Outcomes of Breast Cancer Screening Strategies Based on Cancer Intervention and Surveillance Modeling Network Estimates.

Background There is ongoing debate about recommendations for breast cancer screening strategies, specifically regarding the frequency of screening and the age at which to initiate screening. Purpose To compare estimates of breast cancer screening outcomes published by the Cancer Intervention and Surveillance Modeling Network (CISNET) to understand the benefits and risks of different screening scenarios. Materials and Methods Modeling estimates published by CISNET are based on hypothetical cohorts in the United States and compare women, starting at 40 years of age, who do and do not undergo breast cancer screening with mammography. The four scenarios assessed in this study, of multiple possible scenarios, were biennial screening ages 50-74 years (2009 and 2016 U.S. Preventive Services Task Force [USPSTF] recommendations), biennial screening ages 40-74 years (2023 USPSTF draft recommendation), annual screening ages 40-74 years, and annual screening ages 40-79 years. For each scenario, CISNET estimates of median lifetime benefits were compared. Risks that included false-positive screening results per examination and benign biopsies per examination were also calculated and compared. Results Estimates from CISNET 2023 showed that annual screening ages 40-79 years improved breast cancer mortality reduction compared with biennial screening ages 50-74 years and biennial screening ages 40-74 years (41.7%, 25.4%, and 30%, respectively). Annual screening ages 40-79 years averted the most breast cancer deaths (11.5 per 1000) and gained the most life-years (230 per 1000) compared with other screening scenarios (range, 6.7-11.5 per 1000 and 121-230 per 1000, respectively). False-positive screening results per examination were less than 10% for all screening scenarios (range, 6.5%-9.6%) and lowest for annual screening ages 40-79 years (6.5%). Benign biopsies per examination were less than 1.33% for all screening scenarios (range, 0.88%-1.32%) and lowest for annual screening ages 40-79 years (0.88%). Conclusion CISNET 2023 modeling estimates indicate that annual breast cancer screening starting at 40 years of age provides the greatest benefit to women and the least risk per examination. © RSNA, 2024 See also the editorial by Joe in this issue.

Mammography Screening Should Begin at Age 40 Years.

The 2023 U.S. Preventive Services Task Force draft recommendation statement on screening for breast cancer recommends lowering the starting age for biennial screening with mammography to age 40 years from 50 years, the age of screening initiation that the Task Force had previously recommended since 2009. A recent Perspective article in the New England Journal of Medicine by Woloshin et al contends that this change will provide no additional benefit and is unjustified. This article reviews the main ideas presented by Woloshin et al and provides substantial evidence not considered by those authors in support of screening mammography in U.S. women starting at age 40 years.

Benefit-to-radiation-risk of low-dose computed tomography lung cancer screening.

BACKGROUND: The US National Lung Screening Trial (NLST) and Dutch-Belgian NELSON randomized controlled trials have shown significant mortality reductions from low-dose computed tomography (CT) lung cancer screening (LCS). NLST, ITALUNG, and COSMOS trials have provided detailed dosimetry data for LCS. METHODS: LCS trial mortality benefit results, organ dose and effective dose data, and Biological Effects of Ionizing Radiation, Report VII (BEIR VII) organ dose-to-cancer-mortality risk data are used to estimate benefit-to-radiation-risk ratios of the NLST, ITALUNG, and COSMOS trials. Data from those trials also are used to estimate benefit-to-radiation-risk ratios for longer-term LCS corresponding to scenarios recommended by United States Preventive Services Task Force and the American Cancer Society. RESULTS: Including only screening doses, NLST benefit-to-radiation-risk ratios are 12:1 for males, 19:1 for females, and 16:1 overall. Including both screening and estimated follow-up doses, benefit-to-radiation-risk ratios for NLST are 9:1 for males, 13:1 for females, and 12:1 overall. For the ITALUNG trial, the benefit-to-radiation-risk ratio is 58-63:1. For the COSMOS trial, assuming sex-specific mortality benefits like those of the NELSON trial, the benefit-to-radiation-risk ratio is 23:1. Assuming a conservative 20% mortality benefit, annual screening in people 50-79 years old with a 20+ pack-year history of smoking has benefit-to-radiation-risk ratios of 23:1 (with follow-up doses adding 40% to screening doses) to 29:1 (with follow-up adding 10%) based on COSMOS dose data. CONCLUSIONS: Based on linear, no threshold BEIR VII dose-risk estimates, benefit-to-radiation-risk ratios for LCS are highly favorable. Results emphasize the importance of using modern CT technologies, maintaining low diagnostic follow-up rates, and minimizing both screening and diagnostic follow-up doses. PLAIN LANGUAGE SUMMARY: The benefits of lung cancer screening significantly outweigh estimates of future harms associated with exposure to radiation during screening and diagnostic follow-up examinations. Our findings emphasize the importance of lung cancer screening practices using state-of-the-art computed tomography scanners and specialized low-dose lung screening and diagnostic follow-up techniques.

Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women.

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) data from 1973-2010 have been used to show that minority women have disproportionately higher percentages of breast cancers diagnosed at younger ages in comparison with White women. METHODS: The authors analyzed SEER 21 invasive breast cancer incidence data for 2014-2017 and National Center for Health Statistics mortality data for 2014-2018 and compared invasive incidence and mortality by age in non-Hispanic Black (NH-Black), Asian American/Pacific Islander (AAPI), Native American, and Hispanic women with those in non-Hispanic White (NH-White) women. They evaluated incidence rates and percentages of invasive breast cancer cases and breast cancer deaths occurring before the age of 50 years along with advanced-stage incidence rates and percentages in minority women versus NH-White women. RESULTS: Recent SEER data showed that invasive breast cancers were diagnosed at significantly younger ages in minority women versus NH-White women. Among women diagnosed with invasive breast cancer, compared with NH-White women, minority women were 72% more likely to be diagnosed under the age of 50 years (relative risk [RR], 1.72; 95% confidence interval [CI], 1.70-1.75), 58% more likely to be diagnosed with advanced-stage breast cancer under the age of 50 years (RR, 1.58; 95% CI, 1.55-1.61), and 24% more likely to be diagnosed with advanced-stage (regional or distant) breast cancer at all ages (RR, 1.24; 95% CI, 1.23-1.25). Among women dying of breast cancer, minority women were 127% more likely to die under the age of 50 years than NH-White women. CONCLUSIONS: NH-Black, AAPI, Native American, and Hispanic women have higher proportions of invasive breast cancers at younger ages and at advanced stages and breast cancer deaths at younger ages than NH-White women. LAY SUMMARY: This study analyzes the most recently available data on invasive breast cancers and breast cancer deaths in US women by age and race/ethnicity. Its findings show that non-Hispanic Black, Asian American/Pacific Islander, Native American, and Hispanic women have a higher percentage of invasive breast cancers at younger ages and at more advanced stages and a higher percentage of breast cancer deaths at younger ages than non-Hispanic White women.

Breast Cancer Screening Recommendations Inclusive of All Women at Average Risk: Update from the ACR and Society of Breast Imaging.

Breast cancer remains the most common nonskin cancer, the second leading cause of cancer deaths, and the leading cause of premature death in US women. Mammography screening has been proven effective in reducing breast cancer deaths in women age 40 years and older. A mortality reduction of 40% is possible with regular screening. Treatment advances cannot overcome the disadvantage of being diagnosed with an advanced-stage tumor. The ACR and Society of Breast Imaging recommend annual mammography screening beginning at age 40, which provides the greatest mortality reduction, diagnosis at earlier stage, better surgical options, and more effective chemotherapy. Annual screening results in more screening-detected tumors, tumors of smaller sizes, and fewer interval cancers than longer screening intervals. Screened women in their 40s are more likely to have early-stage disease, negative lymph nodes, and smaller tumors than unscreened women. Delaying screening until age 45 or 50 will result in an unnecessary loss of life to breast cancer and adversely affects minority women in particular. Screening should continue past age 74 years, without an upper age limit unless severe comorbidities limit life expectancy. Benefits of screening should be considered along with the possibilities of recall for additional imaging and benign biopsy and the less tangible risks of anxiety and overdiagnosis. Although recall and biopsy recommendations are higher with more frequent screening, so are life-years gained and breast cancer deaths averted. Women who wish to maximize benefit will choose annual screening starting at age 40 years and will not stop screening prematurely.

