Grade: B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.
The USPSTF recommends biennial screening mammography for women aged 50 to 74 years.*The Department of Health and Human Services, in implementing the Affordable Care Act under the standard it sets out in revised Section 2713(a)(5) of the Public Health Service Act, utilizes the 2002 recommendation on breast cancer screening of the USPSTF. In 2015, Congress enacted separate legislation as part of the Comprehensive Omnibus Funding law that ensured this provision remains in effect. This recommendation states: The USPSTF recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older (B recommendation). We provide this information here to help primary care providers understand the implications this may have on co-payments and coverage related to screening patients for breast cancer.
Frequency of Service
The USPSTF Recommends biennial (every 2 years) screening.
Risk Factor Information
Advancing age is the most important risk factor for breast cancer in most women, but epidemiologic data from the BCSC suggest that having a first-degree relative with breast cancer is associated with an approximately 2-fold increased risk for breast cancer in women aged 40 to 49 years.2, 9 Further, the CISNET models suggest that for women with about a 2-fold increased risk for breast cancer, starting annual digital screening at age 40 years results in a similar harm-to-benefit ratio (based on number of false-positive results or overdiagnosed cases per 1000 breast cancer deaths avoided) as beginning biennial digital screening at age 50 years in average-risk women.7, 8 This approach has not been formally tested in a clinical trial; therefore, there is no direct evidence that it would result in net benefit similar to that of women aged 50 to 74 years. However, given the increased burden of disease and potential likelihood of benefit, women aged 40 to 49 years who have a known first-degree relative (parent, child, or sibling) with breast cancer may consider initiating screening earlier than age 50 years. Many other risk factors have been associated with breast cancer in epidemiologic studies, but most of these relationships are weak or inconsistent and would not likely influence how women value the tradeoffs of the potential benefits and harms of screening. Risk calculators, such as the National Cancer Institute’s Breast Cancer Risk Assessment Tool (available at www.cancer.gov/BCRISKTOOLThis link goes offsite. Click to read the external link disclaimer), have good calibration between predicted and actual outcomes in groups of women but are not accurate at predicting an individual woman’s risk for breast cancer.10
Benefit of ScreeningThe results of the meta-analysis of clinical trials from the systematic evidence review commissioned by the USPSTF are summarized inTable 1. Over a 10-year period, screening 10,000 women aged 60 to 69 years will result in 21 (95% CI, 11 to 32) fewer breast cancer deaths. The benefit is smaller in younger women: screening 10,000 women aged 50 to 59 years will result in 8 (CI, 2 to 17) fewer breast cancer deaths, and screening 10,000 women aged 40 to 49 years will result in 3 (CI, 0 to 9) fewer breast cancer deaths.2, 3 Most of these trials began enrollment more than 30 years ago, and these estimates may not reflect the current likelihood of avoiding a breast cancer death with contemporary screening mammography technology. Mammography imaging has since improved, which may result in more tumors being detected at a curable stage today than at the time of these trials. However, breast cancer treatments have also improved, and as treatment improves, the advantage of earlier detection decreases, so that some of the women who died of breast cancer in the nonscreened groups in these trials would survive today.
Harms of ScreeningThe most important harm of screening is the detection and treatment of invasive and noninvasive cancer that would never have been detected, or threaten health, in the absence of screening (overdiagnosis and overtreatment). Existing science does not allow for the ability to determine precisely what proportion of cancer diagnosed by mammography today reflects overdiagnosis, and estimates vary widely depending on the data source and method of calculation used.2, 4 In the United States, the rate of diagnosis of invasive plus noninvasive breast cancer increased by 50% during the era of mammography screening (Figure).5 It is not possible to know with certainty what proportion of that increase is due to overdiagnosis and what proportion reflects other reasons for a rising incidence. If overdiagnosis is the only explanation for the increase, 1 in 3 women diagnosed with breast cancer today is being treated for cancer that would never have been discovered or caused her health problems in the absence of screening. The best estimates from randomized, controlled trials (RCTs) evaluating the effect of mammography screening on breast cancer mortality suggest that 1 in 5 women diagnosed with breast cancer over approximately 10 years will be overdiagnosed.6 Modeling studies conducted in support of this recommendation by the Cancer Intervention and Surveillance Modeling Network (CISNET) provide a range of estimates that reflect different underlying assumptions; the median estimate is that 1 in 8 women diagnosed with breast cancer with biennial screening from ages 50 to 74 years will be overdiagnosed. The rate increases with an earlier start age or with annual mammography.7, 8 Even with the conservative estimate of 1 in 8 breast cancer cases being overdiagnosed, for every woman who avoids a death from breast cancer through screening, 2 to 3 women will be treated unnecessarily.
