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  • 1.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Small breast cancers: Diagnosis, prognostic factors and clinical outcome in a screening population1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Breast cancer ≤ 10 mm together with ductal in situ cancer of the breast (DCIS) today constitute more than 40% of screening detected breast malignancies. Prognostic factors, diagnosis and clinical outcome for invasive breast cancers ≤ 10 mm and local recurrence in DCIS were evaluated.

    Histopathological grading was done in 248 ductal breast cancers and grade III was correlated to aneuploidy, increased S-phase fraction and receptor negative tumours. Life table analysis showed a significant increase in breast cancer mortality in grade III tumours (p < 0.001).

    Hormone receptors and cytometric variables were studied in ≤ 10 mm breast cancers. Around 60% of these small cancers were evaluable. Aneuploidy was found in 52% and SPF ≥ 10 in 20%. Mean SPF was 4.8 in diploid and 7.6 in aneuploid tumours. A potentially high risk group with high SPF figures and receptor negative tumours comprise 7% of the patients.

    Diagnostic surgery was performed in 314 non-palpable breast lesions. Insufficient excisions were observed in 16 cases (5%), mostly in lesions with microcalcifications and in situ cancers ≥ 30 mm in extent. Underestimation of in situ cancers is the main reason for inadequate surgery.

    DCIS comprises approx 10% of breast malignancies. In 38 cases operated with breast preserving surgery 13% got local recurrence in median 60 months follow-up.

    Recurrence free survival in patients with ≤ 10 mm breast cancers were evaluated for 324 cases. Only 8% of these patients had adjuvant treatment. Lymph node involvement was found in 9% of screening detected and 20% in clinically detected cancers (p < 0.03). Median prospective follow-up time was 7 years and distant metastases appeared in 8 patients, local recurrence in 3. Life table analysis showed 97% overall distant recurrence free survival, 99% in node negative and 79% in node positive patients (p < 0.001).

    We can today, by grading and cytometric variables, find subgroups with high risk of recurrence after breast cancer surgery in small breast cancers. These are probably the only patients that benefit from adjuvant treatment and need follow-up outside mammography screening. Breast conserving surgery can be performed in the majority of DCIS patients.

  • 2.
    Arnesson, Lars-Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: endokir.
    Ahlgren, J
    Omitting axillary surgery for low-risk breast cancer patients. A Swedish prospective cohort study.2000In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 39, p. 291-294Article in journal (Refereed)
  • 3. Emdin, SO
    et al.
    Granstrand, B
    Ringberg, A
    Sandelin, K
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Nordgren, H
    Andersson, H
    Garmo, H
    Holmberg, L
    Wallgren, A
    SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening2006In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 45, no 5, p. 536-543Article in journal (Refereed)
    Abstract [en]

    We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1 046 operated women to postoperative RT or control between 1987 and 1999. The primary endpoint was ipsilateral local recurrence. Secondary endpoints were contralateral breast cancer, distant metastasis and death. After a median follow-up of 5.2 years (range 0.1-13.8) there were 44 recurrences in the RT group corresponding to a cumulative incidence of 0.07 (95% confidence interval (CI) 0.05-0.10). In the control group there were 117 recurrences giving a cumulative incidence of 0.22 (95% CI 0.18-0.26) giving an overall hazard ratio of 0.33 (95% CI 0.24-0.47, p <0.0001). Twenty two percent of the patients had microscopically unknown or involved margins. We found no evidence for different effects of RTon the relative risk of invasive or in situ recurrence. Secondary endpoints did not differ. Women undergoing sector resection for DCIS under conditions of population based screening mammography benefit from postoperative RT to the breast. Seven patients needed RT-treatment to prevent one recurrence. © 2006 Taylor & Francis.

  • 4. Fredriksson, I
    et al.
    Liljegren, G
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: endokir.
    Emdin, SO
    Palm-Sjovall, M
    Fornander, T
    Frisell, J
    Holmberg, L
    Time trends in the results of breast conservation in 4694 women2001In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 37, no 12, p. 1537-1544Article in journal (Refereed)
    Abstract [en]

    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.

  • 5. Fredriksson, I
    et al.
    Liljegren, G
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Emdin, SO
    Palm-Sjövall, M
    Fornander, T
    Holmqvist, M
    Holmberg, L
    Frisell, J
    Consequences of axillary recurrence after conservative breast surgery2002In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 89, no 7, p. 902-908Article in journal (Refereed)
    Abstract [en]

    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.

