Met-low patients" cancer français

¡Escribe tu texto aquí!INTRODUCTION

Breast cancer is the most frequent type of non-skin cancer and the most frequent cause of cancer death in women worldwide, and it is the second most frequent cause of cancer death in United States women. (See "Clinical features, diagnosis, and staging of newly diagnosed breast cancer", section on 'Introduction' and "Clinical features, diagnosis, and staging of newly diagnosed breast cancer", section on 'Epidemiology' and "Diagnostic evaluation of women with suspected breast cancer", section on 'Introduction'.)

The majority of breast cancers in the United States are diagnosed as a result of an abnormal screening study, although a significant number are first brought to attention by a patient. Findings suggest that screening mammography both reduces the odds of dying of breast cancer and facilitates the use of early treatment. While breast cancer mortality has dropped dramatically since the 1980s, it is thought that improvements in breast cancer treatment are more likely responsible for this reduction in mortality than screening [1-5].

Recommendations for breast cancer screening, taking into account the risk of developing breast cancer, other parameters that might affect screening decisions, and benefits and harms of screening, are discussed here.

Identification and management of women with a genetic predisposition to breast cancer, and surveillance in women with a personal history of breast cancer, are discussed in detail separately. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes" and "Cancer risks and management of BRCA carriers without cancer" and "Approach to the patient following treatment for breast cancer".)

The evidence for the effectiveness and harms of screening for breast cancer in women, and performance characteristics of mammography, are discussed in detail separately. (See "Screening for breast cancer: Evidence for effectiveness and harms" and "Breast imaging for cancer screening: Mammography and ultrasonography".)

RISK DETERMINATIONScreening is of greatest value for patients who are most likely to develop breast cancer and for whom early treatment is more effective than later treatment in reducing mortality. Thus, it is important to determine a patient’s risk of developing breast cancer and use that information both to recommend the modality and frequency of screening and also to determine whether referrals are needed for genetic testing and for consideration of chemoprevention and/or prophylactic surgery. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes" and "Cancer risks and management of BRCA carriers without cancer".)

Initial assessment of risk — The first step in determining a risk category is to assess for major risk factors to identify women at average risk, which is the category for most women, and to identify the smaller number of women at moderate or high risk of developing breast cancer. The risk categories are delineated according to the lifetime risk of being diagnosed with breast cancer (not according to the risk of dying due to breast cancer). Although there is no standardization or consensus about the exact percentages of lifetime risk of developing breast cancer within each risk category, generally they are as follows: average (less than 15 percent), moderate (approximately 15 to 20 percent), or high (greater than 20 percent) lifetime risk.

Most women can be categorized based on history alone; for others, risk prediction models are available for use if needed. (See 'Clinical use of risk prediction models' below and "Factors that modify breast cancer risk in women".)

Major factors used to determine a risk category, based on a patient’s history, are:

●Personal history of breast, ovarian, tubal, or peritoneal cancer

●Family history of breast, ovarian, tubal, or peritoneal cancer

●Ancestry (eg, Ashkenazi Jewish) associated with BRCA1 or 2 mutations

●Known carrier of a pathogenic mutation for a hereditary breast and ovarian cancer syndrome in self or relative (see "Overview of hereditary breast and ovarian cancer syndromes associated with genes other than BRCA", section on 'High-penetrance genes for breast and/or ovarian cancer')

●Previous breast biopsy indicating high-risk lesion (eg, atypical hyperplasia)

●Radiotherapy to the chest between age 10 and age 30

Women who have none of these risk factors are usually considered at average risk [6,7]. Most women are in this average-risk category, with an average lifetime risk of being diagnosed with breast cancer estimated at 12.4 percent. It is important to remind patients that this is the risk of being diagnosed with breast cancer, not of dying from breast cancer [8]. The approach to screening for average-risk women is discussed below. (See 'Average risk: Screening' below.)

Risk prediction tools are available to stratify the patient’s risk (see 'Clinical use of risk prediction models' below). These risk tools take into account multiple concurrent risk factors (eg, family history of cancer, prior breast biopsy of atypical hyperplasia) and can help assess whether the patient has an elevated risk of breast cancer to determine if referral for more detailed risk analysis is appropriate. Certain tools may be more appropriate than others depending on the strength of the family history. Use of these tools can estimate the risk of developing breast cancer, which can be then used to categorize the risk as average, moderate, or high, as above. Many women who have a family history of breast cancer still have an average risk. Screening recommendations are in part dependent on this categorization. (See 'Average risk: Screening' below and 'Moderate risk: Screening' below and 'High risk: Screening' below.)

Women who have a personal history of breast cancer, a confirmed or suspected genetic mutation known to increase the risk of breast cancer (eg, BRCA1 or BRCA2, PTEN, TP53), or a history of previous radiotherapy to the chest between ages 10 and 30 are at high risk. As an example, women with a BRCA1 mutation have a nearly 60 percent absolute risk of developing a breast cancer by the time they are 70 years old [9]. However, because a BRCA1 or 2 mutation is relatively rare in the general population (1 in 300 to 500), they account for only between 5 to 10 percent of all breast cancer cases [10,11]. Information about hereditary breast cancer and indications for testing for genetic mutations are discussed elsewhere. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Criteria for genetic risk evaluation' and "Overview of hereditary breast and ovarian cancer syndromes associated with genes other than BRCA", section on 'High-penetrance genes for breast and/or ovarian cancer'.)

Clinical management of high-risk women, including genetic counseling, indications for prophylactic therapies, and screening, is discussed elsewhere. (See 'High risk: Screening' below and "Cancer risks and management of BRCA carriers without cancer" and "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes".)

Although there are other factors associated with increased risk for developing breast cancer, such as use of exogenous estrogen, such features are not necessarily incorporated into the initial risk assessment to determine screening approach. These and other risk factors for breast cancer are discussed in detail elsewhere (table 1). (See "Factors that modify breast cancer risk in women".)

