Imaging Surveillance after Definitive Treatment for Breast Cancer

With diagnosis of breast cancer at earlier stages and improvements in local-regional and systemic treatments, there is an increase in the proportion of patients in survivorship who need follow-up care. Oncology societies in the United States and Europe recommend that breast cancers survivors undergo history and physical examinations and mammography on an annual basis [1]. There is no recommendation for routine surveillance imaging for detection of distant recurrence except for evaluation of individuals with symptoms or clinical findings suspicious for a recurrence event. This is based on data from randomized trials reporting that routine imaging screening for distant metastases in asymptomatic patients following treatment does not affect survival nor quality of life, and it increases costs [2] [3] [4]. The American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) recommend screening for metastases in patients who are experiencing symptoms or clinical signs of disease and strongly urge to avoid asymptomatic screening with bone scans and PET/CT scans [5] [6]. Asymptomatic patients undergoing surveillance imaging contribute to the increased cost of care and utilize resources that might be allocated for other individuals. Potential risks of intense follow-up include excess radiation exposure, false positive results that need further workup, and an increase in psychological distress and anxiety to patients [1]. Despite the availability of guidelines recommending against surveillance imaging, it has been reported that patients still undergo at least one advanced imaging modality following curative treatment [7]. However, no studies have shown whether the lack of adherence to guidelines is due to overuse in asymptomatic patients or if imaging is ordered based on clinical signs and symptoms.

In the current issue of the Annals of Surgical Oncology, Schumacher et al. used the National Cancer Database (NCDB) to assess the number of surveillance systemic imaging studies that were performed post-breast cancer treatment and worked with local cancer registrars to determine whether imaging was obtained for evaluation of symptoms or performed for routine surveillance [8]. They included women with stage II or III breast cancer diagnosed in 2006–2007 who were treated with curative intent and had 5 year follow-up. They randomly selected 10 patients (7 with stage II and 3 with stage III disease) from 1,231 facilities accredited by the Commission on Cancer since this reflects the ratio of stage II to stage III patients nationally. Importantly, they trained facility registrars to review relevant patient records from their own institution and any outside facilities where the patient received care.

They found that 48% (n= 5,220) of women received ≥ 1 cancer-related advanced imaging scan during follow-up. However, once the intent of the scan was considered, 30% (n=3,254) received ≥1 asymptomatic surveillance scan, and only 12% (n=1,308) had ≥2 surveillance scans. Most of the scans took place in the first year after treatment and factors significantly associated with ordering asymptomatic scans included: stage III disease, triple negative tumors, HER2-positive tumors, receipt of chemotherapy and treatment with mastectomy.

Although a rate of 30% of patients receiving asymptomatic surveillance is lower than that reported in prior studies [7] [9], a shortcoming to this study is the lack of information about which type of physician ordered the screening. It has been shown that the type of physician (primary care vs. cancer specialists - including medical oncology, radiation oncology, and surgery) a patient sees after breast cancer treatment may influence the type of surveillance received. Keating et al., used Surveillance, Epidemiology, and End Results-Medicare data, a cohort of 44,511 breast cancer survivors, and concluded that specialists, especially medical oncologists, order more tests in the follow-up period. However their study failed to differentiate the intent of testing, whether it was due to symptoms or just overuse [3]. Similarly, in a retrospective review of 11,219 asymptomatic breast cancer survivors, Grunfeld et al. showed a variation in adherence among oncologists and primary care physicians with respect to guidelines and interestingly, one quarter of the women had fewer than the commended annual mammograms and half had more imaging than recommended for surveillance of metastatic disease [2] [9]. Potential physician barriers that may lead to lack of adherence to published guidelines include lack of awareness, lack of agreement with guidelines, practice environment, and patient preferences [10]. Creation of a survivorship care plan can be a useful tool to counteract these barriers and educate patients and providers alike on recommendations [11]. Using these tools early on in the follow-up period can be important such that patients know what to expect at their future follow-up visits and providers can focus on addressing any change in clinical signs and symptoms.

Schumacher and colleagues noted that surveillance imaging was more frequent in patients based on approximated subtype. They report that the study cohort was diagnosed during a time period (2006–2007) when HER2 status was not routinely tested and HER2-targeted treatment was not routinely administered. With the advancement of HER2-targeted therapies and improvement in outcomes for this subtype, the rate of ordering unnecessary tests and the likelihood of breast cancer distant recurrence is likely to decrease.

In an era where the optimal strategy for surveillance of breast cancer patients continues to be debated, we congratulate Schumacher and colleagues on their work, as this is the first study of this magnitude to look at a large national database in order to report the rate of follow-up imaging scans ordered and to define scan intent. With their analysis we understand a bit more about who is being imaged, when they are likely to be imaged, what scans are being obtained and why they were obtained. It suggests that compliance with current guidelines is higher than previously reported, and informs us that women who do receive imaging are at higher risk of recurrence. Physicians appear to be guided by tumor biology and treatment rendered when it comes to ordering tests for early detection of metastases. However, it also raises the question, is this clinical practice pattern warranted and effective to screen this subgroup of patients?

There are now many more sophisticated tools to help us understand which patients are at highest risk of recurrence and who therefore might warrant surveillance imaging studies. Sparano and colleagues recently reported on the identification and enumeration of circulating tumor cells (CTCs) in stage II-III high risk patients with hormone receptor-positive, HER2-negative disease following systemic chemotherapy [11]. They found that a single positive CTC result 5 years after diagnosis was prognostic for late recurrence. Circulating tumor DNA (ctDNA) has also been shown to predict recurrence in patients with early stage breast cancer, with a median lead time of 7.9 months reported in one study [12] The c-TRAK TN is using ctDNA screening in patients with triple negative breast cancer who have completed standard of care systemic therapy (NCT03145961; PI Nick Turner, MD, PhD). Those patients detected to have ctDNA will be randomized to observation or pembrolizumab treatment for one year. Similar to surveillance imaging studies, it is unclear how frequently these liquid biopsies should be obtained and in which patients. Should they be used to guide surveillance imaging strategies or to determine who should receive additional adjuvant therapy? To realize the full potential we will need to design clinical trials to address these important questions.