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RS for 40-year-old, 1.5-cm node+ (1 node) ER+ IDC? No. of MammaPrint® (70-gene signature) assays ordered in past 1 y?

Would you order an Oncotype DX assay for a 40-year-old premenopausal woman with a 1.5-cm, ER-positive, HER2-negative IDC and 1 positive node?

Approximately how many MammaPrint® assays have you ordered in the past year?

Kimberly L Blackwell, MD
Professor of Medicine
Director, Breast Cancer Program
Duke Cancer Institute
Durham, North Carolina
Answer: Yes; 0

I would order the assay for this 40-year-old patient with 1 positive node. I value the information that the assay provides, and I believe it allows me to better understand the biology of early breast cancer that is hormone driven. It sometimes helps me further define the risks and benefits of chemotherapy. I would not, however, order the assay for patients with N2 disease or for those for whom I would not consider administering chemotherapy.

I have not ordered any MammaPrint assays in the past year. The Oncotype DX assay serves my needs and it has been my practice pattern to use that assay. I believe the various genomic assays each have value, but most important is for practicing clinicians to pick an assay that they can understand and that has been validated in a population that is equivalent or similar to the patient population they are treating. It is important that clinicians understand the assay they choose and use it in the manner for which it has been developed.

Lisa A Carey, MD
Richardson and Marilyn Jacobs Preyer
Distinguished Professor for
Breast Cancer Research
Chief, Division of Hematology
and Oncology
Physician-in-Chief
North Carolina Cancer Hospital
Associate Director for
Clinical Research
Lineberger Comprehensive
Cancer Center
Chapel Hill, North Carolina
Answer: No; 0

I typically don’t order this assay for patients with N1 disease. I do support the RxPONDER (SWOG-S1007) trial, which will evaluate whether patients with hormone receptor-positive breast cancer, 1 to 3 positive nodes and Oncotype DX Recurrence Scores of 25 or lower benefit from the addition of chemotherapy to hormonal therapy after surgery.

I have never ordered a MammaPrint assay. I have not seen data validating an actual threshold for initiating chemotherapy or adding chemotherapy with MammaPrint as I have seen with the Oncotype DX assay. Both the MammaPrint and the Oncotype DX assays are helpful in ER-positive, HER2-negative disease, but they don’t provide much information elsewhere. I believe a better sense of the heterogeneity of the disease comes from the PAM50 signature or more intrinsic subtyping methods. However, I am uncertain as to how we are to use that approach in clinical practice.

Julie R Gralow, MD
Professor, Medical Oncology
Jill Bennett Endowed Professorship in Breast Cancer
University of Washington
School of Medicine
Director, Breast Medical Oncology
University of Washington School of
Medicine/Seattle Cancer Care Alliance
Member, Clinical Research Division
Fred Hutchinson Cancer
Research Center
Seattle, Washington
Answer: Yes, depending tumor biology; 0

I would consider an Oncotype DX assay for the 40-year-old patient, but it would depend on the tumor biology. If the tumor was high grade and had a lower level of ER expression, I might not recommend it because I would administer chemotherapy anyway.

I have not ordered a MammaPrint assay off study, although I have ordered a few as part of the I-SPY2 trial. I don’t believe that MammaPrint adds to the information that we obtain already from the Oncotype DX assay. I do believe that our field is heading toward the use of genomic predictor assays to assist with treatment decision-making, but I also believe that a combination of stage and biology will come into play. It’s not just one or the other. We need to figure out how to use the information on biology that we obtain from genomic assays along with the stage of the tumor.

Clifford Hudis, MD
Chief, Breast Cancer Medicine Service
Solid Tumor Division
Department of Medicine
Memorial Sloan-Kettering
Cancer Center
Professor of Medicine
Weill Cornell Medical College
New York, New York
Answer: Probably yes; 0

For the 40-year-old with a positive lymph node, I would lean toward ordering the Oncotype DX assay.

For patients with node-positive disease, as for those with node-negative disease, I would order an Oncotype DX assay to make a decision on the utility of chemotherapy in addition to hormone therapy. But the risk of omitting chemotherapy is greater in absolute terms when a node is positive. That’s the reason for a slightly more conservative stance for patients with positive nodes. However, my personal bias is that the biology that the Oncotype DX assay is describing is independent of the nodal status and having a positive lymph node does not render a tumor chemosensitive.