Screening considerations specifically regarding dense breasts are discussed in detail elsewhere. (See 'Dense breast tissue' below and "Breast density and screening for breast cancer".)

Clinical use of risk prediction models — There are multiple breast cancer risk models for more specific categorization of breast cancer risk; some models also calculate risk of being a carrier of BRCA1 and BRCA2 [12-23]. Models vary; they may concentrate more on family history or may include personal variables such as history of breast biopsies, parity, and mammographically determined breast density. The models discussed below are available online. Other models are not readily available to practicing clinicians.

The most widely used tool to calculate breast cancer risk is the Breast Cancer Risk Assessment Tool, also known as the Gail Model (see 'Gail model' below). However, for women who have strong family histories of breast cancer (eg, more than two first-degree relatives with breast cancer), other models are more useful because of limitations of the Gail model. (See 'Models predicting pathogenic BRCA1/2 mutations' below.)

Clinical judgment must be factored in with the model-based predictions to determine when to refer for genetic counseling, when to refer for consideration of prophylactic therapies including chemoprevention or surgery, and what screening to recommend [24]. This is because the accuracy of risk assessment tools at predicting whether an individual woman will develop breast cancer is only modest, partly because not all important risk factors have been identified, and partly because accurate stratification requires that risk factors be strongly predictive, whereas most risk factors for breast cancer are not very strong risk factors. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Pretest genetic counseling' and "Cancer risks and management of BRCA carriers without cancer", section on 'Risk-reducing surgery' and "Cancer risks and management of BRCA carriers without cancer", section on 'Chemoprevention'.)

Gail model — The Gail Model is readily available at the National Cancer Institute website and is easy to use in general office practice [12,14]. The Gail model is intended for women who have never had a diagnosis of breast cancer, ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) and who do not have a strong family history suggesting inherited breast cancer. The Gail model takes into account the patient’s age, race and ethnicity, history of breast disease, age at onset of menses, parity, and relevant family history in first-degree relatives.

The Gail model calculates an individual’s approximate risk of developing breast cancer before age 90 and her risk of developing breast cancer within the next five years. These numbers are compared with the predicted risk for a woman of the same age who has average risk factors. There are no confidence intervals around the estimates. As an example, the percentage of white women at a given age who will develop breast cancer over a five-year period and until age 90 is shown in a table (table 2). For clinical decisions about screening and for better understanding of risk by patients, a shorter timeframe (usually 5 to 10 years) may be more helpful than a lifetime risk estimate.

Limitations of the Gail model — There are a number of limitations to the Gail model. It may be less precise for older women with competing risks of noncancer death. For the rarer women with strong family history of breast and/or ovarian cancer, the Gail model is less useful because of factors it does not consider. Specifically, it is not applicable to women with more than two first-degree relatives with breast cancer; it does not consider more distant relatives, the age at which relatives developed breast cancer, or a family history of ovarian cancer; and it is not useful for women with a strong family history of breast cancer on the paternal side. In women who have strong family histories, other models may be more useful. (See 'Models predicting pathogenic BRCA1/2 mutations' below.)

The Gail model does not estimate the risk of carrying a deleterious BRCA1 or BRCA2 gene mutation.

Risk estimates for races or ethnicities other than Caucasian and black may not be as accurate with the Gail model, because either no studies have been conducted or fewer data have been analyzed.

The predictive value of the Gail model is limited for an individual woman. The sensitivity of the Gail model to identify women who will develop breast cancer is relatively low, reported as 28 to 44 percent [25,26], using a five-year risk of 1.67 percent as the cut point between "high" and "low" risk. The specificity of the Gail model is also modest, reported as 66 to 88 percent [25,26]. A figure showing the Gail model’s estimated risk of developing breast cancer for each of 80,000 women illustrates the limited ability of the Gail model to separate women into groups who will and will not develop breast cancer (figure 1). In the figure, the curve showing the percent of women at each estimated-risk point who did develop breast cancer overlaps substantially with the curve showing the percent who did not develop breast cancer, and there is no point along the estimated-risk continuum that appears to be predictive to separate women who developed breast cancer from those who did not [26].

Efforts to improve on the Gail model have mainly centered on adding mammographic breast density to other risk factors [15,16,25] or updating the information on race or ethnicity sub-groups [27].

Models predicting pathogenic BRCA1/2 mutations — Risk prediction models have been developed for patients who have family member(s) with breast, ovarian, tubal, or peritoneal cancer. These models assess the risk of carrying a pathogenic BRCA1 or BRCA2 gene mutation. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes" and "Overview of hereditary breast and ovarian cancer syndromes associated with genes other than BRCA".)

For women with any personal or family history of breast, ovarian, tubal, or peritoneal cancer, or whose ancestry is associated with a pathogenic BRCA1 or BRCA2 mutation, the US Preventive Services Task Force (USPSTF) recommends use of a familial risk assessment screening tool to identify those who need genetic counseling and possible genetic testing [10,28]. The recommended risk assessment tools include:

●Ontario Family History Risk Assessment Tool (table 3) [29]

●Manchester Scoring System (table 4) [30]

●Referral Screening Tool (table 5) [31]

●Pedigree Assessment Tool (table 6) [32]

●7-Question Family History Screen (FHS-7) (table 7) [33]

●International Breast Cancer Intervention Study Model (Tyrer-Cuzick) [34]

●BRCAPRO

Indications for testing for BRCA1 and BRCA2 mutations are discussed elsewhere. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Criteria for genetic risk evaluation'.)

Several more complex risk prediction models are available online; these tend to be used by geneticists and others who conduct a detailed risk assessment. These models include the BRCAPRO (complete version), IBIS, and BOADICEA models, the specifics and limitations of which are discussed in detail elsewhere. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Risk assessment models'.)

