Niels Kroman

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (112)479.11 Total impact

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    ABSTRACT: The aim of this study was to investigate the use of sentinel lymph node dissection (SLND) in the treatment of patients with locally recurrent breast cancer. A total of 147 patients with locally recurrent breast cancer were included from five different breast surgery departments in Denmark. Data on previous breast and axillary surgery, adjuvant treatment, second operation in the breast and axilla, and lymphoscintigraphy were collected retrospectively from the original patient files. SLND after recurrence (SLNDAR) was successful in 72 of 144 patients (50 %). The detection rate was significantly higher after previous SLND (66 %) compared with previous ALND (34 %) [p = 0.0001]. Thirty-seven patients (51 %) who had previous SLND had a negative sentinel node. These patients could be spared an ALND. Six patients (8 %) who had a previous ALND had a metastatic sentinel node at recurrence; 17 % of patients had a sentinel node located outside the ipsilateral axilla; and eight patients with negative sentinel node at SLNDAR underwent completion ALND. None of these patients had metastases at completion ALND, corresponding to a false negative rate of 0 %. SLNDAR seems to be a feasible procedure in locally recurrent breast cancer and can spare a clinically significant number of patients an unnecessary ALND and the following risk of sequelae. In patients who had previous ALND, SLNDAR identified metastases that would have been overlooked following the current guidelines. A large proportion of patients had aberrant drainage, suggesting a need for lymphoscintigraphy.
    Annals of Surgical Oncology 01/2015; · 3.94 Impact Factor
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    ABSTRACT: Participation bias may be a problem in couple-based psychosocial studies. Therefore, it is important to investigate the characteristics associated with participation. The aim of this study was to analyze whether participation in a longitudinal psychosocial questionnaire study among couples affected by breast cancer was associated with socioeconomic, breast cancer-specific, and other health-related characteristics of the patients and partners. The analyzes are based on 2254 couples who were invited to participate in a nationwide survey on psychosocial adjustment among couples dealing with breast cancer. Participating couples (N = 792) were compared with non-participating couples (N = 1462) with regard to socioeconomic and health-related characteristics obtained from nationwide clinical and administrative registers. Associations were seen between various socioeconomic variables and couple participation. The patient characteristics older age (OR = 0.15 [95 % CI = 0.07-0.55]), low education (OR = 1.95 [95 % CI = 1.46-2.68]), disability pension (OR = 0.59 [95 % CI = 0.39-0.55]), or non-western ethnicity (OR = 0.36 [95 % CI = 0.15-0.82]) reduced couple participation. The partner characteristics older age (OR = 0.23 [95 % CI = 0.15-0.43]), low education (OR = 1.67 [95 % CI = 1.25-2.22]), receiving disability pension (OR = 0.46 [95 % CI = 0.25-0.82]), non-western ethnicity (OR = 0.17 [95 % CI = 0.06-0.49]), or high morbidity (OR = 0.76 [95 % CI = 0.60-0.96]) also reduced couple participation. Furthermore, couples with low income (OR = 1.49 [95 % CI = 1.16-1.95]) had reduced participation. No associations were found between couple participation and breast cancer-related variables. Socioeconomic characteristics of patients and partners, and morbidity of partners may influence participation in couple-based psychosocial breast cancer research. Breast cancer-related characteristics do not seem to influence participation.
    Supportive Care Cancer 12/2014; · 2.50 Impact Factor
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    ABSTRACT: We examined the association between the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of women with primary breast cancer and the risk of axillary lymph node (ALN) involvement at the time of diagnosis. Information on 20,009 women diagnosed with primary breast cancer between 2008 and 2012 was retrieved from the Danish Breast Cancer Cooperative Group database. The associations between clinical and pathological variables and ALN involvement at the time of diagnosis were evaluated in univariate and multivariate regression analyses, as well as the significance of tumor subtypes in ALN involvement. The risk of ALN metastases at the time of diagnosis was significantly reduced in HR-negative patients compared to HR-positive patients [adjusted odds ratio (OR) 0.69; 95 % CI 0.63-0.76; P = 0.0009]. A HER2-positive status was associated with an increased risk of ALN involvement at diagnosis compared to a HER2-negative status (OR 1.37; 95 % CI 1.24-1.50; P < 0.0001). An interaction between HER2 and HR was observed, with a HER2-positive status significantly associated with ALN involvement at the time of diagnosis only in HR-negative patients (P < 0.0001). The triple-negative breast cancer (TNBC) patients showed a significantly reduced risk of ALN involvement at the time of diagnosis compared to patients with HR-positive/HER2-negative tumors (OR 0.55; 95 % CI 0.49-0.62; P < 0.0001). The HR and HER2 statuses are significantly associated with ALN involvement at the time of diagnosis. Despite the poor prognosis, TNBC patients have a reduced risk of ALN involvement at the time of diagnosis compared to patients with other subtypes, when adjusting for other risk factors. This may indicate that TNBC tends to spread hematogenously rather than lymphogenously.
