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Region Hovedstaden - en del af Københavns Universitetshospital
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Uddannelse

01.09.2008 – 19.06.2015: Cand. Med. Københavns Universitet.

Ansættelser

01.02.2016 - 30.07.2016: Almen Praksis v. Marianne Halgreen, Gentofte. Klinisk Basisuddannelse (KBU).

01.08.2015 - 31.01.2016: Gastroenheden, Hvidovre. KBU.

01.09.2014 - 01.07.2015: Neurologisk afdeling, Glostrup. Reservelægevikar.

Kliniske aktiviteter

01.08.2013 - 19.12.2013: Brystkirurgisk klinik, Rigshospitalet. Forskningsassistent/Specialestuderende.

01.07.2013 - 21.07.2013: Brystkirurgisk klinik, Rigshospitalet. Valgfrit klinisk ophold.

01.07.2012 - 01.08.2012: Plastikkirurgisk afdeling, Mater Dei Hospital, Malta. IMCC udvekslingsophold.

Undervisning

01.03.2015 - 01.07.2015: Frivillig underviser: Coding Pirates - Datalogisk Institut Københavns Universitet.

Oktober 2013: Brystkirurgisk klinik, Rigshospitalet Undervisning/foredrag v. lægefaglig konference: Reduced Risk of Axillary Lymphatic Spread in Triple-negative Breast Cancer.

Akademiske aktiviteter

05.03.2016 - 06.03.2916: Årsmøde, Yngre plastikkirurger (YPK), Korsør.

23.12.2015: Teoretisk kursus i basal plastikkirurgi, Herlev.

Organisatoriske aktiviteter

01.09.2014 - 01.11.2014: Medlem af arbejdsgruppen for Forsknings- og uddannelsesfaciliteter v. projektorganisationen for Universitetssygehuset i Køge, Køge.

Publikationer

[1] Holm-Rasmussen EV, Jensen MB, Balslev E, Kroman N, Tvedskov TF: Reduced Risk of Axillary Lymphatic Spread in Triple-negative Breast Cancer.  Breast Cancer Res Treat. 2015, Jan;149(1):229-236

Poster og abstract, international konference

Marts 2014: 9th European Breast Cancer Conference (EBCC9), Glasgow, Scotland. Poster præsentation og abstract: Holm-Rasmussen EV, Jensen MB, Balslev E, Kroman N, Tvedskov TF: Reduced Risk of Axillary Lymphatic Spread in Triple-negative Breast Cancer.  Breast Cancer Res Treat. 2015, Jan;149(1):229-236

Poster og abstract, national konference

Oktober 2013: Dansk Mammakirurgisk årsmøde, København. Oral præsentation og abstract: Holm-Rasmussen EV, Jensen MB, Balslev E, Kroman N, Tvedskov TF: Reduced Risk of Axillary Lymphatic Spread in Triple-negative Breast Cancer.  Breast Cancer Res Treat. 2015, Jan;149(1):229-236

Legater

2010-2012: Tre gange modtager af Peter og Emma Thomsens legat à 120.000kr

Primære forskningsområder

Brystcancer.

Kort præsentation

Efter vi i Danmark er begyndt at screene kvinder for brystkræft, får flere stillet diagnosen i et tidligere stadie end hidtil. Dette gør at behandlingen kan påbegyndes hurtigere.

Hvis brystkræft spreder sig, er det typisk til lymfeknuderne i armhulen. For at undersøge for spredning, fjernes en eller flere lymfeknuder ved operation. Selvom der ofte kun fjernes få lymfeknuder, får nogle patienter alligevel senfølger efter operationen i form af føleforstyrrelser, hævelse af armen og smerter. Der er kun en lille risiko for, at brystkræft i et tidligt stadie spreder sig, og derfor har mange af kvinderne ikke gavn af en operation i armhulen.

Vi vil undersøge, hvilke former for brystkræft i det tidlige stadie, der er tilbøjelige til at sprede sig til lymfeknuderne. Det gør vi ved at analysere data fra den danske brystkræftdatabase. Hvis vi kan identificere, de patienter, der har risiko for spredning, kan antallet af kvinder, der behøver at få fjernet lymfeknuder minimeres. Med mere viden om spredning af sygdommen, kan man tilbyde en mere skånsom operation og måske på sigt afkorte operationstiden og samlet set nedsætte risikoen for, at kvinderne får varige mén efter operationen.

Aktuel forskning

Background

Axillary nodal status is the most important prognostic factor in breast cancer. Axillary lymph node dissection (ALND) was previously the standard procedure for staging of the axilla. However, this procedure is associated with considerable morbidity (1,2) and is redundant for women without lymph node metastases. Sentinel lymph node dissection (SLND) can be used to accurately stage the axilla by removing on average only two lymph nodes and results in less morbidity than ALND (3). ALND is offered only in cases of metastases to the sentinel node. SLND has gradually replaced ALND as the standard procedure for staging of the axilla in patients with primary breast cancer. Today, more than 3000 SLNDs are performed in Denmark every year as a part of the surgical treatment of breast cancer. This procedure spares thousands of Danish breast cancer patients the risk of arm morbidity.