Although several breast cancer susceptibility gene loci have been found, individually they confer far lower risk of breast cancer than BRCA mutations [35,36]. Thus, unless the woman has a strong family history or specific (eg, BRCA) genetic mutations, incorporating genetic profiling to evaluate gene combinations that contribute to cancer risk remains theoretical rather than practical for use in determining screening recommendations [37]. As an example, a study that compared classification of risk using either the Gail model, or the Gail model plus 10 common genetic susceptibility variants other than those associated with BRCA1 or BRCA2, found that inclusion of the common genetic factors only modestly improved performance of the risk model for predicting breast cancer [35]. In combination, these and other genes could identify subgroups of women at moderate to high risk for breast cancer. As more such alleles are identified, the precision of risk estimates is expected to improve.

AVERAGE RISK: SCREENING

Age-related screening approach — The majority of women are at average risk (less than 15 percent lifetime risk) of developing breast cancer. In these women, age is the most important factor in her decision about when to be screened, because breast cancer incidence rises with age. Breast cancer incidence is quite low under the age of 40, then begins to rise as women age. The sensitivity and specificity of mammography are also age-dependent, being higher in older women than in younger women [38,39]. Thus, in younger women, the risk of developing breast cancer over the succeeding 10 years is quite low, and the benefits of screening may not outweigh the costs, inconvenience, emotional stress, occasional direct physical harm, and potential for overtreatment as a result of screening [40].

When counseling women on screening, we discuss the potential benefits and harms of breast cancer screening and encourage them to consider their own values and preferences. We support women in making a decision that is best for them. We tailor this discussion based on age. (See 'Age under 40' below and 'Age 40 to 49' below and 'Age 50 to 74' below and 'Age 75 and older' below.)

A number of expert groups have developed recommendations related to age to initiate screening (table 8 and figure 2) [6,7,41-49]. These recommendations can also be useful during discussion and shared decision making.

Age under 40 — We suggest not screening average-risk women who are under 40 years of age. Among women younger than 40, the incidence of breast cancer is low, there are no randomized trials of breast cancer screening, and performance characteristics of mammography are poor. In a review of results of 73,335 initial screening mammograms in women aged 35 to 39 years, the positive predictive value was only 1.3 percent [50].

Age 40 to 49 — Most expert groups encourage shared decision-making for women in their 40s because of trade-offs between benefits and harms (table 8 and figure 2). For average-risk women in their 40s, we raise the topic of screening for breast cancer to answer any questions the women might have. Raising the topic is different from strongly "recommending" screening; we engage in shared decision-making to encourage women to individualize the decision based on the benefits and harms of screening and their personal values and preferences (see 'Shared medical decision-making' below). For women who decide to initiate screening in their 40s, we typically suggest screening mammography every two years. (See 'Frequency of screening with mammography' below.)

Decisions on screening in this age group are highly dependent on a patient’s values and preferences. As an example, shared decision-making may result in a 40-year-old woman at average risk choosing to be screened if she has substantial concerns about breast cancer and is willing to accept the possibility of either a false-positive result or overdiagnosis and the resulting evaluation and treatment. On the other hand, a different 40-year-old woman may find that the information gathered during shared decision-making, including the frequency of false positives and overdiagnosis, provides her with a compelling reason to decide to defer mammography screening.

The net benefits of breast cancer screening are less clear for younger women. Although the benefits of screening women in their 40s appear favorable when considering the number of years of life potentially saved [6,44], for the individual average-risk woman, the absolute benefits of screening, when measured by number of breast cancer deaths prevented, are relatively low. A systematic review and meta-analysis of nine randomized trials showed a trend suggesting that for 10,000 women screened over 10 years, three deaths from breast cancer could be prevented [51]. There was an 8 percent relative reduction of breast cancer mortality in women ages 39 to 49 who were randomly assigned to mammographic screening, which did not achieve statistical significance (relative risk [RR] 0.92, 95% CI 0.75-1.02). Furthermore, in an analysis of the pooled results of four included trials, screening in women aged 39 to 49 years did not impact the risk of advanced breast cancer (RR 0.98, 95% CI 0.74-1.37) [51]. Similarly, the age trial in the United Kingdom suggested that breast cancer mortality at a mean follow-up of 10.7 years was decreased in the group of women who were invited for mammogram screening at age 40, compared with a usual care group, although the difference was not significant (RR 0.83, 95% CI 0.66-1.04) [52]. Risk reduction for breast cancer mortality was greater, though still not statistically significant, when only those women who actually attended the first screening were compared with the control group (RR 0.76, 95% CI 0.51-1.01). (See 'Benefits' below.)

Mammography is less sensitive in younger than older women. As an example, mammography is estimated to detect about 73 percent of breast cancers in women in their early 40s compared with 85 percent of breast cancers in women in their early 60s [53].

Given the modest benefits of screening in the 40 to 49 age group, the harms can be relatively more consequential. In particular, false positives are more common in younger than older women. The harms of screening are discussed in detail elsewhere. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Harms from screening'.)

Expert guidelines vary in their recommendations about when to initiate screening and how frequently to screen average-risk women in the 40 to 49 age group (table 8 and figure 2). For example, the American Cancer Society (ACS) recommends that mammography screening start at age 45 based on the finding that the absolute risks of breast cancer occurrence and death for women ages 45 to 49 are more similar to those for women ages 50 to 54 than ages 40 to 44 [6,40,54,55]. The ACS concluded that this similarity in risks of occurrence and mortality outweighs the higher false-positive mammogram rates in women under age 50. The ACS recommends continuing annual screening until age 55, then decreasing to every two years [55].

Age 50 to 74 — We suggest breast cancer screening with mammography for average-risk women aged 50 to 74 years. We typically screen every two years, unless the prior screening identified a finding for which more frequent breast imaging was advised. (See 'Frequency of screening with mammography' below.)

