Limitations of current technologies - breast cancer detection
Andrey Nailor, M.D.·Published 26 April 2011·10 min read
Key points
Despite its demonstrated ability to detect breast cancer early and reduce disease-specific mortality rates to some degree, mammography has inherent limitations and risks like any cancer screening technology (including physical examination).
One limitation with the current technology for mammography is the high rate of false-positive results, which are abnormal findings in patients who are subsequently found to be free of breast cancer.
No screening or diagnostic technology is perfect, and thus, some false-negative results are inevitable.
The risk of breast cancer increases with age throughout a woman's lifetime, and the sensitivity and positive predictive value of screening mammography also improve as women age (Kerlikowske et al., 1993; Mushlin et al., 1998) (Table 1-4).
Despite its demonstrated ability to detect breast cancer early and reduce disease-specific mortality rates to some degree, mammography has inherent limitations and risks like any cancer screening technology (including physical examination). Because the sensitivity and specificity are not 100 percent, screening programs will necessarily produce some false findings, both false-positive and false-negative findings, which can have detrimental effects on the screened population. Furthermore, identification of breast cancer by screening mammography does not guarantee that a woman will not die of breast cancer. Even small tumors may develop the ability to metastasize, and in these cases, early detection and treatment will not necessarily produce a cure. Some cancers will also rapidly develop during the period between screenings (termed interval cancers), and such aggressive tumors may not be amenable to treatment.
False-Positive Results
One limitation with the current technology for mammography is the high rate of false-positive results, which are abnormal findings in patients who are subsequently found to be free of breast cancer. To avoid large numbers of false-positive results, the specificity of a test must reach 99 percent or more, but most screening tests for cancer have much lower specificities. For published reports on mammography, specificities generally fall in the range of 90 to 98 percent (Mushlin et al., 1998). The risk of having a false-positive result by mammography during routine yearly screening may be as high as 10 percent (Brown et al., 1995). One study suggests that among women who receive annual mammograms for 10 years, half will have at least one false-positive result that leads to additional tests such as diagnostic mammography, ultrasound, or biopsy (Christiansen et al., 2000; Elmore et al., 1998a). Currently, as many as three-fourths of all biopsy specimens turn out to be benign lesions. As acceptance and use of mammographic screening become more widespread, the increasing number of false-positive results becomes a cause for concern.
Short-term studies have shown that abnormal mammograms negatively affect a woman's psychological and emotional state (Lowe et al., 1999). Even when further evaluation rules out cancer, some women report impaired moods and daily functioning for up to 3 months after a suspicious finding on a mammogram (Lerman et al., 1991). A study in Norway examined perceptions of quality of life 18 months following a false-positive mammogram. Most women in that study regard their experience with a false-positive mammogram as one of the many minor stressful life incidences, with only a temporary decrease in quality of life (Gram et al., 1990). However, women with false-positive mammograms also experience heightened levels of concern about breast cancer (Lowe et al., 1999; Gram et al., 1990). Previously, it was commonly believed that fear could prevent women from returning for a second screening following a false-positive result. However, a recent study showed that women with false-positive mammograms, especially those who had no previous mammograms, were actually more likely to come in for their next scheduled visit (Burman et al., 1999; Pisano et al., 1998a).
Written and revised by
Andrey Nailor, M.D.
Our doctors write and review articles for accuracy and keep them up to date.
health.am provides general information, not medical advice. Always consult a qualified health professional about your own health.
The medical procedures that are necessary after a suspicious mammogram have additional consequences, both physical and financial. Follow-up work to an initial screening test can include diagnostic mammograms, ultrasound examinations, and needle or surgical biopsies. Pain and reduced sexual sensitivity due to surgical biopsy are possible side effects (Gram et al., 1990). Lost productivity as a result of time off for surgery and recuperation is an additional cost. Retrospective studies show that the additional costs of evaluating false-positive results can add up to one-third of the total cost of screening for all women (Elmore et al., 1998a; Lidbrink et al., 1996). Furthermore, scarring of the tissue following surgical biopsy may result in cosmetic concerns and could potentially interfere with subsequent cancer detection. However, improvements in biopsy techniques have led to smaller and less invasive procedures and have thus reduced some of these concerns.
