| 31. |
- de Boniface, Jana, 1971-
(författare)
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Sentinel Node Biopsy in Breast Cancer : Clinical and Immunological Aspects
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The most important prognostic factor in breast cancer is the axillary lymph node status. The sentinel node biopsy (SNB) is reported to stage the axilla with an accuracy > 95 % in early breast cancer. Tumour-related perturbation of T-cell function has been observed in patients with malignancies, including breast cancer. The down-regulation of the important T-cell activation molecules CD3-ζ and CD28 may cause T-cell dysfunction, anergy, tolerance and deletion.The expression of CD3-ζ and CD28 was evaluated in 25 sentinel node biopsies. The most pronounced down-regulation was seen in the paracortical area, where the best agreement between both parameters was observed. CD28 expression was significantly more suppressed in CD4+ than in CD8+ T-cells.From the Swedish sentinel node database, 109 patients with breast cancer > 3 cm planned for both SNB and a subsequent axillary dissection were identified. The false negative rate (FNR) was 12.5%. Thirteen cases of tumour multifocality were detected on postoperative pathology. The FNR in this subgroup was higher (30.8%) than in patients with unifocal disease (7.8%; P = 0.012).From the Swedish SNB multicentre cohort trial, 2246 sentinel node-negative patients who had not undergone further axillary surgery were selected for analysis. After a median follow-up time of 37 months (range 0-75), 13 isolated axillary recurrences (13/2246; 0.6%) were found. In another 14 cases, local or distant failure preceded or coincided with axillary relapse (27/2246; 1.2%). In conclusion, the immunological analysis of the sentinel node might provide valuable prognostic information and aid selection of patients for immunotherapy. SNB is encouraged in breast cancer larger than 3 cm, if no multifocal growth pattern is present. The axillary recurrence rate after a negative SNB in Sweden is in accordance with international figures. However, a longer follow-up is mandatory before the true failure rate of the SNB can be determined.
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| 32. |
- de Boniface, J., et al.
(författare)
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Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial
- 2017
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference. Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1: 1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years. Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.
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| 33. |
- de Boniface, J., et al.
(författare)
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The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 180:1, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- Purpose None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015
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| 34. |
- Eaker, Sonja, et al.
(författare)
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Breast cancer, sickness absence, income and marital status : A study on life situation 1 year prior diagnosis compared to 3 and 5 years after diagnosis
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3, s. e18040-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improved cancer survival poses important questions about future life conditions of the survivor. We examined the possible influence of a breast cancer diagnosis on subsequent working and marital status, sickness absence and income. MATERIALS: We conducted a matched cohort study including 4,761 women 40-59 years of age and registered with primary breast cancer in a Swedish population-based clinical register during 1993-2003, and 2,3805 women without breast cancer. Information on socioeconomic standing was obtained from a social database 1 year prior and 3 and 5 years following the diagnosis. In Conditional Poisson Regression models, risk ratios (RRs) and 95% confidence intervals (CIs) were estimated to assess the impact of a breast cancer diagnosis. FINDINGS: Three years after diagnosis, women who had had breast cancer more often had received sickness benefits (RR = 1.49, 95% CI 1.40-1.58) or disability pension (RR = 1.47, 95% CI 1.37-1.58) than had women without breast cancer. We found no effect on income (RR = 0.99), welfare payments (RR = 0.98), or marital status (RR = 1.02). A higher use of sickness benefits and disability pension was evident in all stages of the disease, although the difference in use of sickness benefits decreased after 5 years, whereas the difference in disability pension increased. For woman with early stage breast cancer, the sickness absence was higher following diagnosis among those with low education, who had undergone mastectomy, and had received chemo- or hormonal therapy. Neither tumour size nor presence of lymph nodes metastasis was associated with sickness absence after adjustment for treatment. INTERPRETATION: Even in early stage breast cancer, a diagnosis negatively influences working capacity both 3 and 5 years after diagnosis, and it seems that the type of treatment received had the largest impact. A greater focus needs to be put on rehabilitation of breast cancer patients, work-place adaptations and research on long-term sequelae of treatment.
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| 35. |
- Eaker, Sonja, et al.
(författare)
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Differences in management of older women influence breast cancer survival : results from a population-based database in Sweden
- 2006
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 3:3, s. e25-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival. METHODS AND FINDINGS: In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50-84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70-84 y of age compared to women aged 50-69 y, and the difference was most pronounced in stage IIB-III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB. CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone.
