Guideline: Can MammaPrint guide treatment decisions?


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The American Society of Clinical Oncology (ASCO) recently updated its guidelines for MammaPrint, a genomic tumor test that guides treatment decisions for patients with early-stage invasive breast cancer. The update was based on results from the MINDACT study (11/16/17). 

Contents

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


STUDY AT A GLANCE

This study is about:

The use of MammaPrint to guide treatment decisions on the use of adjuvant chemotherapy for patients with early-stage invasive breast cancer.

Background:

The "Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy" (MINDACT) is a study that looked at almost 7,000 European women with early-stage invasive breast cancer. Researchers compared participants’ risk of recurrence using two separate means:

  • Clinical risk of recurrence using a program called Adjuvant! Online
  • Genomic risk of recurrence to determine risk for recurrence using MammaPrint—a tumor genomic test that looked at 70 genes within the tumor tissue.

Participants with discordant clinical and genomic risk (either high clinical risk and low genomic risk or low clinical risk and high genomic risk) were randomly assigned to have chemotherapy or not. Results from the MINDACT study published August 2016 in the New England Journal of Medicine showed that 94.7% of patients with high clinical risk but low genomic risk as assessed by MammaPrint who did not receive chemotherapy were alive without distant metastasis at 5 years. This is 1.5% fewer than the number of similar patients who received chemotherapy, demonstrating that chemotherapy does not provide benefit for the vast majority of these patients.

Why is this study important?

Reducing overtreatment in patients with early-stage breast cancer is important. Based on the results of the MINDACT trial, the American Society of Clinical Oncology (ASCO) recently updated their Clinical Practice Guidelines. While ASCO guidelines are regularly updated, guidelines are also revised when new, potentially practice-changing data is published. In August, 2017 ASCO updated it guidelines on the use of MammaPrint to help early-stage invasive breast cancer patients and health care providers to decide which women can forgo adjuvant chemotherapy based on the MINDACT trial results.    

Study finding: 

The MINDACT study showed that the MammaPrint test could predict which patients will have a favorable prognosis without adjuvant chemotherapy.

What does this mean for me?

ASCO now recommends that MammaPrint may be used to help clinicians identify which early-stage invasive breast cancer patients may have limited benefit from adjuvant chemotherapy.

The MammaPrint test is appropriate for patients with hormone receptor-positive (ER–positive and PR-positive) HER2-negative breast cancer with 0-3 positive lymph nodes for whom Adjuvant! Online predicts a high clinical risk. However, no test is perfect. Some patients in the MINDACT study developed recurrent disease, even though MammaPrint testing suggested otherwise; other patients with poor MammaPrint scores remain disease free, even without chemotherapy. 

If you have recently been diagnosed with early-stage invasive breast cancer, your physician may recommend the MammaPrint test. Based on the results, you may choose to forego adjuvant chemotherapy

Expert Guidelines

The American Society of Clinical Oncology (ASCO) has published guidelines on the use of different biomarker tests to guide decisions on adjuvant chemoatherapy or hormone therapy in early-stage breast cancer. Among their recommendations. Strength of recommendation is noted in parentheses):

  • OncotypeDx
    • For ER/PR-positive, HER2-negative, node-negative breast cancer, the clinician may use 21-gene recurrence score (21-gene RS; Oncotype DX; Genomic Health, Redwood, CA) to guide decisions for adjuvant systemic chemotherapy. (strong)
    • For ER/PR-positive, HER2-negative, node-positive breast cancer, the clinician should not use the 21-gene RS to guide decisions for adjuvant systemic chemotherapy. (moderate)
    • For patients older than 50 and whose tumors have Oncotype DX recurrence scores <26, and for patients <50 whose tumors have Oncotype DX recurrence scores <16, there is little to no benefit from chemotherapy. Clinicians may offer endocrine therapy alone. (strong)
    • For patients 50 years of age or younger with Oncotype DX recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. (moderate)
    • Patients with Oncotype DX recurrence scores >30 should be considered candidates for chemoendocrine therapy. (strong)
    • Based on Expert Panel consensus, oncologists may offer chemoendocrine therapy to patients with Oncotype DX scores of 26 to 30 (moderate)
  • Mammaprint
    • For patients with ER/PR-positive, HER2-negative, node-negative, breast cancer, the MammaPrint assay may be used in those with high clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good prognosis population with potentially limited chemotherapy benefit. (strong)
    • For patients with ER/PR-positive, HER2-negative, node-negative, breast cancer, the MammaPrint assay should not be used in those with low clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy as women in the low clinical risk category had excellent outcomes and did not appear to benefit from chemotherapy even with a genomic high risk cancer. (strong)
    • For patients with ER/PR-positive, HER2-negative, node-positive, breast cancer, the MammaPrint assay may be used in patients with 1-3 positive nodes and at high clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good prognosis population with potentially limited chemotherapy benefit. However, such patients should be informed that a benefit of chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. (moderate)
    • For patients with ER/PgR-positive, HER2-negative, node-positive, breast cancer, the MammaPrint assay should not be used in patients with 1-3 positive nodes and at low clinical risk per MINDACT categorization to inform decisions on withholding adjuvant systemic chemotherapy. There are insufficient data on the clinical utility of MammaPrint in this specific patient population (moderate)
  • Prosigna Breast Cancer Prognostic Gene Signature Assay
    • If a patient has ER/PgR-positive, HER2-negative, node-negative breast cancer, the clinician may use the PAM50 risk of recurrence score, in conjunction with other clinicopathologic variables, to guide decisions about adjuvant systemic therapy. (strong)

Additional information on other tumor types and biomarker tests can be found on the ASCO website.

