Multigene profiles to guide the use of neoadjuvant chemotherapy for breast cancer: a Copenhagen Breast Cancer Genomics Study.

Estrogen receptor (ER) and human epidermal growth factor 2 (HER2) expression guide the use of neoadjuvant chemotherapy (NACT) in patients with early breast cancer. We evaluate the independent predictive value of adding a multigene profile (CIT256 and PAM50) to immunohistochemical (IHC) profile regarding pathological complete response (pCR) and conversion of positive to negative axillary lymph node status. The cohort includes 458 patients who had genomic profiling performed as standard of care. Using logistic regression, higher pCR and node conversion rates among patients with Non-luminal subtypes are shown, and importantly the predictive value is independent of IHC profile. In patients with ER-positive and HER2-negative breast cancer an odds ratio of 9.78 (95% CI 2.60;36.8), P < 0.001 is found for pCR among CIT256 Non-luminal vs. Luminal subtypes. The results suggest a role for integrated use of up-front multigene subtyping for selection of a neoadjuvant approach in ER-positive HER2-negative breast cancer.

Ultrasound Elastography in Breast Cancer Diagnosis.

Ultrasound elastography is an established method for characterization of focal lesions in the breast. Different techniques and analyses of the images may be used for the characterization. This article addresses the use of ultrasound elastography in breast cancer diagnosis. In the first part of the article the techniques behind both strain- and shear-wave-elastography are explained and followed by a section on how to obtain adequate elastography images and measurements. In the second part of the article the application of elastography as an adjunct to B-mode ultrasound in clinical practice is described, and the potential diagnostic gains and limitations of elastography are discussed.

Breast density and outcome of mammography screening: a cohort study.

The purpose of this study was to investigate the effect of breast density on breast cancer (BC) mortality in a mammography screening programme. The cohort included 48 052 women participating in mammography screening in Copenhagen, Denmark, where biennial screening is offered to women aged 50-69 years. We collected information for the years 1991-2001 on screening outcome, incident BCs (screen-, interval-, and later detected), and BC deaths. Breast density was dichotomised into fatty (F) and mixed/dense (M/D) breasts. Screening sensitivity was measured as the odds ratio of interval versus screen-detected cancer for dense versus F breasts. Poisson regression was used to estimate the ratios for BC incidence, case fatality, and mortality between women with M/D and F breasts. For women with M/D breasts, the odds ratio of an interval cancer was 1.62 (95% confidence interval, CI, 1.14-2.30), and the age-adjusted rate ratios were 2.45 (95% CI 2.14-2.81) for BC incidence, 0.60 (95% CI 0.43-0.84) for case fatality, and 1.78 (95% CI 1.17-2.72) for BC mortality. The study shows that BC in women with M/D breasts is more frequent, but on average less severe, than in women with F breasts.

Compliance with European guidelines for diagnostic mammography in a decentralized health-care setting.

PURPOSE: To evaluate the compliance of Danish mammography clinics with requirements concerning organization, activity volume, and assessment procedures from two European guidelines for quality assurance in diagnostic mammography (EUSOMA and EUREF). MATERIAL AND METHODS: We used individual records on all diagnostic mammographies performed in Denmark in 2000, and questionnaires given to Danish mammography clinics in 2000, 2002, and 2004. RESULTS: The study showed a marked centralization of the diagnostic activity from 2000 to 2004 to a smaller number of public breast assessment centers with full multidisciplinary breast assessment. However, a relatively large number of these centers did not comply with the activity volume requirement of 2000 mammograms per clinic per year. The number of private diagnostic mammography clinics performing basic diagnostic mammography has remained fairly stable in the period 2000 to 2004. Compared with public breast assessment centers, the private diagnostic mammography clinics had a lower compliance with activity volume requirements. CONCLUSION: A marked proportion of Danish public breast assessment centers operate with less than optimal activity volume, suggesting that further centralization would be appropriate. The situation in private diagnostic mammography clinics may cause concern, as our study showed that the majority of these clinics did not meet the activity volume requirements.

Ultrasound-guided drainage of breast abscesses: results in 151 patients.

