Imaging Surveillance of Women With a Personal History of Breast Cancer

Plain Language Summary

Following successful treatment of first breast cancers, women remain at risk of cancer recurrence in the treated breast and also new cancers in the other breast (second breast cancers), which are associated with increased rates of cancer detection in other parts of the body and with death from breast cancer. Imaging surveillance after breast cancer treatment aims to detect second breast cancers before symptoms develop, permitting treatments which may improve survival and maintain quality of life.

This chapter reviews the evidence which supports the use of annual mammography for imaging surveillance in women with a history of breast cancer. Evidence that mammography is underused among breast cancer survivors, especially as time since completing treatment increases, offers an opportunity to improve how mammography can be used to improve survival. In addition, new technologies for detecting breast cancer, such as digital breast tomosynthesis (DBT), breast ultrasound, and breast magnetic resonance imaging (MRI) will be reviewed. DBT, also known as “3D mammography,” uses the same X-ray source as digital mammography and moves in an arc around the breast to collect digital information. By presenting images of thin “slices” within the breast, DBT more clearly shows true breast lesions and reduces false-positive findings due to overlapping normal breast tissue. MRI uses strong magnetic fields to image the breast, rather than ionizing radiation. Its ability to detect cancers is very high, and MRI is recommended for breast cancer screening in women with very strong family histories, especially those who are at very high risk of developing breast cancer due to gene mutations such as BRCA1 and BRCA2 . The benefit of breast MRI use in breast cancer survivors who do not have these risk factors is still being studied. Breast ultrasound uses high frequency sound waves to examine breast tissue, and a strength of ultrasound is its ability to differentiate cystic from solid breast masses. The main limitation of breast ultrasound when it is used for breast cancer screening or surveillance, is the high number of biopsies which are recommended, most of which have benign (not cancer) results.

We are also improving our understanding of cancer biology, and new information about breast cancer subtypes may help to guide treatment selection and improve survival. Information about how breast cancer subtype is related to detection of first and second cancers is needed to help women decide which imaging tests should be used for imaging surveillance. Other factors, such as quality of life, costs of care, and care that takes into account a woman’s individual preferences and values, are also important. It is critical for patients and their doctors to consider these additional factors when making decisions about treatment and imaging surveillance, so that women can lead longer, healthier lives once their treatment is done. This chapter will review the current evidence and highlight critical knowledge gaps where further study is needed to improve clinical care and outcomes.

Background

Globally, 28.8 million individuals alive in 2008 were cancer survivors who had been diagnosed within the last 5 years. When identifying survivors by cancer site, female breast cancer is the most prevalent neoplasm worldwide, at approximately one in six cancer survivors. In the United States alone, approximately 232,000 women were diagnosed with invasive breast cancer in 2013. Advances in screening and treatment of primary breast cancer (PBC) have improved survival for many of these women, and the number of breast cancer survivors will continue to increase. Women who survive their initial diagnosis of breast cancer remain at risk of subsequent local recurrence (LR) and new primary cancers in the contralateral breast (second breast cancers), which are associated with increased rates of distant metastases and breast cancer mortality.

Posttreatment surveillance aims to detect asymptomatic second breast cancers, permitting interventions to potentially improve survival and maintain quality of life. Based on randomized controlled trials (RCTs) demonstrating the effectiveness of screening mammography in reducing breast cancer mortality (see also chapter: Estimates of Screening Benefit: The Randomized Trials of Breast Cancer Screening ) and on observational studies suggesting effectiveness for posttreatment surveillance, current guidelines are consistent in their recommendations supporting the use of mammography in women following treatment for PBC.

With advances in breast imaging technology, additional options beyond mammography are now available for screening and surveillance. These modalities include DBT, as well as breast ultrasound and MRI. In addition, improvements in our understanding of tumor biology, and specifically in the classification of tumors by gene expression profiles or “molecular subtypes,” are providing independent prognostic information to guide tailored selection of breast cancer treatment. The provision of clinical care is increasingly focusing on patient centered outcomes beyond survival, such as quality of life, costs of care, and shared decision making based on patient preferences and values.

This chapter will consider these three recent trends influencing imaging surveillance regimen selection.

Selecting an Appropriate Surveillance Regimen

Surveillance testing extends beyond application of the test itself. Rather, it is an episode of care that begins with the surveillance test and also includes the subsequent cascade of diagnostic evaluation of positive test results and incidental findings, as well as treatment of the targeted disease. Achieving an overarching balance of benefits and harms with surveillance includes consideration of events within entire episodes of care ( Fig. 12.1 ).