Despite the obvious advantages of SLND, the procedure is not without side effects. It has been shown that 25–50% of patients experience pain two to three years after SLND and 31–56% experience sensory disturbances (1,2). Today, all patients with primary invasive breast cancer are offered axillary surgery—either SLND or ALND. Axillary surgery is sometimes even offered to patients with only ductal carcinoma in situ (DCIS) because in 13–40% of these patients, an unsuspected small area with invasive carcinoma is found upon histopathological examination after the final surgery (4,5). In the vast majority of patients diagnosed with only DCIS or microinvasive disease <1 mm, the sentinel node is without metastasis and SLND is therefore redundant (6). International studies have shown that metastases are found in the sentinel node in only 1–3% of patients diagnosed with only DCIS or microinvasion of the breast (7-9).The risk of metastases to other lymph nodes in these cases is basically unknown, and thus the need for completion ALND. The number of patients diagnosed with DCIS or microinvasive disease <1 mm increased after the introduction of the National Mammographic screening program, thereby increasing the risk of overtreatment with unnecessary SLNDs (10).

Lymphatic spread in the case of DCIS could be due to a small occult cancer in the breast not found during histopathological examination. However, it could also be caused by iatrogenic displacement of tumor cells. Studies have shown a significant association between the risk of sentinel node metastases and a recent excisional or needle biopsy in patients with invasive carcinomas (11) and DCIS (12). The need for ALND in the case of iatrogenically displaced tumor cells in the sentinel nodes of patients with DCIS in unknown.

Due to the low risk of sentinel node metastases in patients with DCIS or microinvasive disease, earlier studies on this subject have only been able to include 14–67 patients with sentinel node metastases (12-14). This small number makes it difficult to identify risk factors for sentinel node metastases or to estimate the risk of non-sentinel node metastases. Identification of risk factors for sentinel and non-sentinel node metastases in these patients could enable a tailor-made treatment of the axilla and prevent overtreatment in the form of redundant SLNDs.

Even in patients with small invasive carcinomas of the breast, the risk of sentinel node metastases is small. Studies have shown that less than 10% of clinically node-negative breast cancer patients with tumors < 1 cm in size have lymph node metastases (15). These patients are all offered an SLND, often with perioperative frozen sections. In patients without metastases in the sentinel node, the prolonged operating time of 20–45 minutes, caused by waiting time for frozen sections, is without benefit for the patient. However, if frozen sections are omitted and metastases are found during conventional postoperative histological examinations, patients must undergo a second operation for completion ALND. It could be advantageous if a subgroup could be identified where the risk of sentinel node metastases is sufficiently small to justify the omission of perioperative frozen sections.

 

Objectives

In Denmark, clinical and histopathological data on women with breast cancer have been collected in a national database managed by the Danish Breast Cancer Cooperative Group (DBCG) since 1977, and clinical and histopathological data on women with DCIS have been collected since 1982. Today, the database contains information on more than 100,000 breast cancer patients (16). The database thus contains data material of a unique size to identify risk factors for sentinel node metastases in patients diagnosed with only DCIS or micro invasion or small cancers under 1 cm in the breast.

This study is planned as a nationwide retrospective register-based study using data from the DBCG database and the aim is to:

1. Identify risk factors for metastases in the sentinel node and the risk of further metastatic spread to non-sentinel nodes in breast cancer patients with DCIS or micro invasive disease in the breast and to identify subgroups of patients who benefit from SLND or even ALND and subgroups for whom axillary surgery can safely be omitted;

2. Investigate whether sentinel node metastases in patients with DCIS in the breast can be caused by iatrogenic displacement after recent surgical excisional biopsy of a breast tumor and to clarify whether an ALND is indicated in this group of patients; and

3. Identify risk factors for sentinel node macrometastases in breast cancer patients with small carcinomas < 1 cm and identify a group with a low risk of lymphatic spread where perioperative frozen sections can be omitted.

 

Method

Risk factors for sentinel node and non-sentinel node metastases in patients with DCIS in the breast:

Patients with metastases in the sentinel node but only DCIS in the breast are registered in the DBCG database as having invasive cancers. The tumor size is registered as “unknown”, “missing”, or “0”. Between 2001 and 2015, 503 breast cancer patients with tumor size “unknown”, “missing” or “0” have been registered in the DBCG database. No axillary metastases were recorded for 124 of these patients. Information on the remaining 379 patients will be validated using the original patient files to identify patients diagnosed with DCIS and sentinel node metastases. Even after validation of the data, we expect a substantially larger sample size compared to earlier studies that included 9–67 patients (12-14). Patients with DCIS and sentinel node metastases will be compared to patients with DCIS but without sentinel node metastases. Information on patients diagnosed with DCIS and offered an SLND between 2001 and 2015 will be retrieved from the DBCG database. The risk of sentinel node and non-sentinel node metastases will be estimated. Information on palpability, size of DCIS, focality, Van Nuys classification, hormone receptor status, HER2 status, nodal status, and recent excision biopsy will be retrieved from the DBCG database. Associations between potential risk factors and sentinel node metastases will be calculated in a multivariate design, including whether an increased risk is found in patients who have had a recent excisional biopsy.