The aim of this paper is to describe the efficacy of ultrasound-guided drainage of breast abscesses with special attention to the risk of recurrence and the need for surgical treatment in a consecutive patient population. 151 patients, 89 with puerperal and 62 with non-puerperal breast abscesses, were treated with ultrasound-guided drainage, by needle or catheter under local anaesthesia. Follow-up punctures were performed at 2 or 3 day intervals until the clinical condition and ultrasound findings had improved. All patients were treated with oral antibiotics. Mammography was performed to search for underlying cancer. 86 (97%) out of 89 patients with puerperal abscesses and 50 (81%) out of 62 with non-puerperal abscesses recovered after the first round of ultrasound-guided drainage. One patient in each group had recurrence in loco but recovered after further ultrasound-guided drainage. 13 patients, 11 with non-puerperal and two with puerperal abscesses, underwent surgical excision of the abscess cavity or fistulas. Breastfeeding continued and 117 patients were treated as outpatients. The median number of follow up examinations in the ultrasound-department was four (range 1-10) for the group of patients with puerperal abscess and three (range 1-7) in the group of patients with non-puerperal abscess. The corresponding figure for the median number of punctures was for both groups one (range 1-6 and 1-4). There were no reports of newly diagnosed breast cancer in the 2 year follow-up period. This study supports the use of ultrasound-guided drainage in puerperal and non-puerperal breast abscesses. The method is less invasive than traditional surgery and has a high rate of success.

Breast cancer incidence after the start of mammography screening in Denmark.

Mammography screening may lead to overdiagnosis of asymptomatic breast cancers, that would otherwise not have given rise to clinical symptoms. This aspect was studied in three regional screening programmes in Denmark, which started in Copenhagen municipality, Fyn county, and Frederiksberg municipality in 1991, 1993, and 1994, respectively. In these regions, we compared time trends in incidence of invasive breast cancer with the rest of Denmark. Since the number of clinical mammograms was relatively low, it was reasonable to assume that the breast cancer incidence outside the three screening regions represented the incidence of a population with low-intensity opportunistic screening. In Copenhagen and Fyn, a prevalence peak in incidence was seen during the first invitation round. During the subsequent invitation rounds, the incidence dropped to a level in line with the incidence expected without screening. The pattern was different in the small municipality of Frederiksberg, where the sensitivity was low during the first invitation round. Inclusion of screen-detected ductal carcinoma in situ cases did not change these results. The experiences from Copenhagen and Fyn show that organised mammography screening can operate without overdiagnosis of breast cancer.

Early outcome of mammography screening in Copenhagen 1991-99.

OBJECTIVES: To evaluate the early outcome of an organised mammography screening programme in an area with little opportunistic screening. SETTING: The municipality of Copenhagen, Denmark, during four invitation rounds 1991-99. METHODS: The following outcome measures were used: rates of participation, recall, false positive, and cancer detection. Benign biopsy, distribution of tumour size, lymph node status, and malignancy grade. RESULTS: A total of 106,933 screens were undertaken, and 824 invasive breast carcinomas or CIS were detected. The detection rate was 11.9 per 1000 participants in the first invitation round, and it continued to be high in subsequent rounds. The percentage of CIS cases was 11%. Coverage declined from 71% in the first round to 62% in the fourth, although 91% of those participating in the previous three rounds attended. The programme operated with a high recall rate. The false positive rate was also high, being 5.6% at first screen, and 1.8% later on. However, 90% of false positives were sorted out already at assessment. The percentage of screen detected invasive breast cancers with a tumour diameter < or = 10 mm was 39% compared with 16% of all invasive breast cancers in these age groups in Copenhagen before screening. CONCLUSION: Copenhagen is an area with a high incidence of breast cancer and with relatively little opportunistic screening. The start of a screening programme with a high recall rate in this area resulted in a detection rate above 1%. The Copenhagen programme met or exceeded most of the interim measures recommended in the European Guidelines.

Prevalence of silicone breast implant rupture among Danish women.

The durability of silicone gel-filled breast implants is of concern, but there are few epidemiological studies on this issue. To date, most of the relevant findings are derived from studies of explantation, which suffer from bias by including women with symptoms or concerns about their implants. As part of a long-term magnetic resonance imaging study of the incidence of rupture, this study involved 271 women with 533 cosmetic breast implants who were randomly selected from among women who underwent cosmetic breast implantation from 1973 through 1997 at one public and three private plastic-surgery clinics in Denmark. The prevalence of rupture was determined from the first magnetic resonance screening. The images were evaluated by four independent readers, using a standardized, validated form. The outcomes under study were rupture, possible rupture, and intact implant. Ruptures were categorized as intracapsular or extracapsular. Overall, 26 percent of implants in 36 percent of the women examined were found to be ruptured, and an additional 6 percent were possibly ruptured. Of the ruptured implants, 22 percent were extracapsular. In multiple regression analyses, age of implant was significantly associated with rupture among second- and third-generation implants, with a 12-fold increased prevalence odds ratio for rupture of implants that were between 16 and 20 years of age, compared with implants between 3 and 5 years of age. Surgitek implants (Medical Engineering Corporation, Racine, Wis.) had a significantly increased prevalence odds ratio of 2.6 for rupture, compared with the reference implants. No significant association was found with the position (subglandular or submuscular) or the type of implant (single- or double-lumen). Extracapsular ruptures were significantly associated with a history of closed capsulotomy (p = 0.001). In the future, the authors plan to examine the women in their cohort with a second magnetic resonance imaging scan to establish the incidence of rupture, a parameter unknown to date in the literature, and to further characterize those factors associated with the actual risk of rupture.