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| 36. |
- Eaker, Sonja, et al.
(författare)
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Social differences in breast cancer survival in relation to patient management within a National Health Care System (Sweden)
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:1, s. 180-187
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologic studies have shown that cancer survival is poorer in low compared with high socioeconomic groups. We investigated whether these differences were associated with disparities in tumour characteristics and management. This cohort study was based on 9,908 women aged 20-79 years at diagnosis with primary breast cancer identified in a Swedish population-based clinical register. Information on socioeconomic standing was obtained from a social database. The 5-year cause-specific survival (CSS) and mortality hazard ratios (HR) were estimated by Cox proportional hazard models to assess differences in survival between socioeconomic groups while adjusting for diagnostic intensity, tumour characteristics and treatment. Following adjustment for age, year and stage at diagnosis, the risk of dying of breast cancer was 35% lower among women with high education compared with that of low education (HR = 0.65, 95% CI 0.53-0.80). When compared with women with high education, a lower percentage of women with low education had been investigated for proliferation (84 vs. 76%) or hormone receptor status (89 vs. 81%), had tumours
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| 37. |
- Eklund, Arne, 1957-, et al.
(författare)
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A cost-minimisation analysis comparing TEP with Lichtenstein for treatment of inguinal hernia in Sweden
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Laparoscopic surgery has emerged as a new treatment modality for inguinal hernia. It is important to analyse its long-term costs in relation to other methods.Methods: A randomized multicenter study comparing totally extraperitoneal laparoscopic repair (TEP) with open repair according to Lichtenstein was performed on men with a primary inguinal hernia. Long-term follow-up collecting data on recurrences and complications up to five years after operation was carried out. Taking treatment costs into consideration, a cost-minimisation analysis was conducted.Results: Altogether 1370 patients were operated, 665 in the TEP and 705 in the Lichtenstein group. The total hospital cost for the index operation was €710.6 higher for TEP (P<0.001). Including costs for recurrences and complications, this difference increased to €795.1 (P<0.001). Taking community costs into account, the difference decreased with €503.1 to €292.0 (P=0.024).Conclusion: With five-year follow-up including complication, reoperation and community costs, there was a small but significant difference in total costs between the two methods.
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| 38. |
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| 39. |
- Eklund, Arne, 1957-
(författare)
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Laparoscopic or Open Inguinal Hernia Repair - Which is Best for the Patient?
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inguinal hernia repair is the most common operation in general surgery. Its main challenge is to achieve low recurrence rates. With the introduction of mesh implants, first in open and later in laparoscopic repair, recurrence rates have decreased substantially. Therefore, the focus has been shifted from clinical outcome, such as recurrence, towards patient-experienced endpoints, such as chronic pain. In order to compare the results of open and laparoscopic hernia repair, a randomised multicentre trial - the Swedish Multicentre trial of Inguinal hernia repair by Laparoscopy (SMIL) - was designed by a study group from 11 hospitals. Between November 1996 and August 2000, 1512 men aged 30-70 years with a primary inguinal hernia were randomised to either laparoscopic (TEP, Totally ExtraPeritoneal) or open (Lichtenstein) repair. The primary endpoint was recurrence at five years. Secondary endpoints were short-term results, frequency of chronic pain and a cost analysis including complications and recurrences up to five years after surgery. In total, 1370 patients, 665 in the TEP and 705 in the Lichtenstein group, underwent operation. With 94% of operated patients available for follow-up after 5.1 years, the recurrence rate was 3.5% in the TEP and 1.2% in the Lichtenstein group. Postoperative pain was lower in the TEP group up to 12 weeks after operation, resulting in five days less sick leave and 11 days shorter time to full recovery. Patients in the TEP group had a slightly increased risk of major complications. Chronic pain was reported by 9-11% of patients in the TEP and 19-25% in the Lichtenstein group at the different follow-up points. Hospital costs for TEP were higher than for Lichtenstein, while community costs were lower due to shorter sick leave. By avoiding disposable laparoscopic equipment, the cost for TEP would be almost equal compared with Lichtenstein. In conclusion, both TEP and Lichtenstein repair have advantages and disadvantages for the patient. Depending on local resources and expertise both methods can be used and recommended for primary inguinal hernia repair.
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| 40. |
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