Breast Cancer Mortality Rates Have Stopped Declining in U.S. Women Younger than 40 Years.

Background National Center for Health Statistics (NCHS) data for U.S. women have shown a steady decline in breast cancer mortality rates since 1989. Purpose To analyze U.S. breast cancer mortality rates by age decade in women aged 20-79 years and in women aged 20-39 years and women aged 40-69 years. Materials and Methods The authors conducted a retrospective analysis of (a) female breast cancer mortality rates from NCHS data for 1969-2017 for all races and by race and (b) age- and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program. Joinpoint analysis was used to determine trends in breast cancer mortality, invasive breast cancer incidence, and distant-stage (metastatic) breast cancer incidence rates. Results Between 1989 and 2010, breast cancer mortality rates decreased by 1.5%-3.4% per year for each age decade from 20 to 79 years (P < .001 for each). After 2010, breast cancer mortality rates continued to decline by 1.2%-2.2% per year in women in each age decade from 40 to 79 years (P < .001 for each) but stopped declining in women younger than 40 years. After 2010, breast cancer mortality rates demonstrated nonsignificant increases of 2.8% per year in women aged 20-29 years (P = .11) and 0.3% per year in women aged 30-39 years (P = .70), results attributable primarily to changes in mortality rates in White women. A contributing factor is that distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years. Conclusion Female breast cancer mortality rates have stopped declining in women younger than 40 years, ending a trend that existed from 1987 to 2010. Conversely, mortality rates have continued to decline in women aged 40-79 years. Rapidly rising distant-stage breast cancer rates have likely contributed to ending the decline in mortality rates in women younger than 40 years. © RSNA, 2021 Online supplemental material is available for this article.

Radiation Doses and Risks in Breast Screening.

This article describes radiation doses and cancer risks of digital breast imaging technologies used for breast cancer detection. These include digital mammography (DM), digital breast tomosynthesis (DBT), and newer technologies such as contrast-enhanced digital or spectral mammography (CEM), whole-breast computed tomography, breast-specific gamma imaging (BSGI), molecular breast imaging (MBI), and positron emission mammography (PEM). This article describes the basis for radiation risk estimates, compares radiation doses and risks, and provides benefit-to-radiation-risk ratios for different breast imaging modalities that use ionizing radiation. Current x-ray-based screening modalities such as DM and DBT have small to negligible risks of causing radiation-induced cancers in women of normal screening age. Possible new screening modalities such as CEM have similar small cancer risks. Potential screening modalities that involve radionuclide injection such as BSGI, MBI, and PEM have significantly higher cancer risks unless efficient detection systems and reduced administered doses are used. Benefit-to-radiation-risk estimates are highly favorable for screening with DM and other modalities having comparable (or higher) cancer detection rates and comparably low radiation doses.

Improving the diagnostic accuracy of a stratified screening strategy by identifying the optimal risk cutoff.