  • 6. Fredriksson, I
    et al.
    Liljegren, G
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Emdin, SO
    Palm-Sjövall, M
    Fornander, T
    Holmqvist, M
    Holmberg, L
    Frisell, J
    Local recurrence in the breast after conservative surgery - A study of prognosis and prognostic factors in 391 women2002In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 38, no 14, p. 1860-1870Article in journal (Refereed)
    Abstract [en]

    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.

  • 7. Fredriksson, I
    et al.
    Liljegren, G
    Palm-Sjövall, M
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Emdin, SO
    Fornander, T
    Lindgren, A
    Nordgren, H
    Idvall, I
    Holmqvist, M
    Holmberg, L
    Frisell, J
    Risk factors for local recurrence after breast-conserving surgery2003In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 90, no 9, p. 1093-1102Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Gimm, Oliver
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Olofsson, Pia
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Morales, Olallo
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Juhlin, Claes
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Super-selective venous sampling in conjunction with quickPTH for patients with persistent primary hyperparathyroidism: report of five cases2012In: Surgery today (Print), ISSN 0941-1291, E-ISSN 1436-2813, Vol. 42, no 6, p. 570-576Article in journal (Refereed)
    Abstract [en]

    Selective venous sampling (SVS) helps to interpret imaging results in patients with persistent primary hyperparathyroidism (pHPT). However, one of the drawbacks of conventional SVS may be low "spatial resolution", depending on the sample size. We modified SVS in the following way: first, patients underwent conventional SVS with up to 11 parathyroid hormone (PTH) samples taken. The quickPTH assay was used to measure PTH levels. The patients subsequently underwent super-selective venous sampling (super-SVS) in the region with the highest quickPTH level in the same session. The subjects were five consecutive patients with persistent pHPT investigated by various imaging techniques, none of which was considered conclusive. Therefore, all five patients underwent super-SVS, which was done successfully in four. Re-evaluation of the imaging results of these four patients resulted in localization of the parathyroid adenoma. Curative surgery was performed successfully in all four patients during the study period. Super-SVS increases the "spatial resolution" of conventional SVS and may have advantages when imaging results of patients with persistent pHPT are interpreted. Its true value must be analyzed in larger studies.

  • 9.
    Gunnarsson, Cecilia
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Olsson, Birgit
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Abnormal expression of 17β-hydroxysteroid dehydrogenases in breast cancer predicts late recurrence2001In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 61, no 23, p. 8448-8451Article in journal (Refereed)
    Abstract [en]

    The 17β-hydroxysteroid dehydrogenase (17β-HSD) enzymes are involved in the interconversion of biologically active and inactive sex steroids and are considered to play a critical role in the in situ metabolism of estrogen, especially in estrogen-dependent breast cancer. The gene encoding 17β-HSD type 2 is located at 16q24.1-2, and earlier studies have shown that allelic loss in this region is an early and frequent event in breast cancer progression. Recurrence of hormone-dependent breast cancer frequently occurs several years after the primary treatment. The aim of this study was to investigate whether the expression of 17β-HSD types 1 and 2 differs in tumors from patients with late relapses (>5 years) compared with controls without recurrence after long-term follow-up. Using real-time reverse transcription-PCR, we found that the normal mammary gland expressed both 17β-HSD types 1 and 2, whereas the tumors frequently lacked detectable levels of type 2. Only 10% of the estrogen receptor-positive tumors expressed type 2, whereas 31% of the ERnegative tumors did so (P = 0.031). In a case-control series of 84 patients, a high level of 17β-HSD type 1 indicated increased risk to develop late relapse of breast cancer (odds ratio, 3.0; 95% confidence interval, 1.0–12.6; P = 0.041), whereas retained expression of type 2 indicated decreased risk (odds ratio, 0.25; 95% confidence interval, 0.05–1.2; P = 0.050). In multivariate analysis of the estrogen receptor-positive patients, the absence of 17β-HSD type 2 combined with a high expression of type 1 showed prognostic significance (P = 0.016) in addition to DNA aneuploidy (P = 0.0058), whereas progesterone receptor status did not (P = 0.71). These findings suggest that abnormal expression of 17β-HSD isoforms has prognostic significance in breast cancer and that altered expression of these enzymes may have importance in breast cancer progression.

