmatic way of overcoming the shortcomings of standard BSA-based dosing.
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| 13. |
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| 14. |
- 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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| 15. |
- Matikas, Alexios, et al.
(författare)
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Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 168:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs. The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up. A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up. In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.
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| 16. |
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| 17. |
- Poikonen-Saksela, Paula, et al.
(författare)
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Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000-1
- 2020
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:7, s. 825-832
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000-1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18-60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m(2)). Patients (n = 1052) with nadir leukopenia grade 0-2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3-4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3-4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74-0.96, p = .008) and overall survival (HR 0.87 (0.76-0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.
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| 18. |
- Suo, Zhenhe, et al.
(författare)
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The expression of EGFR family ligands in breast carcinomas
- 2002
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Ingår i: International Journal of Surgical Pathology. - Thousand Oaks, USA : Sage Publications. - 1066-8969 .- 1940-2465. ; 10:2, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- Expression of EGF, HB-EGF, TGF-alpha, HRG-alpha, HRG-beta1, and HRG-beta3 in 100 frozen breast carcinoma materials was immunohistochemically studied. Among these tumors, 67% were positive for EGF, 53% for HB-EGF, 57% for TGF-alpha, 60% for HRG-alpha, 53% for HRG-beta1, and 63% for HRG-beta3 in the neoplastic epithelial cells. No significant associations between expression of the growth factors and clinicopathological features like tumor size, histologic grade, node status, ploidy, ER status, and c-erbB-4 expression were observed, with the exceptions that significant relations were present between EGF expression and tumor size (p = 0.01) and between HRG-beta3 expression and node status (p = 0.02). The expressions of these growth factors showed no association with cancer-specific survival by the Kaplan Meier analysis.
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| 19. |
- Villman, Kenneth, et al.
(författare)
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A phase II study of epirubicin, cisplatin and capecitabine as neoadjuvant chemotherapy in locally advanced or inflammatory breast cancer
- 2007
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 43:7, s. 1153-1160
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To assess the efficacy and safety of epirubicin, capecitabine and cisplatin (EXC) combination therapy in locally advanced breast cancer (LABC) and investigate the predictive value of selected biomarkers. Methods: Newly diagnosed LABC patients received four 3-weekly cycles of neoadjuvant EXC (epirubicin 60 mg/m2 day 1; capecitabine 1000 mg/m2 bid, days 1-14; cisplatin 60 mg/m2day 1) and two cycles of post-operative EXC. Results: Eight (17%) of 48 patients had inflammatory breast cancer. Overall response rate was 74% (95% CI: 59-86%), including complete responses in 13% (95% CI: 5-26%). Nine (22%; 95% CI: 11-38%) of 41 patients undergoing surgery achieved pathologic complete response (pCR), giving a pCR rate of 19% (95% CI: 9-33%) in the intent-to-treat population. Haematological toxicity was manageable. The most problematic toxicities were chemotherapy-induced nausea/vomiting and hypercoagulative disorders. None of the biomarkers investigated, including HER2, predicted response. Conclusion: EXC showed high efficacy in LABC, with high clinical response and pCR rate. Nausea and vomiting were unexpectedly frequent, and more aggressive prophylaxis and management of these side effects is recommended in future studies of this combination.
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| 20. |
- Villman, Kenneth, 1958-
(författare)
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Chemosensitivity in Breast Cancer
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer mortality in Sweden is now in decline, thanks to early detection and the wide use of adjuvant endocrine therapy and chemotherapy. While hormone receptor status is predictive of response to endocrine treatment, there is no clinically useful predictive marker of a patient’s response to chemotherapy. Consequently, patients receive chemotherapy with considerable toxicity but minimal benefit. The aim of this thesis was to investigate a number of methods with the potential to predict response to chemotherapy and thus enhance treatment efficacy in breast cancer patients.We found that topo IIα, the key target enzyme of topo II inhibitors, is significantly expressed in nonproliferating breast cancer cells. This finding may explain why topo II inhibitors are effective in patients with slow growing tumors and a low proliferation rate.Topo IIα gene amplification was suggestive of increased response to anthracyclines in advanced breast cancer, whereas the oncogene HER2 had no predictive value by itself. These findings are in accordance with current knowledge.Cyclin A, a marker of cell proliferation, showed good prognostic value but did not predict response to chemotherapy in advanced breast cancer.In vitro chemosensitivity testing with FMCA predicted tumor response in patients with advanced breast cancer with a sensitivity of 89% and a specificity of 53%. Our results are consistent with the results from similar assays, which predict drug resistance with good accuracy while clinical drug sensitivity is less reliably predicted. The use of FMCA and similar assays is not yet recommended outside clinical trials; their main utility is in preclinical testing of new anti-cancer drugs, including targeted therapies.The combination of epirubicin, capecitabine, and cisplatin (EXC) demonstrated high clinical response rate (74%) and pathological complete response rate (22%) in locally advanced breast cancer, but with cumbersome toxicity. The fluoropyrimidine biomarkers TS, TP, and DPD did not predict response to the EXC regimen.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Villman, Kenneth, et al.
(författare)
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TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer
- 2006
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:5, s. 590-6
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively).
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| 25. |
- Villman, Kenneth, et al.