Clinical report: contrast enhancement of tumor perfusion as a guidance for biopsy.

We describe three cases where biopsies from various tumors were guided by contrast enhancement of tumor perfusion. After i.v. administration of Levovist (Schering AG, Berlin, Germany), the tumors showed both hyper- and hypovascular areas. Biopsies from the latter showed marked necrosis or fibrosis. This may cause biopsies not being conclusive. To ensure fully diagnostic biopsies from irregular tumors we propose the biopsy to be performed from the most vascular part demonstrated by contrast enhancement.

Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.

The results from a prospective randomized trial comparing two different radiation schedules for treatment of painful bone metastases in women with recurrent breast cancer are presented. A total of 217 patients with painful bone metastases were randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W) or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain assessment, the radiological response and the degree of side-effects. The patients were rated at start of treatment and after 1, 3, 6 and 12 months. No difference between the two radiation regimes was found, neither in achieved pain relief, improvement in level of activity and medication, nor was there any difference in radiological response and side-effects from treatment. Both regimes resulted in a significant improvement in both pain score and level of activity 1 month after treatment, an improvement which persisted during the follow-up period. We conclude that 15 Gy given in three fractions 2F/W is as effective as 30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost to society.

Pressure/cross-sectional area relations in the proximal urethra of healthy males. Part 1: Elastance and estimated pressure in the uninstrumented urethra.

The pressure/cross-sectional area relation in the resting urethra during the storage phase was studied in 31 healthy male volunteers aged 23-85 years. Measurements were performed at 5-mm intervals from the bladder neck and beyond the region of high pressure, and the elastance and estimated pressure in the uninstrumented urethra (Po) were calculated at each measurement location. All subjects were further evaluated by means of symptom score, prostatic volume determined by rectal ultrasound, urethral pressure profile, cystometry, and pressure flow. The elastance and Po both varied along the urethra, with significantly higher values of both parameters in the sphincteric region as compared to the prostatic area. A significant positive correlation was found between Po and age in the prostatic parts of the urethra, whereas no correlation could be demonstrated between elastance and age in any part of the urethra. These results indicate that the prostatic parts of the urethra are readily distensible at modest intraluminal pressures as compared to the sphincteric segment, and that the intraluminal pressure required to obtain a given distension of this segment of the urethra seems to increase with age. It is suggested that the technique may prove of value in the elucidation of pathophysiological mechanisms related to benign prostatic hyperplasia, and that the technique may bring new insight into the mode of action of various treatment modalities for this disease.

Pressure/cross-sectional area relations in the proximal urethra of healthy males. Part 2: Power generation during voluntary contraction.

The power generation in the proximal urethra during voluntary squeezing was studied in 30 healthy male volunteers aged 23-85 years. Measurements were performed at 5-mm intervals from the bladder neck and beyond the region of high pressure, and the maximum power generation during contraction was calculated at each measurement location. All subjects were further evaluated by means of symptom score, prostatic volume determined by rectal ultrasound, urethral pressure profile, cystometry, and pressure flow. There was a significant variation in power generation along the urethra, with minimum values in the prostatic segments and an approximately 5-fold increase in the high pressure zone. Power generation remained high in the urethral segment distal to the high pressure zone. No correlation between age and power generation could be demonstrated in any part of the urethra. The technique employed does not allow for a differentiation of the individual muscles involved, however, it is suggested that the pelvic floor dominates above the level of the perineal membrane, whereas the striated muscles of the penis may influence the proximal part of the spongious urethra. Physiologically, the contractile capability of the male urethra is probably important for the continence function, as well as it may be of significance for the normal ejaculatory function.

[Ultrasound and lymphography in malignant lymphoma. Comparison with consideration to staging]. / Ultralyd og lymfografi ved malignt lymfom. Sammenligning med henblik på stadieinddeling.