  • 10.
    Holmberg, L
    et al.
    Kings Coll London, England .
    Wong, Y N S
    Kings Coll London, England .
    Tabar, L
    Uppsala University, Sweden .
    Ringberg, A
    University Hospital MAS, Sweden .
    Karlsson, P
    Sahlgrens University Hospital, Sweden .
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandelin, K
    Karolinska University Hospital, Sweden .
    Anderson, H
    Lund University, Sweden .
    Garmo, H
    Kings Coll London, England .
    Emdin, S
    Umeå University Hospital, Sweden .
    Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study2013In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, no 4, p. 812-819Article in journal (Refereed)
    Abstract [en]

    Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. less thanbrgreater than less thanbrgreater thanMethods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. less thanbrgreater than less thanbrgreater thanResults: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). less thanbrgreater than less thanbrgreater thanConclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

  • 11.
    Holmberg, Lars
    et al.
    Kings Coll London, Div Canc Studies, London SE1 9RT, England.
    Garmo, Hans
    Regional Oncologic Center, University Hospital, Uppsala.
    Granstrand, Bengt
    Norrland University Hospital, Umeå.
    Ringberg, Anita
    Malmö University Hospital.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sandelin, Kerstin
    Karolinska Hospital, Stockholm.
    Karlsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Anderson, Harald
    University Hospital, Lund.
    Emdin, Stefan
    Norrland University Hospital, Umeå.
    Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast2008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 8, p. 1247-1252Article in journal (Refereed)
    Abstract [en]

    Purpose Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection. Patients and Methods A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat. Results There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy. Conclusion Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful.

  • 12.
    Johansson, Patrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fohlin, Helena
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Dufmats, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjoeld, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Improved survival for women with stage I breast cancer in south-east Sweden: A comparison between two time periods before and after increased use of adjuvant systemic therapy2009In: ACTA ONCOLOGICA, ISSN 0284-186X, Vol. 48, no 4, p. 504-513Article in journal (Refereed)
    Abstract [en]

    Purpose. Continuous minor steps of improvement in the management of breast cancer have resulted in decreased mortality rates during the last decades. The aim of this study was to compare the clinical outcome of patients with stage I breast cancer diagnosed during two time periods that differed with respect to adjuvant systemic therapy. Material and methods. The studied population consisted of all women 60 years of age, who were diagnosed breast cancer stage I between 1986 and 1999 in south-east Sweden, a total of 1 407 cases. The cohort was divided into two groups based on the management programmes of 1986 and 1992, hereafter referred to as Period 1 and Period 2. Before 1992 the only adjuvant systemic therapy recommended was tamoxifen for hormone receptor positive patients aged 50 years or older. During Period 2 the use of adjuvant treatment was extended to younger patients at high risk, identified by a high tumour S-phase fraction, with either hormonal or cytotoxic treatment. Results. The estimated distant recurrence-free survival rate was significantly higher during Period 2 than during Period 1 (p = 0.008). Subgroup analysis showed that the most evident reduction of distant recurrence risk was among hormone receptor-negative patients (HR = 0.58, 95% CI 0.31-1.09, p = 0.09) and among patients with a high tumour S-phase fraction (HR = 0.53, 0.30-0.93, p = 0.028). The risk reduction between the periods was still statistically significant in multivariate analysis when adjusting for different tumour characteristics and treatment modalities, indicating an influence of other factors not controlled for. One such factor may be the duration of tamoxifen treatment, which likely was more frequently five years during Period 2 than during Period 1. Conclusions. We conclude that the causes of the increase in distant recurrence free survival for women with breast cancer stage I are complex. The results support though that high-risk subgroups of stage I breast cancer patients did benefit from increased use of systemic therapy as a consequence of an updated management programme.

  • 13.
    Linderholm, B K.
    et al.
    Sahlgrens Acad, Sweden .
    Linder, S
    Karolinska Institute, Sweden .
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Identification of intermediate risk breast cancer patients with1-3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis2013In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 22, no 5, p. 643-649Article in journal (Refereed)
    Abstract [en]

    Background: According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. less thanbrgreater than less thanbrgreater thanAim: Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. less thanbrgreater than less thanbrgreater thanMaterial and methods: Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. less thanbrgreater than less thanbrgreater thanResults: A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/mu gDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p andlt; 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Coxs proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. less thanbrgreater than less thanbrgreater thanConclusion: By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.

