Ilse Vejborg

Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study

Abstract Objectives To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991. Design Cohort study. Setting The mammography service screening programme in Copenhagen, Denmark. Participants All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used. Main outcome measures The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region. Results Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%. Conclusions In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.

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.

Socio-demographic determinants of participation in mammography screening

Our objective was to use individual data on socio‐demographic characteristics to identify predictors of participation in mammography screening and control to what extent they can explain the regional difference. We used data from mammography screening programmes in Copenhagen, 1991–1999, and Funen, 1993–2001, Denmark. Target groups were identified from the Population Register, screening data came from the health authority, and socio‐demographic data from Statistics Denmark. Included were women eligible for at least 3 screens. The crude RR of never use versus always use was 3.21 (95%CI, 3.07–3.35) for Copenhagen versus Funen, and the adjusted RR was 2.55 (95%CI, 2.43–2.67). The adjusted RR for never use among women without contact to a primary care physician was 2.50 (95% CI, 2.31–2.71) and 2.89 (95% CI, 2.66–3.14), and for women without dental care 2.94 (95% CI, 2.77–3.12) and 2.88 (95% CI, 2.68–3.10) for Copenhagen and Funen, respectively. Other important predictive factors for nonparticipation were not being married and not being Danish. In conclusion, to enhance participation in mammography screening programmes special attention needs to be given to women not using other primary health care services. All women in Copenhagen, irrespective of their socio‐demographic characteristics, had low participation. Screening programmes have to find ways to handle this urbanity factor.

Untreated Silicone Breast Implant Rupture

Implant rupture is a well-known complication of breast implant surgery that can pass unnoticed by both patient and physician. To date, no prospective study has addressed the possible health implications of silicone breast implant rupture. The aim of the present study was to evaluate whether untreated ruptures are associated with changes over time in magnetic resonance imaging findings, serologic markers, or self-reported breast symptoms. A baseline magnetic resonance imaging examination was performed in 1999 on 271 women who were randomly chosen from a larger cohort of women having cosmetic breast implants for a median period of 12 years (range, 3 to 25 years). A follow-up magnetic resonance imaging examination was carried out in 2001, excluding women who underwent explantation in the period between the two magnetic resonance imaging examinations (n = 44). On the basis of these examinations, the authors identified 64 women who had at least one ruptured implant at the first magnetic resonance imaging examination and, for comparison, all women who had intact implants at both examinations (n = 98). Magnetic resonance images from the two examinations were compared and changes in rupture configuration were evaluated. Comparisons were also made for self-reported breast symptoms occurring during the study period and for changes in serum values of antinuclear antibodies, rheumatoid factor, and cardiolipin antibodies immunoglobulin G and immunoglobulin M. The majority of the women with implant rupture had no visible magnetic resonance imaging changes of their ruptured implants. For 11 implants (11 percent) in 10 women, the authors observed progression of silicone seepage, either as a conversion from intracapsular into extracapsular rupture (n = 7), as progression of extra-capsular silicone (n = 3), or as increasing herniation of the silicone within the fibrous capsule (n = 1); however, in most cases, these changes were minor. Some changes could be ascribed to trauma, but others seemed spontaneous. There was no increase in levels of autoantibodies during the study period in either study group. Women with untreated implant ruptures reported a significant increase in nonspecific breast changes (odds ratio, 2.1; 95 percent confidence interval, 1.2 to 3.8) compared with women without ruptures. On the basis of this first study of women with untreated silicone breast implant rupture, the authors conclude that implant rupture is a relatively harmless condition, which only rarely progresses and gives rise to notable symptoms. Even so, because of a small risk of silicone spread, the authors suggest that women with implant ruptures be followed clinically, if not operated on. Because implant ruptures often occur asymptomatically, any woman with silicone implants, regardless of rupture status, should be evaluated at regular intervals.

The presence of tumor cells in bone marrow at the time of first recurrence of breast cancer.