The National Comprehensive Cancer Network (NCCN) has expert-developed guidelines for treating breast cancer. NCCN guidelins for node-negative, ER-positive, Her2-negative breast cancer includes the following recommendations. 

  • For tumors greater than 0.5 cm, strongly consider Oncotype DX. 
    • Adjuvant endocrine therapy is recommended for patients with a recurrence score of less than 26. 
    • Consider adjuvant chemotherapy in women 50 years of age or younger with a recurrence score of 16-25 based on the TAILORx study.
    • Adjuvant endocrine therapy or adjuvant chemotherapy followed by endocrine therapy is recommended for patients with a recurrence score of 26-30.
    • Adjuvant endocrine therapy and adjuvant chemotherapy both recommended for patients with a recurrence score of 31 or higher. 
  • NCCN notes that data are limited with regards to the use of Oncotype in men. Available data suggests that the test provides prognostic information for men. 

NCCN notes that other prognostic tumor tests are available for treatment decision-making. The NCCN guidelines state that the Oncotype Dx 21-gene panel is preferred by the Breast Cancer Panel for node negative breast cancer.  

These guidelines are up-to-date as of 09/29/19.

Questions To Ask Your Health Care Provider

  • What is a genomic test versus a genetic test?
  • What exactly is MammaPrint?
  • Are you aware of the updated ASCO guidelines on using MammaPrint to guide adjuvant treatment?
  • Is MammaPrint a test I should consider based on my diagnosis and stage of breast cancer?
  • What costs are associated with MammaPrint testing? Will my insurance cover it? 
  • What are the risks of overtreating my cancer? What are the risks of undertreating it?
  • Does my MammaPrint score agree with my clinical risk score?

Open Clinical Trials

The following study is looking at tumor prognostic tests used for decision-making in early-stage breast cancer: 

IN-DEPTH REVIEW OF RESEARCH

Study background:

From 2001 to 2007 researchers organized a large randomized trial in Europe to see whether a commercial genomic tumor test called MammaPrint could reduce overtreatment with chemotherapy in patients with early-stage invasive breast cancer. More than 6,600 women participated at 112 institutions in 9 nations. Each participant’s clinical risk of cancer recurrence was determined using a web-based tool called Adjuvant! Online. Patient’s tumors were also tested using MammaPrint, which produced a genomic score. Participants with discordant clinical and genomic risk (either high clinical risk and low genomic risk or low clinical risk and high genomic risk) were randomly assigned to receive adjuvant chemotherapy or not. The results, which were published in the New England Journal of Medicine in August 2016, suggest that approximately 46% of women with breast cancer who are at high clinical risk for recurrence might not benefit from adjuvant chemotherapy. As a result, ASCO updated guidelines on the use of MammaPrint to guide decisions on the use of adjuvant chemotherapy in an ASCO Special Article published in the Journal of Clinical Oncology in August, 2017.

Researchers of this study wanted to know:

Can MammaPrint, a commercially available genomic test, help to reduce overtreatment in patients with early-stage breast cancer?

Population(s) looked at in the study:

MINDACT was a randomized trial that looked at 6,693 women with operable invasive breast cancer, 0 to 3 positive lymph nodes, and no distant metastases. Eligible patients were women between the ages of 18 and 70. Initially, only patients with node-negative disease were enrolled; however, the study was later amended in 2009 to include women with 1 to 3 positive nodes. Researchers determined participants’ clinical risk (using a modified version of Adjuvant! Online), genomic risk (using MammaPrint) and tumor samples.

The patients were divided into 4 main groups according to their clinical and genomic risk, and received either adjuvant chemotherapy or no therapy:

  • Low clinical risk and low genomic risk: 2,745 patients (41.0%)
    • No adjuvant therapy
  • Low clinical risk and high genomic risk: 592 patients (8.8%)
    • Randomized to chemotherapy or no chemotherapy
  • High clinical risk and low genomic risk: 1,550 patients (23.2%)
    • Randomized to chemotherapy or no chemotherapy
  • High clinical risk and high genomic risk: 1,806 patients (27.0%)
    • Adjuvant chemotherapy

Study findings: 

Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence and did not receive chemotherapy, the 5-year survival rate was 94.7%; the survival rate for those who did receive chemotherapy was 96.2%. This difference of 1.5 percentage points suggests that approximately 46% of women with early-stage invasive breast cancer who are at high clinical risk and low genomic risk do not receive benefit from adjuvant chemotherapy

Conclusions:

ASCO used the results of the MINDACT trial to revise its clinical guidelines regarding the use of MammaPrint for decision making regarding use of adjuvant chemotherapy for patients with early-stage invasive breast cancer. MammaPrint may inform patients with ER-positive or PR-positive, HER2-negative breast cancer and 0-3 positive lymph nodes and their clinicians whether or not to forego adjuvant chemotherapy. Although MammaPrint can be used to identify patients with high clinical risk who may receive limited benefit from chemotherapy, women with low clinical risk of recurrence did not benefit from chemotherapy, regardless of their MammaPrint risk group. Thus, ASCO does not recommend the use of MammaPrint for patients with low clinical risk. 

Posted 11/16/17

References

Krop I, Ismaila N, Andre F, et al.  “Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update.” Journal of Clinical Oncology 35, no. 24 (August 2017) 2838-2847.

Harris L, Ismaila N, McShane L, et. al. "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.Journal of Clinical Oncology 34, no. 10 (April 2016) 1134-1150.

Cardosa F, Van t’ veer LJ, Boegerts J, et al. “70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.New England Journal of Medicine 2016; 375:717-729 August 25, 2016

 

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