BACKGROUND: The American Cancer Society (ACS) suggests using a stratified strategy for breast cancer screening. The strategy includes assessing risk of breast cancer, screening women at high risk with both MRI and mammography, and screening women at low risk with mammography alone. The ACS chose their cutoff for high risk using expert consensus. METHODS: We propose instead an analytic approach that maximizes the diagnostic accuracy (AUC/ROC) of a risk-based stratified screening strategy in a population. The inputs are the joint distribution of screening test scores, and the odds of disease, for the given risk score. Using the approach for breast cancer screening, we estimated the optimal risk cutoff for two different risk models: the Breast Cancer Screening Consortium (BCSC) model and a hypothetical model with much better discriminatory accuracy. Data on mammography and MRI test score distributions were drawn from the Magnetic Resonance Imaging Screening Study Group. RESULTS: A risk model with an excellent discriminatory accuracy (c-statistic [Formula: see text]) yielded a reasonable cutoff where only about 20% of women had dual screening. However, the BCSC risk model (c-statistic [Formula: see text]) lacked the discriminatory accuracy to differentiate between women who needed dual screening, and women who needed only mammography. CONCLUSION: Our research provides a general approach to optimize the diagnostic accuracy of a stratified screening strategy in a population, and to assess whether risk models are sufficiently accurate to guide stratified screening. For breast cancer, most risk models lack enough discriminatory accuracy to make stratified screening a reasonable recommendation.

Breast cancer deaths averted over 3 decades.

BACKGROUND: From 1975 to 1990, female breast cancer mortality rates in the United States increased by 0.4% per year. Since 1990, breast cancer mortality rates have fallen between 1.8% and 3.4% per year, a decrease that is attributed to increased mammography screening and improved treatment. METHODS: The authors used age-adjusted female breast cancer mortality rate and population data from the Surveillance, Epidemiology, and End Results (SEER) program to estimate the number of breast cancer deaths averted by screening mammography and improved treatment since 1989. Four different assumptions regarding background mortality rates (in the absence of screening mammography and improved treatment) were used to estimate deaths averted for women aged 40 to 84 years by taking the difference between SEER-reported mortality rates and background mortality rates for each 5-year age group, multiplied by the population for each 5-year age group. SEER data were used to estimate annual and cumulative breast cancer deaths averted in 2012 and 2015 and extrapolated SEER data were used to estimate deaths averted in 2018. RESULTS: The number of single-year breast cancer deaths averted ranged from 20,860 to 33,842 in 2012, from 23,703 to 39,415 in 2015, and from 27,083 to 45,726 in 2018. Breast cancer mortality reductions ranged from 38.6% to 50.5% in 2012, from 41.5% to 54.2% in 2015, and from 45.3% to 58.3% in 2018. Cumulative breast cancer deaths averted since 1989 ranged from 237,234 to 370,402 in 2012, from 305,934 to 483,435 in 2015, and from 384,046 to 614,484 in 2018. CONCLUSIONS: Since 1989, between 384,000 and 614,500 breast cancer deaths have been averted through the use of mammography screening and improved treatment.

Screening Mammography in Women 40-49 Years Old: Current Evidence.

OBJECTIVE: Breast cancer is an important health problem for women 40-49 years old, yet screening mammography for this age group remains controversial. This article reviews recent guidelines and supporting evidence on screening mammography in women of this age group. CONCLUSION: Evidence supports the benefit of annual screening mammography in women 40-49 years old. Models of different breast cancer screening strategies consistently show the greatest breast cancer mortality reduction and life-years gained with annual screening starting when women reach 40 years old.

Current Issues in the Overdiagnosis and Overtreatment of Breast Cancer.

OBJECTIVE: The discovery of breast cancer at earlier stages with screening brings the risk that some cancers will be overdiagnosed or overtreated. Reasonable estimates show the overdiagnosis rate due to screening mammography to be low, 1-10%. CONCLUSION: Overdiagnosis should not be used as a reason to delay the onset or decrease the frequency of screening, because neither strategy will decrease overdiagnosis. Improvements in personalized treatment will diminish the morbidity of treatment and, therefore, the significance of overdiagnosis.

Obligate Overdiagnosis Due to Mammographic Screening: A Direct Estimate for U.S. Women.

