Results Summary
What was the research about?
After women complete treatment for breast cancer, they may still be at risk for cancer to come back. But not all breast cancer is the same. For example, some breast cancers have hormone receptors. Cancers that have these receptors depend on hormones, like estrogen and progesterone, to grow. Breast cancers can also have a high level of a protein called HER2. Doctors call these cancers HER2+. These cancers grow faster than other cancers.
Women and their doctors watch for signs of cancer coming back. To check for these signs, women usually get regular mammograms. In addition to regular mammograms, doctors may recommend extra imaging tests. Some doctors recommend extra imaging tests even when patients feel well. Others only recommend additional imaging tests if their patients have physical signs of cancer coming back.
The research team did two studies. In the first study, the team wanted to know if there was a link between different types of breast cancer and the chance that cancer will come back, and how long it takes to come back. In the second study, the team looked at the extra imaging tests many women receive. They wanted to know if women without physical signs of cancer who got extra imaging tests had a higher chance of survival from cancer that came back within five years. The team compared these women to women who got extra imaging tests only if they had physical signs of cancer.
What were the results?
Study 1. Cancer came back sooner and more often for women whose cancer didn’t have hormone receptors and also wasn’t HER2+ compared with women whose cancer had other combinations of hormone receptors and HER2.
Study 2. Compared with women who received extra imaging only if they had physical signs of cancer, two groups of women who received extra imaging without physical signs of cancer had higher chances of survival:
- Women with cancer that didn’t have either type of hormone receptors and wasn’t HER2+
- Women with cancer that was HER2+
For women with cancer that was not HER2+ but had hormone receptors, there was no difference in survival based on which way they received follow-up imaging tests.
What did the research team do?
In the first study, the research team analyzed data from 17 research studies to see if hormone receptors and the HER2 protein affected the chance that breast cancer would come back. The studies included 10,357 women with breast cancer.
In the second study, the research team analyzed data from 10,076 women to see if women who had extra imaging tests without physical signs of cancer had higher chances of survival from cancer that came back. The team compared these women to women who only had extra imaging tests if they had physical signs of cancer.
A group of 31 cancer survivors, patient advocates, and cancer specialists helped design both studies.
What were the limits of the study?
The research team didn’t have information about other risk factors, such as family history of breast cancer. These risk factors may be important when deciding how to look for signs of breast cancer that comes back.
Future research could assign patients by chance to get extra imaging tests or not. These studies could help make sure that if there are differences in survival, the differences are due to how women get extra imaging tests and not due to other things.
How can people use the results?
Patients and doctors can use the results from this study to help plan follow-up care after breast cancer treatment.
Professional Abstract
Objective
To use clinical trial data to evaluate characteristics associated with breast cancer recurrence, and to compare the effectiveness of routine imaging for asymptomatic patients versus imaging only in symptomatic patients who completed treatment for stage II and III breast cancer
Study Design
| Design Elements | Description |
|---|---|
| Design | Empirical analysis |
| Data Sources and Data Sets |
Objective 1: Data from 17 clinical trials involving 10,357 women with stage I, II, or III breast cancers Objective 2: National cancer registry data and medical record review for 10,076 adult women who completed treatment for stage II and III breast cancer |
| Analytic Approach | Retrospective observational study |
|
Objective 1: time to and probability of cancer recurrence Objective 2: survival within 5 years |
Objective 1. Researchers conducted a retrospective analysis of 17 clinical trials involving 10,357 women who had surgery and adjuvant therapy for stage I, II, or III breast cancer between 1997 and 2013. Researchers analyzed the time to and probability of cancer recurrence based on cancer characteristics including whether the cancer had either estrogen or progesterone receptors (ER/PR+) or were HER2+.
Objective 2. Researchers retrospectively examined whether survival improved when a cancer recurrence was detected using routine imaging within three years of diagnosis of primary breast cancer for asymptomatic patients, compared with imaging only after the development of symptoms. Using a national cancer registry and health records, researchers analyzed data from 10,076 women with stage II or III breast cancer diagnosed between 2006 and 2007 to determine which patients died within five years of their initial diagnosis. They then compared women’s survival based on how the recurrence was detected.
A group of 31 cancer survivors, patient advocates, and oncology specialists served as advisors and helped with study design and identifying outcomes that were most important for patients.
Results
Objective 1: For patients who had cancer recurrences, 75% occurred by
- 1.8 years for patients with ER/PR-, HER2- cancer
- 3.1 years for patients with ER/PR-, HER2+ cancer
- 3.3 years for patients with ER/PR+, HER2- cancer
- 5.0 years for patients with ER/PR+, HER2+ cancer
Patients with ER/PR-, HER2- stage III cancer had the highest cumulative probability of cancer recurrence at five years (13.4% for patients that had stage II cancer and 43.2% for patients that had stage III cancer).
Objective 2: Recurrence detection with asymptomatic imaging correlated with higher survival compared with symptom-based detection for patients with ER/PR-, HER2- cancer (hazard ratio [HR]=0.66; 95% confidence interval [CI]: 0.48, 0.91) and patients whose cancer was HER2+ (HR=0.40; 95% CI: 0.24, 0.68). Researchers found no significant difference in survival rates among patients with ER/PR+, HER2-, which represents the majority of breast cancer patients.
Limitations
Researchers did not have data on other risk factors, such as family history of breast cancer, which may have been important when deciding on posttreatment surveillance for breast cancer recurrence.
Conclusions and Relevance
Researchers found that having ER/PR-, HER2- cancer was associated with a higher chance of breast cancer recurrence. Routine imaging for asymptomatic patients may provide a survival benefit for patients who had ER/PR-, HER2- cancer or HER2+ cancer. However, two-thirds of all breast cancers are ER/PR+, HER2-, and these patients are unlikely to benefit from routine surveillance to detect recurrent cancer.
Future Research Needs
Future research could include randomized trials to compare routine versus non-routine imaging tests for breast cancer patients who have completed active treatment and have a high risk of recurrence.
Final Research Report
View this project's final research report.
Journal Citations
Results of This Project
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented, and the researchers made changes or provided responses. The comments and responses included the following:
- Reviewers asked whether the decision tool developed in this study to help inform surveillance strategies would address patients’ family history or genetic mutation status. The researchers agreed that family history was particularly important as a determinant of future risk for breast cancer. However, the tool did not incorporate family history and genetic status since this information was not routinely collected in the study data and medical records that the study analyzed. The researchers added this as a study limitation.
- Reviewers asked whether clinicians and patients would have the literacy and numeracy to be able to convey and understand the probabilities the decision tool provides. The researchers agreed that this is a critical issue, but that they intended the initial tool to inform clinicians as they develop follow-up recommendations to share with patients. The researchers did not design the tool to replace joint physician-patient decision making. However, future iterations of the tool will be formally tested with clinicians and patients to be more directly applicable to joint decision making.
- Reviewers requested additional information on the subjects in the 17 legacy clinical trials which the researchers analyzed to evaluate how recurrence varies based on patient and cancer characteristics, to assess the representativeness of the patients in these trials. The researchers added a table of the subjects’ demographic and clinical characteristics. They also clarified in the report that patients enrolled in clinical trials may not represent the broader population of cancer survivors as they tended to be healthier and less ethnically and economically diverse.