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Concept: Mammography

463

Background The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002). Results After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality. Conclusions Although the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.

Concepts: Epidemiology, Cancer, Breast cancer, Metastasis, Oncology, Tumor, Neoplasm, Mammography

327

Pathologists and radiologists spend years acquiring and refining their medically essential visual skills, so it is of considerable interest to understand how this process actually unfolds and what image features and properties are critical for accurate diagnostic performance. Key insights into human behavioral tasks can often be obtained by using appropriate animal models. We report here that pigeons (Columba livia)-which share many visual system properties with humans-can serve as promising surrogate observers of medical images, a capability not previously documented. The birds proved to have a remarkable ability to distinguish benign from malignant human breast histopathology after training with differential food reinforcement; even more importantly, the pigeons were able to generalize what they had learned when confronted with novel image sets. The birds' histological accuracy, like that of humans, was modestly affected by the presence or absence of color as well as by degrees of image compression, but these impacts could be ameliorated with further training. Turning to radiology, the birds proved to be similarly capable of detecting cancer-relevant microcalcifications on mammogram images. However, when given a different (and for humans quite difficult) task-namely, classification of suspicious mammographic densities (masses)-the pigeons proved to be capable only of image memorization and were unable to successfully generalize when shown novel examples. The birds' successes and difficulties suggest that pigeons are well-suited to help us better understand human medical image perception, and may also prove useful in performance assessment and development of medical imaging hardware, image processing, and image analysis tools.

Concepts: Medicine, Cancer, X-ray, Medical imaging, Radiology, Medical physics, Mammography, Image processing

179

A decline in breast cancer mortality has been observed in western European Countries since the middle of the 1990s.Different methodological approaches, including case-control studies, incidence-based mortality studies, and trend studies, have been used to assess the effectiveness of mammography screening programmes in reducing breast cancer mortality. However, not all methods succeed in distinguishing the relative contributions of service screening and taking correctly into consideration the potential source of bias that might affect the estimate.Recently, a review of six case-control studies confirmed a breast cancer mortality reduction ranging from 38% to 70% among screened women. This figure is in accordance with the estimate obtained from incidence-based mortality studies if screening compliance is taken into account. We will describe the methodological constraints of mortality trend studies in predicting the impact of screening on mortality and the necessary caution that must be applied when interpreting the results of such studies.In conclusion, when appropriate methodological approaches are used, it is evident that mammographic screening programmes have contributed substantially to the observed decline in breast cancer mortality.

Concepts: Scientific method, Epidemiology, Cancer, Breast cancer, Metastasis, Europe, Breast, Mammography

128

Fibroglandular tissue may mask breast cancers, thereby reducing the sensitivity of mammography. Here, we investigate methods for identification of women at high risk of a masked tumor, who could benefit from additional imaging.

Concepts: Cancer, Breast cancer, Oncology, Volume, Type I and type II errors, Mammography, Mask, Masks

118

In mammography, breast compression is applied to reduce the thickness of the breast. While it is widely accepted that firm breast compression is needed to ensure acceptable image quality, guidelines remain vague about how much compression should be applied during mammogram acquisition. A quantitative parameter indicating the desirable amount of compression is not available. Consequently, little is known about the relationship between the amount of breast compression and breast cancer detectability. The purpose of this study is to determine the effect of breast compression pressure in mammography on breast cancer screening outcomes.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, Biopsy, Type I and type II errors, Breast, Mammography

62

Populationwide mammography screening has been associated with a substantial rise in false-positive mammography findings and breast cancer overdiagnosis. However, there is a lack of current data on the associated costs in the United States. We present costs due to false-positive mammograms and breast cancer overdiagnoses among women ages 40-59, based on expenditure data from a major US health care insurance plan for 702,154 women in the years 2011-13. The average expenditures for each false-positive mammogram, invasive breast cancer, and ductal carcinoma in situ in the twelve months following diagnosis were $852, $51,837 and $12,369, respectively. This translates to a national cost of $4 billion each year. The costs associated with false-positive mammograms and breast cancer overdiagnoses appear to be much higher than previously documented. Screening has the potential to save lives. However, the economic impact of false-positive mammography results and breast cancer overdiagnoses must be considered in the debate about the appropriate populations for screening.