I have never ordered a MammaPrint assay. I’m a pragmatist, and for me the only assay that can help is an assay that can provide guidance on treatment. ER positivity guides me to administer hormone therapy, HER2 positivity leads me to administer anti-HER2 therapy, and a high Oncotype DX score informs me that chemotherapy should be used. None of the other genomic tests have that predictive ability yet.

Ian E Krop, MD, PhD
Associate Physician
Dana-Farber Cancer Institute
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Answer: Depends; 0

For a 40-year-old patient with node-positive disease, I would not order an Oncotype DX assay because it would be unlikely to change my treatment strategy. The exceptions would be if the tumor was low grade or the patient was chemotherapy averse because, unless the score were low, I would recommend chemotherapy.

I believe that the Oncotype DX assay can be useful for patients with node-positive cancer. The Oncotype Recurrence Score predicts sensitivity to and benefits of chemotherapy in both node-negative and node-positive disease. The absolute recurrence risks are lower for patients with negative nodes, but the ability of the assay to determine benefit from chemotherapy is similar.

I have never ordered a MammaPrint assay, and in the vast majority of cases if I needed a genomic predictor, I would use Oncotype DX. MammaPrint is potentially useful for hormone receptor-negative disease, for which Oncotype DX is not appropriate. However, the vast majority of these patients will end up with high-risk MammaPrint scores, so the test has limited utility for the vast majority.

Kathy D Miller, MD
Associate Director (Clinical Research)
Co-Director
IU Simon Cancer Center Breast Cancer Team
Sheila D Ward Scholar of Medicine
Associate Professor of Medicine
The Indiana University Melvin and
Bren Simon Cancer Center
Indianapolis, Indiana
Answer: Yes; 0

I would order an Oncotype DX assay in this scenario.

The factors that influence my decision to order the assay for a patient with negative versus positive nodes differ little, if at all. Oncotype DX tells us about the biology of the disease and the relative benefits of adding chemotherapy. I do not believe that a tumor that is inherently chemoresistant becomes sensitive to chemotherapy simply because it’s in a lymph node.

I have not ordered a MammaPrint assay because MammaPrint provides good prognostic data but not predictive data. I do not order an Oncotype DX assay to determine a patient’s prognosis. I order it to help me determine if the patient will benefit from chemotherapy. Currently, MammaPrint and PAM50 do not have that predictive information.

Joyce O’Shaughnessy, MD
Co-Director
Breast Cancer Research Program
Baylor-Charles A Sammons
Cancer Center
Texas Oncology
US Oncology
Dallas, Texas
Answer: Depends; 0

For this patient, I would order an Oncotype DX assay depending on the tumor biology. I would consider characteristics such as extent of ER/PR positivity, HER2 status and Ki-67 staining. If any adverse features were present I’d order the assay. Data from several studies have shown that the outcome of a patient who has 1 positive node and a low Recurrence Score is similar to that of a patient who has negative nodes.

I have never ordered a MammaPrint assay for any of my patients.

Hope S Rugo, MD
Professor of Medicine
Director
Breast Oncology and
Clinical Trials Education
University of California, San Francisco
Helen Diller Family Comprehensive
Cancer Center
San Francisco, California
Answer: Depends; 2

I would order an Oncotype DX assay for a 40-year-old patient with 1 positive node if she had a low-grade tumor and was highly resistant to chemotherapy. But I generally would not recommend it for a patient who has a high-grade tumor unless she is resistant to chemotherapy. I would also consider the extent of nodal involvement. If the patient had 3 millimeters of disease, I’d be more likely to recommend an Oncotype DX assay than for a patient who had a replaced node with extranodal extension.

I have ordered the MammaPrint study off protocol twice in situations where I needed to adjudicate Oncotype DX results because discordance was apparent between the Oncotype DX results and the clinicopathological features of the tumor. We are the lead institution for the multicenter I-SPY2 trial developed by Laura Esserman, and every patient who is screened for this trial has a MammaPrint assay performed. As part of this study, I have ordered many MammaPrint assays.