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Using Genomic Assays to Learn Which Patients With Breast Cancer Could Get Less Treatment


Coverage from the July 25, 2023, session of the Institute for Value-Based Medicine®, presented by The American Journal of Managed Care® in partnership with Emory's Winship Cancer Institute.

Being treated for breast cancer is taxing enough without receiving more therapy than necessary. Thanks to the current generation of genomic assays—and a wave of research surrounding them—clinicians are gaining insights into how much therapy individual patients need when treated for early-stage HR-positive, HER2-negative breast cancer (HR+/HER2–), according to Kevin Kalinsky, MD, MS, of Emory University’s Winship Cancer Institute.



Kalinsky is the associate professor of medicine and Louisa and Rand Glenn Family Chair in Breast Cancer Research; and director of Breast Medical Oncology at Winship and the Glenn Family Breast Center. He shared an overview of recent studies on precision medicine at the July 25 session of the Institute for Value-Based Medicine®, presented by The American Journal of Managed Care® in partnership with Emory.

At Winship, use genomic assays can determine “who needs chemotherapy or not, for de-escalation or even opting out of therapy,” Kalinsky said. This has value, he said, because some patients can be treated just with endocrine-based therapy and avoid chemotherapy.

He began with a review of the landmark TAILORx study (NCT00310180), funded by the National Cancer Institute (NCI), which brough clarity to the use of the OncotypeDX assay in making decision on adjuvant therapy in early-stage HR+/HER2– breast cancer.1 Just over 10,200 women took part in the study and 69% had mid-range recurrence scores (11 to 25) where use of chemoendocrine therapy was not clear-cut. Results showed there was little difference between the chemoendocrine and endocrine-only groups, but chemotherapy seemed to offer some benefit for women younger than 50 years with a recurrence score of 16 to 25.

But was it the chemotherapy, or something else? The initial TAILORx study was presented in 2018, and now investigators have 13 years of follow-up data, and Kalinsky took a deep dive into questions that breast cancer researchers have been pondering ever since. Updated data presented in December at the San Antonio Breast Cancer Symposium found that the predictive value of the assay held across the different groups in the study.2

In this trial, the cutoff of age 50 acted as a surrogate for menopause, Kalinsky said. “There were some patients who did benefit in an exploratory analysis from the addition of chemotherapy, which begs the question, is that benefit that we're seeing? Because this is really a pre-menopausal population.”

Is the benefit from the chemotherapy, or “Is it because these are all estrogen-driven breast cancers? Is it because we're stopping their periods? Is this an expensive and unsophisticated way of just stopping patients periods, which is really what's driving the benefit? That remains an ongoing question within our field.”

Kalinsky said TAILORx has shown that the recurrence score by itself cannot be viewed in isolation. “It’s the incorporation of clinical features like grade and tumor size, and other pathologic features that really inform risk,” he said. An online tool that incorporates all these elements, RSClin, is now available.3

“We’re moving away from a one-size-fits-all approach. We’re offering precision medicine where we can say to patients, ‘Your risk is x, and you don't need chemotherapy based upon the biology of your tumor.’”

A later study, RxPONDER (NCT01272037), examined women with node-positive cancer and also upended old beliefs, he said. Decades ago, this clinical feature would have always indicated chemotherapy. But when a study was done with the assay, postmenopausal women with recurrence scores of 0 to 25 did not have to have chemotherapy.4

“So this is saving tens of thousands of women—and men—unnecessary side effects and toxicities and all the things that are associated with giving chemotherapy,” Kalinsky said.

Once again, the premenopausal women in the study benefited from chemotherapy.

Other data from RxPONDER, which are still maturing, will show how ovarian function affects the brain’s ability to keep producing estrogen. Women with optimal ovarian suppression appear to fare better, but of course, the downsides are significant. “We’re putting patients into menopause and it’s not easy to tolerate,” he said. “It causes lots of side effects, including hot flashes, mood dysfunction, bone issues, and cardiac dysfunction.”

One facet that Kalinsky reported at the San Antonio meeting in December is that despite better medication adherence, Black and Hispanic women fared worse.5

Helping women avoid unnecessary chemotherapy has important quality-of-life implications, he said, because the cognitive effects are quite real, as seen in patient-reported data from RxPONDER.6 “This is something that patients complain about, which might have heard: the term chemo brain,” he said. “The data support this.”

Kalinsky said he’s looking ahead to a national study coming soon that will randomize high-risk, node-negative and node positive patients to receive ovarian function suppression plus hormonal therapy, with or without chemotherapy. “This is the study that’s going to define, in a genomically defined population, whether or not we should be giving chemotherapy.”

Other assays, such as MammaPrint, are on the American Society of Clinical Oncology (ASCO) guidelines, he noted, but they are not all the same. Guidelines suggest sticking with one type of assay for a patient instead of switching back and forth.

He said the breast cancer field is seeing interest in circulating tumor DNA markers, but that, “Our colorectal colleagues are the ones who are furthest along in terms of escalation and de-escalation of therapy based upon circulating tumor DNA. This is not quite ready for primetime in patients with breast cancer."

“One of the issues that we face that others in this room likely face as well, is that if you check the test in a patient who has curable disease, and you have a positive assay, what do you do about it except for worry?”

Should a patient on an endocrine therapy switch to a different one, or to a different drug class? Does that increase or decrease the rate of recurrence? “This is something that we don't have the answer for yet. But there are a number of studies,” Kalinsky said. “There's an NCI-sponsored study that should hopefully be opening with the year to address this question.”


  1. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111-121. doi: 10.1056/NEJMoa1804710
  2. Sparano JA, Gray RJ, Makower DF, et al. Trial assigning individuaLized options for treatment (TAILORx): An update including 12-year event rates. Presented at: San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX; Abstract GS1-05.
  3. Helwick C. Prognostic tool RSClin introduced for early breast cancer. ASCO Post. March 10, 2021. Accessed August 3, 2023. https://ascopost.com/issues/march-10-2021/prognostic-tool-rsclin-introduced-for-early-breast-cancer/
  4. Kalinsky K. Barlow WE, Gralow JR, et al. 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med. 2021;385:2336-2347. DOI: 10.1056/NEJMoa2108873
  5. Study finds Black women have worst HR-positive, HER2-negative breast cancer outcomes of all racial and ethnic groups. News release. Winship Cancer Institute. December 6, 2022. Accessed August 3, 2023. https://bit.ly/3rTKj46
  6. Kang I, Forschmiedt J, Loch M, et al. Patient-reported cognitive impairment in women participating in the RxPONDER trial (SWOG S1007) by menopausal status. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS1-04.
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