Search

IMPORTANCE: In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment. OBJECTIVE: To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND. DESIGN, SETTING, AND PARTICIPANTS: The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024. EXPOSURE: Predictors of high nodal burden. MAIN OUTCOMES AND MEASURES: High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration. RESULTS: Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83). CONCLUSIONS AND RELEVANCE: The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02240472

Implant-based reconstruction is performed in the majority of women offered primary reconstruction for breast cancer.

Objectives/HypothesisFor cutaneous malignant melanoma (CMM) of the head and neck, neither prognostic factors in population‐based groups, nor outcome with respect to surgical resection margins is clear. Therefore, we analyzed data in a regional registry to align treatment results for CMM of the head and neck with prognosis and survival times.

This presentation describes the organization and first-round results of the Stockholm mass mammo-graphy screening program, and discusses ways of checking the quality of an ongoing screening program. The Stockholm mammography screening program started in 1989 at five independent screening units, and comprises more than 150 000 women aged 50 to 69 years. The first round was completed in June 1991. Compliance during the studied period was 70.6%, and the recall rate was 3.0% of the attending women. Breast cancer was diagnosed in 676 women, of whom 90 (13.3%) had a cancer in situ. The cancer prevalence rate was thus 6.3 cancers per 1 000 screened women. Surgery was performed on 925 women, of whom 249 had benign lesions, giving a benign/malignant ratio of 0.37 to 1. Fifty-two per cent of the cancer patients were operated with breast conserving surgery. The median size of the invasive cancers was 12 mm; almost 80% were node-negative. Experience from the first two years of this mass mammography screening program shows that it meets the major quality requirements. One of the main future goals is to maintain the high quality of the program. Another important goal is a further increase in compliance.

Objective –To apply an indirect method for estimation of the breast cancer related excess mortality in the Swedish randomised mammography screening trials.Setting –Randomised trials on mammography screening have, in Sweden, been performed in the counties of Kopparberg (W) and Östergötland (E), the so called WE study, and in the three largest cities in Sweden, Stockholm (southern part), Gothenburg, and Malmö. An overview of the trials was presented in the Lancetin 1993 and included 156 911 women in the invited group and 125 866 in the control group.Methods –The excess mortality in the breast cancer subgroups was estimated by indirect standardisation using official national cause of death statistics according to Statistics Sweden as a reference. Results—The estimated reduction of the breast cancer related mortality was 24% for the whole group (40–74 years at randomisation). The corresponding figures for the age groups 40–49, 50–59, and 60–69 years were 6%, 28%, and 34% respectively.Conclusion –The results are very similar to those presented earlier based on the traditional comparison of the breast cancer mortality in the invited and in the control group. This analysis further strengthens previous reports on a beneficial effect of mammography screening, which is especially pronounced in the age group 50–69.

Except for hip fracture surgery, emergency surgery has been only exceptionally studied concerning thromboprophylaxis. There are, however, several reasons to believe the frequency to be fairly high and that the patient group would be in need of prophylaxis. This paper discusses various emergency situations and also gives the design for an ongoing controlled study on the effect of postoperative start of thromboprophylaxis with low molecular weight heparin in emergency abdominal surgery.

In a randomized, prospective, double-blind multicenter trial, the effect of low-dose conventional heparin (5,000 IU/12 h) was compared to a low molecular weight (LMW) heparin fragment (5,000 antifactor Xa U/24 h). 432 patients 40 years or older undergoing elective abdominal surgery were included, 382 correctly treated. 45% had malignant diseases. The groups did not differ in risk factors. Analysis was made both on the basis of intention to treat and correct prophylaxis. No difference in results between these 2 groups was seen. Deep vein thrombosis (125I-fibrinogen) occurred in 4.3% of the low-dose heparin group and in 6.4 of the LMW heparin group. There was a significant delay in the onset of deep vein thrombosis in the LMW heparin group. Mortality, peroperative blood loss, transfusions or infectious complications did not differ. Hemorrhagic complications occurred significantly more often in the LMW heparin group (11.6%) than in the low-dose heparin group (4.6%). Significantly fewer patients experienced local injection pain in the LMW heparin group. APTT and AT III were similar in both groups, but anti-Xa activity was significantly higher in the LMW heparin group. Single daily LMW heparin injection reduced the frequency of deep vein thrombosis to the same level as low-dose heparin twice daily. The dose or administration interval of LMW heparin in this study caused significantly more bleeding complications.

