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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Fredriksson, I, et al.
(författare)
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Consequences of axillary recurrence after conservative breast surgery
- 2002
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 89:7, s. 902-908
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. Methods: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. Results: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. Conclusion: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.
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- Fredriksson, I, et al.
(författare)
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Local recurrence in the breast after conservative surgery - A study of prognosis and prognostic factors in 391 women
- 2002
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 38:14, s. 1860-1870
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (=2 years) recurrence in the same quadrant as the primary tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and 56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in the probability of breast cancer-specific survival, as measured from the recurrence, between women who initially did or did not receive radiotherapy (P=0.0123). However, when measured from primary treatment, there was no significant difference, indicating that the difference in prognosis could be due to a lead-time bias. Independent prognostic factors for breast cancer-specific survival in women with local recurrences were time to local recurrence and the Nottingham Prognostic Index (NPI). ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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- Fredriksson, I, et al.
(författare)
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Risk factors for local recurrence after breast-conserving surgery
- 2003
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 90:9, s. 1093-1102
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. Method: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. Results: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. Conclusion: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.
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- Fredriksson, I, et al.
(författare)
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Time trends in the results of breast conservation in 4694 women
- 2001
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 37:12, s. 1537-1544
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based cohort of 4694 women with invasive breast cancer, operated upon with breast conserving surgery (BCS) in 1981-1990 and followed through to 1997, we studied how this technique had been adopted into clinical practice, especially with reference to the use of radiotherapy (RT). Our main aim was to see whether there was a drift in the risk of local recurrence and breast cancer death over time. During the 30 151 person-years of observation in the cohort, there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to other causes. Postoperative RT was given to 70.2%, but usage increased over the period. The women not receiving RT were mostly elderly, but also in women <70 years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6 and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local recurrence at 10 years. Thus, the choice not to irradiate failed to target women at a low risk. In a multivariate Cox analysis taking tumour size, nodal status, age at operation and RT into account, there was a trend for a higher risk of local recurrence in the later time period, relative hazard 1.5 (95% confidence interval (CI) 1.0-2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years, respectively. ⌐ 2001 Elsevier Science Ltd. All rights reserved.
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