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  • 1.
    Wadsten, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Garmo, H.
    Umeå University.
    Fredriksson, I.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Warnberg, F.
    DCIS and the risk of breast cancer death: a case control study2017In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 77Article in journal (Refereed)
    Abstract [en]

    Introduction: The risk of breast cancer death after a primary ductal carcinoma in situ (DCIS) is less than 2 % after 10 years. Whereas in situ recurrences do not influence survival, a 17-fold elevated risk of breast cancer specific mortality has been shown for invasive recurrences. Adjuvant radiotherapy (RT) effectively reduces recurrences after breast conserving surgery (BCS) for DCIS, but no studies have been able to demonstrate a survival benefit from adjuvant RT treatment or from choosing mastectomy instead of BCS. Here patient and tumour related risk factors for breast cancer death in women with a pure primary DCIS were studied.

    Patients and methods: Women registered with a primary DCIS, between 1992-2012 in three of Sweden´s health care regions with a population of approximately 5.2 million, were enrolled in a nested case-control study. Out of 6,964 women with DCIS, 96 patients who later died from breast cancer were identified. Four controls per case (n=318) were randomly selected by incidence density sampling. We retrieved medical records and pathology reports and calculated OR with 95% CIs for various variables using conditional logistic regression.

    Results: Of the 96 cases, 10 patients developed distant metastasis without a known local recurrence. In 56 patients death was preceded by an invasive ipsilateral recurrence and in 3 patients by a recurrent ipsilateral DCIS. Seven patients had invasive breast events in both the ipsilateral and the contralateral breast. Seventeen patients had contralateral invasive breast cancer and 3 patients contralateral DCIS.

    Multifocality and tumour size over 25mm (OR 2.6 (1.6 to 4.2)), positive or uncertain margin status (OR 2.8 (1.6 to 4.9)) and detection outside screening (OR 2.1 (1.2 to 3.9)) increased the risk of breast cancer death in univariate analysis, when adjusted for age and year of diagnosis. Suspicion of micro-invasion and nuclear grade 3 was associated with a nonsignificant increased risk, OR 1.8 (0.6 to 5.0) and 2.6 (0.9-6.5), respectively. The risk was not affected by age or treatment. Tumour size and margin status remained significant in the multivariable analysis, when adjusted for treatment and for contralateral breast cancer (OR 2.0 (1.2 to 3.7)).

    Conclusion: In the present study, large tumours and positive or uncertain margin status were significant risk factors for later breast cancer death after a primary DCIS. More extensive treatment was not related to a lower risk. The significance of tumour biology and nuclear grade will be further examined and evaluated.

  • 2.
    Wadsten, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Department of Surgery, Sundsvall Hospital, Sundsvall ; Department of Surgical Sciences, Uppsala University.
    Garmo, H.
    Fredriksson, I.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Warnberg, F.
    Risk of death from breast cancer after treatment for ductal carcinoma in situ2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 11, p. 1506-1513Article in journal (Refereed)
    Abstract [en]

    Background Studies to date have failed to demonstrate any survival benefit from preventing local recurrence after treatment for ductal breast carcinoma in situ (DCIS). Patient- and tumour-related risk factors for death from breast cancer in women with a primary DCIS were analysed here in a large case-control study.

    Methods A nested case-control study was conducted in a population-based cohort of women with primary DCIS between 1992 and 2012. Women who later died from breast cancer were identified. Four controls per case were selected randomly by incidence density sampling. Medical records and pathology reports were retrieved. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 per cent confidence intervals for risk of death from breast cancer.

    Results From a cohort of 6964 women, 96 who died from breast cancer were identified and these were compared with a group of 318 controls. Tumour size over 25mm or multifocal DCIS (OR 255, 95 per cent c.i. 153 to 425), a positive or uncertain margin status (OR 391, 159 to 961) and detection outside the screening programme (OR 212, 116 to 386) increased the risk of death from breast cancer. The risks were not affected by age or type of treatment. In the multivariable analysis, tumour size (OR 195, 106 to 367) and margin status (OR 269, 115 to 711) remained significant.

    Conclusion In the present study, large tumour size and positive or uncertain margin status were associated with a higher risk of death from breast cancer after treatment for primary DCIS. More extensive treatment was not associated with lower risk, which may be due to confounding by indication, or indicate that some DCIS has an inherent potential for metastatic spread. Rare, but worse for large tumours and uncertain margins.

  • 3.
    Wadsten, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Heyman, Hanna
    Holmqvist, Marit
    Ahlgren, Johan
    Lambe, Mats
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Warnberg, Fredrik
    A validation of DCIS registration in a population-based breast cancer quality register and a study of treatment and prognosis for DCIS during 20 years: Two decades of DCIS in Sweden2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 11, p. 1338-1343Article in journal (Refereed)
    Abstract [en]

    Aims: Sweden has a long history of population-based cancer registration. The aim of our study was to assess the validity of DCIS registration in a regional Breast Cancer Quality Register (BCQR) and to analyze trends in incidence, treatment and outcome of DCIS, over a 20-year period.Material and methods: All patients with a diagnosis of primary DCIS reported in the BCQR of the Uppsala-orebro healthcare region in Sweden 1992-2012 were included. Three hundred women were randomly selected and their medical records were compared to register data. The study period was divided into four time periods.Results: A total of 2952 women were registered with a DCIS diagnosis. In the final validation cohort of 295 patients, 23 were found to have either recurrent DCIS or invasive breast cancer and eight had LCIS. The completeness and validity of key variables were 91-99%. Twenty of 31 local recurrences were registered (65%).The proportion of DCIS to all breast cancers was 9.5%. Tumor size increased over time. The frequency of mastectomy increased from 23.0% to 39.0%. The proportion of patients receiving radiotherapy after breast conserving surgery increased from 30.1% to 67.6%. The reported local recurrence rate was 9.7% after 10 years. Reported recurrences after BCS and mastectomy were 12.0 and 7.0%, respectively. The recurrence rate did not differ between women undergoing BCS with or without radiotherapy.Conclusion: Only 89.5% of reported DCIS was a primary pure DCIS. The completeness of primary treatment and tumor data was high. The proportion of reported local recurrences was disappointingly low, 65%. The proportion of DCIS was stable over time with a trend towards more intensified treatment. The reported recurrence rate was low independent of treatment and can reflect adequate patient selection, but also over treatment. Our results address the necessity to validate register data on a regular basis.

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