Tips for Addressing Screening Concerns: “Harms of Screening”

Abstract

Early detection decreases deaths from breast cancer. Yet, there are conflicting recommendations about screening mammography by major professional medical organizations, including the age and frequency with which women should be screened. The controversy over breast cancer screening is centered on 3 main points: the impact on mortality, overdiagnosis, and false positive results. Some studies claim that adverse psychological effects such as anxiety or distress are caused by screening mammography. The purpose of this article is to address negative breast cancer screening concerns including overdiagnosis and overtreatment, effect on mortality, false positive results, mammography-related anxiety, and fear of radiation.

Introduction

Although early detection by screening mammography decreases deaths from breast cancer,^1–5 there are conflicting recommendations about screening mammography by major professional medical organizations (Table 1). Mammography screening starting at age 40 provides the greatest mortality reduction, as shown by multiple randomized controlled trials.⁵ More recently, a publication assessing Cancer Intervention and Surveillance Modeling Network estimates of screening outcomes from 2009, 2016, and 2023 verified that annual screening between ages 40 and 79 offered the greatest reduction in breast cancer deaths (41.7%) and that screening annually between ages 40 and 74 provided a greater mortality reduction compared to biennial screening (37% vs 30%).⁶ Despite the fact that annual screening results in more screen-detected, smaller tumors with fewer interval cancers than longer screening intervals,³ there is persistent disagreement regarding the age and frequency with which individuals should be screened for breast cancer, including concerns related to overdiagnosis and overtreatment, screening mammography–related anxiety, and fear of radiation.

Overdiagnosis and overtreatment

Overdiagnosis

The usefulness of screening has been questioned due to the perceived negative effects of overdiagnosis and the claim that there is no significant impact on mortality.^7,8 Overdiagnosis could result in treatment (overtreatment) that may lead to psychological or physical morbidity. Because older people are more likely to have comorbidities, the risk of overdiagnosis is higher for this age group. Overdiagnosis of breast cancer has mainly been cited for in situ disease because there are no data reporting overdiagnosis of invasive cancer. Neal et al divide overdiagnosis into 2 types.⁹ The first (obligate overdiagnosis) is the discovery of a cancer that will not be responsible for the death of the individual and that would not have been diagnosed during the individual’s lifetime without screening. This definition takes into consideration the negative (personal, familial, or social) effects of the diagnosis and treatment of a cancer.^7–10 The second (nonobligate overdiagnosis) is defined as a breast cancer that is extremely indolent (nonobligate progression) or may even regress.⁹ However, breast cancer regression is extremely unlikely. In a survey of the fellows of the Society of Breast Imaging published by Arleo et al,¹¹ 25 281 invasive cancers and 9360 cases of in situ disease were diagnosed after reviewing a total of 6.8 million screening examinations over a 10-year period. The authors identified 479 untreated patients; zero spontaneously resolved or regressed on follow-up.¹¹

Currently, there is no method to determine which individual case of breast cancer is a result of overdiagnosis, and the rate of overdiagnosis can only be estimated at a population level. Work done to quantify overdiagnosis of breast cancer exists, but the estimates vary widely, leading to debate over the reported rates.^12–15 For example, in 2012, Bleyer and Welch reported an overdiagnosis rate of 31%.¹³ However, there were several incorrect key assumptions made in this article. First, they used data for people under 40 years of age for the number of expected breast cancers. This is flawed because the vast majority of breast cancers are found in those over the age of 40. Second, the authors predicted that the annual increase in breast cancer was only 0.25% when breast cancer incidence is increasing at a rate of 1% to 2% per year.¹⁵ Third, the authors combined in situ disease and invasive cancers in their calculations.¹⁶ According to a study by Zakrisson et al, the rate of overdiagnosis of breast cancer 15 years after the end of the Malmo trial was 10%.¹⁷