Systematic reviews of multiple randomized trials over the past 50 years found that mammogram screening for women aged 50 to 70 decreases the risk of breast cancer mortality; however, these results largely reflect trials that used older mammography imaging techniques and did not involve current breast cancer treatment protocols, a factor which may limit the predictive value of the results. Subsequently, a 2016 systematic review of screening mammography found fair-quality evidence that mammography decreases the RR for breast cancer mortality for women 50 to 59 years (RR 0.86, 95% CI 0.68-0.97, seven trials), with a more significant reduction for women 60 to 69 years (RR 0.67, 95% CI 0.54-0.83, five trials) [51]. Screening also reduced the risk of advanced breast cancer in women aged 50 years and older (RR 0.62, 95% CI 0.46-0.83). These benefits are generally thought to outweigh the harms of screening for average-risk women in this age group. (See 'Benefits and harms of screening' below.)

All expert groups recommend routine screening with mammography for women at average risk who are age 50 or older, and most agree to continue screening through age 74 years (at least) (table 8 and figure 2). However, recommendations on the frequency of mammography screening for this age group vary [7,41,42,56-58].

Age 75 and older — We suggest that women over the age of 74 be offered screening only if their life expectancy is at least 10 years. For women in this age group who elect to be screened, we typically screen with mammography every two years. (See 'Frequency of screening with mammography' below.)

There is not a clear upper age limit or ideal frequency for screening in healthy women, since the incidence of breast cancer remains high into the 80s, but the number of life-years saved will decrease with age [40]. A framework that includes life expectancy, risk of dying of cancer, and the number needed to screen over the remaining lifetime to prevent cancer death (table 9) can be useful for guiding decision-making about screening older women for breast and other cancers [59]. It is important to ensure that shared decision-making occurs, with information about both the potential harms and benefits of screening. Most potential harms of screening occur relatively soon, whereas a potential benefit may occur up to 10 years later [60]. (See 'Benefits and harms of screening' below.)

Screening mammography may be less beneficial in women age 75 and older, although data from randomized trials for this age group are limited. In two observational studies, screening was associated with a reduction in mortality due to breast cancer up to age 75 but not among older women [61,62]. Similarly, a cohort study of 2011 women 80 years and older found no difference in breast cancer rate, stage, or death between women who did and did not undergo screening mammography after age 80 [63]. However, observational studies may be biased, because older women who participate in screening are likely to be healthier at baseline than those who do not. Furthermore, while screening mammography in older women may result in lower-stage cancer at diagnosis, this may not lead to a decrease in mortality [64-66]. This reflects several factors: a shorter life expectancy decreases the potential that screening will prolong life; the incidence of ductal carcinoma in situ (DCIS) increases with age, but it is not clear that treatment of DCIS affects mortality; and screening-detected cancers are usually lower-stage cancers than those detected clinically, due to lead-time bias [61-63].

Several expert group recommendations do not explicitly state at what age breast cancer screening should stop. Some groups take into consideration life expectancy and consider stopping if life expectancy is under 5 or 10 years. Some groups use age 75 as an age to consider whether or not to continue screening (table 8).

Screening modalities — Mammography (digital or film) is the primary modality for breast cancer screening in average-risk women. Other radiologic techniques, including ultrasound and magnetic resonance imaging (MRI), are reserved for further evaluation of findings on mammography or for screening of women at a higher risk for breast cancer. Breast examination by the clinician or by the patient is not recommended as the only screening method, and it is controversial as to whether clinician breast examination (CBE) or patient breast self-examination (BSE) are beneficial as an adjunct to mammography. It is important to educate women about breast awareness and to encourage women to report any breast concerns.

Mammography as preferred screening modality — Among a variety of imaging modalities developed for breast cancer screening, mammography is the best-studied and the only imaging technique that has been shown to decrease mortality as demonstrated in multiple randomized trials (figure 3). However, it is important to know that, even in the best circumstances, mammography may miss up to 20 percent of underlying breast cancers [67]. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Mammography'.)

Mammography is available as digital and as film mammography. The choice between them generally depends on availability. The vast majority of locations in the United States use digital mammography. For women with dense breasts, digital mammography, if available, is preferred because of higher sensitivity; the sensitivity of mammography is inversely correlated with breast density, especially with older film techniques [68]. The relative benefits of digital and film mammography are discussed in further detail elsewhere [69-71]. (See "Breast imaging for cancer screening: Mammography and ultrasonography".)

Prior to the mammogram, it is helpful for women to know that the compression of breasts is transient but important to reduce motion artifact, improve image quality, and reduce the amount of radiation required. Premenopausal women should not schedule their mammogram around the time of their menstrual period as it may be more painful then and have lower sensitivity, and women should provide access to their prior mammogram films for comparison if they go to a different mammography facility than they used previously.

Other imaging modalities — For average-risk women, there is a lack of medical evidence to routinely recommend other radiologic modalities or supplemental radiologic screening with ultrasound, magnetic resonance imaging (MRI), or newer imaging technologies [72]. However, these technologies are useful as adjuncts to screening for certain higher-risk patients and as diagnostic, rather than screening, tools.

●Screening ultrasound is not recommended for average-risk women. Ultrasound has not been evaluated as a screening strategy to reduce breast cancer mortality in the average-risk population, including among women with dense breasts. However, in the United States, some states mandate that ultrasound be mentioned to patients as a potential adjunct to mammography in women with increased breast density. Ultrasonography is commonly used for diagnostic follow-up of an abnormality seen on screening mammography to clarify features of a potential lesion. (See "Breast density and screening for breast cancer", section on 'Whole-breast ultrasound screening' and "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Role of ultrasound'.)

●Screening MRI is not recommended for average-risk women, according to supplemental screening MRI guidelines from the ACS [73]. MRI performed in combination with mammography is used primarily to screen high-risk patients. (See "MRI of the breast and emerging technologies", section on 'Indications for breast MRI' and "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Role of ultrasound'.)

