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Study: A new blood test may help predict early-stage breast cancer patients at highest risk for recurrence

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Contents

At a glance                  Questions for your doctor
Findings               In-depth                
Clinical trials Limitations
Guidelines Resources


STUDY AT A GLANCE

This study is about:

Whether a test for circulating tumor () might be useful for finding patients who are at increased risk of recurrence.

Why is this study important?

This study looks at whether one test, the detection of , is a reliable predictor of patients with breast cancer who will relapse. A test that predicts recurrence before it is currently clinically detectable would allow earlier or perhaps different treatment and may improve survival outcomes.

Study findings: 

  1. Detection of in the blood was a strong indicator of recurrence among study participants. Patients for whom was detected after initial treatment were 25 times more likely to recur than patients without detected after initial treatment.
  2. was useful in predicting recurrence for all breast cancer subtypes examined (HER-positive, HER-negative and triple-negative cancers).
  3. Detection of before surgery or other treatment was also correlated with recurrence. Patients with detected before treatment were nearly 6 times more likely to recur than patients with no detected at diagnosis.
  4. was more likely to be detected for metastases in locations in the body other than the brain compared to metastases in the brain. In this study, was not able to find patients whose only recurrence was in the brain.
  5. While appears to be good predictor of which patients would eventually experienced a recurrence, 25% of patients who recurred did not have detected in this study. Lack of does not rule out recurrence.

What does this mean for me?

Most breast cancer will respond well to treatment without recurrence. However, some breast cancers may recur. For this reason, current guidelines recommend follow-up doctor visits after treatment. Finding recurrence earlier may provide patients with more treatment options. Once your treatment ends, it is important to speak with your doctor about your post-treatment follow up care, including a discussion of:

  • frequency of follow up visits
  • which providers you should see
  • what tests will be ordered
  • any symptoms you should report to your doctor

Research on detection as a tool to monitor relapse is ongoing. While this test is  promising, it has not yet been shown to improve survival outcomes in patients. Longer follow-up to testing is needed to determine if this information may be clinically useful. 

Posted 11/14/19

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Reference

Garcia-Murillas I, Chopra N, Comino-Méndez, et al. “Assessment of molecular relapse detection in breast cancer.” JAMA Oncology. 5(10):1473-1478. Published online August 1, 2019. doi:10.1001/jamaoncol.2019.1838.
 

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

People with early-stage breast cancer

This article is also relevant for:

Breast cancer survivors

ER/PR +

Her2+ breast cancer

Women under 45

Women over 45

Newly diagnosed

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IN-DEPTH REVIEW OF RESEARCH

Study background:

Ninety-five percent of women with breast cancer have no indication of metastases at the time of diagnosis. Many of these patients will not experience a relapse.  The 5-year survival rate for women with local breast cancer is 98% and it is 88% for women with regional breast cancer.

Relapse or recurrence is attributed to small groups of cancer cells that remain after treatment (called “molecular residual disease” or “MRD”). There are too few of these cells to observe easily. When these remaining cancer cells may migrate to other parts of the body they are called metastases. Early detection and treatment is optimal for patients who relapse.

But what is the best way to predict who will relapse and who will not? Those remaining tumor cells will sometimes lead to tumor in the blood of patients, called circulating tumor or . Tumor cells in patients with in their blood may subsequently grow until they are clinically detectable and/or causing symptoms—a recurrence of their primary cancer.

This study’s researchers wanted to know whether detection accurately predicts the chance of recurrence in breast cancer patients. The key to using is to find a mutation that has occurred only in the tumor during its growth (not an inherited mutation). To do this, from the primary tumor is sequenced to find mutations that differ from the patient's non-tumor . These mutations act as a signature of the tumor cells.

Researchers of this study wanted to know:

Whether in a patient's blood indicates that they are at greater risk of relapse. The underlying question is whether detection might be a useful tool clinically for identify patients at increased risk of relapse.

Populations looked at in this study:

This study included 170 women with a mean age of 54 years from 5 UK hospitals.

All patients had primary breast cancer with no evidence of metastases by standard monitoring methods.

Study design:

This was a multicenter study in the United Kingdom from November 2011 to October 2016. All participants had breast cancer. In 140 participants, breast cancer was treated neoadjuvantly (before surgery); 30 other participants had surgery and treatment (after surgery).

To determine if was a useful tool to predict relapse, blood samples from each participant were taken before and after their initial treatment. At the time of surgery, each participant's primary tumor was sequenced to identify mutations that uniquely identified the tumor cells. Blood samples from patients were then collected every 3 months for the first year and 6 months in subsequent years for up to 5 years. Each sample was tested for the presence of tumor-specific (), and data was collected about whether the patient had experienced a relapse.

To have sufficient numbers for a comparison of different cancer subtypes, data analysis of the group of 101 participants was combined with data from the initial proof-of-principle study of 43 patients, for a total group of 144 patients. Among these 144 patients, 29 relapsed during the study. 

