It is a counterintuitive thing in the world of cancer medicine to suggest that we want to put a premium on early detection in general for early-stage disease, but we don’t want to put a premium on early detection for metastatic disease.
—Harold J. Burstein, MD, PhD
Patients who have been treated for breast cancer may overestimate the value of follow-up testing and may expect—or even ask for—more testing than recommended, Harold J. Burstein, MD, PhD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, told participants at the Lynn Sage Breast Cancer Symposium in Chicago.1 “Patients place a lot of value in testing, and it takes a fair amount of work to explain to them why they are not getting tests,” Dr. Burstein said.
The major reason is “relatively limited value for surveillance chest x-rays or for laboratory studies that patients frequently get,” Dr. Burstein stated. “Even with intensive surveillance,” he noted, “less than 25% of recurrences are detected among asymptomatic patients.”
In addition, the “significant false-positive rates” of laboratory and radiologic studies “can contribute to excess evaluation and, in some instances, patient discomfort or anxiety,” Dr. Burstein said. “False-positives do carry consequences and often lead clinical teams down a path with lots of testing that may or may not be so helpful,” Dr. Burstein noted.
“Treatment innovations in advanced breast cancer additionally diminish the potential value of earlier detection of metastatic disease. Until we come up with either locoregional therapies for metastatic disease or other compelling reasons to find cancer when it remains a very small burden,” Dr. Burstein said, the benefits of early detection remain unclear.
Dr. Burstein pointed out that both ASCO and the National Comprehensive Cancer Network (NCCN) have “been pretty aggressive in articulating a minimalist surveillance strategy.”
Why Do Patients Still Want Tests?
If surveillance of patients treated for breast cancer is of such limited value, why do patients need to be convinced? “Because it is a counterintuitive thing in the world of cancer medicine to suggest that we want to put a premium on early detection in general for early-stage disease, but we don’t want to put a premium on early detection for metastatic disease, and it is surprisingly complicated to explain that,” Dr. Burstein said.
“The other problem is that there is tremendous practice heterogeneity, and so I have patients coming in to see me who say, ‘Well, I was sitting in the waiting room, and someone else is getting all these scans and lab tests; how come you are not doing that?’ That is a nontrivial problem,” admitted Dr. Burstein.
Most symptoms that patients experience following treatment for early-stage breast cancer “are not related to metastatic disease,” Dr. Burstein said. Most recurrences are, however, “heralded by symptoms, coughs that don’t go away, fatigue, or pain out of proportion to daily experiences, and obviously those symptoms warrant a thorough evaluation.”
Surveillance Testing for Asymptomatic Patients
All patients treated for breast cancer should have a careful history and physical examination, mammography, and gynecologic follow-up.
The history and physical examination should be done every 3 to 6 months during the first 3 years after primary treatment, every 6 to 12 months in years 4 and 5 post treatment, and then annually. “We are looking for new findings in the breast or regional lymph nodes or symptoms that might strongly suggest recurrence of disease,” Dr. Burstein said, although they “are notoriously nonspecific.” Patients should also be counseled about symptoms of possible recurrence, such as new lumps; dyspnea; persistent headaches; and bone, chest, and abdominal pain.
Although the importance of breast self-examination is currently being debated, guidelines recommend that women perform monthly breast self-examination after a breast cancer diagnosis. They should be reminded that this does not replace mammography, Dr. Burstein added.
“Mammograms are an essential part of surveillance to look for either second tumors or ipsilateral breast recurrences,” Dr. Burstein stated. “We typically get the first one about 6 months after radiotherapy is complete to essentially establish a baseline and then more or less annually thereafter.”
Over the course of their lives, many patients have additional images of the breast with ultrasound or magnetic resonance imaging (MRI), because something in the breast feels abnormal or looks atypical on a mammogram. “But when it comes to MRI as a routine procedure after breast cancer, don’t do it,” Dr. Burstein stressed. Routine breast MRI or ultrasound is not endorsed, even if mammography “missed” the original tumor.
Gynecologic follow-up is recommended for all women who have been treated for breast cancer, but it is particularly important for women who are taking tamoxifen, as they are at increased risk for developing endometrial cancer. “Neither ASCO guidelines nor association guidelines have suggested that you need an annual imaging or pelvic ultrasonography or other tests to explore whether or not there is a risk of endometrial cancer,” Dr. Burstein revealed. “Obviously, women who have atypical vaginal bleeding require evaluation, but in a healthy woman, there is no routine need for that.”
Coordination of Care
“Probably one of the biggest challenges we are facing right now is continuity of care and coordination of care,” Dr. Burstein said. “As patients transition toward survivorship models, many of us are struggling with how to manage them in the confines of the oncology practice. We have tried midlevel practitioners and allied health professionals to help up with this. We need more primary care doctors as well.”
Studies have shown that these health professionals “do a very good job of routine surveillance,” Dr. Burstein noted, and follow-up by primary care physicians seems to lead to the same health outcomes as follow-up by specialists, with good patient satisfaction. For oncologists, “what you do lose, and it is hard to quantify this,” he said, is the gratification of seeing patients do well in the long run. In addition, symptom control and compliance with therapy “are real issues that warrant ongoing input from the oncology team on a regular basis,” added Dr. Burstein. “So I have been rather loath to part with these patients, but it is becoming a pressing challenge on a day-to-day basis.”