●Newer and emerging breast imaging techniques, potentially applicable in special situations, include digital breast tomosynthesis and molecular imaging [74,75]. These techniques are discussed in detail elsewhere. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Role of ultrasound'.)

Performance specifics of radiologic imaging techniques for breast cancer screening are discussed separately. (See "Screening for breast cancer: Evidence for effectiveness and harms" and "Breast imaging for cancer screening: Mammography and ultrasonography" and "MRI of the breast and emerging technologies".)

Role of clinical breast examination — We suggest not performing CBE as part of screening of average-risk women; however, CBE remains an important part of the evaluation for women with breast complaints or abnormalities. There is a lack of evidence showing any benefit of screening CBE alone or with screening mammography, a lack of data on whether CBE improves patient outcomes, and evidence suggesting an increase in false-positive rates. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Clinical breast examination'.)

Although there is expert consensus that CBE should not be the only screening method used, recommendations of major societies differ as to whether or not to include CBE as an adjunctive screening modality [6,7,41,44].

In locations where imaging modalities for breast cancer screening have limited availability, CBE may have a greater screening role. The World Health Organization (WHO) states that CBE may be an appropriate screening approach for women 50 to 69 years of age in low-resource settings with weak health systems [76,77].

Role of breast self-examination — We suggest that average-risk women not perform BSE. Several studies have shown lack of benefit and a higher rate of breast biopsy that shows benign disease with routine BSE. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Breast self-examination'.)

Women who nonetheless choose to perform BSE should receive careful instruction to differentiate normal tissue from suspicious lumps and understand that BSE is an adjunct, but not a substitute, for mammography. Women should be encouraged to bring abnormal breast findings promptly to the attention of their clinician.

Although many expert groups do not encourage BSE, many do encourage educating women about breast self-awareness, general breast health, and benefits and limitations of BSE, as well as advising women to seek medical attention soon if they note concerning breast abnormalities; [7,41,43,44,78]. The WHO recommends BSE as a way to empower women and raise awareness among women at risk, rather than as a screening method [58,79].

Frequency of screening with mammography — For average-risk women who wish to undergo screening, we suggest screening mammography every two years. Although data are limited and mixed on the optimal frequency for performing mammography, annual screening is associated with more harms and costs than screening every two years, and the difference in absolute benefits between annual and biennial screening is small. While some data suggest benefit for annual screening for some women (eg, premenopausal), this benefit needs to be weighed against the increased risk of false-positive mammogram findings and overdiagnosis.

Expert group recommendations for frequency of mammography screening vary between annual and every two years screening, depending mostly upon the patient’s age. Specific groups’ recommendations are summarized in the attached table (table 8).

Randomized trials have found that screening every two years achieves reduction in breast cancer mortality. In a systematic review for the US Preventive Services Task Force (USPSTF) 2016 update of breast cancer screening recommendations [7], observational studies found that the 10-year cumulative false-positive mammography rates and biopsy rates were more favorable with biennial screening (42 and 5 percent, respectively) than with annual screening (61 and 7 percent, respectively) [80].

Models also find that screening every two years achieves most of the benefit of screening annually without as many harms. A modeling study of screening mammography using United States data found that per 1000 women screened, biennial screening compared with no screening, for women aged 50 to 74 years, avoided seven breast cancer deaths, while annual screening for this age group had similar benefits but caused more harms [81]. Annual screening in women 40 to 74 years avoided 10 breast cancers but led to nearly 2000 more false-positive results and 11 more overdiagnoses per 1000 screened women.

The relative benefits of annual versus biennial screening may differ based on a woman’s hormonal status (eg, whether they are premenopausal or use menopausal hormone therapy); however, the evidence varies. A 2015 study from the Breast Cancer Surveillance Consortium, which sampled United States mammography registries, evaluated the effectiveness of varied frequencies of screening among women who were later diagnosed with breast cancer [81]. Among premenopausal women and postmenopausal women who used menopausal hormone therapy, biennial screening was associated with higher proportions of cancers that were less favorable (stage IIB or higher) compared with annual screening. However, in postmenopausal women who did not use menopausal hormone replacement therapy, tumor characteristics were similar for those screened annually or biennially. By contrast, an earlier (2013) Breast Cancer Surveillance Consortium study, using age to stratify women, found that hormonal status did not alter the relative benefit of mammography: screening biennially versus annually for women aged 50 to 74 did not increase the risk of tumors with advanced stage or large size, regardless of the women's breast density or hormone therapy use [82].

Breast density may also be associated with benefits that vary with different screening frequencies. As an example, in the same Breast Cancer Surveillance Consortium study, among women 50 to 74 years of age with scattered fibroglandular or fatty breasts, biennial or triennial mammography screening lowered false-positive results compared with annual screening [82]. However, for younger women with dense breasts, frequency of mammography screening did impact the risk of advanced-stage cancer, which was increased for women aged 40 to 49 years with dense breasts who had biennial, compared with annual, mammograms.

Intervals of more than two years between screenings might be appropriate in certain age groups. A 2016 modeling study suggests that annual screening for higher-risk women with high breast density may be indicated, and triennial screening may be the preferred approach for patients aged 50 years and older with average risk for breast cancer and low breast density [83]. Further confirmation is required before adopting this practice [7,84].

MODERATE RISK: SCREENINGFor women with moderate risk (ie, approximately 15 to 20 percent lifetime risk of breast cancer), including most women who have a family history of breast cancer in a first-degree relative but do not have a known genetic syndrome, we suggest that the same screening approach, including the age to begin mammography screening, and frequency of screening be used as for women at average risk. (See 'Average risk: Screening' above.)

While some have suggested that screening be initiated at an earlier age if a first-degree relative had premenopausal breast cancer, there are few high-quality data supporting this approach in the absence of a known genetic syndrome. As an example, in a case-control study of breast cancer screening among United States women aged 40 to 65 years, there was only a non-statistical trend towards greater protection in women at moderately increased compared with average breast cancer risk [85].