In the interval between screening examinations, some cases of breast cancer are invariably detected clinically in patients whose mammogram was considered to be normal at the earlier screening. During the first interval in the Stockholm study, 60 interval cancers were detected, giving a rate of 1.8 cases/1000 examinations/24 months. About half of these interval cases (31/60) were true interval tumours in that no sign of them could be found on the first mammogram; the other half, non-true, were possible to trace on the first mammogram. It is mainly women under 50 who feature in the interval group, above all in the sub-group of true interval cancers (p<0.05).

In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40–64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP).

Results from several randomised mammography screening trials haveshown that it is possible to reduce mortalityin breast cancer by mammographic screening at leastfor women above 50 years of age. Thepurpose of this article is to present dataon mortality in breast cancer in study andcontrol groups of the Stockholm trial after 11years of followup, to analyse which age groupbenefits most from screening. In March 1981, 40,318women in Stockholm, aged 40 through 64 years,entered a randomized trial of breast cancer screeningby single view mammography alone, versus no interventionin a control group of 20 000 women.Two screening rounds were performed and the attendancerate was over 80% in the two rounds.During 1986 the control group was invited onceto screening. Totally 428 and 217 cases ofbreast cancer were diagnosed in the study andcontrol groups respectively. After a mean follow-up of11.4 years a nonsignificant mortality reduction of 26%was observed for the whole study group, witha relative risk (RR) of death in breastcancer of 0.74 (CI(confidence interval)=0.5–1.1). Forwomen aged 50–64 years a significant 38% mortalityreduction was observed with a RR of 0.62(CI=0.38–1.0). For women aged 40–49 yearsno effect on mortality was found, with aRR of death in breast cancer of 1.08(CI=0.54–2.17). The breakpoint for benefit inthis study seemed to be at 50 yearsof age when 5-year age groups were analysed,but this tendency is uncertain because of thelow statistical power in the analysis of theyounger age groups. Long screening intervals, the useof single-view mammography, and the fact that morethan 50% of the women in age group40–49 years were still below 50 years ofage when the study was closed, were allfacts that could have influenced the results inage group 40–49 years. Larger studies are neededto answer the question whether mammographic screening canbe successful in younger age groups.

Between 1976 and 1982, four randomized mammography screening trials started in five screening centres in Sweden, involving 282 777 women (156 911 invited and 125 866 controls) with the aim to study if invitation to screening reduced the breast cancer mortality. An overview of the trials was performed to reduce the confidence intervals for the relative risk estimates. All 1 296 deaths occurring in women with breast cancer detected after randomization were evaluated by an independent endpoint committee (EPC), consisting of four physicians who reviewed collected medical information that was blinded regarding mammography screening. If there was disagreement between the EPC members at the initial individual evaluation the final classification was made at concensus meetings. In only 6.9% (n = 89) of the cases was there disagreement as to whether breast cancer was or was not the underlying cause of death. It was also found that 'breast cancer as underlying cause of death' and 'breast cancer as underlying or contributory cause of death' according to Statistics Sweden resulted in relative risk estimates very similar to those based on the classification by the EPC. The study thus supports the use of official health statistics in the evaluation of randomized breast screening trials in Sweden.