Negative Test Results

A highly specific surveillance test, one which correctly excludes patients without the targeted disease, is an essential characteristic of a surveillance test. Ideally, these patients with true negative results will gain reassurance that they do not have disease recurrence. When recurrence is present but the test result is negative (false-negative), the disease will continue to progress until it presents symptomatically, and the patient will not have gained the benefits of earlier detection. A negative surveillance test could potentially provide false reassurance and cause an individual to delay seeking care for a symptom, causing further harm.

Positive Test Results

Because a population under screening or surveillance has no signs or symptoms of disease, it is important to consider the diagnostic consequences of a positive test result. An important potential harm of surveillance is false-positive results. Individuals with false-positive results will incur all the subsequent diagnostic consequences of a positive test—invasive biopsies, increased costs, and anxiety about having a life-threatening recurrence—but gain none of the benefits, as recurrent disease is not present. The likelihood of having false-positive results increases with an increased surveillance timeframe or with more frequent surveillance intervals, both of which increase the total number of lifetime surveillance episodes, and also with decreasing disease prevalence. Because of these factors, the potential harms of false-positive surveillance results are most likely to accrue in individuals at lower risk of having recurrent disease.

A highly sensitive surveillance test should detect most patients with the targeted disease (a high true-positive proportion), enabling earlier diagnosis of recurrence and access to effective treatments. These patients are the only ones with the potential to benefit from surveillance and to achieve improved long-term outcomes, such as reduced breast cancer mortality and increased overall survival.

Even with a highly sensitive test, an important consequence of screening and surveillance is the potential for harm from overdiagnosis and overtreatment. Overdiagnosis and overtreatment occur when surveillance testing detects asymptomatic disease that would not have become clinically apparent over an individual’s lifetime, or when detection results in treatment of disease that would not have shortened an individual’s life expectancy (see also Challenges in Understanding and Quantifying Overdiagnosis and Overtreatment, Treatment of Screen-Detected Breast Cancer: Can We Avoid or Minimize Overtreatment? ). Both of these scenarios occur more frequently when older populations with higher competing mortality risks undergo surveillance. Due to the invasiveness of treatment and associated morbidity, overdiagnosis and overtreatment may be among the most significant potential harms associated with surveillance.

Incidental Findings

Incidental findings, discovered during image interpretation that are unrelated to the indication of the study, are a routine part of diagnostic radiology. In examinations with larger fields of view, such as breast MRI, there is potential for the discovery of incidental findings that are unrelated to the targeted disease. For example, Niell et al. reported that of 2324 patients receiving breast MRI examinations performed for any indication, 86 patients (3.7%) had extramammary findings for which additional imaging evaluation was recommended, and nine patients (0.4%) had clinically important findings. Potential harms from incidental findings may result from complications of unnecessary invasive procedures, increased costs, and undue patient anxiety for what is ultimately determined to be a benign lesion. These “incidentalomas” place patients and their providers in a difficult situation, as it may not be possible to predict which will be clinically significant and which will not at the time of examination interpretation.

Balancing the Benefits and Potential Harms of Surveillance

The burden of proof for the effectiveness of screening and surveillance is higher than that for diagnostic tests and treatments. Of all the individuals who will undergo surveillance, only those with true-positive test results who receive effective treatment and are not overdiagnosed/overtreated will obtain its primary benefits, which include decreased morbidity and mortality. As we increasingly focus on providing value-based healthcare, with the goal of improving patient outcomes while maintaining or decreasing healthcare costs, the important outcomes to measure extend beyond those of mortality reduction. Outcomes that matter are condition-specific and multidimensional—including overall survival, time without symptoms, quality of life, and the financial consequences of choosing alternative treatments. No single outcome will fully capture the effects of surveillance. Implementation of new imaging-based surveillance tests in clinical practice will increasingly hinge on the successful conduct of research on a scale and with a level of rigor not seen in the past.

The challenge and opportunity for future research studies of imaging-based surveillance are to provide evidence on multiple outcomes to characterize not only its benefits but also its downstream consequences and potential harms. Improved quality of life or reduced disease-specific mortality must be considered in the context of radiation-induced risks, utilization of additional resources to evaluate incidental findings, false-positive test results, and the potential for overdiagnosis and overtreatment. The budget impact and cost-effectiveness of new surveillance regimens are also important factors for which examination prior to adoption and implementation should be considered.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here