  • 14.
    Nordenskjold, A. E.
    et al.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences. Regional Cancer Centre South East Sweden, Linkoping, Sweden.
    Albertsson, P.
    Sahlgrens University Hospital, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Chamalidou, C.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Einbeigi, Z.
    Sahlgrens University Hospital, Sweden.
    Holmberg, E.
    Regional Cancer Centre, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Karlsson, P.
    Sahlgrens University Hospital, Sweden.
    No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 6, p. 1149-1154Article in journal (Refereed)
    Abstract [en]

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

  • 15.
    Ringberg, A.
    et al.
    Department of Plastic Surgery, Malmö University Hospital, Malmö, Sweden.
    Nordgren, H.
    Department of Pathology, University Hospital, Uppsala, Sweden.
    Thorstensson, S.
    Department of Pathology, Central Hospital, Kalmar, Sweden.
    Idvall, I.
    Department of Pathology, Malmö University Hospital, Malmö, Sweden.
    Garmo, H.
    Regional Oncologic Center, University Hospital, Uppsala, Sweden.
    Granstrand, B.
    Department of Surgery, Norrland University Hospital, Umeå, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sandelin, K.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Wallgren, A.
    Department of Oncology, Sahlgenska University Hospital, Gothenburg, Sweden.
    Anderson, H.
    Regional Oncologic Center, University Hospital, Lund, Sweden.
    Emdin, S.
    Department of Surgery, Norrland University Hospital, Umeå, Sweden.
    Holmberg, L.
    Regional Oncologic Center, University Hospital, Uppsala, Sweden.
    Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast - Results from the Swedish randomised trial2007In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 43, no 2, p. 291-298Article in journal (Refereed)
    Abstract [en]

    Aim: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. Setting: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. Methods: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. Results: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (? = 0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. Conclusion: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area. © 2006 Elsevier Ltd. All rights reserved.

  • 16.
    Stenmark-Askmalm, Askmalm Marie
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gentile, Massimiliano
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Protein accumulation and gene mutation of p53 in bilateral breast cancer2001In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 40, no 1, p. 56-62Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the frequency of p53 alterations in bilateral breast cancer and to evaluate a possible clonal relationship between the paired tumours regarding p53 alteration and other pathobiological variables. Tumours from 34 patients were investigated with immunohistochemistry, single strand conformation polymorphism analysis and DNA-sequence analysis applied to exons 5-8. Fifteen percent of the 68 tumours showed positive immunoreaction and/or presence of mutation. The occurrence of p53 accumulation was 9% and the prevalence of gene mutation 10%. No significant concordance was found between the tumours in the same patient for p53 alterations, progesterone receptor status or DNA ploidy. S-phase fraction showed a weak correlation, not statistically significant. Oestrogen receptor status was the only variable that exhibited a significant concordance. No convincing evidence was found for other associations between the paired tumours or for a high prevalence of p53 alterations in bilateral breast cancer.

  • 17.
    Sundquist, M
    et al.
    Kalmar County Hospital.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Brudin, L
    Kalmar County Hospital.
    Fohlin, H
    Tejler , G
    Västervik Hospital.
    When do locoregional recurrencies occur and how common is contralateral breast cancer?2009In: in CANCER RESEARCH, vol 18, 2009, Vol. 18, p. S76-S76Conference paper (Refereed)
  • 18. Tejler, G
    et al.
    Norberg, B
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Arnesson, Lars-Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Survival after treatment for breast cancer in a geographically defined population2004In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 91, no 10, p. 1307-1312Article in journal (Refereed)
    Abstract [en]