Purpose To determine obligate overdiagnosis rates, defined as the percentage of women diagnosed with screen-detected breast cancer who die of causes other than breast cancer prior to clinical presentation of that cancer, for ductal carcinoma in situ (DCIS), invasive breast cancer, and all breast cancers. Materials and Methods Age-specific all-cause mortality rates from the Human Mortality Database, age-specific breast cancer incidence and mortality rates from Surveillance, Epidemiology, and End Results data, and estimates of mean lead times and lead time distributions from breast cancer screening trials are used to estimate obligate (or type 1) overdiagnosis rates for DCIS, invasive breast cancer, and all breast cancers (DCIS plus invasive) for U.S. women undergoing screening mammography. Mortality rates by age are used to estimate the number of women who die of causes other than breast cancer during the lead time afforded by screening mammography. Resulting age-dependent overdiagnosis rates, along with screen-detected breast cancer incidence by age, are used to estimate type 1 overdiagnosis rates for the U.S. screening population. Results Obligate overdiagnosis rates depend strongly on the age at which a woman is screened, ranging from less than 1% at age 40 years to 30%, 21%, and 22.5% at age 80 years for DCIS, invasive breast cancer, and all breast cancers, respectively. Type 1 overdiagnosis rates among screened women in the United States are estimated to be 9% for DCIS and approximately 7% for both invasive breast cancer and all breast cancers. Screening of women ages 40-49 years (or premenopausal women, as determined from patient history, starting at age 40 years) adds little to obligate overdiagnosis rates (0.15% for DCIS and less than 0.1% for invasive breast cancer and all breast cancers). Conclusion Type 1 overdiagnosis rates increase rapidly with age at screening. Obligate overdiagnosis occurs in 9% of DCIS and approximately 7% of both invasive breast cancer and all breast cancers in the U.S. mammographic screening population, with screening of women ages 40-49 years (or premenopausal women starting at age 40 years) making a negligible contribution of 0.15% to obligate overdiagnosis of DCIS and a contribution of less than 0.1% to the obligate overdiagnosis rates of invasive breast cancer and all breast cancers. © RSNA, 2017 Online supplemental material is available for this article.

Comparison of recommendations for screening mammography using CISNET models.

BACKGROUND: Currently, there are several different recommendations for screening mammography from major national health care organizations, including: 1) annual screening at ages 40 to 84 years; 2) screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years; and 3) biennial screening at ages 50 to 74 years. METHODS: Mean values of six Cancer Intervention and Surveillance Modeling Network (CISNET) models were used to compare these three screening mammography recommendations in terms of benefits and risks. RESULTS: Mean mortality reduction was greatest with the recommendation of annual screening at ages 40 to 84 years (39.6%), compared with the hybrid recommendation of screening annually at ages 45 to 54 years, then biennially at ages 55 to 79 years (30.8%), and the recommendation of biennial screening at ages 50 to 74 years (23.2%). For a single-year cohort of US women aged 40 years, assuming 100% compliance, more breast cancers deaths would be averted over their lifetime with annual screening starting at age 40 (29,369) than with the hybrid recommendation (22,829) or biennial screening ages 50-74 (17,153 based on 2009 CISNET estimates, 15,599 based on 2016 CISNET estimates). To achieve the greatest mortality benefit, this single-year cohort of women would have the greatest total number of screening mammograms, benign recalls, and benign biopsies performed over the course of screening by following annual screening starting at age 40 years (90.2 million, 6.8 million, and 481,269, respectively) than by following the hybrid recommendation (49.0 million, 4.1 million, and 286,288, respectively) or biennial screening at ages 50 to 74 years (27.3 million, 2.3 million, and 162,885, respectively). CONCLUSION: CISNET models demonstrate that the greatest mortality reduction is achieved with annual screening of women starting at age 40 years. Cancer 2017;123:3673-3680. © 2017 American Cancer Society.

Breast Cancer Screening for Average-Risk Women: Recommendations From the ACR Commission on Breast Imaging.