 

Risk factors for sentinel node and non-sentinel node metastases in patients with micro invasive disease in the breast:

Patients with tumor size < 1 mm offered SLND between 2001 and 2014 will be identified in the DBCG database. Information on histological type, focality, malignancy grade, hormone receptor status, HER2 status, Ki67 index, lymphovascular invasion, and nodal status will be retrieved from the DBCG database. The risk of sentinel node and non-sentinel node metastases will be estimated, and associations between potential risk factors and sentinel node metastases will be calculated in a multivariate design.

 

Risk of sentinel node metastases in patients with small breast cancers:

Patients treated with SLND for primary breast cancers < 1 cm between 2001 and 2014 will be included in this part of the study. Nationwide information on tumor size, nodal status, histological type, malignancy grade, hormone receptor status, lymphovascular invasion, Ki67 index, and HER2 status will be retrieved from the DBCG database. A logistic regression analysis will be performed to identify the risk factors for sentinel node metastases, and a model will be developed to identify a group of patients with a low risk of sentinel node metastases where perioperative frozen sections can be omitted. A less than 10% risk of sentinel node metastases is considered acceptable.

 

References

(1) Gartner R, Jensen MB, Nielsen J et al. Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 2009; 302(18):1985-92.

(2) Gartner R, Jensen MB, Kronborg L et al. Self-reported arm-lymphedema and functional impairment after breast cancer treatment--a nationwide study of prevalence and associated factors. Breast 2010; 19(6):506-15.

(3) Christiansen P, Friis E, Balslev E, Jensen D, Moller S. Sentinel node biopsy in breast cancer: five years experience from Denmark. Acta Oncol 2008; 47(4):561-8.

(4) Doyle B, Al-Mudhaffer M, Kennedy MM et al. Sentinel lymph node biopsy in patients with a needle core biopsy diagnosis of ductal carcinoma in situ: is it justified? J Clin Pathol 2009; 62(6):534-8.

(5) Polom K, Murawa D, Wasiewicz J, Nowakowski W, Murawa P. The role of sentinel node biopsy in ductal carcinoma in situ of the breast. Eur J Surg Oncol 2009; 35(1):43-7.

(6) Gojon H, Fawunmi D, Valachis A. Sentinel lymph node biopsy in patients with microinvasive breast cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2014; 40(1):5-11.

(7) Intra M, Rotmensz N, Veronesi P et al. Sentinel node biopsy is not a standard procedure in ductal carcinoma in situ of the breast: the experience of the European institute of oncology on 854 patients in 10 years. Ann Surg 2008; 247(2):315-9.

(8) Veronesi P, Intra M, Vento AR et al. Sentinel lymph node biopsy for localised ductal carcinoma in situ? Breast 2005; 14(6):520-2.

(9) Xiao S. et al. Sentinel lymph node biopsy in patients with breast ductal carcinoma in situ: Chinese experiences. Oncol Lett. 2015; 10(3): 1932–1938.

(10) Christiansen P, Vejborg I, Kroman N et al. Position paper: Breast cancer screening, diagnosis, and treatment in Denmark. Acta Oncol 2014.

(11) Tvedskov TF, Jensen MB, Kroman N, Balslev E. Iatrogenic displacement of tumor cells to the sentinel node after surgical excision in primary breast cancer. Breast Cancer Res Treat 2011.

(12) AM, Haugen CE, Grimes LM et al. Is Sentinel Lymph Node Dissection Warranted for Patients with a Diagnosis of Ductal Carcinoma In Situ? Ann Surg Oncol 2015.

(13) Meretoja TJ, Heikkila PS, Salmenkivi K, Leidenius MH. Outcome of patients with ductal carcinoma in situ and sentinel node biopsy. Ann Surg Oncol 2012; 19(7):2345-51.

(14) Lyons JM, III, Stempel M, Van Zee KJ, Cody HS, III. Axillary node staging for microinvasive breast cancer: is it justified? Ann Surg Oncol 2012; 19(11):3416-21.

(15) Meretoja TJ, Heikkila PS, Mansfield AS et al. A predictive tool to estimate the risk of axillary metastases in breast cancer patients with negative axillary ultrasound. Ann Surg Oncol 2014; 21(7):2229-36.

(16) Moller S, Jensen MB, Ejlertsen B et al. The clinical database and the treatment guidelines of the Danish Breast Cancer Cooperative Group (DBCG); its 30-years experience and future promise. Acta Oncol 2008; 47(4):506-24.

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