The other principal harms of screening are false-positive results, which require further imaging and often breast biopsy, and false-negative results. Table 2 summarizes the rates of these harms per screening round using registry data for digital mammography from the Breast Cancer Surveillance Consortium (BCSC), a collaborative network of 5 mammography registries and 2 affiliated sites with linkages to tumor registries across the United States.2, 9 (Note that Table 2 describes a different time horizon than Table 1 [per screening round rather than per decade]).
When to Start ScreeningClinical trials, observational studies, and modeling studies all demonstrate that the likelihood of avoiding a breast cancer death with regular screening mammography increases with age, and this increase in benefit likely occurs gradually rather than abruptly at any particular age. In contrast, the harms of screening mammography either remain constant or decrease with age. For example, about the same number of breast biopsies are performed as a result of screening mammography in women aged 40 to 49 years as in those aged 60 to 69 years, but many more of these biopsies will result in a diagnosis of invasive cancer in the older age group. Thus, the balance of benefit and harms improves with age (Table 3).
The USPSTF concludes that while there are harms of mammography, the benefit of screening mammography outweighs the harms by at least a moderate amount from age 50 to 74 years and is greatest for women in their 60s. For women in their 40s, the number who benefit from starting regular screening mammography is smaller and the number experiencing harm is larger compared with older women. For women in their 40s, the benefit still outweighs the harms, but to a smaller degree; this balance may therefore be more subject to individual values and preferences than it is in older women. Women in their 40s must weigh a very important but infrequent benefit (reduction in breast cancer deaths) against a group of meaningful and more common harms (overdiagnosis and overtreatment, unnecessary and sometimes invasive follow-up testing and psychological harms associated with false-positive test results, and false reassurance from false-negative test results). Women who value the possible benefit of screening mammography more than they value avoiding its harms can make an informed decision to begin screening.
Neither clinical trials nor models can precisely predict the potential benefits and harms that an individual woman can expect from beginning screening at age 40 rather than 50 years, as these data represent population effects. However, model results may be the easiest way for women to visualize the relative tradeoffs of beginning screening at age 40 versus 50 years. CISNET conducted modeling studies to predict the lifetime benefits and harms of screening with contemporary digital mammography at different starting and stopping ages and screening intervals. The models varied their assumptions about the natural history of invasive and noninvasive breast cancer and the effect of detection by digital mammography on survival. The models assumed the ideal circumstances of perfect adherence to screening and current best practices for therapy across the life span. Table 3 compares the median and range across the models for predicted lifetime benefits and harms of screening biennially from ages 50 to 74 years with screening biennially from ages 40 to 74 years. (Note that Table 3 differs from Tables 1 and 2 in terms of population metrics [per 1000 vs. 10,000 women] and time horizon considered [lifetime vs. 10-year or single event]).
