Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.

Cost-effectiveness of anterior surgical decompression surgery for cervical degenerative disk disease: a systematic review of economic evaluations.

PURPOSE: No clear consensus exists on which anterior surgical technique is most cost-effective for treating cervical degenerative disk disease (CDDD). One of the most common treatment options is anterior cervical discectomy with fusion (ACDF). Anterior cervical discectomy with arthroplasty (ACDA) was developed in an effort to reduce the incidence of clinical adjacent segment pathology and associated additional surgeries by preserving motion. This systematic review aims to evaluate the evidence regarding the cost-effectiveness of anterior surgical decompression techniques used to treat radiculopathy and/or myelopathy caused by CDDD. METHODS: The search was conducted in PubMed, EMBASE, Web of Science, CINAHL, EconLit, NHS-EED and the Cochrane Library. Studies were included if healthcare costs and utility or effectivity measurements were mentioned. RESULTS: A total of 23 studies were included out of the 1327 identified studies. In 9 of the 13 studies directly comparing ACDA and ACDF, ACDA was the most cost-effective technique, with an incremental cost effectiveness ratio ranging from $2.900/QALY to $98.475/QALY. There was great heterogeneity between the costs of due to different in- and exclusion criteria of costs and charges, cost perspective, baseline characteristics, and calculation methods. The methodological quality of the included studies was moderate. CONCLUSION: The majority of studies report ACDA to be a more cost-effective technique in comparison with ACDF. The lack of uniform literature impedes any solid conclusions to be drawn. There is a need for high-quality cost-effectiveness research and uniformity in the conduct, design and reporting of economic evaluations concerning the treatment of CDDD. TRIAL REGISTRATION: PROSPERO Registration: CRD42020207553 (04.10.2020).

Detection of secondary metastatic breast cancer by measurement of plasma CA 15.3.

BACKGROUND: Most current guidelines do not recommend the serial analysis of tumour marker CA 15.3 in the follow-up of asymptomatic patients treated for early breast cancer (EBC). These guidelines are based on small-scale studies carried out in an era with more limited treatment options than today. In our large academic centre, serial measurements of CA 15.3 are used routinely in the follow-up of EBC, whereas imaging for distant metastases is only carried out on indication. PATIENTS AND METHODS: In this retrospective single-centre study, patients were included if they were treated for EBC between 1 January 2000 and 1 January 2018, diagnosed with secondary metastatic disease at least 6 months after initial surgery and had CA 15.3 available at the time of diagnosis of metastases. The primary objective was to evaluate the proportion of patients in whom metastatic disease was discovered by an increasing CA 15.3. Information on the method of metastases detection, CA 15.3 evolution and survival was collected after approval of the ethics committee. RESULTS: At the moment of diagnosis of metastases, 451 of 730 included patients (62%) had CA 15.3 levels above the upper limit of normal (>30 kU/l). In 269 patients (37%), an increasing CA 15.3 was the first sign that led to the diagnosis of metastases. This was most frequent in luminal A-like tumours (48%) and in liver (45%) and bone (41%) localisation of metastases. By contrast, reported symptoms triggered the diagnosis of metastatic disease in 48% of the patients. Median overall survival was significantly longer when the relapse was discovered by CA 15.3 elevation versus those discovered by another trigger (abnormal clinical examination or history, abnormal laboratory tests or an incidental finding) (35 versus 22 months; P = 0.0027). CONCLUSION: When CA 15.3 is systematically used in the follow-up of EBC patients, the diagnosis of metastatic disease is made in 37% by a CA 15.3 increase.

Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort.

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. CONCLUSION: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC.

A randomized controlled TRIal of cognitive BEhavioral therapy for high Catastrophizing in patients undergoing lumbar fusion surgery: the TRIBECA study.