Puliti et al conducted a literature review of research articles (13 primary studies in 7 European countries) giving defined estimates of breast cancer overdiagnosis in 2012.¹⁸ The authors reported that overdiagnosis can correctly be estimated by comparing the incidence in screened and unscreened populations if both groups have similar breast cancer risks.¹⁸ Another important consideration of estimating overdiagnosis is taking account of lead time (the duration of time between the detection of disease by screening and its usual clinical presentation) to extract overdiagnosed from early-diagnosed cases.¹⁸ If the lead time exceeds an individual’s remaining years of life, this would be considered overdiagnosis. Cases whose lead time does not exceed the future lifetime of the patient will cause an increase in incidence to be observed but should not be included in the estimation of overdiagnosis. When adjusted for breast cancer risk and corrected for lead time, the most reasonable estimate for overdiagnosis ranges from 1% to 10%. The authors concluded that the higher published overdiagnosis estimates are likely due to the lack of adjustment for breast cancer risk and/or lead time.¹⁸

Overtreatment

Overtreatment is the use of the same treatment strategies for patients with early-stage and favorable disease as for those with biologically aggressive disease. For instance, some low-grade in situ disease will not lead to mortality because this entity may remain noninvasive for several decades. Standard breast cancer treatment for these patients may be considered overtreatment because such therapies may expose them to negative side effects from radiation therapy. Offering operations for this subset of patients may result in possible complications without a clear long-term benefit. Patient-reported outcomes have emphasized the morbidity of common breast cancer treatments. As the cost of breast cancer care has continued to increase, reduction in the overtreatment of breast cancer is becoming more important.¹⁹

Strategies to decrease overtreatment of ductal carcinoma in situ (DCIS) depend on the ability to identify subsets of patients with DCIS with a low risk of progression to invasive carcinoma. Currently, it is not possible to distinguish indolent cancers from progressive cancers. Of note, Duffy et al analyzed data for >5 million screening mammograms and found a significant negative association of the screen-detected in situ cancers with the rate of interval invasive cancers, concluding that treating in situ disease would help prevent future invasive disease.²⁰ As our knowledge of breast cancer genetics and targeted therapies improves, it may be possible to identify nonprogressive indolent cancers allowing for limited or no treatment. There are currently ongoing randomized controlled trials and a single-arm prospective trial investigating the safety of active surveillance in patients with low-risk DCIS.²¹ In the meantime, we should continue mammography screening to reduce mortality through early detection.

Anxiety and fear

Adverse psychological effects have been attributed to screening mammography, and therefore, anxiety has been described as a harm of breast cancer screening.²² To better understand the psychological effects of screening mammography, it is important to identify exactly what elements of the mammography screening process evoke fear, anxiety, and worry in women. The underlying etiologies of mammography anxiety vary among women, and often, different etiologies overlap. However, the reasons can be divided into several broad categories: fear of breast cancer, anxiety related to a false positive result, anxiety related to pain/discomfort of the mammography examination, and fear of radiation.^23,24 These fears may have diverse effects on screening behavior.

Anxiety related to false positive examination results

With an accepted recall rate from screening mammography of ~10% and an accepted positive predictive value (PPV) of cancer from screening of only ~5%, a number of women who undergo routine screening mammography will require additional work-up to rule out breast cancer.²⁵ In 2016, the breast cancer screening guidelines from the United States Preventive Services Task Force (USPSTF) stated that “false-positive results are common and lead to unnecessary and sometimes invasive follow-up testing, with the potential for psychological harms (such as anxiety).”²⁶

Many studies examining the severity, duration, and consequences of false positive results show few long-term negative effects. Tosteson et al measured the effect of false positive mammograms on quality of life by assessing personal anxiety, health utility, and attitudes toward future screening. The authors concluded that false positive mammogram results were associated with increased short-term anxiety, but not long-term anxiety, and that there was no measurable decrease in health utility.²⁷ In fact, the false positive mammogram result increased women’s intention to undergo future breast cancer screening. Ekeberg et al also showed that recall after mammography was associated with only transiently increased levels of anxiety and depression in women without cancer.²⁸ Similarly, Lampic et al reported that 46% of the women in their study experienced borderline or clinically significant anxiety before a mammography recall visit. However, a few days after the visit, anxiety and depression had decreased significantly in women informed about normal or benign results, suggesting that false positive results do not result in long-term anxiety or depression for a majority of women.²⁹ Bredal et al also found that recall after mammography was associated with only a transient increase in anxiety, and 4 weeks after screening, the level of anxiety was the same and depression was lower compared with the general population.³⁰ In this study, nearly all women felt they would attend the next screening.