Combined morphological and cytochemical malignancy grading in addition to tumor stage was applied to assess the malignant potential of so-called interval carcinomas from the Stockholm randomized mammography screening study. Only interval carcinomas surfacing within two years from screening were included. Fifty-four percent of the tumors were in stage I and 46% of the carcinomas eligible for DNA analysis were diploid, i.e. low-malignant. An overrepresentation of prognostically unfavorable tumor characteristics was found only within the subgroup 'true' and 'early' interval cancer.

Objectives –To analyse the cause of death pattern in the cohorts of women included in the Swedish randomised mammography screening trials by comparing the groups of invited and control women both with each other and with the general population of Swedish women.Setting –Since 1977 four randomised trials of mammography screening have been performed in Sweden: Malmö, Kopparberg and ÖOstergötland (the two county trial), Stockholm, and Gothenburg.Design –Overview of four randomised mammography screening trials.Results –The total numbers of deaths in the invited and control groups respectively were 15 695 and 11 887 corresponding to a relative risk (RR) of 1.00. There were no significant differences between the invited and control groups for cause-specific mortality, except for breast cancer. When the total mortality in the invited and the control groups was compared with that for Swedish women in general the standardised mortality ratio was close to 100.Conclusions –The cause of death pattern in the invited group was, except for breast cancer, very similar to that in the control group, showing that the groups were comparable. Similarly, the total mortality including breast cancer mortality in the control group was almost identical to that in Swedish women in general. The same was true, with the exception of breast cancer, for the invited group. These observations confirm that the trial cohorts are representative of Swedish women and indicate that the quantitative results from these trials may safely be generalised to the Swedish population.

The purpose of this overview is to estimate more precisely the long-term effect of mammography screening by adding four more years of follow-up to women aged 40-49 years in the four Swedish trials on mammography screening. Data from the four trials were merged and linked to the Swedish Cancer and Cause of Death Register for 1958-1993 and 1951-1993 respectively to identify date of breast cancer diagnosis and cause and date of death. The invited and control groups comprised 48,569 and 40,247 women respectively. At the December 1993 follow-up, 602 and 482 breast cancer cases were identified in the two groups respectively, of which 104 and 111 had breast cancer as the underlying cause of death. This corresponds to a relative risk (RR) of 0.77 (95% CI: 0.59-1.01) for the two groups. In the 40-44 age group at randomization, 94% of breast cancer patients in the study and 89% in the control group were diagnosed before the age of 50; however, among breast cancer deaths in this age group, only two in the invited and five in the control group died after age 50. At follow-up of women 40-44 years at randomization 208 women in the invited and 184 in the control group were reported to the Cancer registry with breast cancer. Out of these 195 (94%) and 163 (89%) respectively were reported before the age of 50. Further, the relative risk for the age group 40-44 years at randomization by age at follow-up was 1.11, 0.51 and 0.46 for the age groups 45-49, 50-54, and 55-59 at follow-up. This study shows a 23% reduction in the breast cancer mortality in women 40-49 years at randomization achieved from a median trial time of 7.0 years, a median follow-up time of 12.8 years, and a screening interval of 18-24 months. Almost all of the effect in the 40-44 year age group at randomization was due to screening before the age of 50.

This article presents updated data on breast cancer mortality for women under age 50 from the Stockholm Mammographic Screening Trial, as well as a review of some side effects associated with screening in this age group. Approximately 40,000 women aged 40-64 (14,842 aged 40-49 years) were randomized to a trial of breast cancer screening by single-view mammography alone; 20,000 women (7,103 aged 40-49) were randomized to a control group. In the 40-49 age group, 24 and 12 breast cancer deaths were found in the study and control groups, respectively, after 11.4 years of follow-up. The relative risk of breast cancer death in screened to nonscreened women was 1.08 (95% confidence interval: 0.54-2.17). The rates of benign surgical biopsies, false positives, and follow-up costs were higher among women under age 50. Large overview studies are needed, however, to determine whether mammography screening consistently reduces mortality in women 40-49 years of age. Side effects such as costs and public health aspects of mammography screening in this age group also warrant further study.