Many experts suggest that in women at moderate risk, the decision to undergo supplemental screening (with either magnetic resonance imaging [MRI] or ultrasound in addition to mammography) should be determined after a discussion with the patient regarding personal preferences for known risks versus possible benefits, availability, and insurance coverage. Supplemental screening ultrasound may be more widely accessible and less expensive than supplemental MRI; however, neither modality is routinely covered by insurance for this risk category in most states. We do not routinely suggest these adjunctive modalities for women at moderate risk, but if women are interested in them, we encourage them to enroll in a clinical trial evaluating their benefit.

Screening modalities for women who have dense breast tissue are discussed elsewhere. (See 'Dense breast tissue' below.)

Recommendations for MRI in women in certain risk subgroups are inconclusive. The American Cancer Society (ACS) advises that there is insufficient evidence to recommend for or against supplemental screening MRI as an adjunct to mammography in moderate-risk women (table 10) [73].

HIGH RISK: SCREENINGFor high-risk women (eg, those who have BRCA or other susceptibility genes, or a history of chest radiation, or a calculated lifetime risk of developing breast cancer of greater than 20 percent), it is important both to emphasize the importance of appropriate screening, generally with enhanced modalities and at an enhanced frequency (table 10), and to refer to a high-risk screening clinic to screen and to consider risk reduction treatment and intensification of surveillance. Specifics are discussed in detail separately. (See "Cancer risks and management of BRCA carriers without cancer", section on 'Management of female BRCA carriers without cancer' and "Overview of hereditary breast and ovarian cancer syndromes associated with genes other than BRCA".)

SPECIFIC CONSIDERATIONS

Dense breast tissue — Dense breasts are associated with an increased risk of breast cancer and can decrease the sensitivity of mammography for small lesions. Nevertheless, we do not alter our general approach to age- and risk-based screening based on breast density. However, for women with dense breasts, we do prefer digital mammography over film mammography, due to greater sensitivity; digital mammography is the modality typically used for mammography in most locations in the United States.

We suggest that most women with dense breasts and no additional risk factors for breast cancer not undergo supplemental screening with other imaging modalities given insufficient evidence demonstrating benefit [7,86]. Nevertheless, some women with dense breasts may reasonably opt to have supplemental screening. For average-risk women who choose to undergo supplemental screening, given its lower cost and availability of more data in this population, ultrasound is preferred over magnetic resonance imaging (MRI) (see "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Breast density'). In moderate-risk women with dense breasts, there are no consensus guidelines to recommend for or against supplemental screening ultrasound.

In the United States, many states have law requiring that patients be informed about their breast density, that dense breast tissue may be a risk factor for breast cancer, and that dense tissue may interfere with cancer detection. The clinician and patient should review the risks and potential benefits of supplemental screening, including the risk of a false-negative mammogram, the risk of a false-positive ultrasound finding leading to unnecessary breast biopsy, and the risk of overdiagnosis if breast cancer is detected. It is also useful for the patient to know there is no evidence that adding ultrasound to mammography in average-risk women reduces breast cancer mortality [87,88].

Considerations in screening for women with dense breast tissue are discussed in detail elsewhere. (See "Breast density and screening for breast cancer".)

Breast implants for benign reasons — Women who have had breast tissue augmentation with implants for benign reasons warrant routine screening mammography to evaluate the native breast tissue; indications and frequency for screening are the same as in women without implants. Mammography screening for breast cancer for women with breast implants includes additional views, because implants may interfere with mammographic visualization. This is discussed in detail elsewhere. (See "Implant-based breast reconstruction and augmentation", section on 'Breast cancer detection' and "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Patients with breast implants'.)

Breast reconstruction related to malignancy — The approach to women who have had mastectomy and reconstruction, either for breast cancer or for prophylaxis due to high risk, is discussed elsewhere. (See "Overview of breast reconstruction", section on 'Surveillance of the reconstructed breast'.)

Multiple comorbid illnesses — Women with multiple comorbid illnesses whose life expectancy is less than 10 years are not likely to benefit from screening, especially when these illnesses might contraindicate effective treatment for breast cancer, or when the comorbid illnesses are likely to substantially limit a patient's lifespan.

BENEFITS AND HARMS OF SCREENINGThere is more scientific evidence related to screening for breast cancer than for any other cancer. There are both substantial benefits and substantial risks of harm associated with screening (figure 4 and table 11). For that reason, a full discussion between the patient and the clinician about screening is very important. (See 'Shared medical decision-making' below.)

Benefits — The primary benefit of screening with mammography is a decrease in breast cancer mortality. In a 2015 systematic review and a 2012 meta-analysis that each included multiple randomized trials that involved over 600,000 women from several countries [89-96], screening mammography was estimated to reduce the odds of dying of breast cancer by approximately 20 percent (figure 3) [40,97]. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Mammography'.)

The absolute benefit of screening depends on the patient’s age and is lower in younger women because they have a lower baseline risk of cancer. A 2016 systematic review analyzed risk reduction by age: with at least 11 years of follow-up, the pooled relative risk for breast cancer mortality was 0.92 (95% CI 0.75-1.02) for women 39 to 49 years of age, 0.86 (0.68-0.97) for women 50 to 59 years of age, and 0.67 (0.54-0.83) for women 60 to 69 years of age [51]. Risk reduction by age is discussed in detail elsewhere. (See 'Age 40 to 49' above and 'Age 50 to 74' above and 'Age 75 and older' above.)

Confidence in the magnitude of the breast cancer mortality reduction based on these aggregated trial results is reduced for several reasons: the trials were performed in the setting of older cancer therapies, so the value of screening to find and treat lesions earlier may be reduced, due to the greater efficacy of currently available treatment; some trials did not blind outcome assessors, and thus results may have been biased in favor of screening; and most trials predated advances in breast imaging that would improve the sensitivity of screening. Nevertheless, observational studies continue to support a risk reduction in breast cancer mortality with mammography. These studies are discussed elsewhere. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Mammography'.)