Conversely, a separate study found that anxiety can persist up to 3 years after the false positive result, although this was greatest for those patients who had undergone biopsy or were followed with a probably benign result.³¹ In this study, the number of women not attending their next routine screening examination was significantly greater for women who received a false positive screening examination (15%) compared to those who received a clear result after screening mammography (8%).³¹ Bolejko et al similarly showed that psychological effects of a false positive mammogram can persist at 1 year, with early recall (probably benign examination results) and dissatisfaction regarding the information received at the time of recall increasing the likelihood of these adverse psychological effects.³²

Interestingly, the studies that showed long-term psychological consequences of false positive examinations measured “breast cancer–specific anxiety.” However, studies measuring general anxiety failed to show long-term psychological consequences of false positive result recalls.²³ The studies evaluating “breast cancer–specific anxiety” used surveys to assess anxiety with questions specifically asking about thoughts or feelings as they related to breast cancer. In addition, a survey of U.S. women’s attitudes toward false positive mammography results found that women largely view false positive test results as an acceptable consequence of screening.³³ Supporting this idea is a study by Ganott et al that found a substantial fraction of women preferred the inconvenience and anxiety associated with a higher recall rate if it resulted in the possibility of detecting breast cancer earlier.³⁴

Anxiety related to fear of breast cancer

Generalized “cancer fear” is defined as anxiety related to cancer, including causes or consequences of cancer such as fear of treatment.³⁵ Women with fear of breast cancer can actually be self-motivated to undergo breast cancer screening because a negative result will reassure them that they do not have cancer, whereas a positive result will promote early detection and treatment.²³ For example, McCaul et al showed that greater concern about breast cancer was related to a higher likelihood that women would choose to have a screening mammogram.³⁶ A meta-analysis by Hay et al demonstrated that breast cancer worries had a small but reliable association with breast cancer screening participation, with greater worry predicting a greater likelihood of screening.³⁷

Fear of mammography pain/discomfort

Pain during the examination has been listed as a barrier to screening mammography for women.³⁸ The percentage of women who experience pain during mammography varies greatly, ranging from 1% to 77% in several systematic reviews.^22,38,39 Although many women experience some pain during mammography, pain intensity is usually minimal to moderate. In 1 study, 96% of women reported that the pain associated with mammography screening was “less than” or “about as expected.”³⁸ What is important is whether the pain affects screening behavior. Although many women have pain, few consider it to be a deterrent to future screening.²² One study showed that most women (94%) would still re-attend mammography screening despite mammography-associated pain.³⁸ However, of the women who do not re-attend mammography screening, a systematic review found that 25% to 46% cited pain as the reason why.⁴⁰ Some mitigation methods to help reduce pain perceived by the patient have been proposed, including giving women information about the procedure before the mammogram, increasing women’s control over compression, and use of breast cushions.⁴¹ Technologists can also play a pivotal role in managing a patient’s fear of pain. Proper communication of examination expectations by technologists has been shown to affect patient perception of discomfort during a mammogram.^41,42 The inclusion of strategies to reduce anxiety before screening could also improve rates of mammography reattendance.⁴³