BACKGROUND: Around 20% of patients undergoing spinal fusion surgery have persistent back or leg pain despite surgery. Pain catastrophizing is the strongest psychological predictor for chronic postsurgical pain. Psychological variables are modifiable and could be target for intervention. However, randomized controlled trials evaluating the effectiveness of psychological interventions to reduce chronic pain and disability after spinal fusion in a population of patients with high preoperative pain catastrophizing scores are missing. The aim of our study is to examine whether an intervention targeting pain catastrophizing mitigates the risk of chronic postsurgical pain and disability. Our primary hypothesis is that targeted perioperative cognitive behavioral therapy decreases the risk of chronic postsurgical pain and disability after spinal fusion surgery in high catastrophizing patients. METHODS: We will perform a two-center prospective, single-blind, randomized, controlled study comparing lumbar spinal fusion surgery outcome between 2 cohorts. Adult patients selected for lumbar spinal fusion with decompression surgery and a minimum score of 24 on the pain catastrophizing scale will be randomized with 1:1 allocation for either perioperative cognitive behavioral therapy (intervention group) or a perioperative education plus progressive exercise program (control group). Patients randomized to the intervention group will receive six individual sessions of cognitive behavioral therapy, two sessions before the operation and four after. Primary outcome is the Core Outcome Measures Index at 12 months. Secondary outcomes include pain, disability, depression and quality of life. DISCUSSION: This is the first trial that evaluates the effectiveness of cognitive behavioral therapy as a perioperative tool to improve pain and disability after spinal fusion surgery in comparison with an educational/exercise control intervention, in patients with high levels of pain catastrophizing. If perioperative cognitive behavioral therapy proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcome after spinal fusion surgery. TRIAL REGISTRATION: Clinicaltrials ( NCT03969602 ). Registered 31 May 2019.

Breast cancer subtype and survival by parity and time since last birth.

BACKGROUND: Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome. PATIENTS AND METHODS: We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000-Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders. RESULTS: Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p < 0.001). Tumors within 5 years of last birth were proportionally more likely triple negative and HER-2 like, even when corrected for age at diagnosis. After a mean follow-up period of 10 years, parous women had a better disease-free survival compared to nulliparous women (HR 0.733; CI 0.560-0.961; p = 0.025, HR 0.738; CI 0.559-0.974; p = 0.032 before and after correction for known prognostic factors, respectively). In parous women, a longer time since last birth was correlated with a longer disease-free survival compared to patients with a recent pregnancy (HR 0.976; CI 0.957-0.996; p = 0.018). However, after correction, this association completely disappeared (HR 1.010; CI 0.982-1.040; p = 0.480). CONCLUSION: We observed a better disease-free survival for parous than nulliparous women. The influence of recent birth on disease-free survival is probably due to tumor and patient characteristics, as recent birth is associated with more aggressive subtypes.

Axillary staging for breast cancer during pregnancy: feasibility and safety of sentinel lymph node biopsy.

BACKGROUND: Safety of sentinel lymph node (SLN) biopsy for breast cancer during pregnancy is insufficiently explored. We investigated efficacy and local recurrence rate in a large series of pregnant patients. PATIENTS AND METHODS: Women diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from the International Network on Cancer, Infertility and Pregnancy, the German Breast Group, and the Cancer and Pregnancy Registry. Chart review was performed to record technique and outcome of SLN biopsy, locoregional and distant recurrence, and survival. RESULTS: We identified 145 women with clinically N0 disease who underwent SLN during pregnancy. The SLN detection techniques were as follows: 99mTc-labeled albumin nanocolloid only (n = 96; 66.2%), blue dye only (n = 14; 9.7%), combined technique (n = 15; 10.3%), or unknown (n = 20; 13.8%). Mapping was unsuccessful in one patient (0.7%) and she underwent an axillary lymph node dissection (ALND). Mean number of SLNs was 3.2 (interquartile range 1-3; missing n = 15). Positive SLNs were found in 43 (29.7%) patients and 34 subsequently underwent ALND. After a median follow-up of 48 months (range 1-177), 123 (84.8%) patients were alive and free of disease. Eleven patients experienced a locoregional relapse, including 1 isolated ipsilateral axillary recurrence (0.7%). Eleven (7.6%) patients developed distant metastases, of whom 9 (6.2%) died of breast cancer. No neonatal adverse events related to SLN procedure during pregnancy were reported. CONCLUSIONS: SLN biopsy during pregnancy has a comparably low axillary recurrence rate as in nonpregnant women. Therefore, this method can be considered during pregnancy instead of standard ALND for early-stage, clinically node-negative breast cancer.

Body mass index, age at breast cancer diagnosis, and breast cancer subtype: a cross-sectional study.