It is, however, a false dichotomy to assume that the only options are to begin screening at age 40 or to wait until age 50 years. As women advance through their 40s, the incidence of breast cancer rises. The balance of benefit and harms may also shift accordingly over this decade, such that women in the latter half of the decade likely have a more favorable balance than women in the first half. Indeed, the CISNET models suggest that most of the benefit of screening women aged 40 to 49 years would be realized by starting screening at age 45.7, 8
Risk Factors That May Influence When to Start ScreeningAdvancing age is the most important risk factor for breast cancer in most women, but epidemiologic data from the BCSC suggest that having a first-degree relative with breast cancer is associated with an approximately 2-fold increased risk for breast cancer in women aged 40 to 49 years.2, 9 Further, the CISNET models suggest that for women with about a 2-fold increased risk for breast cancer, starting annual digital screening at age 40 years results in a similar harm-to-benefit ratio (based on number of false-positive results or overdiagnosed cases per 1000 breast cancer deaths avoided) as beginning biennial digital screening at age 50 years in average-risk women.7, 8 This approach has not been formally tested in a clinical trial; therefore, there is no direct evidence that it would result in net benefit similar to that of women aged 50 to 74 years. However, given the increased burden of disease and potential likelihood of benefit, women aged 40 to 49 years who have a known first-degree relative (parent, child, or sibling) with breast cancer may consider initiating screening earlier than age 50 years. Many other risk factors have been associated with breast cancer in epidemiologic studies, but most of these relationships are weak or inconsistent and would not likely influence how women value the tradeoffs of the potential benefits and harms of screening. Risk calculators, such as the National Cancer Institute’s Breast Cancer Risk Assessment Tool (available atwww.cancer.gov/BCRISKTOOLThis link goes offsite. Click to read the external link disclaimer), have good calibration between predicted and actual outcomes in groups of women but are not accurate at predicting an individual woman’s risk for breast cancer.10
How Often to ScreenOnce a woman has decided to begin screening, the next decision is how often to undergo screening. No clinical trials compared annual mammography with a longer interval in women of any age. In the randomized trials that demonstrated the effectiveness of mammography in reducing breast cancer deaths in women aged 40 to 74 years, screening intervals ranged from 12 to 33 months.2, 3 There was no clear trend for greater benefit in trials of annual mammography, but other differences between the trials preclude certainty that no difference in benefit exists. Available observational evidence evaluating the effects of varying mammography intervals found no difference in the number of breast cancer deaths between women aged 50 years or older who were screened biennially versus annually.2, 3
Regardless of the starting age for screening, the models consistently predict a small incremental increase in the number of breast cancer deaths averted when moving from biennial to annual mammography, but also a large increase in the number of harms (Table 4).7, 8 The USPSTF concludes that for most women, biennial mammography screening provides the best overall balance of benefit and harms.
When to Consider Stopping ScreeningClinical trial data for women aged 70 to 74 years are inconclusive. In its 2009 recommendation,11 the USPSTF extended the recommendation for screening mammography to age 74 years based on the extrapolation that much of the benefit seen in women aged 60 to 69 years should continue in this age range, and modeling done at the time supported this assumption. Current CISNET models suggest that women aged 70 to 74 years with moderate to severe comorbid conditions that negatively affect their life expectancy are unlikely to benefit from mammography.7, 8, 12 Moderate comorbid conditions include cardiovascular disease, paralysis, and diabetes. Severe comorbid conditions include (but are not limited to) AIDS, chronic obstructive pulmonary disease, liver disease, chronic renal failure, dementia, congestive heart failure, and combinations of moderate comorbid conditions, as well as myocardial infarction, ulcer, and rheumatologic disease.12
Screening in Women Aged 75 Years or OlderThe USPSTF found insufficient evidence to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. CISNET models suggest that biennial mammography screening may potentially continue to offer a net benefit after age 74 years among women with no or low comorbidity,7, 8 but no randomized trials of screening included women in this age group.2, 3
DBT as a Primary Screening StrategyThe USPSTF found insufficient evidence to assess the balance of benefits and harms of DBT as a primary screening method for breast cancer.
BackgroundEvidence on DBT is limited; a single study on the test characteristics of DBT as a primary screening strategy for breast cancer met the inclusion criteria of the systematic evidence review.13
Potential BenefitsFrom the limited data available, DBT seems to reduce recall rates (that is, follow-up for additional imaging or testing) and increase cancer detection rates compared with conventional digital mammography alone.13 However, current study designs cannot determine whether all of the additional cases of cancer detected would have become clinically significant (that is, the degree of overdiagnosis) or whether there is an incremental clinical benefit to detecting these cancers earlier than with conventional digital mammography. In addition, no studies of DBT looked at clinical outcomes, such as breast cancer morbidity or mortality or quality of life.13
Potential HarmsAs currently practiced in most settings, DBT exposes women to approximately twice the amount of radiation as conventional digital mammography.13 In 2013, the U.S. Food and Drug Administration approved a method to generate synthetic reconstruction of 2-dimensional images from 3-dimensional views, which reduces the total radiation dose associated with DBT. Although the extent to which this new software technology has been implemented in mammography screening centers is not precisely known, it is currently thought to be low. In women with abnormal findings, DBT may also increase the rate of breast biopsy compared with conventional digital mammography.13
Primary and Adjunctive Screening in Women With Dense BreastsThe USPSTF found insufficient evidence to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, MRI, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram.