Data are limited as to how much of the reduction in mortality seen over time is attributable to advances in imaging techniques for screening and how much is due to improved effectiveness of therapy. In one study of simulation models, about one-third of the decrease in breast cancer mortality in 2012 was attributable to screening, with the balance attributed to treatment [5]. The contribution of screening mammography to mortality reduction varied among different molecular subtypes of breast cancer.

Harms — "Harms" associated with breast cancer screening include the potential for overdiagnosis, false-positive findings, patient anxiety, and unnecessary treatment and its associated risks. The risk of harms is substantial (table 11) [98].

●Overdiagnosis – Overdiagnosis occurs when screening leads to identification of breast cancer that would not have caused clinical consequences in a woman's lifetime had it not been detected. Estimates for overdiagnosis in breast cancer range from 10 percent or less to over 50 percent of all women diagnosed with breast cancer. Variation in these estimates is likely related to differences in definition (eg, whether ductal carcinoma in situ [DCIS] is included and what age group is studied) and approaches used for study design, measurement, and estimation [99-101]. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Overdiagnosis' and "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Ductal carcinoma in situ'.)

Several studies have suggested that many cancers, especially those confined to the mammary ducts (ie, DCIS), are biologically insignificant and would never become clinically evident in the patient's lifetime [102-104]. It is not possible to distinguish biologically insignificant cancers from those that will proceed to grow, metastasize, and lead to the patient's death at this time. Thus, almost all patients with a diagnosis of breast cancer, regardless of its stage, receive some sort of local therapy (eg, surgery, with or without radiation therapy) and often systemic therapy as well. Thus, the overdiagnosis of what may be biologically insignificant cancers leads to substantial treatment that is potentially unnecessary.

●False-positive mammogram result – For each woman whose life is saved by mammography, many women will experience false-positive mammograms. The estimated risk of a false positive varies based on a number of factors, including the woman’s age and breast density (figure 5) [84]. Factors that increase the possibility of a false-positive mammogram include young age, increased breast density, family or personal history of breast cancer, prior breast biopsies, current estrogen use, three years between screenings, lack of comparison to prior mammograms, and an individual radiologist’s tendency to over-read [105-107]. In the United States, about 10 percent of screening mammography exams are false positives [108], and after a decade of annual screening about 50 percent of women have experienced a false positive. The false-positive rate is much lower in other countries [106,109]. Specifics about the incidence of false-positive mammograms and the associated anxiety are discussed elsewhere. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'False-positive tests' and "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Anxiety related to false-positive findings'.)

●Radiation – Although radiation can increase the risk of breast cancer, radiation from screening mammography is low enough that, for average-risk women over age 40, the benefits of screening outweigh the risks of radiation from mammography. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Radiation'.)

However, there is concern about an increased risk of radiation in women with BRCA1 or BRCA2 mutations, which is discussed separately. (See "Cancer risks and management of BRCA carriers without cancer", section on 'Cancer surveillance'.)

●Discomfort – Mammographic screening can be uncomfortable or painful. Techniques to reduce discomfort are discussed elsewhere. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Discomfort'.)

SHARED MEDICAL DECISION-MAKINGThe decision to perform mammography should be determined with shared decision-making, in which the clinician helps the patient to make an informed, values-based decision about whether to undergo screening [110,111]. Shared decision-making is an opportunity to indicate that the benefits and harms of breast cancer screening are more finely balanced than once believed [51,80]. (See 'Benefits and harms of screening' above.)

Counseling a patient — It is important to discuss the patient’s risk of developing breast cancer, the potential benefits and harms of screening, and the patient’s values [112,113]. Graphics and tables that quantitate benefits and harms can be useful in such discussions (figure 4 and table 11).

Discussion points to help a patient with decision making can include:

●The vast majority of women are at average risk of breast cancer. Furthermore, the risk of a woman being diagnosed with breast cancer is lower than most women realize.

●There is potential inaccuracy when estimating an individual’s risk of developing breast cancer, due to the relatively low sensitivity and specificity of the breast cancer risk stratification tools at the individual level. These tools work best for estimating risk of breast cancer for a group of women with similar clinical attributes.

●The likelihood is that a patient, even if she is in a high-risk group, will not develop breast cancer, especially over a five-year period, unless she is one of the relatively few women with known deleterious BRCA mutations.

●A patient may, by choosing to be screened, avert death from breast cancer or gain quality-adjusted life-years (QALY).

●Screening may result in overdiagnosis, which means finding an abnormality that results in further testing and treatment, although had it not been found it would not have caused harm to the patient.

●Screening may produce a false-positive result, for which the sequelae can include further testing and anxiety.

●A patient may experience anxiety about the evaluation, diagnosis, and treatment.

Although women may feel well informed by shared decision-making discussions with clinicians, there may be important components the patient did not learn of during the conversation. For example, in a nationwide survey, women reported feeling informed by their clinician before undergoing breast cancer screening. However, while 96 percent said they were told of the benefits of screening, most women reported that their provider did not ask them about their screening preferences, and only 20 percent said their provider discussed the potential harms of screening [114].

Decision aids — Decision aids (eg, leaflets, booklets, videos, and websites) can encourage patients to interpret evidence in the context of their personal goals and concerns. The effect of using decision aids on the length of an office visit varies, ranging from shortening, to no change, to lengthening the visit.

Decision aids have been noted to reduce the number of patients choosing cancer screening [115]. In an Australian randomized trial of breast cancer screening decision aids for women 48 to 50 years of age, compared with control women whose decision aids did not include information on overdiagnosis, more women who were informed about overdiagnosis met the threshold for adequate overall knowledge, and fewer expressed positive attitudes toward screening or intent to be screened in the future [116]. The breast cancer screening decision aid used in this trial is based on data from Australia; rates of false-positive mammograms are higher in the United States.