False-Negative Results
No screening or diagnostic technology is perfect, and thus, some false-negative results are inevitable. A normal mammogram does not guarantee that a woman is free of breast cancer because some tumors are not detected by mammography. The sensitivity of screening mammography (ability to detect occult cancer) ranges from 83 to 95 percent in published studies (Mushlin et al., 1998). Failure to detect breast cancer can generally be attributed to one of four main reasons: inherent limitations of mammography, inadequate radiographic technique, subtle or unusual lesion characteristics, and errors of interpretation. A number of studies have shown that a significant portion of breast cancers detected at follow-up mammography are visible in retrospect on the previous mammogram that was interpreted as normal (Harvey et al., 1993; van Dijck et al., 1993; Warren Burhenne et al., 2000). Regardless of the cause, a false-negative finding on a mammogram can be quite harmful to the woman whose cancer has been missed. Normal findings on a mammogram may produce a false sense of security that could prevent women from seeking appropriate medical attention, even for symptomatic lesions. A delay in diagnosis will delay treatment, perhaps in some cases to the point where treatment will no longer be effective because the tumor has had sufficient time to progress and metastasize. Because of these potential dire consequences associated with false-negative findings, the number of medical malpractice lawsuits stemming from missed cancer diagnoses has increased considerably since screening programs were widely introduced.
In fact, a recent report suggests that lawsuits alleging a missed or delayed breast cancer diagnosis are now the most prevalent of all medical malpractice suits filed against radiologists and physicians in general (Berlin, 1999; Physicians Insurers Association of America, 1995, 1997).
{pagebreak}
Lack of Data for Older Women
The risk of breast cancer increases with age throughout a woman's lifetime, and the sensitivity and positive predictive value of screening mammography also improve as women age (Kerlikowske et al., 1993; Mushlin et al., 1998) (Table 1-4). However, few data are available on the benefits of screening mammography in women age 70 and older, and thus, uniform recommendations do not exist for women in this age group.
The efficacy of mammography in older women is unknown because only two randomized controlled trials included women over age 65, and the numbers were too small too provide meaningful results (Table 1-2). Furthermore, screening of some older women may be less beneficial and cost-effective because of their shortened life expectancies compared with those for women in younger age groups.
TABLE 1-4The Probability of Developing Breast Cancer is Age Dependent
SOURCE: National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program, Publication 97-3536, 1997.
When a woman has serious comorbid conditions that are life limiting and would deter intervention if a tumor were discovered, screening mammography would not be helpful and is generally not recommended. However, because of the lack of data, it is difficult to determine who is likely to benefit from screening, and thus, the decision is often made on an individual basis. Recently, a retrospective cohort study among women ages 66 to 79 years suggested that some women in this age group might benefit from the continuation of screening mammography.
TABLE 1-2 Results of Randomized Clinical Trials of Screening Mammography
Results indicated an increased probability for detecting localized breast cancer in conjunction with a significantly reduced risk for detecting metastatic breast cancer among screened women (Smith-Bindman et al., 2000). A case-control study from Holland found that regular screening mammography for women ages 65 to 75 was associated with a 55 percent reduction in mortality from breast cancer, although there was no reduction in breast cancer mortality associated with screening of women over age 75 (Van Dijck et al., 1996). Another recent study suggests that for women over age 70, screening mammography may be most beneficial and cost-effective for individuals with higher bone mineral density, a characteristic associated with a higher risk for breast cancer (Kerlikowske et al., 1999).
Challenges in Younger Women
Breast cancer screening for women under age 50 remains controversial (Lerner, 2001). Some studies have reported a survival benefit of mammography, and many organizations advocate regular screening in this age group, but questions have been raised as to whether the benefits outweigh the risks and costs of screening younger women (Table 1-5).