Study findings:  

Of 170 patients participating in this study, 101 had a tumor-specific mutation:

  • All 101 patients had at least one tumor-specific mutation:
    • 78 patients had 1 tumor-specific mutation.
    • 23 patients had multiple tumor-specific mutations.
  • 69 patients had no tumor-specific mutations identified.

Blood samples and personal cancer history were collected over an average of 35 months from the 101 participants with an identified tumor mutation.

Key findings include:

1. Detection of in the blood was a strong indicator of relapse among these participants. Patients with that was detected after initial treatment were 25 times more likely to relapse than patients who did not have detected after initial treatment.

Among the 101 participants in this study, the presence of in the blood was associated with subsequent relapse.

  • 16 of 101 (nearly 16%) patients had detected in their blood
    • 9 relapsed during the study.
    • 7 had not relapsed at the time the study was published.
    • On average, there was 38 months between initial treatment/surgery and detection.
  • 12 (nearly 12%) patients relapsed during this study of 101 patients.
    • 9 had detected prior to relapse (75%).    
    • 3 did not have detected (25%).

2. was similarly useful as a predictor of relapse for all breast cancer subtypes examined (HER-positive, HER-negative, triple-negative cancers).

To have sufficient numbers for comparison of different cancer subtypes, data from the group of 101 participants were combined with data from the initial proof-of-principle study of 43 patients for a total group of 144 patients.

Among these 144 patients:

  • 29 of 144 patients relapsed.
    • 23 of 29 patients (79%) had detected in their blood prior to their relapse.
    • 6 of 29 (21%) patients did not have detected prior to their relapse.
      • Among the 6 patients without detected, all had one site of relapse:
        • 3 at the brain only.
        • 1 at the ovary only.
        • 2 at one site near their primary breast cancer site.
  • detection occurred 10.7 months before clinical relapse for all breast cancer types.

3. Detection of before surgery or other treatment was also correlated with relapse.

  • was detected in 41 of 80 (51%) patients in blood samples taken before treatment.
  • Patients with detected before treatment were nearly 6 times more likely to relapse than patients with no detected before diagnosis.
  • Detection at diagnosis was associated with larger tumor size and higher grade tumors.

4. was more likely to be detected for metastases in locations in the body other than the brain compared to metastases in the brain. In this study, relapse sites that were only in the brain were not detected by .

  • was detected in 22 of 23 patients (96%) who relapsed when the relapse site was not the brain.
  • was detected in 1 of 6 patients (17%) who relapsed when the relapse site was in the brain.

5. While appears to be a good predictor of patients who eventually experienced a clinical relapse, some patients who did not have detected relapsed during this study—lacking does not mean that relapse will not happen.

  • Among the group of 101 patients, 3 of 9 (33%) patients who relapsed had no detected.
  • Among the combined group of 144 patients, 6 of 29 (21%) patients who relapsed had no detected.

Limitations:

Because this study was conducted in only one geographical area—the UK—results may or may not be generalizable to other regions and populations.

Tumor-specific mutations were identified in 101 of 170 participants. For 69 participants, the presence or absence of were not tracked; in a clinical setting, one would want to identify mutations for a given patient's tumor.

Although this study indicates that detection is a promising tool for predicting who will need more monitoring or treatment, the numbers of participants represented are small. Additionally, two groups of participants, those from this study and those from original proof-of-principle study, showed different rates of relapse. While combining these groups was planned, this may represent unknown biases in the two groups. A larger trial with a longer follow-up period is needed to assess whether this technique is truly useful in a clinical setting and whether it helps improve outcomes.

Among patients with brain metastases, none were detected by in this study. This suggests that additional tools or more refined detection will be required to monitor for relapse of this type.

Conclusions:

While promising, this tool is not yet validated for clinical use. If it becomes validated, the presence of might be useful to determine earlier treatment approaches prior to symptoms of cancer relapse. However, as the study researchers stated, "Our results demonstrate clinical validity for mutation tracking...but do not demonstrate clinical utility. Without evidence that mutation tracking can improve patient

outcome[s], our results should not be recommended yet for routine clinical practice."

A phase II clinical trial for is underway to assess whether use of in a clinical setting will improve patient outcomes.

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Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Given my breast cancer, what are my chances of relapse?
  • What are the best ways I can be monitored for relapse?
  • What are the signs or symptoms of relapse for my breast cancer?
  • Should my primary tumor be sequenced?
  • Is it useful to monitor or circulating tumor cells for my situation?
  • How often should I have follow-up exams or ?
  • Can you provide me with a survivorship care plan?

Open Clinical Trials
Open Clinical Trials

The following research studies are looking at  and cancer. 

Visit our Featured Research Page and Research Search and Enroll Tool to find additional studies enrolling people with, or at high risk for cancer. 

Updated: 11/23/2022

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