(författare)
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Topoisomerase II-α expression in different cell cycle phases in fresh human breast carcinomas
- 2002
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Ingår i: Modern Pathology. - Baltimore : Lippincott Williams & Wilkins. - 0893-3952 .- 1530-0285. ; 15:5, s. 486-491
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase II-alfa (topo IIalfa) is the key target enzyme for the topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo IIalfa is expressed predominantly in the S/G2/M phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo IIalfa is both higher and less dependent on proliferation state in the cell. We studied fresh specimens from 50 cases of primary breast cancer. The expression of topo IIalfa in different cell cycle phases was analyzed with two-parameter flow cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The expression of topo IIalfa was significantly higher in the S/G2/M phase of the cell cycle than in the G0/G1 phase in both DNA diploid and DNA nondiploid tumors. In 18 of 21 diploid tumors, and in 25 of 29 nondiploid tumors, >50% of the topo IIalfa–positive cells were in the G0/G1 phase. This significant expression of topo IIalfa in the G0/G1 phase of the cell cycle may have clinically important implications for treatment efficacy of topoisomerase II inhibitors.
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| 26. |
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| 27. |
- Wickberg, Åsa, 1972-, et al.
(författare)
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Omitting radiotherapy in women >= 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe
- 2018
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 44:7, s. 951-956
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET).Patients and Methods: Eligibility criteria were: consecutive patients with age >= 65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival.Results: Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65-90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%).Conclusion: BCS and ET without RT seem to be a safe treatment option in women >= 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
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| 28. |
- Wickberg, Åsa, 1972-, et al.
(författare)
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Reply to a. Levy et Al.
- 2014
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:29, s. 3340-3341
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Wickberg, Åsa, 1972-, et al.
(författare)
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Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer : 20-Year Results of a Randomized Trial
- 2014
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:8, s. 791-797
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate how radiotherapy (XRT) adds to tumor control using a standardized surgical technique with meticulous control of surgical margins in a randomized trial with 20 years of follow-up.Patients and Methods: Three hundred eighty-one women with pT1N0 breast cancer were randomly assigned to sector resection with (XRT group) or without (non-XRT group) postoperative radiotherapy to the breast. With follow-up through 2010, we estimated cumulative proportion of recurrence, breast cancer death, and all-cause mortality.Results: The cumulative probability of a first breast cancer event of any type after 20 years was 30.9% in the XRT group and 45.1% in the non-XRT group (hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.82). The benefit of radiotherapy was achieved within the first 5 years. After 20 years, 50.4% of the women in the XRT group died compared with 54.0% in the non-XRT group (HR, 0.92; 95% CI, 0.71 to 1.19). The cumulative probability of contralateral cancer or death as a result of cancer other than breast cancer was 27.1% in the XRT group and 24.9% in the non-XRT group (HR, 1.17; 95% CI, 0.77 to 1.77). In an anticipated low-risk group, the cumulative incidence of first breast cancer of any type was 24.8% in the XRT group and 36.1% in the non-XRT group (HR, 0.61; 95% CI, 0.35 to 1.07).Conclusion: Radiotherapy protects against recurrences during the first 5 years of follow-up, indicating that XRT mainly eradicates undetected cancer foci present at primary treatment. The similar rate of recurrences beyond 5 years in the two groups indicates that late recurrences are new tumors. There are subgroups with clinically relevant differences in risk.
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| 30. |
- Wu, Qinghua, et al.
(författare)
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Expression of Ephb2 and Ephb4 in breast carcinoma
- 2004
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Ingår i: Pathology and Oncology Research. - Budapest, Hungary : Arányi Lajos Foundation. - 1219-4956 .- 1532-2807. ; 10:1, s. 26-33
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Tidskriftsartikel (refereegranskat)abstract
- Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, play key roles in diverse biological processes. Eph receptors comprise the largest family of receptor tyrosine kinases consisting of eight EphA receptors (with five corresponding ephrinA ligands) and six EphB receptors (with three corresponding transmembrane ephrinB ligands). Originally identified as neuronal pathfinding molecules, EphB receptors and ephrinB ligands are later proved to be crucial regulators of vasculogenesis and embryogenesis. More studies indicate that Eph receptors are involved in angiogenesis and tumorigenesis. This study aimed to investigate the expression of EphB2 and EphB4 in breast carcinomas. Semiquantitative RT-PCR and immunohistochemistry were used to examine the expression patterns of EphB2 and EphB4. Clinicopathological and survival correlations were statistically analyzed in a series of 94 breast carcinomas, 9 normal specimens and 4 breast carcinoma cell lines. 1(1%), 16(17%), 29(31%), 48(51%) of the 94 tumors were negative, weak, moderate and strong EphB2 protein expression, respectively. 6(6%), 27(29%), 28(30%), 33(35%) of the tumors were negative, weak, moderate and strong EphB4 expression, respectively. Both EphB2 and EphB4 RTPCR products could be detected in all specimens. Increased EphB2 protein expression was negatively associated with overall survival, and there was a trend that increased EphB2 protein expression was correlated with shorter disease free survival, while EphB4 protein expression was associated with histological grade and stage. EphB4 membrane staining was increased with S phase fraction and associated with DNA aneuploidy. These findings indicate that both EphB2 and EphB4 are involved in the development of breast cancer and that both molecules could be potential predictive markers.
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