Rune Gärtner

Prevalence of and factors associated with persistent pain following breast cancer surgery.

CONTEXT Persistent pain and sensory disturbances following surgical treatment for breast cancer is a significant clinical problem. The pathogenic mechanisms are complex and may be related to patient characteristics, surgical technique, and adjuvant therapy. OBJECTIVE To examine prevalence of and factors associated with persistent pain after surgical treatment for breast cancer. DESIGN, SETTING, AND PATIENTS A nationwide cross-sectional questionnaire study of 3754 women aged 18 to 70 years who received surgery and adjuvant therapy (if indicated) for primary breast cancer in Denmark between January 1, 2005, and December 31, 2006. A study questionnaire was sent to the women between January and April 2008. MAIN OUTCOME MEASURES Prevalence, location, and severity of persistent pain and sensory disturbances in 12 well-defined treatment groups assessed an average of 26 months after surgery, and adjusted odds ratio (OR) of reported pain and sensory disturbances with respect to age, surgical technique, chemotherapy, and radiotherapy. RESULTS By June 2008, 3253 of 3754 eligible women (87%) returned the questionnaire. A total of 1543 patients (47%) reported pain, of whom 201 (13%) had severe pain, 595 (39%) had moderate pain, and 733 (48%) had light pain. Factors associated with chronic pain included young age (18-39 years: OR, 3.62; 95% confidence interval [CI], 2.25-5.82; P < .001) and adjuvant radiotherapy (OR, 1.50; 95% CI, 1.08-2.07; P = .03), but not chemotherapy (OR, 1.01; 95% CI, 0.85-1.21; P = .91). Axillary lymph node dissection (ALND) was associated with increased likelihood of pain (OR, 1.77; 95% CI, 1.43-2.19; P < .001) compared with sentinel lymph node dissection. Risk of sensory disturbances was associated with young age (18-39 years: OR, 5.00; 95% CI, 2.87-8.69; P < .001) and ALND (OR, 4.97; 95% CI, 3.92-6.30; P < .001). Pain complaints from other parts of the body were associated with increased risk of pain in the surgical area (P < .001). A total of 306 patients (20%) with pain had contacted a physician within the prior 3 months for pain complaints in the surgical area. CONCLUSION Two to 3 years after breast cancer treatment, persistent pain and sensory disturbances remain clinically significant problems among Danish women who received surgery in 2005 and 2006.

Self-reported arm-lymphedema and functional impairment after breast cancer treatment – A nationwide study of prevalence and associated factors

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.

Persistent pain and sensory disturbances after treatment for breast cancer: six year nationwide follow-up study

Objective To examine the development of persistent pain after treatment for breast cancer and to examine risk factors associated with continuing pain. Design Repeated cross sectional study in a previously examined nationwide cohort. All eligible women who underwent surgery for primary breast cancer in Denmark in 2005 and 2006 and were examined in 2008 were surveyed again with the same questionnaire. Setting Surgical centres in Denmark. Main outcome measures Prevalence, location, and severity of persistent pain after treatment for breast cancer in well defined treatment groups and changes in pain reporting and sensory disturbances from 2008 to 2012. Participants In 2012, 2828 women were eligible in our database, and 108 were excluded. Exclusion criteria were death; new, recurrent, or other cancer; reconstructive breast surgery; and emigration. Results 2411 (89%) women returned the questionnaire. Prevalence of persistent pain after treatment for breast cancer ranged from 22% to 53% depending on treatment. In 2012, 903 (37%) women reported such pain, a fall from 45% in 2008. Of these, 378 (16%) reported pain of ≥4 on a numerical rating scale (scale 0-10), a fall from 19%. Among women reporting pain in 2008, 36% no longer reported it in 2012. In contrast, 15% of the women who did not report pain in 2008 reported it in 2012. Risk factors for having pain were axillary lymph node dissection rather than sentinel lymph node biopsy (odds ratio 2.04, 95% confidence interval 1.60 to 2.61; P<0.001) and age ≤49 (1.78, 1.25 to 2.54; P<0.001). No particular method of treatment or age was associated with an increase in pain from 2008 to 2012. Conclusions Persistent pain after treatment for breast cancer remains an important problem five to seven years later. The problem is not static as it can either progress or regress with time. Trial registration Clinicaltrials.gov NCT No 01543711.

Accuracy of the Danish version of the ‘distress thermometer’

Objective: Short screening instruments have been suggested to improve the detection of psychological symptoms. We examined the accuracy of the Danish version of the ‘Distress Thermometer’.

Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

BackgroundSelective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.MethodsWe conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery), and former users (SSRI prescription more than 30 days before initial breast cancer surgery). We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR) of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders.Results389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI) = 1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3).ConclusionsCurrent use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.

Persistent pain, sensory disturbances and functional impairment after adjuvant chemotherapy for breast cancer: Cyclophosphamide, epirubicin and fluorouracil compared with docetaxel + epirubicin and cyclophosphamide

Abstract Background. Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for persistent pain after breast cancer treatment (PPBCT) and sensory disturbances. The purpose was to compare patients treated with cyclophosphamide, epirubicin and fluorouracil (CEF) and cyclophosphamide and epirubicin + docetaxel (CE + T) in relation to PPBCT, sensory disturbances, peripheral sensory disturbances and functional impairment. Material and methods. A comparative nationwide cross-sectional questionnaire study on two cohorts treated with CEF respectively CE + T, based on the Danish Breast Cancer Cooperative Groups database. Inclusion criteria: women treated with chemotherapy as adjuvant treatment for primary breast cancer, age 18–69 years, without recurrence. Results. One thousand two hundred and forty-one patients allocated to CEF in 2005–2006 and 1652 patients allocated to CE + T in 2007–2008 were included. Six hundred and sixty-four (53%) with CEF and 861 (53%) patients with CE + T reported pain. In the multivariate analysis including available risk factors, CE + T did not confer an increased risk of PPBCT, OR 0.95 (95% CI 0.81–1.11), p = 0.52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, OR 0.75 (95% CI 0.62–0.90), p = 0.002. More CE + T patients reported peripheral sensory disturbances in the hands, OR 1.56 (95%CI 1.27–1.92), p < 0.0001, and in the feet, OR 2.0 (95% CI 1.66–2.42) p < 0.0001, compared to CEF. There was no difference in functional impairment (p = 0.62). Conclusion. Docetaxcel as adjuvant treatment for breast cancer does not increase the risk of PPBCT, sensory disturbances in the surgical area or functional impairment, but increase risk for peripheral sensory disturbances.

Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external breast radiotherapy for breast cancer: A randomized trial

Persistent pain after breast cancer treatment (PPBCT) affects between 25 and 60% of patients depending on surgical and adjuvant treatment. External breast radiotherapy (EBRT) has been shown to be a riskfactor for PPBCT, raising the question whether intraoperative radiation therapy (IORT), with its smaller radiation field may reduce the development of PPBCT. Using data from the TARGIT-A trial, the aim of this study was to compare these two treatments with regard to development of PPBCT. A total of 281 patients enrolled in the TARGIT-A trial from the Copenhagen University Hospitals was screened for participation, and a total of 244 patients were included and received a detailed questionnaire. The response rate was 98%, leaving 238 patients for the final analysis. Pain prevalence were 33.9% in the EBRT group and 24.6% in the IORT group (p = 0.11). Treatment with IORT may not alter the risk of PPBCT.

Development in self-reported arm-lymphedema in Danish women treated for early-stage breast cancer in 2005 and 2006 – A nationwide follow-up study

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.

Persistent pain, sensory disturbances and functional impairment after immediate or delayed axillary lymph node dissection

BACKGROUND Patients treated with 2-step axillary lymph node dissection (ALND) may be at increased risk of nerve damage due to more challenging surgery than an ALND immediately after a sentinel lymph node biopsy (SLNB), and thus more at risk for persistent pain after breast cancer treatment (PPBCT). The aim of this study was to examine PPBCT, sensory disturbances and functional impairment in patients treated with a 2-step ALND compared to patients with an SLNB followed by an immediate ALND, and patients with ALND without a prior SLNB. METHODS The study is a cross-sectional questionnaire study, comparing 2847 women treated with ALND in Denmark in 2005-2008. 196 patients treated with a 2-step ALND were compared with 1558 patients treated with an ALND after SLNB and 1093 with an ALND without a prior SLNB. RESULTS Overall prevalence of PPBCT and sensory disturbances was high, with about 55% reporting PPBCT and 77% reporting sensory disturbances in all groups. No differences were found between the groups on prevalence and intensity of PPBCT (p = 0.92), sensory disturbances (p = 0.32), and functional consequences (p = 0.35). CONCLUSIONS A 2-step ALND does not modify the risk of developing PPBCT compared to an immediate ALND.

Breast reconstruction with an expander prosthesis following mastectomy does not cause additional persistent pain: A nationwide cross-sectional study

INTRODUCTION 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. METHOD 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. RESULTS 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). CONCLUSION Breast reconstruction with a subpectoral implant after tissue expansion does not confer increased prevalence of persistent pain.