Concepts: Cancer, Breast cancer, Carcinoma in situ, Mammography

46

Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, United States, Breast, Mammography, Louisiana

46

Background To reduce mortality, screening must detect life-threatening disease at an earlier, more curable stage. Effective cancer-screening programs therefore both increase the incidence of cancer detected at an early stage and decrease the incidence of cancer presenting at a late stage. Methods We used Surveillance, Epidemiology, and End Results data to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older. Results The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer that are detected each year, from 112 to 234 cases per 100,000 women - an absolute increase of 122 cases per 100,000 women. Concomitantly, the rate at which women present with late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women - an absolute decrease of 8 cases per 100,000 women. With the assumption of a constant underlying disease burden, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease. After excluding the transient excess incidence associated with hormone-replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years of age, we estimated that breast cancer was overdiagnosed (i.e., tumors were detected on screening that would never have led to clinical symptoms) in 1.3 million U.S. women in the past 30 years. We estimated that in 2008, breast cancer was overdiagnosed in more than 70,000 women; this accounted for 31% of all breast cancers diagnosed. Conclusions Despite substantial increases in the number of cases of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with advanced cancer. Although it is not certain which women have been affected, the imbalance suggests that there is substantial overdiagnosis, accounting for nearly a third of all newly diagnosed breast cancers, and that screening is having, at best, only a small effect on the rate of death from breast cancer.

Concepts: Epidemiology, Cancer, Breast cancer, Metastasis, Carcinoma in situ, Cancer staging, Neoplasm, Mammography

38

Mammography screening for breast cancer is widely available in many countries. Initially praised as a universal achievement to improve women’s health and to reduce the burden of breast cancer, the benefits and harms of mammography screening have been debated heatedly in the past years. This review discusses the benefits and harms of mammography screening in light of findings from randomized trials and from more recent observational studies performed in the era of modern diagnostics and treatment. The main benefit of mammography screening is reduction of breast-cancer related death. Relative reductions vary from about 15 to 25% in randomized trials to more recent estimates of 13 to 17% in meta-analyses of observational studies. Using UK population data of 2007, for 1,000 women invited to biennial mammography screening for 20 years from age 50, 2 to 3 women are prevented from dying of breast cancer. All-cause mortality is unchanged. Overdiagnosis of breast cancer is the main harm of mammography screening. Based on recent estimates from the United States, the relative amount of overdiagnosis (including ductal carcinoma in situ and invasive cancer) is 31%. This results in 15 women overdiagnosed for every 1,000 women invited to biennial mammography screening for 20 years from age 50. Women should be unpassionately informed about the benefits and harms of mammography screening using absolute effect sizes in a comprehensible fashion. In an era of limited health care resources, screening services need to be scrutinized and compared with each other with regard to effectiveness, cost-effectiveness and harms.

Concepts: Cancer, Breast cancer, Metastasis, Carcinoma in situ, Cancer staging, Breast, Effect size, Mammography

31

Background: Experiencing a false positive (FP) screening mammogram is economically, physically, and emotionally burdensome, which may affect future screening behavior by delaying the next scheduled mammogram or by avoiding screening altogether. We sought to examine the impact of a FP screening mammogram on the subsequent screening mammography behavior.Methods: Delay in obtaining subsequent screening was defined as any mammogram performed more than 12 months from index mammogram. The Kaplan-Meier (product limit) estimator and Cox proportional hazards model were used to estimate the unadjusted delay and the hazard ratio (HR) of delay of the subsequent screening mammogram within the next 36 months from the index mammogram date.Results: A total of 650,232 true negative (TN) and 90,918 FP mammograms from 261,767 women were included. The likelihood of a subsequent mammogram was higher in women experiencing a TN result than women experiencing a FP result (85.0% vs. 77.9%, P < 0.001). The median delay in returning to screening was higher for FP versus TN (13 months vs. 3 months, P < 0.001). Women with TN result were 36% more likely to return to screening in the next 36 months compared with women with a FP result HR = 1.36 (95% CI, 1.35-1.37). Experiencing a FP mammogram increases the risk of late stage at diagnosis compared with prior TN mammogram (P < 0.001).Conclusions: Women with a FP mammogram were more likely to delay their subsequent screening compared with women with a TN mammogram.Impact: A prior FP experience may subsequently increase the 4-year cumulative risk of late stage at diagnosis. Cancer Epidemiol Biomarkers Prev; 1-7. ©2017 AACR.

Concepts: Cancer, Breast cancer, Proportional hazards models, Type I and type II errors, Breast, Mammography, Hazard ratio, David Cox