    Breast Cancer Research and Treatment 12/2014; · 4.47 Impact Factor
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    ABSTRACT: Apocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast apocrine differentiation spectrum from benign metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is strongly associated with apocrine differentiation; their expression is retained by most invasive apocrine carcinomas (IAC) showing positive immunoreactivity in 100% and 78% of apocrine carcinomas, respectively, as compared to non-apocrine tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was shown to be associated with more aggressive stages of apocrine carcinomas. In addition, when added to the panel of apocrine biomarkers previously reported by our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may represent a golden molecular standard for defining the apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)- identifies IACs with a greater sensitivity (79%) as compared with the steroidal profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed immunohistochemical analysis of breast apocrine lesions with a panel of antibodies against proteins which correspond to 10 genes selected from published transcriptomic signatures that currently characterize molecular apocrine subtype and shown that except for melanophilin that is overexpressed in benign apocrine lesions, these proteins were not specific for morphological apocrine differentiation in breast.
    PLoS ONE 11/2014; 9(11):e112024. · 3.53 Impact Factor
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    ABSTRACT: Moderate to severe pain in the first week after axillary lymph node dissection (ALND) for breast cancer is experienced by approximately 50% of the patients. Damage to the intercostobrachial nerve (ICBN) has been proposed as a risk factor for the development of persistent pain following breast cancer surgery but with limited information on acute post-operative pain. The aim of the present study was to examine the influence of ICBN handling on pain during the first week after ALND.
    Acta Anaesthesiologica Scandinavica 11/2014; 58(10):1240-8. · 2.36 Impact Factor
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    ABSTRACT: To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer.
    Journal of Clinical Oncology 10/2014; 32(34). · 17.88 Impact Factor
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    ABSTRACT: Objectives The association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated. Study design: Female participants from the prospective cohort “Diet, Cancer, and Health” diagnosed with breast cancer (BC) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis. Main outcome measure: Breast cancer specific mortality Results Of the 1 212 patients originally considered 1 064 were included. Of these, 105 women died from breast cancer during a median follow-up of 6.3 years (range 0.2-14.3 years). In multivariate analyses women who used HRT at enrolment into the cohort study had 47% lower risk of dying from breast cancer as compared to women who had previously or never used HRT (adjusted HR: 0.53; 95% CI, 0.37-0.85). Pre-diagnostic HRT use was associated with smaller tumour size at the time of diagnosis and a higher frequency of receptor positive breast cancer. Paradoxically, a high pre-diagnostic intake of vitamin D supplements was associated with HRT use but also with a higher BC specific mortality (HR: 1.47; 95% CI, 1.07-2.00) Conclusions HRT-use at enrolment was associated with breast tumours of smaller size at the time of diagnosis and positive receptor status, and with a lower BC mortality. The found association between vitamin D from supplements and higher BC mortality warrants further exploration.
    Maturitas 09/2014; · 2.84 Impact Factor
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    ABSTRACT: Currently, no consistent evidence-based guidelines for the management of synchronous bilateral breast cancer (SBBC) exist and it is uncertain how presenting with SBBC affects patients' prognosis. We conducted a review of studies analyzing the association between SBBC and prognosis. The studies that reported adjusted effect measures were included in meta-analyses of effect of bilaterality on breast cancer mortality. From 57 initially identified records 17 studies from 11 different countries including 8,050 SBBC patients were included. The quality of the studies varied but was generally low with small sample sizes, and lack of consistent, detailed histo-pathological information. When doing meta-analysis on the subgroup of studies that provided adjusted effect estimates on breast cancer mortality (nine studies including 3,631 SBBC cases), we found that bilaterality in itself had a negative impact on prognosis after adjustment for known prognostic factors (pooled HR 1.37, 95 % CI 1.24-1.50, p < 0.0001). Multiple sensitivity analyses indicated robustness of the overall estimate. This review summarizes the current evidence of the association between SBBC and prognosis. The previously accepted convention that appropriate adjuvant treatment can be determined by considering the higher risk cancer was not confirmed in this review; rather it seems that being diagnosed with two tumors simultaneously entails a worse prognosis above and beyond that of the unilateral cancers of the same stage. To determine the true association between SBBC and breast cancer prognosis, studies of large and updated samples of SBBC should be done and include thorough histo-pathologic information.
