In an update to its 2016 clinical practice guideline on the use of biomarkers in early invasive breast cancer, the American Society of Clinical Oncology (ASCO) has outlined specific recommendations for using the MammaPrint (Agendia) genomic test to identify patients who can safely skip adjuvant chemotherapy.
The new paper, titled "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" was published onlineJuly 10 in the Journal of Clinical Oncology. Only the MammPrint test was reviewed for this update.
"Some women with breast cancer are more likely to have a recurrence of cancer and need to receive chemotherapy to lower this risk," Vered Stearns, MD, co-chair of the ASCO expert panel that developed the guideline update, said in a statment.
"The MammaPrint test can now be added to the list of tests that help clinicians identify women who need chemotherapy and those who do not," said Dr Stearns, who is co-director of the Breast Cancer Program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
The recommendations are based on findings from MINDACT (Microarray for Node-Negative Disease May Avoid Chemotherapy Trial). It showed that in more than 6500 women with early-stage breast cancer who had undergone surgery, the 70-gene assay was associated with a 46% reduction in chemotherapy prescription.
As previously reported by Medscape Medical News, the MINDACT results were initially presented at the American Association for Cancer Research 2016 Annual Meeting in New Orleans, Louisiana, and were then publishedin the New England Journal of Medicine.
"The MINDACT trial results provide level 1A evidence that using MammaPrint could change clinical practice by substantially de-escalating the use of adjuvant chemotherapy and sparing many patients an aggressive treatment they will not benefit from," said principal investigator, Martine Piccart, MD, PhD, head of the Department of Medicine at the Jules Bordet Institute in Brussels, Belgium, and cofounder and chair of the Breast International Group.
However, the test isn't suitable in all women with early breast cancer, said Ian Krop, MD, PhD, ASCO expert panel co-chair, in the statement. "We do not recommend it for women with HER2 [human epidermal growth factor receptor 2]-positive tumors or those with triple-negative breast tumors," said Dr Krop, a medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts.
Commenting to Medscape Medical News, Dr Krop said, "It is important that patients be informed that while the MammaPrint assay may be able to determine that their prognosis is relatively favorable, it cannot rule out that chemotherapy may still provide a small benefit."
"In addition, patients should understand that no biomarker test is perfect, and that some patients with favorable test results still have recurrence and that many patients with high-risk assay results remain disease free," Dr Krop added.
Other Genomic Assays
Other biomarker genomic assays that measure the expression of a relatively small number of genes in breast tumor tissue can also provide important prognostic and possibly predictive information and were included in the 2016 ASCO clinical practice guideline, the update authors point out. The genomic signatures identified as being useful in patients with node-negative estrogen receptor/progesterone receptor–positive cancers include Oncotype DX (Genomic Health Inc), EndoPredict (Myriad Genetics), PAM50 risk of recurrence score, and the Breast Cancer Index.
"None of these assays are perfect," the update authors acknowledge. Available data show that some patients developed recurrent disease despite favorable assay results, and many others with poor-prognosis genomic scores remain disease free without chemotherapy. "Thus, improvements are needed in the assays to additionally reduce overtreatment but minimize risk of recurrence," they conclude.
Recommended Use of the Test
The update of the 2016 clinical practice guideline recommends that MammaPrint be considered in women with estrogen receptor–positive or progesterone receptor–positive, HER2-negative, node-negative breast cancer who are at a high clinical risk for recurrence in order to determine whether adjuvant systemic chemotherapy would be beneficial.
It should also be considered in women with estrogen receptor–positive or progesterone receptor–positive, HER2-negative breast cancer with one to three positive lymph nodes who are at a high clinical risk for recurrence. "However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node," the update authors point out.
In any patients who meet these criteria and have a low MammaPrint score, hormone therapy alone is recommended because it is unlikely that chemotherapy will provide substantial additional benefits, they say.
It is not recommended that MammaPrint be used in women with a low clinical risk for recurrence. Thus, clinicians should not use MammaPrint to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, or any patient with HER2-positive or triple-negative breast cancer.
MINDACT results showed that women in the low clinical risk category did not benefit from chemotherapy "regardless of genomic MammaPrint risk," the update authors note. "Therefore, the MammaPrint assay does not have clinical utility in such patients," they add.
In addition, only a small number of patients with triple-negative breast cancer were included in MINDACT, and most of these patients were classified as high risk. As a result, most received chemotherapy and were not analyzed separately.
"Given that no other therapies (eg, endocrine therapy or HER2-targeted therapy) are recommended for these patients, the Panel felt strongly that until data from larger data sets are available, the MammaPrint assay should not be used to guide clinical decisions in patients with triple-negative breast cancer," the update authors write.
Another Use for the Test?
Recent results from a long-term follow-up study of patients with "ultralow-risk" breast cancers indicate the assay may also be helpful in identifying postmenopausal patients who can forgo standard endocrine treatment after surgery, although this particular use is not currently recommended by ASCO. The study was published online June 29 in JAMA Oncology .
As reported in Medscape Medical News, the study showed that patients with tumors that scored under the ultralow-risk threshold on MammaPrint and who did not receive tamoxifen had an "exceedingly low" risk for death from breast cancer during 20 years of follow-up.
"This is an exciting advance because approximately 20% to 25% of tumors diagnosed today may be ultralow risk," said lead investigator of that study, Laura Esserman, MD, from the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, in a press statement.
Dr Krop is an employee of AMAG Pharmaceuticals and also has relationships with Genentech and Novartis. Dr Stearns reports relationships with AbbVie, Merck, Pfizer, MedImmune, Novartis, Celgene, and Puma Biotechnology. Several other members of the expert panel also disclose potential conflicts of interest, which are available at jco.org .
J Clin Oncol. Published online July 10, 2017. Abstract