Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a ...markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making.
Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of ...the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer.
Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors.
After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements.
An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.
Beginning around 1972 with the introduction of CT, a steady transition from analog to digital imaging in radiology took place. Here, I offer a personal perspective of the exciting multi‐institutional ...and multidisciplinary team effort of developing digital mammography. That effort required the collaboration of visionary individuals in academic research labs, industry, and the clinical arena, catalyzed by a focused commitment from government (NCI and The Office of Women's Health). This collaboration greatly accelerated the timeline from laboratory prototypes to clinical systems and evaluation, resulting in a new imaging modality and, later, several spinoff applications (CAD, contrast‐enhanced mammography, tomosynthesis) that provide improved earlier detection of breast cancer.
Lay Summary
Breast cancer cases are elevated in younger women in minority cohorts in the United States.
Much of this is due to their younger age distributions, particularly for Hispanic women, but ...beyond this there are elevated risks in younger Black and Asian women.
Disparities increase further for minority women when being diagnosed with more advanced disease or dying of breast cancer before the age of 50 years is considered.
Strategies for culturally appropriate education about breast cancer, better access to screening, and prompt treatment must be implemented.
There are marked disparities in the age dependence of breast cancer incidence, stage at diagnosis, and death between ethnic and racial minority cohorts and non‐Hispanic White women in the United States. The increased burden of breast cancer in younger minority women must be addressed through education, policy, research, and improved access to screening and high‐quality treatment for these women.
Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. ...In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associated with variations in breast density, and the biological plausibility of the associations with risk of breast cancer. We also discuss the potential for improved risk prediction that might be achieved by using alternative breast imaging methods, such as magnetic resonance or ultrasound. After adjustment for other risk factors, breast density is consistently associated with breast cancer risk, more strongly than most other risk factors for this disease, and extensive breast density may account for a substantial fraction of breast cancer. Breast density is associated with risk of all of the proliferative lesions that are thought to be precursors of breast cancer. Studies of twins have shown that breast density is a highly heritable quantitative trait. Associations between breast density and variations in breast histology, risk of proliferative breast lesions, and risk of breast cancer may be the result of exposures of breast tissue to both mitogens and mutagens. Characterization of breast density by mammography has several limitations, and the uses of breast density in risk prediction and breast cancer prevention may be improved by other methods of imaging, such as magnetic resonance or ultrasound tomography.
Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to ...method of cancer detection is unknown.
We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age.
As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval CI, 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram.
Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.
To assess a schema for estimating the risk of radiation-induced breast cancer following exposure of the breast to ionizing radiation as would occur with mammography and to provide data that can be ...used to estimate the potential number of breast cancers, cancer deaths, and woman-years of life lost attributable to radiation exposure delivered according to a variety of screening scenarios.
An excess absolute risk model was used to predict the number of radiation-induced breast cancers attributable to the radiation dose received for a single typical digital mammography examination. The algorithm was then extended to consider the consequences of various scenarios for routine screening beginning and ending at different ages, with examinations taking place at 1- or 2-year intervals. A life-table correction was applied to consider reductions of the cohort size over time owing to nonradiation-related causes of death. Finally, the numbers of breast cancer deaths and woman-years of life lost that might be attributable to the radiation exposure were calculated. Cancer incidence and cancer deaths were estimated for individual attained ages following the onset of screening, and lifetime risks were also calculated.
For a cohort of 100 000 women each receiving a dose of 3.7 mGy to both breasts and who were screened annually from age 40 to 55 years and biennially thereafter to age 74 years, it is predicted that there will be 86 cancers induced and 11 deaths due to radiation-induced breast cancer.
For the mammographic screening regimens considered that begin at age 40 years, this risk is small compared with the expected mortality reduction achievable through screening. The risk of radiation-induced breast cancer should not be a deterrent from mammographic screening of women over the age of 40 years.
Observational studies of cancer screening are subject to bias associated with the self-selection of screening participants for whom the underlying probability of cancer death may be different from ...those who do not participate. Dibden et al. reviewed data on mortality reduction from 27 observational studies of mammography screening expressed in terms of relative risk for women who were screened versus not screened. Results were given, both unadjusted and after application of a correction for self-selection. The correction was based on a constant (1.17)—the ratio of risks of death in screening non-attenders versus those not invited, derived from a Swedish study. For some of the studies this correction had a large effect in diminishing the measured mortality benefit associated with screening. In particular, application to The Pan-Canadian Study of Mammography Screening, a study whose authors had previously tested for and found no evidence of self-selection bias, caused the estimated benefit to decrease from 40% to 10%. The appropriateness of applying a correction based on a constant to a population whose healthcare environment and screening participation rates are very different from those from which it was derived is questionable.
Mammographic density has been strongly associated with increased risk of breast cancer. Furthermore, density is inversely correlated with the accuracy of mammography and, therefore, a measurement of ...density conveys information about the difficulty of detecting cancer in a mammogram. Initial methods for assessing mammographic density were entirely subjective and qualitative; however, in the past few years methods have been developed to provide more objective and quantitative density measurements. Research is now underway to create and validate techniques for volumetric measurement of density. It is also possible to measure breast density with other imaging modalities, such as ultrasound and MRI, which do not require the use of ionizing radiation and may, therefore, be more suitable for use in young women or where it is desirable to perform measurements more frequently. In this article, the techniques for measurement of density are reviewed and some consideration is given to their strengths and limitations.
Population-based cancer screening can reduce cancer burden but was interrupted temporarily due to the COVID-19 pandemic. We estimated the long-term clinical impact of breast and colorectal cancer ...screening interruptions in Canada using a validated mathematical model.
We used the OncoSim breast and colorectal cancers microsimulation models to explore scenarios of primary screening stops for 3, 6, and 12 months followed by 6-24-month transition periods of reduced screening volumes. For breast cancer, we estimated changes in cancer incidence over time, additional advanced-stage cases diagnosed, and excess cancer deaths in 2020-2029. For colorectal cancer, we estimated changes in cancer incidence over time, undiagnosed advanced adenomas and colorectal cancers in 2020, and lifetime excess cancer incidence and deaths.
Our simulations projected a surge of cancer cases when screening resumes. For breast cancer screening, a three-month interruption could increase cases diagnosed at advanced stages (310 more) and cancer deaths (110 more) in 2020-2029. A six-month interruption could lead to 670 extra advanced cancers and 250 additional cancer deaths. For colorectal cancers, a six-month suspension of primary screening could increase cancer incidence by 2200 cases with 960 more cancer deaths over the lifetime. Longer interruptions, and reduced volumes when screening resumes, would further increase excess cancer deaths.
Interruptions in cancer screening will lead to additional cancer deaths, additional advanced cancers diagnosed, and a surge in demand for downstream resources when screening resumes. An effective strategy is needed to minimize potential harm to people who missed their screening.
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