    Breast Cancer Research and Treatment 07/2014; · 4.47 Impact Factor
  • Acta oncologica (Stockholm, Sweden) 06/2014; · 2.27 Impact Factor
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    ABSTRACT: The main purpose of this nationwide follow-up study was to examine the development of self-reported lymphedema in the population of women with early-stage breast cancer in Denmark. In 2008 and 2012 two identical questionnaires were sent to the women aged 18-70 years treated for unilateral primary breast cancer in 2005 and 2006. 2293 women (87%) reported on lymphedema in 2008 and 2012. Overall 37% reported lymphedema in 2008 while 31% reported lymphedema in 2012 and severity of symptoms decreased. 50% of women treated with SLNB and reporting lymphedema in 2008 did not report symptoms by 2012 in contrast to 30% treated with ALND. However, 19% of women treated with ALND and not reporting lymphedema in 2008 had developed lymphedema by 2012. In conclusion lymphedema remains a frequent problem, years after treatment for breast cancer, though, number of women reporting lymphedema and overall severity of symptoms decreased.
    Breast (Edinburgh, Scotland) 04/2014; · 2.09 Impact Factor
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    ABSTRACT: Background We cross-validated three existing models for the prediction of non-sentinel node metastases in patients with micrometastases or isolated tumor cells (ITC) in the sentinel node, developed in Danish and Finnish cohorts of breast cancer patients, to find the best model to identify patients who might benefit from further axillary treatment. Material and method Based on 484 Finnish breast cancer patients with micrometastases or ITC in sentinel node a model has been developed for the prediction of non-sentinel node metastases. Likewise, two separate models have been developed in 1577 Danish patients with micrometastases and 304 Danish patients with ITC, respectively. The models were cross-validated in the opposite cohort. Results The Danish model for micrometatases was accurate when tested in the Finnish cohort, with a slight change in AUC from 0.64 to 0.63. The AUC of the Finnish model decreased from 0.68 to 0.58 when tested in the Danish cohort, and the AUC of the Danish model for ITC decreased from 0.73 to 0.52, when tested in the Finnish cohort. The Danish micrometastatic model identified 14-22 % of the patients as high-risk patients with over 30 % risk of non-sentinel node metastases while less than 1 % was identified by the Finish model. In contrast, the Finish model predicted a much larger proportion of patients being in the low-risk group with less than 10% risk of non-sentinel node metastases. Conclusion The Danish model for micrometastases worked well in predicting high risk of non-sentinel node metastases and was accurate under external validation.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 04/2014; · 2.56 Impact Factor
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    ABSTRACT: Background. During the last decades the diagnosis, treatment, and prognosis of breast cancer have changed and improved in Denmark. The first mammography screening programme started in 1991. However, for many years only about 20% of Danish women aged 50-69 were offered screening. The national roll-out of screening took place in 2008-2010. Material and methods. Based on published Danish data, this overview describes the status of diagnosis and treatment, and the screening programme. For further evaluating the potential overdiagnosis and overtreatment, additional Danish Breast Cancer Cooperative Group (DBCG) data are included. Results and conclusion. Using incidence-based mortality method, reduction in breast cancer mortality was estimated to be 25% in the target group of women after 10 years of screening in Copenhagen; an outcome comparable to that of randomised controlled trials. A recent Danish study has indicated overdiagnosis to be around 4%. Others have estimated overdiagnosis to be 33%. National DBCG data showed that the rude breast cancer incidence increased during the period 1990-2011 from 126 to 206 per 100 000. The incidence was almost constant for women younger than 50 years. In regions not offering screening, the incidence increased with 3% per year for women aged 50-69 years with similar trends for small and large tumours. After introduction of screening the increase in the age group 50-69 years was confined to small tumours ≤ 20 mm, and most pronounced for node negative patients. From the 1990s, the use of breast conserving surgery has increased from around 25% to 69% in 2010. Screening has not increased the number of mastectomies. Breast cancer treatment in Denmark is evidence based and in agreement with international recommendations. After the introduction of mammography screening the absolute number of patients with a more advanced stage at diagnosis and the absolute number of patients undergoing mastectomy have decreased.