    Background: South East Sweden with 976000 inhabitants is served by nine hospitals with specialized breast surgeons. Population-based mammographic screening was introduced in 1986 for women aged 40-74 years. Patients with primary breast cancer were treated according to a joint management programme. Methods: All patients were reported to a regional cancer registry from which breast cancer incidence, treatment and survival in this defined population were reported. Results: A total of 7892 women had their first invasive breast cancer diagnosed between 1986 and 1999. The median tumour size was 17 mm and 29.9 per cent had axillary metastases. Some 49.8 per cent of these women had a modified radical mastectomy and 31.9 per cent had a segmental resection with axillary clearance. Postoperative radiotherapy was given to 40.3 per cent of the women after mastectomy and to 87.1 per cent after breast-conserving surgery. Tamoxifen and chemotherapy were used as adjuvant treatment except in low-risk patients. Breast cancer-specific survival rate for all stages was 83.5 per cent at 5 years and 74.0 per cent at 10 years. Respective values were 95.8 and 90.9 per cent for patients with stage T1 N0 M0 tumours, and 77.7 and 62.4 per cent for those with T1-2 N1 M0 tumours. Conclusion: Breast specialists treating women with breast cancer according to a joint management programme have achieved very good survival rates.

  • 19.
    Vitak, B
    et al.
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Olsen, K E
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology. Linköping University, Faculty of Health Sciences.
    Månson, Jan-Christer
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology. Linköping University, Faculty of Health Sciences.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening: a comparison of true interval and missed interval cancers1999In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 9, no 3, p. 460-469Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients with invasive interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were evaluated with regard to age, radiological category, interval between the latest screen and diagnosis and tumour characteristics at the time of diagnosis. We investigated possible relationships between the survival rate of patients with interval cancer and the interval between the latest screen and diagnosis, tumour characteristics and radiological category of the interval tumours. The study focused on comparison of patients with true interval and missed interval cancer. Women with mammographically occult tumours were younger than those in the other radiological categories. Comparisons of true interval cancers with overlooked or misinterpreted tumours showed equal distributions of age, tumour size, TNM stage and lymph node status. The overlooked or misinterpreted tumours showed significantly higher proportions of grade-I tumours (22 vs 11 %), tumours with low S-phase fraction (SPF; 44 vs 24 %) and oestrogen receptor (ER) positive tumours (72 vs 57 %). However, analyses of survival rates disclosed no clear differences between the two radiological categories. Radiological category and interval between the latest screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive tumours and tumours with low SPF in the latter group.

  • 20.
    Warnberg, Fredrik
    et al.
    Uppsala University, Sweden.
    Garmo, Hans
    Uppsala University, Sweden; Kings Coll London, England.
    Emdin, Stefan
    Umeå University Hospital, Sweden.
    Hedberg, Veronica
    Gavle Central Hospital, Sweden.
    Adwall, Linda
    Uppsala University, Sweden.
    Sandelin, Kerstin
    Karolinska University Hospital, Sweden.
    Ringberg, Anita
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Karlsson, Per
    Sahlgrens University Hospital, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Anderson, Harald
    Lund University, Sweden.
    Jirstrom, Karin
    Lund University, Sweden.
    Holmberg, Lars
    Uppsala University, Sweden; Kings Coll London, England.
    Effect of Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma in Situ: 20 Years Follow-Up in the Randomized SweDCIS Trial2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 32, p. 3613-+Article in journal (Refereed)
    Abstract [en]

    Purpose Four randomized studies show that adjuvant radiotherapy (RT) lowers the risk of subsequent ipsilateral breast events (IBEs) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) by approximately 50% after 10 to 15 years. We present 20 years of follow-up data for the SweDCIS trial. Patients and Methods Between 1987 and 1999 1,046 women were randomly assigned to RT or not after BCS for primary DCIS. Results up to 2005 have been published, and we now add another 7 years of follow-up. All breast cancer events and causes of death were registered. Results There were 129 in situ and 129 invasive IBEs. Absolute risk reduction in the RT arm was 12.0% at 20 years (95% CI, 6.5 to 17.7), with a relative risk reduction of 37.5%. Absolute reduction was 10.0% (95% CI, 6.0 to 14.0) for in situ and 2.0% (95% CI, -3.0 to 7.0) for invasive IBEs. There was a nonstatistically significantly increased number of contralateral events in the RT arm (67 v 48 events; hazard ratio, 1.38; 95% CI, 0.95 to 2.00). Breast cancer-specific death and overall survival were not influenced. Younger women experienced a relatively higher risk of invasive IBE and lower effect of RT. The hazard over time looked different for in situ and invasive IBEs. Conclusion Use of adjuvant RT is supported by 20-year follow-up. Modest protection against invasive recurrences and a possible increase in contralateral cancers still call for a need to find groups of patients for whom RT could be avoided or mastectomy with breast reconstruction is indicated.

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