PURPOSE: Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. Because it is not well known whether this is subtype dependent, we studied the association between body mass index (BMI) and age at breast cancer diagnosis, or the probability of being diagnosed with a specific breast cancer phenotype, by menopausal status. METHODS: All patients with non-metastatic operable breast cancer from the University Hospital Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n = 7020) in this cross-sectional study. Linear models and logistic regression were used for statistical analysis. Allowing correction for age-related BMI-increase, we used the age-adjusted BMI score which equals the difference between a patient's BMI score and the population-average BMI score corresponding to the patient's age category. RESULTS: The quadratic relationship between the age-adjusted BMI and age at breast cancer diagnosis (p = 0.0207) interacted with menopausal status (p < 0.0001); increased age at breast cancer diagnosis was observed with above-average BMI scores in postmenopausal women, and with below-average BMI scores in premenopausal women. BMI was linearly related to the probabilities of Luminal B and HER2-like breast cancer phenotypes, but only in postmenopausal women. The relative changes in probabilities between both these subtypes mirrored each other. CONCLUSION: BMI associates differently before and after menopause with age at breast cancer diagnosis and with the probability that breast cancer belongs to a certain phenotype. The opposite effect of increasing BMI on relative frequencies of Luminal B and HER2-like breast cancers suggests a common origin.

The effect of adjuvant chemotherapy on symptom burden and quality of life over time; a preliminary prospective observational study using individual data of patients aged ≥70 with early stage invasive breast cancer.

OBJECTIVES: We aim to assess short and long term effects of chemotherapy on patient-reported quality of life (QOL) and patient versus clinician symptom reporting in older patients with breast cancer adjusted for tumour and aging parameters. MATERIAL AND METHODS: In this prospective, multicentre, non-interventional, observational study, women aged ≥70years were enrolled after surgery and assigned to a TC chemotherapy (docetaxel and cyclophosphamide) group or a control group depending on their planned adjuvant treatment. Longitudinal multivariate models were used to assess the statistical and minimal clinically important difference (MCID) in the impact of TC chemotherapy over time on QOL and symptom burden adjusted for baseline aging and tumour parameters. Statistical significance was set at 5% and MCID at 10 points. RESULTS: In total, 57 patients were enrolled in the chemotherapy and 52 patients in the control group. Within the chemotherapy group, clinical deterioration was reported at 3months for Fatigue (17.73), Dyspnoea (17.05), Diarrhoea (12.06) and Appetite Loss (17.05) scores (all p<0.001). However, the scores had returned to baseline (or even better for Role Functioning) at year 1. No clinical deterioration was reported in the control group. Symptom scores as reported by patients were significantly (p<0.05) higher than those reported by the clinicians, even more so for Fatigue, Dyspnoea, and Pain. CONCLUSION: Our results show that symptom burden and diminished QOL in an older breast cancer population receiving adjuvant TC chemotherapy are short-lived and disappear after a while with no long-term differences compared to a similar population not receiving chemotherapy.

Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome.

OBJECTIVE: Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. METHODS: This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. RESULTS: Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2±4.8 versus 12.8±3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0±2.0 versus 7.0±1.6, P=0.041) and in the total number of video-rated tics (259.6±107.3 versus 49.6±24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. CONCLUSION: Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects.

Uterine artery embolisation for symptomatic adenomyosis with polyzene F-coated hydrogel microspheres: three-year clinical follow-up using UFS-QoL questionnaire.

PURPOSE: This study was designed to assess midterm outcome of uterine artery embolisation (UAE) for women with therapy-resistant adenomyosis using polyzene F-coated hydrogel microspheres. METHODS: Between September 2006 and January 2010, 29 consecutive women with adenomyosis (15 in combination with fibroids) were treated with UAE using polyzene F-coated hydrogel microspheres. Junction zone thickness was assessed with MRI at baseline and 3 months. Women filled out the uterine fibroid symptom and quality of life questionnaire at baseline, 3 months and after a mean clinical follow-up of 37 months (median 35, range 29-64 months). RESULTS: At baseline, symptom severity score of 29 women was mean 67 (median 72, range 23-100). At 3 months, this score decreased to mean 22 (median 15, range 0-66) and mean 15 (median 17, range 0-34) at final follow-up. At final follow-up of mean 37 months (median 35, range 29-64 months), 22 of 29 (76 %) patients were asymptomatic. Of these 22 women, 3 underwent a second UAE at 6, 7, and 14 months. The remaining seven patients clinically improved but still had symptoms; one underwent a hysterectomy. There was no difference in outcome between women with pure adenomyosis and women with additional fibroids. The junction zone of 4 women with additional therapy was significantly thicker compared with the remaining 25 patients. CONCLUSIONS: In women with therapy resistant adenomyosis, UAE using polyzene F-coated hydrogel microspheres resulted in 3 years preservation of the uterus in 28 of 29 (97 %) with good clinical outcome in the vast majority of patients. Initial thickness of the junction zone is related to additional therapy.

An atypical case of necrotizing fasciitis of the breast.