Epidemiology of Dense BreastsIn the United States, the most commonly used classification system for breast density is the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) 4-category scale (a = the breasts are almost entirely fatty; b = there are scattered areas of fibroglandular density; c = the breasts are heterogeneously dense, which may obscure small masses; or d = the breasts are extremely dense, which lowers the sensitivity of mammography). Data from the BCSC indicate that about 25 million women (about 43%) aged 40 to 74 years are classified as having heterogeneously or extremely dense breasts. The proportion of women with dense breasts is highest among those aged 40 to 49 years and decreases with age.14
Increased breast density is a risk factor for breast cancer. Data from the BCSC indicate that, compared with women with average breast density, women aged 40 to 49 years with heterogeneously or extremely dense breasts have a relative risk (RR) of 1.23 for developing invasive breast cancer. For women aged 50 to 64 years with heterogeneously or extremely dense breasts, the RR is 1.29, and for women aged 65 to 74 years, it is 1.30.7 However, women with dense breasts who develop breast cancer do not have an increased risk for dying from the disease, after adjustment for stage, treatment, method of detection, and other risk factors, according to data from the BCSC.15
Primary Screening Test Performance CharacteristicsIncreased breast density reduces the sensitivity and specificity of mammography for detecting cancer. A BCSC study of more than 300,000 women found that sensitivity decreased from 87% in the lowest density category to 63% in the highest, and specificity decreased from 96% to 90% as breast density increased.16
A woman’s BI-RADS breast density classification can be inconstant over time. Good-quality studies of U.S. radiologists demonstrate that major recategorization of sequential screening examinations (that is, from “dense” [c/d] to “nondense” [a/b] or vice versa) occurs in approximately 13% to 19% of women.17, 18 These studies excluded women taking hormone medications or those with other medical conditions that may have resulted in physiologic changes that would explain the difference in breast density classification observed between examinations. Reclassification of breast density status from year to year complicates women’s assessment of their underlying breast cancer risk, as well as informed screening and care decisions.
Primary Screening FrequencyIn 1 BCSC study, biennial screening mammography was associated with greater risk for advanced-stage cancer (stage IIB or greater) (odds ratio, 2.39 [CI, 1.06 to 3.39]) or a breast tumor larger than 20 mm (odds ratio, 2.39 [CI, 1.37 to 3.18]) in women aged 40 to 49 years with extremely dense breasts (BI-RADS category d) compared with annual screening; this risk was not seen in women aged 50 to 74 years.19 No significant differences in lymph node involvement were observed in either age group. Information about morbidity or mortality end points is not available, so whether these women ultimately fared any differently in their clinical outcomes is not known.17, 19
All women aged 40 to 74 years with increased breast density are at increased risk for a false-positive result, an unnecessary breast biopsy, or a false-negative result compared with women with average breast density. Screening more frequently (that is, annually vs. biennially) further increases the probability that a woman will experience one of these screening-related harms. Data from the BCSC indicate that the cumulative probability that a woman aged 40 to 49 years with extremely dense breasts screened annually for a decade will receive a false-positive result is about 69%, compared with about 21% for biennial screening. Similarly, unnecessary breast biopsy rates are 12% for annual screening versus 3% for biennial screening.17, 18
Adjunctive ScreeningPotential benefits. Current evidence on adjunctive screening is very limited, but it suggests that for women identified to have dense breasts on an otherwise negative mammogram, ultrasonography or MRI will detect additional breast cancer but will also result in a higher number of false-positive results. Data on DBT in women with dense breasts are limited, but in the short term, DBT also detects additional breast cancer. Most of the additional cancer detected by these methods are invasive tumors rather than ductal carcinoma in situ (DCIS).17, 18 A short-term increase in the number of cancer cases detected does not allow for the conclusion that adjunctive screening reduces treatment-related morbidity or breast cancer deaths or improves women’s quality of life. Although adjunctive screening may detect more breast cancer, these cancers may fall into 1 of 3 categories: 1) those for which earlier detection leads to improved outcomes, 2) those that would have had the same outcome when detected later, or 3) those that are overdiagnosed and would not have caused a health problem during a woman’s lifetime and may result in harms from unnecessary treatment. Existing data do not allow for estimation of the proportion of cancer that falls into each category; therefore, the benefits on health cannot be estimated.