Fear of radiation

The concept of “radiation” can elicit fear and anxiety in patients who worry about the amount of radiation they are exposed to and the effects of this exposure. This fear can affect how physicians make use of imaging modalities or therapeutic procedures while further influencing patients’ decisions to follow through with recommendations for mammography.^44,45 Previous studies have shown that misconceptions about the radiation risks associated with mammograms exist even though many patients have had the risks and benefits of mammography explained to them.⁴⁶ Misinformation and misunderstanding regarding the risks associated with ionizing radiation have created heightened public concern and fear, which may result in avoidance of diagnostic procedures.⁴⁶ Aro et al showed that fear of radiation exposure was the reason for nonattendance in 11% of women surveyed.⁴⁷ In a study by Hollada et al,⁴⁶ although 65% of the women receiving a mammogram responded that they had been informed of the risks and benefits of the examination, 60% overestimated the amount of radiation associated with a mammogram. Given that the risk of radiation-induced breast cancer from mammography is infinitesimally low, education is needed to alleviate this misconception.^48,49 It has been suggested that any estimates of cancers thought to be caused by medical imaging be conveyed with a cautionary statement that such estimates are “highly speculative” and should also only be presented with simultaneous estimates of the reductions in morbidity and mortality from the use of these imaging procedures.⁵⁰

The radiation dose and associated risk delivered to each woman for a single mammography examination is dependent upon age, breast density, and breast thickness. The representative mean calculated average glandular doses are 1.74 and 2.10 mGy for digital mammography and digital breast tomosynthesis, respectively,^51–57 average glandular doses that are well below the Food and Drug Administration limit of 3 mGy. Although the dose absorbed by the breast and adjacent organs during mammography is a small component of the lifetime accumulated dose from medical imaging and other sources, the popular press tends to emphasize the radiation risk of mammography, particularly screening mammography.⁴⁸ Chetlen et al measured the scatter radiation overlying the thyroid gland, salivary gland, lens of the eye, sternum, and uterus during a routine screening digital mammographic examination in a representative patient population.⁵⁸ Scatter radiation dose at the skin overlying organs of interest is a small fraction of the entrance skin dose to the breast.⁵⁸ Effective doses from mammography fall below the lower limit of empiric data used to make risk estimates. Consequently, debate continues over whether the risks are actually lower than predicted from the classic linear, nonthreshold model. Even if the risk coefficients are accurate, the probability is extremely low that we could ever detect radiation-attributable breast cancers considering the background level of such cancers.⁵⁸

When should we stop screening?

Recommendations regarding when to stop screening mammography are affected by concerns for overdiagnosis and other perceived harms. Should older individuals undergo screening mammography when other health issues may be more critical? Do the benefits of diagnosis outweigh the risks (including the risks of subsequent treatment options)? In older patients, does screening mammography find tumors that are clinically important or is there significant overdiagnosis in this age group? Are there risks associated with radiation exposure from extended screening?

Similar to the variable recommendations regarding the age to start screening and the frequency of screening, there are differences in the recommendations regarding when screening should stop. The American Society of Breast Surgeons supports screening mammography until life expectancy is <10 years,⁵⁹ whereas the USPSTF recommends screening until age 74, citing insufficient evidence to evaluate the harms and the benefits of screening in women beyond 74 years.⁶⁰ Because previous randomized controlled trials did not include older women, these recommendations have been based on studies evaluating the utility of screening mammography in older patients through predictions based upon literature review, modeling, or observational studies.^61–65

Malmgren et al⁶⁶ sought to evaluate the clinical benefit of screening mammography in older patients by prospectively examining a cohort of patients diagnosed with breast cancer aged 75 and above (11% of their overall breast cancer registry), assessing stage, treatment modalities utilized, outcomes, and method of detection. Their cancers were diagnosed with mammography in 64% and on physical examination in 36%. During the study period, an increasing percentage of women were diagnosed with breast cancer on mammography vs palpation, which was associated with an overall decrease in stage 2 and stage 3 cancer diagnoses and an increase in DCIS, whereas rates of stage 4 and stage 1 cancer did not change significantly. Those diagnosed with mammographically detected stage 1 to 3 disease were more likely to undergo lumpectomy, more likely to undergo operation with radiation, and less likely to receive adjuvant chemotherapy. Relapse-free survival was improved for mammographically detected tumors compared with those detected on physical examination (5-year relapse-free survival of 96% vs 87%), leading to improved mortality for stage 1 to 3 disease when adjusting for operation, radiation therapy, use of hormone treatment, and chemotherapy and when adjusting only for age.