Necrotizing fasciitis is a rare and aggressive soft tissue infection involving the fascia and subcutaneous tissues. It carries a high mortality and morbidity rate. In literature, the few case reports on necrotizing fasciitis of the breast, describe the need for a mastectomy in 90% of the cases. We report on a case of a 72-year old Caucasian women with an atypical presentation of necrotizing fasciitis of the breast in combination with an acute abdomen, successfully treated with breast-conserving debridement and secondary wound closure.

A prospective assessment of musculoskeletal toxicity and loss of grip strength in breast cancer patients receiving adjuvant aromatase inhibitors and tamoxifen, and relation with BMI.

Aromatase inhibitor (AI) therapy for estrogen receptor-positive breast cancer is known to induce or enhance musculoskeletal problems. We have previously reported that loss of grip strength is more pronounced in AI-users with extremes in BMI. We here report results from a larger prospective study. Postmenopausal early breast cancer patients scheduled to start AI or tamoxifen therapy were recruited. A functional assessment grip strength test was performed at baseline, 3, 6, and 12 months of therapy. BMI was assessed, and a rheumatologic questionnaire was completed at each visit. 188 patients on an AI and 104 patients on tamoxifen were enrolled. 74 % of AI-users reported new/worsened musculoskeletal complaints compared with 37 % in the tamoxifen group. This was translated in a larger grip strength decrease in patients experiencing AI-induced pain opposed to patients without new/worsened complaints (p = 0.0002). 15 % of AI-users discontinued therapy due to musculoskeletal symptoms, who were characterized by a larger grip strength reduction versus adherent patients (p = 0.0107). Young age (p = 0.0135), taxane-based chemotherapy (p = 0.0223), and baseline VAS score >4 (p = 0.0155) were predictors for AI-related musculoskeletal pain. In addition, a quadratic trend of BMI with grip strength change (p = 0.0090) and probability of discontinuation was observed (p = 0.0424). Musculoskeletal events were a substantial problem in AI-treated patients and an important reason for treatment discontinuation. The decrease in grip strength was larger in AI- than in tamoxifen-users, with a more pronounced change in symptomatic patients. The inverse relationship between BMI extremes and grip strength change was confirmed in this large group of AI-patients.

Prognostic implications of lobular breast cancer histology: new insights from a single hospital cross-sectional study and SEER data.

BACKGROUND: Invasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC. METHODS: Primary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation. RESULTS: In lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380-7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309-0.703), p = 0.0003) and BCSS (HR 0.441 (0.247-0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4-5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown). CONCLUSION: The prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority ( = node negative) of ILCs.

Applying the 2011 St Gallen panel of prognostic markers on a large single hospital cohort of consecutively treated primary operable breast cancers.

BACKGROUND: Many easily measurable and readily available factors are now established as being prognostic in primary operable breast cancer. We here applied the 2011 St Gallen surrogate definition for breast cancer subclassification using tumor grade instead of Ki67. PATIENTS AND METHODS: Four thousand three hundred and eighteen consecutive patients who had surgery for primary operable breast cancer (1 January 2000 and 31 December 2009) in UZ Leuven excluding primary metastastic male breast cancers and those receiving neoadjuvant therapy. Five different surrogate phenotypes were created using the combined expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 together with tumor grade. Disease-free interval (DFI), distant metastastis-free interval (DMFI), locoregional relapse-free interval (LRRFI), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated. RESULTS: Surrogate phenotypes present with significant differences in DFI, DMFI, LRRFI, BCSS and OS. 'Luminal A' tumors presented with the best outcome parameters but the effect weakened at longer follow-up. CONCLUSIONS: The four surrogate markers, agreed upon by the 2011 St Gallen consensus, defined five prognostic surrogate phenotypes in a large series of consecutively treated breast cancer patients. Their prognostic value changed with longer follow-up. The added value of gene expression profile over classical pathological assessment remains to be defined.

Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up.

BACKGROUND: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. MATERIALS AND METHODS: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. RESULTS: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8). CONCLUSION: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.

Long-term follow-up of uterine artery embolization for symptomatic adenomyosis.