The occurrence of bone marrow carcinosis was investigated in 380 patients at the time of first recurrence of breast cancer. Results were related to results from radiographic bone survey, 99mTc MDP bone scintigraphy, clinical examination and serum alkaline phosphatase and serum calcium levels. Eighty‐seven patients (23%) had tumor cells in the bone marrow. X‐rays showed metastases in 78% of the patients with and in 16% of the patients without bone marrow carcinosis. The diagnostic efficiency of x‐rays with bone marrow biopsy as the key diagnostic factor was 83%, and it was superior to that of other investigation methods. Bone tissue biopsies were positive alone in 15 patients (17%) and marrow aspirations were positive alone in seven patients (8%). Imprint preparations were positive alone in 7% of the patients and bone tissue biopsy in 5% of the patients. Heavy tumor infiltration (≥50%) of the bone marrow was associated with the occurrence of numerous regions of radiographically involved bone lesions and with histopathologic evidence of bone destruction. Furthermore, pronounced bone formation and marrow fibrosis were more commonly seen in patients with osteosclerotic bone metastases than in patients with osteolytic bone metastases. This study provides evidence that the primary soil of metastatic bone disease in human breast cancer is the bone marrow and that radiographic evidence of bone metastases is a result of an invasion and destruction of the bone tissue matrix by tumor cells from the marrow cavity.

Overdiagnosis in screening mammography in Denmark: population based cohort study

Objective To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography. Design Population based cohort study. Setting Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark. Participants 57 763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009. Main outcome measures Overdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups. Results In total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening. Conclusions On the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval −3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.

Do nonattenders in mammography screening programmes seek mammography elsewhere

The objectives of our study were to analyse the use of diagnostic mammography among nonattenders and attenders in organised mammography screening in Denmark in 2000, to assess the contamination from organised screening of noninvited age groups and to measure the impact of local policy on opportunistic screening. Data on all diagnostic mammographies performed in Denmark in 2000 and data on women targeted by the 2 organised mammography screening programmes in Copenhagen and the county of Fyn were collected. All data were linked by the Danish personal identification number. Information on the official policy in 2000 with regard to opportunistic screening was collected from all counties. The proportion of women using diagnostic mammography was only 1–3% for both attenders and nonattenders in organised mammography screening, but it was significantly higher in Copenhagen than in Fyn, due to availability of mammography in private clinics. The proportion of women using diagnostic mammography varied from 1–4% across counties. The official policy on access to diagnostic mammography and contamination from organised mammography screening of adjacent age groups had no impact on the use. Instead, urbanisation was positively correlated with use of diagnostic mammography. In conclusion, our results clearly showed that nonattenders in organised mammography screening programmes do not seek mammography outside the programme. Since a positive policy toward opportunistic screening did not have any effect, our results add further evidence to existing knowledge that the only reasonable way to achieve high mammography coverage is through a well‐organised screening programme.

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.

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 doublelumen). 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. (Plast. Reconstr. Surg. 108: 848, 2001.)

Incidence and methodologic aspects of the occurrence of liver metastases in recurrent breast cancer

The occurrence of liver metastases was evaluated by ultrasonic scanning and correlated with prognostic factors, pattern of metastases, clinical examination, biochemical liver function tests from serum, and liver biopsy specimens in 394 consecutive evaluable patients with first recurrence of breast cancer. Fifty‐nine patients (15%) had a positive scan, and liver metastases were the only sign of recurrent disease in 11 of these patients. The presence of liver metastases was not associated with age, menopausal status, size of the primary tumor, regional lymph node status, or the length of the recurrence‐free interval; but patients with liver metastases were significantly closer to the menopause than those without (P = 0.02). The diagnostic value of clinical examinations was comparable to that of serum bilirubin and serum aspartate aminotransferase (ASAT) analyses, but was significantly better than alkaline phosphatase (AP) and lactate dehydrogenase (LDH) analyses. Analysis of serum AP was not a valuable diagnostic tool in the diagnosis of liver metastases, since it was elevated in 58% of the patients with bone metastases, and since metastases in this site were found in one third of the patients without liver metastases. If all four tests were negative, liver metastases were excluded in 99% of the patients, and if more than two of the four tests were positive, liver metastases were found in 95%. Valid (>80%) diagnosis of liver metastases by serum LDH or serum ASAT alone, required an elevation of three or five times the upper normal limits, respectively. Thirty‐nine patients with positive ultrasonography results underwent biopsy. The ultrasonographic diagnosis could not be confirmed histologically in three patients (8%).