The diagnostic value of abdominal ultrasound and lymphography was compared in the staging of 88 consecutive patients with malignant lymphoma, examined during the period March 1990 to April 1991. Lymphography was used as the reference method in the evaluation of the paraaortic and iliac lymphnodes. In 19% of the patients ultrasound examination could not be accomplished optimally, and these results were evaluated in a separate group. Lymphography demonstrated involvement of retroperitoneal lymphnodes in 27 patients, among these ultrasound was false negative in seven (= 26%). In ten patients ultrasound examination demonstrated lymphoma outside the lymphographic area. No false positive ultrasound examinations were found in the group with negative lymphography. Ultrasound cannot replace lymphography, but is an important supplement, and in those cases where ultrasound reveals lymphomas in the lymphographic area, lymphography can be omitted as ultrasound has a high predictive value.

A technique for measurement of related values of pressure and cross-sectional area in the male urethra.

A probe for measurement of related values of cross-sectional area and pressure in the male urethra was constructed. The probe allows induction of variable pressures or fluid volumes in a distensible balloon located in the urethra and simultaneous recording of related values of cross-sectional area and pressure. Cross-sectional area is measured in the range of 11-102 mm2 using the field-gradient principle. Pressure is measured in the range of 0-250 cmH2O using tip transducers. The time constant for cross-sectional area measurement is 0.02 s and that for pressure measurement, 0.007 s. The pressures required to reach the maximal and minimal cross-sectional areas of the balloon are 2.8 and -2.4 cmH2O, respectively. The shape of the probe after its placement in the urethra was studied by transrectal ultrasound in five volunteers. The results showed that the measurement error caused by the slope of the balloon walls or the forced bending of the catheter did not exceed 5%. The method enables a description of the biomechanical properties of the male urethra at rest in terms of estimated pressure at zero cross-sectional area, elastance, and stress-relaxation and at voluntary contraction in terms of work and power as evaluated at well-defined anatomical locations.

[Congenital duodenal obstruction caused by an abnormal superior mesenteric vein]. / Kongenit duodenal obstruktion forårsaget af abnormt forløbende vena mesenterica superior.

A case of congenital duodenal obstruction caused by an abnormal superior mesenteric vein is presented. The obstruction was successfully treated by duodenoduodenostomy anterior to the vein.

Metastatic pattern in recurrent breast cancer. Special reference to intrathoracic recurrences.

The anatomical and temporal patterns of recurrence were studied in 401 patients with first recurrence of breast cancer. All patients underwent the same scheduled investigation program: history, physical examination, blood tests, bone scanning, bilateral iliac crest biopsy, radiologic bone survey, chest x-rays, and ultrasound scanning of the liver. The current article focuses on the diagnosis of intrathoracic (ITH) recurrence. Most patients recurred in a single site and 50% of the recurrences were diagnosed within the first 2 years from initial diagnosis. Chest x-ray revealed ITH recurrence in 27% (109 patients), and in 8% the lung, pleura, and/or mediastinum were the only signs of recurrence. Generally, the status of primary demographic, clinical, and pathoanatomical characteristics were not predictive as to the development of ITH recurrence, although patients with pleural recurrences often had centrally located primary tumors, locally advanced disease, and often received adjuvant radiotherapy. Clinical symptoms and signs of ITH recurrence were present in only one third of the patients, and the diagnostic specificity and sensitivity of serum lactate dehydrogenase were only 33% and 85%, respectively. Since ITH recurrences often are silent, and since recurrence in this site may have both prognostic and therapeutical implications, routine chest x-ray is indicated in all patients with first recurrence of breast cancer.

Clinical and radiologic characteristics of bone metastases in breast cancer.

Metastatic bone disease was evaluated in 380 consecutive patients at the time of first metastasis of breast cancer. Studies included radiographic examination, radionuclide examination, and bone marrow biopsy. Radiographs of the skeleton demonstrated metastases in 120 patients (32%), and in 40 of these patients (13%) the bone was the only site of metastases. The diagnostic efficiency was 82% for bone scanning, 80% for pain evaluation, 59% for s-calcium analyses, and 77% for s-alkaline phosphatase analyses. Bone scanning is an effective method to exclude metastatic bone disease (sensitivity: 96%). A positive scan, however, requires radiologic confirmation (specificity: 66%). Bone scanning of the skeleton should be the initial staging procedure in all patients with recurrent breast cancer with no clinical or biochemical signs of bone metastases. Bilateral posterior iliac crest bone marrow aspirations and bone biopsies were positive in 82 out of the 320 patients who underwent biopsy. The frequency of positive bone marrow biopsy was significantly correlated with both the site of radiographic metastases and with the total number of involved bone regions. Routine bone marrow biopsies are indicated in patients with a positive bone scan, but a negative x-ray examination. In these cases biopsies should be performed bilaterally.