INTRODUCTION: Long-term results of uterine artery embolization (UAE) for adenomyosis are largely unknown. We assess long-term outcome of UAE in 40 women with adenomyosis. MATERIALS AND METHODS: Between March 1999 and October 2006, 40 consecutive women with adenomyosis (22 in combination with fibroids) were treated with UAE. Changes in junction zone thickness were assessed with magnetic resonance imaging (MRI) at baseline and again at 3 months. After a mean clinical follow-up of 65 months (median 58 [range 38-129]), women filled out the uterine fibroid symptom and quality of life (UFS-QoL) questionnaire, which had additional questions on the long-term evolution of baseline symptoms and adverse events. RESULTS: During follow-up, 7 of 40 women (18%) underwent hysterectomy. Among these 7 women, the junction zones were significantly thicker, both at baseline (mean 23 vs. 16 mm, P = 0.028) and at 3-month follow-up (mean 15 vs. 9 mm, P = 0.034). Of 33 women with preserved uterus, 29 were asymptomatic. Four patients had symptom severity scores of 50 to 85 and overall QoL scores of 60 to 66, indicating substantial clinical symptoms. There was no relation between clinical outcome and the initial presence of fibroids in addition to adenomyosis. CONCLUSION: In women with therapy-resistant adenomyosis, UAE resulted in long-term preservation of the uterus in the majority. Most patients with preserved uterus were asymptomatic. The only predictor for hysterectomy during follow-up was initial thickness of the junction zone. The presence or absence of fibroids in addition to adenomyosis had no relation with the need for hysterectomy or clinical outcome.

Lobular and non-lobular breast cancers differ regarding axillary lymph node metastasis: a cross-sectional study on 4,292 consecutive patients.

Invasive lobular carcinoma (ILC) accounts for 8-14% of all breast cancers and carries distinct prognostic and biologic implications. The goal of our study was to investigate the impact of lobular histology on axillary lymph node (ALN) involvement. This is a cross-sectional study of 4,292 consecutive patients surgically treated for breast carcinoma at the University Hospitals Leuven. Logistic regression analysis was used to relate ILC to lymph node involvement while controlling for the following clinicopathologic features: tumor size, multifocal disease, tumor grade, lobular subtype and the combined steroid, and Her-2 status. Odds ratios (ORs) and 95% confidence intervals (CIS) were computed. A subgroup analysis was performed for patients that underwent a sentinel lymph node (SLN) procedure. The observed incidence of ILC was 13%. ILCs were larger, were more often grade II, multifocal, steroid receptor positive and Her-2 negative, and tended to be present in older patients. Incidence of ALN involvement was 42.0% for ILCs versus 38.3% for other tumors (OR 1.17, 95% CI 0.97-1.40). For the SLN subgroup, ILCs were less often ALN positive than non-ILCs (20.5% versus 28.3%, OR 0.66, 95% CI: 0.41-1.00). In the multivariable analysis, the lobular subtype was identified as less likely to have ALN involvement (adjusted OR 0.66, 95% CI 0.53-0.82). The analysis for the SLN subgroup showed comparable results (adjusted OR 0.49, 95% CI 0.30-0.78). This study has demonstrated that the lobular subtype is an independent predictor of lymph node involvement with ILC having a lower incidence of involved lymph nodes. The mildly higher incidence of ALN metastasis in lobular cancers in univariable analysis is not due to the lobular subtype, but due to confounding factors that interact with lymph node involvement.

Prediction of lymph node involvement in breast cancer from primary tumor tissue using gene expression profiling and miRNAs.

The aim of this study was to investigate whether lymph node involvement in breast cancer is influenced by gene or miRNA expression of the primary tumor. For this purpose, we selected a very homogeneous patient population to minimize heterogeneity in other tumor and patient characteristics. First, we compared gene expression profiles of primary tumor tissue from a group of 96 breast cancer patients balanced for lymph node involvement using Affymetrix Human U133 Plus 2.0 microarray chip. A model was built by weighted Least-Squares Support Vector Machines and validated on an internal and external dataset. Next, miRNA profiling was performed on a subset of 82 tumors using Human MiRNA-microarray chips (Illumina). Finally, for each miRNA the number of significant inverse correlated targets was determined and compared with 1000 sets of randomly chosen targets. A model based on 241 genes was built (AUC 0.66). The AUC for the internal dataset was 0.646 and 0. 651 for the external datasets. The model includes multiple kinases, apoptosis-related, and zinc ion-binding genes. Integration of the microarray and miRNA data reveals ten miRNAs suppressing lymph node invasion and one miRNA promoting lymph node invasion. Our results provide evidence that measurable differences in gene and miRNA expression exist between node negative and node positive patients and thus that lymph node involvement is not a genetically random process. Moreover, our data suggest a general deregulation of the miRNA machinery that is potentially responsible for lymph node invasion.