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Oncotype DX May Be Helpful in Guiding Neoadjuvant Breast Cancer Treatment Decisions

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NEW YORK – Three new studies presented at the American Society of Clinical Oncology's virtual annual meeting are highlighting the potential value of Exact Sciences' Oncotype DX Breast Recurrence Score test for helping to determine whether women with hormone receptor positive, HER2-negative breast cancer can avoid the use of neoadjuvant chemotherapy.

One of the studies showed that the test could be especially beneficial in the decision-making process for younger patients in need of neoadjuvant therapy, which could lead to an expanded use of the test.

Two years ago, the TAILORx study concluded that women with Oncotype DX recurrence scores from a low-risk threshold of 11 up to a high-risk threshold of 25 appear to benefit equally when treated with endocrine therapy alone compared to hormonal therapy with added chemotherapy, as long as they are over the age of 50. The question about the test's predictive power had already been answered when it came to higher and lower prediction scores, but TAILORx told doctors how they should look at intermediate scores as well.

However, for women younger than 50, the picture was still a bit complicated. Unlike older women who all had negligible added benefit from chemo up to a risk score cutoff point of 25, an exploratory analysis in the TAILORx study revealed that there was still a small benefit from chemotherapy for women under 50 with risk scores above 15. This left some doctors reluctant to change their treatment practices and made it clear that more research was needed.

"The historical standard approach for young women in particular has been chemotherapy, regardless of what their cancer is like under the microscope, regardless of its characteristics or its phenotype," said Ann Partridge, a breast cancer oncologist at the Dana-Farber Cancer Institute and senior author on one of the three new studies presented at ASCO. "We've switched in postmenopausal women or older women when they have an ER-positive-looking tumor when they need neoadjuvant therapy, and we've given them hormonal therapy. But in premenopausal women, we've been reluctant to do that because it's been hard to give up chemotherapy in younger patients."

The study Partridge co-authored looked at whether Oncotype DX could predict response to neoadjuvant chemotherapy in young women with estrogen receptor-positive early breast cancer. The researchers assembled a cohort of 76 patients and performed Oncotype analyses on tumor specimens removed prior to neoadjuvant chemotherapy either as part of clinical care or retrospectively for research.

They found that the mean recurrence score was significantly higher among tumors that achieved a pathologic complete response (pCR) compared to the tumors that had a non-pCR response. The pCR rate in patients with a recurrence score greater than 25 was 21 percent compared to 5 percent in patients with a recurrence score of less than 25.

"This particular study is looking at, 'What does chemo do for these young women? Does it behave differently in these young women by the Oncotype test or genomic expression prediction assay?' Indeed, it does," Partridge said.

The results aren't surprising, she added, but the data is important as oncologists think toward the future of the most efficacious way to treat patients in the neoadjuvant setting. "If your goal is to get active cancer therapy that shrinks your tumor and might make it go away, chemotherapy in a lower risk Oncotype does not appear to be the answer preoperatively, based on these data in younger women, similarly to what we knew already about older women," Partridge said.

Although the data is important, there isn't yet enough evidence to change clinical practice for young women, she noted. For certain patients, such as those women needing neoadjuvant therapy who have particularly large tumors or nodal involvement, it's going to be hard to avoid chemotherapy and stick to endocrine therapy alone until there's some other treatment to combine with the hormones, Partridge said. The key is to develop more targeted therapies to treat both younger and older women. What this study speaks to, she added, is that oncologists may be able to shift lower risk genomic tumors to treatments with a hormone backbone so that less harm is done with chemotherapy.

"So, I don't think it's practice changing. I think it's research changing at this point because, of course, we don't have outcomes associated with it, and we don't have necessarily a great partner for it yet, although certainly there are studies that are being planned and are underway to try and partner other therapies with hormonal therapy or to make chemotherapy better," Partridge said. "But, of course, we'd love to get away from the toxicity of chemotherapy when we can."

The two other studies Exact presented at ASCO also looked at Oncotype in the neoadjuvant setting, finding it to be similarly efficacious. In one, researchers from Spain analyzed a prospective cohort of 63 early luminal breast cancer patients with a median age of 54, who received neoadjuvant chemotherapy after Oncotype testing. They found that Oncotype score was the most significant predictor of pathological response compared to Ki67 biomarker status, estrogen receptor status, and initial tumor size. Further, all the patients who achieved a complete pathological response had a recurrence score result of 26 or higher.

"The Oncotype DX Recurrence Score could be a useful tool to select early breast cancer patients who will benefit from neoadjuvant chemotherapy," the authors wrote. "Oncotype DX is the most significant predictor variable of pathological response, and patients with a Recurrence Score of 25 or greater are five times more likely to obtain a histological response type 0-1."

In the other study, researchers from the Middle East and France presented results from the SAFIA Phase III trial, which aimed to predict response to neoadjuvant hormonal therapy using Oncotype recurrence scores.

A total of 308 patients with stages II and IIIA Luminal A/B HER2 negative breast cancer underwent upfront recurrence scoring to be selected for induction hormone therapy. They found that about 97 percent of patients with a recurrence score of 0 to 30 who received neoadjuvant endocrine therapy without chemotherapy had a clinical response or stable disease after four months, suggesting that patients with a recurrence score of less than 31 can be offered neoadjuvant endocrine therapy alone with minimal risk of disease progression.

For their part, Partridge and her colleagues are already considering new research studies to follow up on the current data. "We are thinking about putting together a meta-analysis, looking at all of the studies that have looked at Oncotype in the neoadjuvant setting, just to get more data pooled," she said. "And then the second big thing is we are working on a study to potentially use Oncotype in a prospective way to dictate therapy, to support people to get chemo or not get chemo based on their Oncotype."

According to Exact Chief Medical Officer Steve Shak, the three new studies are likely to lead to an expansion of Oncotype's use. He also pointed to a new use for Oncotype in the neoadjuvant setting — as a tool to help oncologists determine how to safely treat patients in order to temporarily keep them out of the operating room as hospitals deal with the flood of COVID-19 patients still overwhelming the healthcare system.

In March, representatives from the American Society of Breast Surgeons, the National Accreditation Program for Breast Centers, the National Comprehensive Care Network, the Commission on Cancer, and the American College of Radiology formed the COVID 19 Pandemic Breast Cancer Consortium and released guidelines on the triage of breast cancer patients during the pandemic.

The organizations "updated their guidelines to recommend guiding neoadjuvant treatment decisions for newly diagnosed patients with a recurrence score, which can determine which patients can be treated with hormone therapy alone so that they could postpone surgery until a time when it can be performed safely," Shak said. "We are delighted to be able to partner with those societies in leading to a very rapid and appropriate modification of a best standard of care, which will allow Oncotype to add value in this unique setting and building on the role that it's already played."

Given these updated guidelines, as well as the data from the three new ASCO studies, Shak believes there will be an "expanded use of the recurrence score in the [neoadjuvant] setting so that patients can get the right treatment before surgery."

And although Partridge had noted that more research will likely be needed before clinical practices change for young women in the neoadjuvant setting, Shak noted that clinical practice may already be changing in the neoadjuvant setting as a whole.

"We collect core biopsies [that are] submitted for testing — those are the ones that are done as an outpatient prior to surgery," Shak said. "Maybe four months ago, they amounted to about 14 percent of the overall Oncotype breast cancer recurrence score submissions. In the last two to three months, the percentage of core biopsies coming in has increased by almost 50 percent. So, we're seeing the effect on practice already."