FOLLOW-UP OF ABNORMAL MAMMOGRAPHY RESULTSThe evaluation of abnormalities detected by screening is discussed separately. (See "Diagnostic evaluation of women with suspected breast cancer" and "Clinical manifestations, differential diagnosis, and clinical evaluation of a palpable breast mass", section on 'Clinical evaluation' and "Breast biopsy" and "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Abnormalities on mammography'.)

SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Screening for breast cancer".)

INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Breast cancer screening (The Basics)")

●Beyond the Basics topic (see "Patient education: Breast cancer screening (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Screening is of greatest value for those patients most likely to develop breast cancer and for whom early treatment is more effective than later treatment in reducing mortality. Thus, screening strategies differ based on the estimated risk of breast cancer. (See 'Risk determination' above.)

●The vast majority of women are at average risk (less than 15 percent lifetime risk) of developing breast cancer. Even women who have some risk factors for breast cancer are still likely to be at average risk, although a risk assessment tool such as the Gail model, or models developed for patients with a strong family history, can be helpful to estimate risk and inform the need for additional testing. Women who have a personal history of breast, ovarian, peritoneal, or fallopian tube cancer, certain genetic mutations (eg, BRCA1 or BRCA2), or a history of previous radiotherapy to the chest between ages 10 and 30 are at high risk for developing breast cancer. (See 'Initial assessment of risk' above and 'Clinical use of risk prediction models' above and "Overview of hereditary breast and ovarian cancer syndromes associated with genes other than BRCA", section on 'High-penetrance genes for breast and/or ovarian cancer'.)

●Average-risk women have less than a 15 percent lifetime risk of developing breast cancer. The majority of women are at average risk. In these women, age is the most important factor in deciding when to be screened, because breast cancer incidence rises with age. (See 'Average risk: Screening' above.)

•For women under age 40, screening is not warranted since the incidence of breast cancer is low and the performance characteristics of mammography are poor. (See 'Age under 40' above.)

•For women age 40 to 49, we raise the topic of screening and individualize the decision based on patient preferences and values. A woman may opt for screening if she has substantial concerns about breast cancer risk and accepts the possibility of a false-positive result or overdiagnosis and the resulting evaluation and treatment. Another woman may find that the frequency of false positives and overdiagnosis provides a compelling reason to defer screening. Although screening in the 40s appears favorable when considering the number of years of life potentially saved, for an average-risk woman, the number of breast cancer deaths prevented is relatively low. (See 'Age 40 to 49' above and 'Frequency of screening with mammography' above.)

•For women age 50 to 74, wesuggest screening (Grade 2B). (See 'Age 50 to 74' above and 'Frequency of screening with mammography' above.)

•For women age 75 and older, we suggest screening only if their life expectancy is at least 10 years (Grade 2C). (See 'Age 75 and older' above and 'Frequency of screening with mammography' above.)

•For average-risk women who decide to be screened, we recommend screening with mammography rather than other modalities (Grade 1B). While ultrasound and magnetic resonance imaging (MRI) are useful for diagnostic evaluation of abnormal findings noted on screening mammography, we do not use these modalities to screen average-risk women. We suggest a mammography screening interval of every two years (Grade 2C). More frequent screening is not likely to improve detection rates and is associated with a higher rate of false positives. (See 'Other imaging modalities' above and 'Frequency of screening with mammography' above.)

•We suggest not using clinical breast examination (CBE) (Grade 2C) or breast self-examination (BSE) (Grade 2B) as part of screening of average-risk women. Women should be educated about breast health awareness. (See 'Role of clinical breast examination' above and 'Role of breast self-examination' above.)

●Moderate-risk womeninclude most women with breast cancer in a first-degree relative but without a known genetic syndrome. For women with moderate risk, we suggest the same screening approach as for average-risk women (Grade 2C). Some practitioners screen earlier if the first-degree relative had premenopausal breast cancer, although there are no data showing a mortality benefit for these women. For women who wish supplemental screening with ultrasound or MRI, for which data are inconclusive, we encourage enrollment in a clinical trial. (See 'Moderate risk: Screening' above and 'Average risk: Screening' above.)

●High-risk women warrant referral to a high-risk screening clinic for evaluation and possible intensified surveillance and consideration of genetic testing and risk reduction treatment (eg, chemoprevention and prophylactic surgery). High-risk women include those who have a personal history of ovarian, peritoneal, tubal, or breast cancer; a family history of ovarian, peritoneal, or tubal cancer or a strong family history of breast cancer; an ancestry (eg, Ashkenazi Jewish) associated with BRCA1 or 2 mutations; a genetic predisposition (eg, known BRCA or other susceptibility genes); prior radiotherapy to the chest; or other breast cancer risk factors, resulting in a calculated lifetime risk of developing breast cancer of greater than 20 percent. (See "Cancer risks and management of BRCA carriers without cancer".)

●Dense breast tissue is associated with an increased risk of breast cancer and can decrease the sensitivity of mammography. Nevertheless, we do not alter our general approach to age- and risk-based screening based on breast density. (See "Breast density and screening for breast cancer".)

●Shared decision-making should be used in discussing screening. Decision aids can be helpful when discussing the patient’s risk of developing breast cancer, the potential benefits and harms of screening, and the patient’s values. (See 'Benefits and harms of screening' above and 'Shared medical decision-making' above.)

•The benefit of screening with mammography is a decrease in breast cancer mortality. However, the absolute benefit is lower in younger women who have a lower baseline risk of cancer, and data are limited as to the benefit of screening using contemporary imaging techniques in the setting of effective modern therapy.

•Harms associated with breast cancer screening include the potential for overdiagnosis, false-positive findings, patient anxiety, and unnecessary treatment and its associated risks.

ACKNOWLEDGMENTThe editorial staff at UpToDate would like to acknowledge Suzanne W Fletcher, MD, who contributed to an earlier version of this topic review.