    Acta oncologica (Stockholm, Sweden) 02/2014; · 2.27 Impact Factor
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    ABSTRACT: The main purpose of this nationwide follow-up study was to examine the development of self-reported lymphedema in the population of women with early-stage breast cancer in Denmark. In 2008 and 2012 two identical questionnaires were sent to the women aged 18–70 years treated for unilateral primary breast cancer in 2005 and 2006. 2293 women (87%) reported on lymphedema in 2008 and 2012. Overall 37% reported lymphedema in 2008 while 31% reported lymphedema in 2012 and severity of symptoms decreased. 50% of women treated with SLNB and reporting lymphedema in 2008 did not report symptoms by 2012 in contrast to 30% treated with ALND. However, 19% of women treated with ALND and not reporting lymphedema in 2008 had developed lymphedema by 2012. In conclusion lymphedema remains a frequent problem, years after treatment for breast cancer, though, number of women reporting lymphedema and overall severity of symptoms decreased.
    The Breast. 01/2014;
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    ABSTRACT: With improved survival rates after breast cancer treatment, more attention is drawn to improve the cosmetic outcome after surgical treatment of breast cancer. In this process the oncoplastic breast surgery was conceived. It supplements the traditional surgical treatments (mastectomy and breast conserving surgery) with increased focus on individualized therapy. The ambition is to obtain the best possible cosmetic outcome without compromising recurrence rates and survival. This article provides an overview of the current oncoplastic breast surgery treatment offered in Denmark.
    Ugeskrift for laeger 11/2013; 175(48A).
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    ABSTRACT: Few studies have examined the prevalence of persistent pain after breast reconstruction with an implant after tissue expansion in comparison to mastectomy without breast reconstruction. Our primary objective was to evaluate the prevalence of persistent pain after breast reconstruction with a subpectoral implant after tissue expansion in a population-based study. Secondary objectives were to evaluate sensory disturbances, lymphoedema and functional impairment. This was a nationwide cross-sectional questionnaire study of breast cancer patients aged 18-69 years who were treated with or without reconstruction after mastectomy for primary breast cancer in Denmark between 1 January 2005 and 31 December 2006. The response rate was 84% for mastectomy without reconstruction and 83% for patients treated with breast reconstruction. A total of 129 patients treated with mastectomy and breast reconstruction with a subpectoral implant were compared with 1131 patients treated with mastectomy without reconstruction. Prevalence of persistent pain for patients treated with mastectomy followed by reconstruction with an implant was 40% compared to 48% of patients treated only with mastectomy. We found no increased risk of persistent pain in patients having a reconstruction with an implant compared with mastectomy without reconstruction (odds ratio (OR) 0.82, 95% confidence interval (CI) 0.55-1.22, P = 0.33) when adjusting for age, axillary procedure, radiotherapy and chemotherapy. We observed no difference in the prevalence of pain between patients treated with immediate or delayed breast reconstruction (P = 0.116). Breast reconstruction with a subpectoral implant after tissue expansion does not confer increased prevalence of persistent pain.
    Journal of Plastic Reconstructive & Aesthetic Surgery 08/2013; · 1.47 Impact Factor
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    ABSTRACT: Background. Benefit from axillary lymph node dissection in sentinel node positive breast cancer patients is under debate. Based on data from 1820 Danish breast cancer patients operated in 2002-2008, we have developed two models to predict high risk of non-sentinel node metastases when micrometastases or isolated tumor cells are found in sentinel node. The aim of this study was to validate these models in an independent Danish dataset. Material and methods. We included 720 breast cancer patients with micrometastases and 180 with isolated tumor cells in sentinel node operated in 2009-2010 from the Danish Breast Cancer Cooperative Group database. Accuracy of the models was tested in this cohort by calculating area under the receiver operating characteristic curve (AUC) as well as sensitivity and specificity. Results. AUC for the model for patients with micrometastases was comparable to AUC in the original cohort: 0.63 and 0.64, respectively. The sensitivity and specificity for predicting risk of non-sentinel node metastases over 30% was 0.36 and 0.81, respectively, in the validation cohort. AUC for the model for patients with isolated tumor cells decreased from 0.73 in the original cohort to 0.60 in the validation cohort. When dividing patients with isolated tumor cells into high and low risk of non-sentinel node metastases according to number of risk factors present, 37% in the high-risk group had non-sentinel node metastases. Specificity and sensitivity was 0.48 and 0.88, respectively, in the validation cohort when using this cut-point. Conclusion. In this independent dataset, the model for patients with micrometastases was robust with accuracy similar to the original cohort, while the model for patients with isolated tumor cells was less accurate. The models may be used to identify patients where axillary lymph node dissection should still be considered.