Breast cancer is the most common non-skin cancer and the second leading cause of cancer death for women in the United States. Before the introduction of widespread mammographic screening in the mid-1980s, the death rate from breast cancer in the US had remained unchanged for more than 4 decades. Since 1990, the death rate has declined by at least 38%. Much of this change is attributed to early detection with mammography. ACR breast cancer screening experts have reviewed data from RCTs, observational studies, US screening data, and other peer-reviewed literature to update our recommendations. Mammography screening has consistently been shown to significantly reduce breast cancer mortality over a variety of study designs. The ACR recommends annual mammography screening starting at age 40 for women of average risk of developing breast cancer. Our recommendation is based on maximizing proven benefits, which include a substantial reduction in breast cancer mortality afforded by regular screening and improved treatment options for those diagnosed with breast cancer. The risks associated with mammography screening are also considered to assist women in making an informed choice.

Radiation Dose to the Breast by 64-slice CT: Effects of Scanner Model and Study Protocol.

RATIONALE AND OBJECTIVES: This work aimed to study the effects of scanner model and study protocol on radiation dose received by breast tissues from 64-slice computed tomography (CT) studies. MATERIALS AND METHODS: Four scanner models and three study protocols were used in scanning an anthropomorphic phantom with breast modules. Each protocol follows recommendations or guidelines from the American Association of Physicists in Medicine and the American College of Radiology. Twenty thermoluminescent dosimeters were placed inside the breast modules to measure breast tissue doses. Both the absolute and the normalized breast tissue doses were analyzed. RESULTS: The mean glandular doses of a lung cancer screening CT, a chest/abdomen/pelvis CT, and a virtual colonoscopy CT are equivalent to less than 1, 5-7, and 1-3 two-view digital mammograms, respectively, for a standard-sized patient. The normalized breast dose differs significantly (P < 0.01) between lung cancer screening CT and chest/abdomen/pelvis CT; however, it shows less than ±10% variation among scanner models for the same protocol. In virtual colonoscopy CT, breast tissue dose decreases with the distance between local tissues to the edge of the x-ray field, although the decreasing trend varies for different scanner models and protocol settings. CONCLUSIONS: When breasts are entirely included in the primary x-ray field, breast dose by 64-slice CT is mainly protocol dependent, with the normalized breast dose about 15% lower for protocols with modulated mA than for those with constant mA; when breasts are only partially included in the primary beam field, breast dose by 64-slice CT is dependent on both the scanner model and the protocol settings.

Benefit to Radiation Risk of Breast-specific Gamma Imaging Compared with Mammography in Screening Asymptomatic Women with Dense Breasts.

Purpose To estimate the benefit-to-radiation risk ratios of mammography alone, breast-specific gamma imaging (BSGI) alone, and mammography plus BSGI in women with dense breasts who were asymptomatic and examined in the 2015 study by Rhodes et al. Materials and Methods This study uses previously published breast cancer detection rates and estimates of radiation dose and radiation risk and is, therefore, exempt from institutional review board approval. By using breast cancer detection rates for mammography alone, BSGI alone, and mammography plus BSGI from the study by Rhodes et al, as well as lifetime estimates of radiation-induced cancer mortality for mammography and BSGI on the basis of the Biologic Effects of Ionizing Radiation VII report, the benefit-to-radiation risk ratios of mammography alone, BSGI alone, and mammography plus BSGI performed annually over 10-year age intervals from ages 40 to 79 years are estimated. Results The benefit-to-radiation risk ratio is estimated to be 13 for women who are 40-49 years old and are screened with mammography, a figure that approximately doubles for each subsequent 10-year age interval up to 70-79 years old. For low-dose BSGI, annual screening benefit-to-radiation risk ratios are estimated to be 5 for women 40-49 years old and to double by age 70-79 years, while mammography plus BSGI has benefit-to-radiation risk ratios similar to those of BSGI alone. There are wide ranges for all of these estimates. Conclusion While lower dose (300 MBq) BSGI has estimated benefit-to-radiation risk ratios well in excess of 1 for screening of asymptomatic women with dense breasts who are 40 years old and older, it does not match the benefit-to-radiation risk ratio of screening mammography. © RSNA, 2016.