Potential harms. Most positive adjunctive breast cancer screening test results are false positive. Compared with mammography alone, adjunctive screening with ultrasonography or MRI seems to increase recall and biopsy rates. Data on the effects of DBT on recall and biopsy rates in women with dense breasts are too limited to draw conclusions.17, 18 The effects of DBT on overdiagnosis rates are unknown.
Current practice. At the present time, 24 states require patient notification of breast density status when mammography is performed; in some states, legislation also includes language to be sent to women informing them that they should consider adjunctive screening.17No clinical practice guidelines explicitly recommend adjunctive screening in women identified to have dense breasts on an otherwise negative screening mammogram.17
AssessmentIncreased breast density is very common. It is an independent risk factor for developing (but not dying of) breast cancer, and it reduces mammography’s ability to find and accurately identify breast cancer. Many women will move between “dense” and “nondense” breast classifications with sequential screening mammograms, and these reclassifications are not primarily due to physiologic causes. More evidence is needed to better understand how the frequency of screening might affect important health outcomes in women with dense breasts. Overall, many important questions remain about the potential role of breast density in individualizing screening approaches, and the current evidence is insufficient to recommend a specific screening strategy for women with increased breast density.
Other Approaches to PreventionThe USPSTF has made recommendations about the use of medications to reduce women’s risk for breast cancer, as well as risk assessment, genetic counseling, and genetic testing for BRCA1- or BRCA2-related cancer (including breast cancer). These recommendations are available on the USPSTF Web site (www.uspreventiveservicestaskforce.org).
Breast cancer is the second-leading cause of cancer death among women in the United States. In 2015, an estimated 232,000 women were diagnosed with the disease and 40,000 women died of it. It is most frequently diagnosed among women aged 55 to 64 years, and the median age of death from breast cancer is 68 years.
Benefit and Harms of Screening and Early Treatment
The USPSTF found adequate evidence that mammography screening reduces breast cancer mortality in women aged 40 to 74 years. The number of breast cancer deaths averted increases with age; women aged 40 to 49 years benefit the least and women aged 60 to 69 years benefit the most. Age is the most important risk factor for breast cancer, and the increased benefit observed with age is at least partly due to the increase in risk. Women aged 40 to 49 years who have a first-degree relative with breast cancer have a risk for breast cancer similar to that of women aged 50 to 59 years without a family history. Direct evidence about the benefits of screening mammography in women aged 75 years or older is lacking.
The USPSTF found adequate evidence that screening for breast cancer with mammography results in harms for women aged 40 to 74 years. The most important harm is the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to a woman’s health, or even apparent, during her lifetime (that is, overdiagnosis and overtreatment). False-positive results are common and lead to unnecessary and sometimes invasive follow-up testing, with the potential for psychological harms (such as anxiety). False-negative results (that is, missed cancer) also occur and may provide false reassurance. Radiation-induced breast cancer and resulting death can also occur, although the number of both of these events is predicted to be low.
The USPSTF found inadequate evidence on the benefits and harms of DBT as a primary screening method for breast cancer. Similarly, the USPSTF found inadequate evidence on the benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, MRI, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. In both cases, while there is some information about the accuracy of these methods, there is no information on the effects of their use on health outcomes, such as breast cancer incidence, mortality, or overdiagnosis rates.
- The USPSTF concludes with moderate certainty that the net benefit of screening mammography in women aged 50 to 74 years is moderate.
- The USPSTF concludes with moderate certainty that the net benefit of screening mammography in the general population of women aged 40 to 49 years, while positive, is small.
- The USPSTF concludes that the evidence on mammography screening in women age 75 years and older is insufficient, and the balance of benefits and harms cannot be determined.