    Acta oncologica (Stockholm, Sweden) 06/2013; · 2.27 Impact Factor
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    ABSTRACT: Lymphedema and impairment of function are well-established sequelae to breast cancer treatment and affect an increasing number of women due to continually improved survival. The aim of the present nationwide questionnaire study was to examine the impact of breast cancer treatment on perceived swelling/sensation of heaviness (lymphedema) and on function, reporting prevalence in 12 subgroups of modern treatment and offering estimates for treatment-related associated factors.3253 Women (87%) returned the study questionnaire. Depending on treatment group prevalence of perceived swelling/heaviness varied from 13 to 65%. Associated factors were young age, axillary lymph node dissection (ALND) and radiotherapy but not type of breast surgery or use of chemotherapy. Depending on treatment group 11–44% had to give up activities. Giving up activities was associated with pain and swelling/heaviness, younger age, ALND, chemotherapy, time elapsed since surgery, and surgery on the dominant side. Radiotherapy and type of breast surgery were of no importance.
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    ABSTRACT: INTRODUCTION: Breast cancer is common among Danish women with more than 4,100 new cases annually. In 2008 the concept of fast-track surgery was introduced at the Department of Breast Surgery at Rigshospitalet, Copenhagen. The aim of this study is to describe the new clinical pathway for breast cancer patients after implementation of a fast-track surgery programme. MATERIAL AND METHODS: A clinical pathway of all involved disciplines was developed including anaesthetic, analgesics, nausea and vomiting, drain and wound management, discharge assessment and psychosocial support. RESULTS: The overall mean length of stay (LOS) decreased from 3.6 days before introduction of fast-track surgery to 1.2 days after its implementation. The largest decrease was observed among patients undergoing mastectomy, where LOS was reduced from 5.0 to 1.6 days. The number of beds at the department was reduced by about 30% and a nurse-led clinic was established which enabled nurses to take charge of wound management, seromas, temporary breast prostheses and psychosocial and rehabilitation aspects in the outpatient clinic. Additionally, the previously available telephone counselling service was intensified to provide immediate advice and support. CONCLUSION: The results confirm that a short stay can be successfully carried out for breast cancer patients. Implementing the fast-track programme involved the introduction of a clear clinical pathway for the patients and more effective daily routines. Patients felt safe and confident after early discharge. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
    Danish Medical Journal 05/2013; 60(5):A4615. · 0.61 Impact Factor
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    ABSTRACT: Long-term breast cancer trends in incidence in the United States (US) show rising ER positive rates and falling ER negative rates. We hypothesized that these divergent trends reflect etiologic heterogeneity and that comparable trends should be observed in other countries with similar risk factor profiles. We, therefore, analyzed invasive female breast cancers in Denmark, a country with similar risk factors as the US. We summarized the overall trend in age-standardized rates with the estimated annual percentage change (EAPC) statistic (1993-2010) and used age-period-cohort models to estimate age-specific EAPCs, cohort rate ratios (CRRs), and projections for future time periods (2011-2018). In Denmark, the overall rate of ER positive cancers rose between 1993 and 2010 by 3·0%/year (95% CI: 2·8 to 3·3%/yr) while the overall rate of ER negative cancers fell by 2·1%/year (95% CI: -2·5 to -1·6%/yr). The ER positive rate increased fastest among postmenopausal women and the ER negative rate decreased fastest among premenopausal women, reflecting that cohorts born after 1944 were at relatively higher risk of ER positive tumors and lower risk of ER negative tumors. If current trends continue, ER positive cancers will increase at least 13% by 2018 in Denmark, ER negative cancers will fall 15% by 2018, and breast cancer overall will increase at least 7% by 2018. Divergent ER-specific trends are consistent with distinct etiologic pathways. If trends in known risk factors are responsible, the Danish and US experience may foreshadow a common pattern worldwide. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2013; · 6.20 Impact Factor

Publication Stats

1k Citations
479.11 Total Impact Points

Institutions

  • 2010–2014
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2009–2014
    • University of Copenhagen
      • Surgical Pathophysiology Unit
      København, Capital Region, Denmark
  • 2008–2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Herlev Hospital
      • Department of Pathology
      Herlev, Capital Region, Denmark
  • 2012–2013
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
  • 2009–2012
    • Rigshospitalet
      • Department of Oncology
      Copenhagen, Capital Region, Denmark
  • 2011
    • Aarhus University Hospital
      • Breast and Endocrine Section
      Aarhus, Central Jutland, Denmark
  • 2005–2008
    • University of Copenhagen Herlev Hospital
      Herlev, Capital Region, Denmark
  • 1996–2007
    • Statens Serum Institut
      • Department of Epidemiology Research
      København, Capital Region, Denmark
  • 2000
    • Breakthrough Breast Cancer
      Londinium, England, United Kingdom
  • 1997
    • Hillerød Hospital
      Hillerød, Capital Region, Denmark