The overall performance metrics of screening mammography in the older population was examined by Sinclair et al through retrospective review of data from the 1996-2006 Vermont Breast Cancer Surveillance System, calculating sensitivity, specificity, PPVs, cancer detection rates (CDRs), and negative predictive values (NPVs) by decade for women ages 50 to 101 using logistic regression analysis.⁶⁷ Their study included 96 193 women aged 50 to 101 with 6782 positive majority film-screen mammographic studies leading to a cancer diagnosis in 1932 women (including 1402 invasive cancers, 496 with in situ cancer, and 34 with unknown tumor type). Overall, the CDR increased with age and was not affected by breast density, body mass index (BMI), or family history of breast/ovarian cancer, whereas NPVs decreased slightly with increasing age. Older age was associated with higher specificity and sensitivity, higher PPV, and higher CDR independent of breast density or BMI.

Several studies have shown that screening in older patients finds smaller, lower-stage tumors, particularly in those who undergo regular screening.^67–69 In addition, because most of the tumors found in those studies were invasive cancers (not DCIS), “overdiagnosis” is felt to be a less significant issue.^67,69 Hartman et al retrospectively reviewed screening mammograms (performed 2007-2013) in women 75 or older, diagnosing 26 breast cancers after 64 biopsies (PPV₂ 40.6%). The CDR was 5.9/1000 screens, and 85% of the cancers were invasive (not DCIS), including 88% stage 0 or 1 cancers, majority (19/25) intermediate to high grade.⁷⁰ In 2019, Destounis published a retrospective review of outpatient community screening mammography in women 75 years and older.⁷¹ The vast majority of malignancies diagnosed presented as mass with or without calcifications (73%), were invasive tumors (82%), exhibited mainly luminal A molecular subtype characteristics (64.7%), and were node negative (92.5%). Roughly 63% were grade 2 or 3. Nearly all patients (98%) pursued treatment (mainly lumpectomy). Overall, the strong performance characteristics of screening mammography in older women support that screening can benefit this population, particularly as life expectancy continues to increase, without significant risk of overdiagnosis.

Lee et al⁷² emphasized that, because life expectancy for older women has been increasing, modeling studies would overestimate harms and underestimate the benefits. When the authors used data from the National Research Council on radiation effects, they found that the lifetime risk of cancer resulting from mammographic screening was extremely low and actually decreased with increasing age. The authors concluded that recommendations for screening mammography in older women should be individualized according to a patient’s overall health and the presence of risk factors and comorbidities.

Conclusion

The controversy over breast cancer screening is centered on the impact on mortality, overdiagnosis, false positive results, and adverse psychological effects. Currently, it is not possible to distinguish indolent cancers from progressive cancers. As our knowledge of breast cancer genetics and targeted therapies improves, it may be possible to identify nonprogressive indolent cancers allowing for little or no treatment. Further research is needed to reduce “overtreatment.” Many studies examining the severity, duration, and consequences of false positive results show few long-term negative effects. Fears of radiation exposure during screening mammography should be addressed with reassurances of the small amount of radiation as compared with natural background radiation, as well as the knowledge that screening mammography is known to reduce morbidity and mortality from breast cancer. Finally, because life expectancy for older women has been increasing, the recommendations for screening in older individuals should be personalized to a patient’s overall health and the presence of risk factors and comorbidities.

Funding

None declared.

Conflict of interest statement

S.V. disclosed her husband works for AstraZeneca and holds stock, but there is no conflict related to this paper. The other authors had no disclosures to declare.

Author contributions

Angela Choe (Writing – original draft, Writing – review & editing), Emel Kaya Aumann (Writing – original draft, Writing – review & editing), Claudia Kasales (Writing – original draft, Writing – review & editing), Alison Chetlen (Writing – original draft, Writing – review & editing), and Rebecca Sivarajah (Writing – original draft, Writing – review & editing)

References