- The USPSTF concludes that the evidence on DBT as a primary screening modality for breast cancer is insufficient, and the balance of benefits and harms cannot be determined.
- The USPSTF concludes that the evidence on adjunctive screening for breast cancer using breast ultrasound, MRI, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram is insufficient, and the balance of benefits and harms cannot be determined.
Research Needs and Gaps Trial data are too limited to directly inform the question of what the best screening strategy is for women or how clinicians can best tailor that strategy to the individual. Overdiagnosis and resulting overtreatment of breast cancer that would otherwise not have become a threat to a woman’s health during her lifetime is the most important harm associated with breast cancer screening. Because it is impossible to determine for any individual patient whether a diagnosed cancer will or will not progress, measurements of overdiagnosis are not straightforward but rather are indirectly quantified. Current estimates of the magnitude of overdiagnosis associated with mammography screening vary widely. Researchers in the field must work together to critically evaluate and ultimately agree on uniform definitions and standards to optimally measure and monitor overdiagnosis and overtreatment in breast cancer screening programs. In addition, research is critically needed to identify ways to reduce the occurrence of overdiagnosis and subsequent overtreatment associated with breast cancer screening. Ductal carcinoma in situ is an example of a breast lesion with the potential for high rates of overdiagnosis and overtreatment. Before the widespread use of screening mammography, 6 cases of DCIS per 100,000 U.S. women per year were identified compared with 37 cases of DCIS per 100,000 women per year after its introduction.5 When classified as cancer, DCIS now accounts for about 1 in 4 of all breast cancer diagnosed in a given year.20 However, its nomenclature has recently been the subject of debate, because by definition, DCIS is confined to the mammary ductal–lobular system and is incapable of metastasis (that is, it is noninvasive and thus lacks the classic characteristic of cancer).21 Ductal carcinoma in situ may therefore be more appropriately classified as a risk factor for future development of cancer; the primary goal in its management is to reduce the incidence of new invasive carcinoma. The natural history of DCIS—particularly screen-detected DCIS—is poorly understood. Although a substantial proportion of these lesions will not progress to invasive cancer,22 which women will and which will not develop such cancer cannot be predicted with certainty. As such, nearly all women diagnosed with DCIS receive treatment (generally either mastectomy or lumpectomy with or without radiation; a chemopreventive agent, such as tamoxifen, may also be offered).23 The 20-year breast cancer mortality rate after treatment of DCIS is as low as 3%;24 whether this is due to the effectiveness of the interventions or the fact that most DCIS cases being treated are essentially benign is a pressing research question. Research is needed to develop better prognostic indicators to distinguish nonprogressive or slowly progressive lesions from tumors that are likely to affect quality or length of life. Research is also needed to compare the long-term benefits and harms of immediate treatment versus observation or surveillance with delayed intervention in women with screen-detected DCIS. Most of the available screening trials and high-quality cohort studies were performed in Europe and predominately enrolled white women younger than age 70 years. Direct evidence about any differential effectiveness of breast cancer screening is lacking for important subgroups of women, such as African American women, who are at increased risk for dying of breast cancer, and older women, for whom balancing the potential benefits and harms of screening may become increasingly challenging with advancing age. Newer technologies, such as DBT for primary screening or ultrasonography and MRI for adjunctive screening in women with dense breasts, are being increasingly used in the United States without clear evidence to demonstrate their effectiveness in improving important health outcomes. Such studies are necessary prerequisites for the appropriate incorporation of these methods into established screening programs.Finally, a large proportion of women in the United States are classified as having dense breasts after screening mammography. Increased breast density is common in the general population; however, critical questions remain about how best to manage this condition and to support these women. Research to help improve the validity and reproducibility of serial BI-RADS assessments would be useful if breast density is to be considered as a factor for personalized, risk-based approaches to breast cancer screening. In addition, long-term randomized trials or longitudinal cohort studies are needed that compare screening outcomes in women with dense breasts who are not otherwise at increased risk for breast cancer who receive adjunctive screening versus those who do not and report important outcomes, such as breast cancer stage at diagnosis, breast cancer recurrence rates, rates of overdiagnosis, and most importantly, breast cancer mortality.