Testing That Is Not Recommended
Not recommended for breast cancer surveillance are routine blood tests and routine imaging studies, including chest x-rays, bone scans, liver ultrasonography, computed tomography (CT) scans, FDG-PET (fluorodeoxyglucose–positron emission tomography) scanning, and breast MRI.
“So far, tumor markers have not been valuable in the long-term prevention of cancer recurrence or better outcomes, and we try to avoid obtaining them. There are clearly false-positives,” Dr. Burstein said, and “we have all seen patients who had advanced cancer with absolutely normal serum tumor markers, so they really are not a valuable asset for the surveillance of patients.”
Cardiac Surveillance and Trastuzumab
A controversial issue concerns cardiac surveillance for women with HER2-positive breast cancer who have received adjuvant trastuzumab (Herceptin). The package insert carries the following black box warning from the U.S. Food and Drug Administration:
Candidates for treatment with Herceptin should undergo thorough baseline cardiac assessment including history and physical exam and one or more of the following: ECG [electrocardiography], echocardiogram, and MUGA [multigated acquisition] scan. There are no data regarding the most appropriate method of evaluation for the identification of patients at risk for developing cardiotoxicity. Monitoring may not identify all patients who will develop cardiac dysfunction. Patients receiving Herceptin should undergo frequent monitoring for deteriorating cardiac function.
Although the FDA warning “doesn’t actually specify what that monitoring should be,” Dr. Burstein noted, “NCCN guidelines have suggested baseline, 3 month, 6 month, and 9 month monitoring, which is a lot of monitoring, and nobody here is doing that level of monitoring.” He cited a study showing that only 36% of patients taking trastuzumab received appropriate monitoring.2
“There isn’t a lot of data to give you more guidance,” Dr. Burstein told the symposium participants. “In my own practice, I get a baseline and then probably once more at around 6 months. The guidelines currently say more frequent testing, and yet practice is tremendously discordant on that point.”
Bone Mineral Density Imaging
Treatments such as aromatase inhibitor therapy or ovarian suppression affect bone health, and Dr. Burstein referred to the ASCO 2003 Bone Health Guidelines, recommending that patients with breast cancer at high risk for osteoporosis have bone mineral density determination. These high-risk patients include women with therapy-associated premature menopause and postmenopausal women receiving aromatase inhibitors.
“The question has been how this has been orchestrated, whether it is the primary care doctor’s bailiwick or the oncology office, and we go back and forth on that,” Dr. Burstein admitted. However, it is “part of a good survivorship plan and something not to be dismissed.”
Surveillance for Metastatic Disease
There is “tremendous heterogeneity of practice” in surveillance for metastatic disease, Dr. Burstein noted. Some patients get scans every 3 months or so, “but at least in my clinic, it is very typical for patients who have minimal disease burdens or have long periods of tumor control to begin to space those out, so it’s more like every 6 or even every 12 months,” he added.
“We also are very influenced by protocols,” Dr. Burstein observed. Many clinical trial protocols have 6-week or 2-month intervals, “because they are looking for early signals of response and activity, which is certainly understandable from the point of view of drug discovery and new regimen development, but it is a very short interval for many of our patients,” he commented.
“When you are doing surveillance for metastatic disease, you never want to look just at once piece of data,” Dr. Burstein noted. “You want to integrate the imaging, the laboratory studies, and, more critically, the patients—where they are in the narrative of their disease and what their own day-to-day experience is like on treatment.” It’s not easy taking all these pieces of data into consideration, he acknowledged, because there are often inconsistencies or discordance among them.
Innovations in Surveillance of Metastatic Disease
“There are a couple of innovations in the surveillance of metastatic disease that are worth knowing about,” Dr. Burstein declared. One has been the critical assessment of circulating tumor cells; Dr. Burstein cited a study that found “measuring circulating tumor cells probably is prognostically significant for women,” although not therapeutically beneficial.3
“A variety of technologies have come together that have allowed people to do genomic sequencing on circulating free DNA, which is DNA that’s in the plasma and has presumably come from numerous tumor cells that died and have been liberated into the bloodstream,” Dr. Burstein explained. Some research has found a “coarse correlation” between the level of circulating free DNA and the cancer burden. “And perhaps most interesting to me,” he added, “has been that you can begin to look for dynamic changes in cancer biology over time, and I think this holds promise of being able to create more opportunities for personalized medicine.”
Serial liquid biopsies over time “may hold the opportunity to do surveillance of cancer burden and to enable precision medicine” in managing breast cancer, Dr. Burstein stated in closing. “Hopefully, in the years to come, we are going to have new technologies such that we can revise the way we monitor tumor burden and biology and begin to further tailor our treatment recommendations based on those kinds of observations.” ■
Disclosure: Dr. Burstein reported no potential conflicts of interest.
1. Burstein H: Surveillance imaging for the healthy breast cancer survivor and the patient with metastatic disease. 2015 Lynn Sage Breast Cancer Symposium. Session 5. Presented October 30, 2015.
2. Chavez-MacGregor M, Niu J, Zhang N, et al: Cardiac monitoring during adjuvant trastuzumab-based chemotherapy among older patients with breast cancer. J Clin Oncol 33:2176-2183, 2015.
3. Smerage JB, Barlow WE, Hortabagyi GN, et al: Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 32:3483-3489, 2014.