TABLE 1-5Results of Randomized Controlled Trials for Women Ages 40 to 49 years
NOTE: RR, relative risk; CI, confidence interval. aInitial randomization was 1978; additional women ages 45-49 years were randomized starting in 1982. SOURCE: adapted from Kerlikowske (1997).
As a result of the controversy, some effort has been made to develop guidelines based on risk to help women make individual decisions about when to begin screening (Gail and Rimer, 1998). It was beyond the charge of the present committee to revisit the issue of whether women under age 50 should undergo routine screening mammography, so the discussion in this report will simply review some of the issues behind the controversy, with an emphasis on how technology development may overcome some of the difficulties associated with the screening of women in this age group.
Statistical analysis of pooled data from seven randomized clinical trials indicated that screening mammography reduced breast cancer mortality by about 16 to 18 percent in women under age 50 (Berry, 1998; Kerlikowske 1997; National Institutes of Health, 1997). However, the lag time between initiation of screening and clear demonstration of a reduced mortality was more than 10 years, whereas it was about 5 years for women over age 50. The lower absolute risk of cancer among women under age 50 implies that even if relative mortality benefits were equal for women under and over age 50, absolute risk reduction would remain considerably lower for younger women. This disparity would not be corrected by improved screening technology or adjustment of screening intervals (Sirovich and Sox, 1999). Furthermore, because breast cancer is less common among women under age 50 than among older women, more individuals need to be screened to identify a case of occult breast cancer or to prevent a death from breast cancer.
One of the difficulties with screening women in their 40s is that most such women are premenopausal and are therefore likely to have greater breast density than postmenopausal women, whose breast tissue often (but by no means always) contains a higher percentage of fatty tissue.
{pagebreak}
(However, postmenopausal women on estrogen replacement therapy may have similar difficulties [Laya et al., 1996], and the number of women on such therapy has been increasing.) This tissue density can make mammograms more difficult to interpret and can thus lead to missed diagnoses, as well as increased rates of false-positive findings (resulting in unnecessary biopsies). One study found that the accuracy of screening mammography in premenopausal women varies with the phase of a woman's cycle at the time of screening (White et al., 1998), suggesting that accuracy might be improved by scheduling the mammogram during a particular phase (the follicular phase during the first 2 weeks of the cycle), but this is not standard practice at present. Physical examination (CBE and BSE) may also be impeded by dense breast tissue (Heimann et al., 1998).
Other screening modalities that are not affected by breast density might be helpful for the screening of women with dense tissue at any age, especially since there may actually be a correlation between breast density and cancer risk (Byng et al., 1998).
Younger women also tend to have a faster average cell growth rate, meaning that interval cancers may be more common and, thus, that screening may need to be conducted more frequently (e.g., annually or, among high-risk women, perhaps even semiannually) to be effective for women in this age group (Kerlikowske et al., 1996; Tabar et al., 1999).
These concerns associated with the screening of younger women are especially relevant to women at high risk. For example, women with inherited mutations in breast cancer susceptibility genes such as BRCA1 and BRCA2 are faced with the decision of choosing between prophylactic bilateral mastectomy or screening, often beginning at an earlier age than the general population (Burke et al., 1997). Women may also opt to participate in chemoprevention trials. Thus far, there are no definitive data to guide the decision-making process. Because of the limitations of mammography, especially for younger women, improved screening methods are seriously needed for this high-risk group. Several institutions are now studying whether alternate screening modalities, such as MRI or ultrasound, may be more effective and cost-effective for this relatively small, specific group. ###
Sharyl J. Nass, I. Craig Henderson, and Joyce C. Lashof
Committee on Technologies for the Early Detection of Breast Cancer
National Cancer Policy Board INSTITUTE OF MEDICINE and Division of Earth and Life Studies NATIONAL RESEARCH COUNCIL
News
News
Guide
