To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects.
This study was carried out under the auspices of the ...Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression.
There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk RR = 0.69; 95% confidence interval: 0.56, 0.84; P < .0001) and consensus data (RR = 0.73; 95% confidence interval: 0.59, 0.89; P = .002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up.
Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.
Background
Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice ...improve her chances of avoiding a death from breast cancer compared with women who choose not to participate?
Methods
To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease‐specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39‐year period (1977‐2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958‐1976). All patients received stage‐specific therapy according to the latest national guidelines, irrespective of the mode of detection.
Results
The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34‐0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44‐0.63) compared with the corresponding risks for nonparticipants.
Conclusions
Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.
After 20 years of follow‐up, women who participate in mammography screening have a 47% lower risk of dying from breast cancer. Although all patients with breast cancer potentially can benefit from advances in breast cancer therapy, women who participate in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than those who do not participate.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by ...measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.
Methods
Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.
Results
Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 P < .001) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 P < .001).
Conclusions
Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
Substantial and significant reductions in the incidence rates of fatal breast cancer and advanced breast cancer with 10 years of follow‐up are observed in this analysis of greater than one‐half million Swedish women participating and not participating in breast cancer screening. These comparisons are contemporaneous, and thus are not influenced by changes in therapeutic regimens.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. ...Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Early breast carcinoma, defined as purely in situ cancer and invasive carcinomas < 15 mm, represents the most frequent category of breast carcinomas in diagnostic routine in a regularly screened ...population. These tumors are usually detected with mammography screening and are preoperatively characterized with radiological imaging. The role of pathology in preoperative settings is to help understand the subgross morphology and to confirm malignancy in biopsy material. Postoperatively, the pathologist needs to verify the size of the cancer (defined as the largest dimension of the largest invasive focus), the extent of the disease (defined as the area or the volume of the breast tissue containing all the malignant foci), the distribution of the in situ and invasive lesions (as unifocal, multifocal, or diffuse), and intratumoral and intertumoral heterogeneity (in addition to determining margin status, histologic tumor type, hormone receptor status, and other parameters). Despite their small size, early breast carcinomas often exhibit complex morphology as they are multifocal/diffuse in about 60% and extensive (occupying an area ≥ 4 cm) in 40% of the cases. Routine use of large-format histopathology technique is a prerequisite for detailed correlation of the radiologic and histopathologic findings and for the correct assessment of these parameters. Breast pathologists must be aware of the advantages and disadvantages of the different imaging modalities and have detailed information about the radiological findings before work-up of the operative specimen. Multidisciplinary preoperative and postoperative tumor board meetings are essential in guiding the pathologists and in confirming the radiological findings. Interdisciplinary diagnosis is inevitably becoming the new gold standard in the diagnosis and management of early breast carcinomas.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
All the information needed for successful diagnosis and management of breast carcinoma Focused on a modern, interdisciplinary approach to diagnosing and managing diseases of the breast, this concise ...book builds on the high standard set in the previous edition. It provides a complete foundation in the basic principles, radiologic appearance and underlying pathology of breast disease, without overwhelming non-pathologist members of the team with excessive detail. For effective communication at every level, Practical Breast Pathology, Second Edition provides the clear information, case examples and superb illustrations that make it an ideal clinical problem solver. Special features of the second edition: High-quality examples of modern multimodality radiology (digital mammography, ultrasound and magnetic resonance imaging) correlated with large-format 2D and 3D histologic slides New findings on such clinically important topics as the lobar nature of breast carcinoma, multifocality, diffuse carcinomas and extent of disease, concept of the sick lobe and more Introduction of the molecular classification of invasive breast cancer Discussion of prognostic and predictive factors in breast carcinoma, such as hormone receptors and HER2 status Updates on preoperative diagnosis, including intact biopsy and radiologic assessment of the extent and distribution of lesions Enriched with new information and stunning illustrations in every chapter, Practical Breast Pathology, Second Edition is a key link in the exchange between pathologists, radiologists, oncologists and breast surgeons, as well as residents and trainees. It provides an essential framework for understanding the mammographic-pathologic correlation, leading to increased cooperation among clinical team members and significantly improved outcomes for patients.
Elucidating whether and how long-term survival of breast cancer is mainly due to cure after early detection and effective treatment and therapy or overdiagnosis resulting from the widespread use of ...mammography provides a new insight into the role mammography plays in screening, surveillance, and treatment of breast cancer. Given information on detection modes, the impact of overdiagnosis due to mammography screening on long-term breast cancer survival was quantitatively assessed by applying a zero (cured or overdiagnosis)-inflated model design and analysis to a 15-year follow-up breast cancer cohort in Dalarna, Sweden. The probability for non-progressive breast cancer (the zero part) was 56.14% including the 44.34% complete cure after early detection and initial treatment and a small 11.80% overdiagnosis resulting from mammography screening program (8.94%) and high awareness (2.86%). The 15-year adjusted cumulative survival of breast cancer was dropped from 88.25% to 74.80% after correcting for the zero-inflated part of overdiagnosis. The present findings reveal that the majority of survivors among women diagnosed with breast cancer could be attributed to the cure resulting from mammography screening and accompanying effective treatment and therapy and only a small fraction of those were due to overdiagnosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer–specific survival as an outcome.
...Methods
We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan–Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression.
Results
All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46–55%) to 81% (95% confidence interval 74–85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40–65%) to 74% (95% confidence interval 72–77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77–84%) to 86% (95% confidence interval 83–88%), a considerably narrower range.
Conclusions
Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.
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