Expert Discusses MINDACT, TAILORx Studies in Breast Cancer

Michelle E. Melisko, MD

Although chemotherapy may have a lesser role in breast cancer treatment for select patients, there are still high-risk populations who will derive benefit from this modality, said Michelle E. Melisko, MD.

Updated findings from the MINDACT trial identified a subset of women who could safely avoid not only adjuvant chemotherapy, but also radiotherapy. The data show that patients with small, low-grade, well-defined breast tumors and a genetic profile showing they are at low risk of the cancer metastasizing were unlikely to benefit from adjuvant chemotherapy.

Among 6693 patients enrolled in the study, treatment decisions were made based on the size, grade, and hormonal status of the tumor. Genetic makeup was investigated using MammaPrint, which analyzes 70 genes to determine risk of recurrence.

Furthermore, results from the phase III TAILORx study presented at the 2018 ASCO Annual Meeting paved the way for physicians to reduce the toxicity of treatment for early-stage breast cancer. The trial utilized the Oncotype DX Breast Recurrence Score to determine the efficacy of hormone therapy plus chemotherapy versus hormone therapy alone in intermediate-risk patients.

In patients with hormone receptor (HR)—positive, HER2-negative breast cancer, TAILORx demonstrated noninferiority for endocrine therapy alone. After 5 years of follow-up, invasive disease-free survival (iDFS) rates were 92.8% for those who had hormone therapy alone and 93.1% for those who also had chemotherapy. At 9 years, IDFS rates were 83.3% and 84.3%, respectively.²

OncLive: Please provide an overview of your presentation at the State of the Science Summit.^TM

In an interview during the 2018 OncLive^® State of the Science Summit™ on Breast Cancer, Melisko, a clinical professor of medicine at the University of California, San Francisco, discussed the clinical implications of the TAILORx and MINDACT studies.Melisko: I reviewed the clinical trials that have recently been published and presented, including MINDACT for MammaPrint and the TAILORx trial, which looked at the value of the Oncotype DX assay to predict the benefit of chemotherapy in patients with HR-positive, HER2-negative breast cancer. I gave a brief historical reference of how we used to give chemotherapy to almost all patients with estrogen receptor (ER)-positive, HER2-negative breast cancers.

Could you discuss the importance of the TAILORx trial?

Things have started to evolve over time, beginning with the introduction of Oncotype DX as far back as the early 2000s; MammaPrint came in the mid-2000s. We started to realize that not all patients may benefit equally from chemotherapy. I reviewed the data from these 2 trials and compared and contrasted the populations and differences in endpoints. I wanted to help the community oncologists decide which of these assays is the best to send for each case.I remember the day this trial reported, and it was actually shocking that [subsequently] so many patients were coming in with high-risk disease—triple-negative breast cancer, HER2-positive breast cancers, young women with 6- to 7-cm tumors, and node-positive disease. They were saying things like, “I just read in the paper today that I don’t need chemotherapy.” I said, “We’ve been using Oncotype DX since about 2002, and if I thought that test would provide value for you, we would have ordered it.”

The problem with the [consumer media] is that they tend to sensationalize things, so they made it seem like we simply didn’t have this test in our practice and had no interest in it. The population of patients in TAILORx—the 11 to 25 recurrent score population—has been a challenge for breast oncologists for a long time. The traditional Oncotype DX intermediate score bucket was not aligned with that—it was about 17 to 30.

The TAILORx trial shifted the population down and sort of said, “OK, now we have a whole population that we don’t know what to do with.” Generally, clinical judgement still weighed in. If I had a patient with a 1.1-cm grade 1 cancer, I would seldom send for an Oncotype DX because I knew what the score was going to be. I knew these women would not need chemotherapy. This test is very helpful for patients on the edge with tumors closer to 2 cm that are of intermediate grade. People need to understand that medical oncologists have already implemented this practice of offering less chemotherapy.

What about the MINDACT trial?

That is one important thing to consider when analyzing these data—the exploratory analysis they did. It looked at women under the age of 50 years; data indicated there was some benefit to chemotherapy in patients with recurrent scores of 20 to 25— maybe even less than 16.It was published 2 years ago. It’s not old news, it’s good news. This trial incorporated patients who had up to 3 positive nodes. Almost always, in the past, if a patient had 3 positive nodes they were recommended for chemotherapy. From the MINDACT trial, we can identify a subset of patients with low-risk disease who may not benefit from chemotherapy. It also shows that some higher-grade tumors may have a more indolent biology because they are ER-positive.

Is there anything else the media has swept under the rug with regard to this research?

How do you distinguish between Oncotype DX and MammaPrint?

Is there anything you would like to add?

MammaPrint looks at 70 genes and at a tumor in different ways. It may give us some greater insight into the biology of the cancer. At 5 years in that group, patients without chemotherapy had almost a 95% chance of being alive and free of distant metastasis. I presented the benefits of chemotherapy often seen within the first 5 years. Although the TAILORx trial had 9 years of follow-up and MINDACT had only 5 years, we think the benefits of chemotherapy are going to be seen early.In the TAILORx presentations, I didn’t hear a single report saying there appears to be an indication that women under the age of 50 years may actually benefit from chemotherapy at the higher end of those recurrence scores. It’s unfortunate these weren’t highlighted. There are obviously clinical factors that still have to be considered. I don’t think the media stressed enough that the TAILORx population was a node-negative population. That doesn’t take away anything from the value of the trial; however, it’s a relatively narrow population.I don’t see any reason to order an Oncotype DX assay in this day and age for a patient with 1 to 3 positive nodes. The test of choice should be MammaPrint. If you have a patient with clinically low-risk disease, that patient would have been considered low risk on MINDACT and would have been assigned to endocrine therapy.Many patients come in with the expectation that they need 1 of these tests. Part of it is age-dependent and part of it is preference-dependent. None of this takes away from the need to talk with patients, get their perspective, and find out what their biases are. If they wish to decline chemotherapy, it’s not worth ordering the test. In patients with what appears to be low-risk disease, neither test will be helpful.

There were data at this meeting that Dr Laura Esserman presented, looking at patients in Sweden with long-term follow-up. These patients received either no endocrine therapy or a short course of endocrine therapy of just 2 years. [Researchers] applied MammaPrint to this population. They found that there’s a threshold under which patients can achieve phenomenal outcomes—97% chance of being alive and without recurrence risk at 20 years. There may be a chance to use a test like MammaPrint to identify those who don’t need endocrine therapy. That’s the important factor of MammaPrint: all of the prognostic information it provides.

References

1. Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treat- ment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi: 10.1056/NEJMoa1602253.
2. Sparano JA, Gray RJ, Wood WC, et al. TAILORx: phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-neg- ative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score. J Clin Oncol. 2018;36(18 suppl; abstr LBA1). doi: 10.1200/ JCO.2018.36.18_suppl.LBA1.