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Gene test identifies women with early breast cancer who can be spared adjuvant chemotherapy
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CHICAGO — The addition of adjuvant chemotherapy to endocrine therapy did not appear to benefit women with hormone receptor-positive, HER-2-negative, axillary node-negative breast cancer with a mid-range recurrence score on a 21-tumor gene expression assay, according to results of the phase 3 TAILORx clinical trial presented during the plenary session at ASCO Annual Meeting.
These findings suggested this patient population — which represented two-thirds of the trial cohort — can safely be spared chemotherapy after surgery.
“For impact on care, application of this test in clinical practice to this population would be estimated to spare chemotherapy in about 70% and select chemotherapy in 30% on average,” Joseph A. Sparano, MD, professor of medicine and obstetrics, gynecology and women's health at the Albert Einstein College of Medicine, and associate chairman for clinical research in the department of oncology at Montefiore Medical Center, said during a press conference.
Fifty-percent of all breast cancers are ER positive, HER-2-negative and axillary node negative. Thirty percent of this population may have incurable recurrence by 10 years.
Adjuvant chemotherapy is recommended for women with early breast cancer. However, the absolute benefit is small, ranging from 3% to 5%.
“Most patients being overtreated because endocrine therapy alone is adequate, but some are undertreated and some who did not receive chemotherapy could have benefitted from it,” Sparano said.
The Oncotype DX Breast Recurrence Score (Genomic Health) — also called the 21-gene expression assay — provides individualized risk assessment for early-stage invasive breast cancer in adjuvant and neoadjuvant settings. Typically, women with a low score (0-10) receive endocrine therapy alone and women with a high score (26-100) receive endocrine therapy plus chemotherapy.
“We knew from previous studies the information provided by this assay was prognostic in the sense that those individuals with low recurrence score had low risk for recurrence with endocrine therapy alone,” Sparano said. “Additionally, it showed large benefit when chemotherapy was added to endocrine therapy for women with a high score, but there was uncertain chemotherapy benefit among patients with a mid-range score.”
The trial included 10,273 women with a low (n = 1,629), mid-range (n = 6,711) or high (n = 1,389) recurrence score.
Researchers randomly assigned women with mid-range recurrence scores of 11 to 25 to receive endocrine therapy alone (n = 3,399) or with chemotherapy (n = 3,312). Thirty-three percent of the women were aged younger than 50 years (median, 55 years) and 63% had tumor size between 1 and 2 cm.
Invasive DFS served as the study’s primary endpoint.
Median follow-up was 7.5 years, at which time 836 events had occurred.
Nine-year DFS rates were comparable between the groups (83.3% vs. 84.3%), for a HR of 1.08 (95% CI, 0.94-1.24). In addition, distant recurrence rates (94.5% vs. 95%) and OS rates (93.9% vs. 93.8%) were similar, indicating patients experienced no benefit from chemotherapy when added to hormone therapy.
Among women with low recurrence score, there was a 3% distant recurrence rate with endocrine therapy alone. Among women with high recurrence score, there was a 13% distant recurrence rate despite chemotherapy.
However, in an exploratory analysis, women aged younger than 50 years with a recurrence score between 16 to 25 showed some benefit from chemotherapy, Sparano said.
“We conducted this analysis to make sure there was no subgroup who could derive some benefit from chemotherapy; we found interaction between age and recurrence score,” Sparano said.
There were 2% fewer recurrences for women with recurrent scores between 16 and 20 and 6% to 7% fewer recurrences for women with scores between 21 to 25.
“This is information that could drive some younger women who have recurrence scores in this range to accept chemotherapy,” Sparano said. – by Melinda Stevens
Reference:
Sparano J, et al. Abstract LBA1. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Sparano reports consultant/advisory roles with AstraZeneca, Celgene, Celldex, Genentech/Roche, Juno Therapeutics, Lilly, Merrimack, Novartis, Pfizer and Prescient Therapeutics; stock and other ownership in Metastat; and research funding to his institution from Deciphera, Genentech/Roche, Merck, Merrimack, Novartis and Prescient Therapeutics. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Harold J. Burstein, MD, PhD, FASCO
These are very important data because this is the most common form of breast cancer in the United States and developed countries. One of the most challenging decisions we make with these patients is to recommend endocrine therapy with all its side effects and potential benefits. With the data provided from this massive trial, the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.
Over the past 12 years, we’ve been using this test on a day-to-day basis. You might ask why we needed this investment to validate that experience. It is important for several reasons. First, the original data for use of recurrence score were based on chemotherapy regimens that were now 25 years old. So, if we use modern chemotherapy, would the results be different? Secondly, we’ve improved our endocrine treatments and antiestrogen approaches, which also may have affected these results. Third, it is important to have a prospective validation of the data. Finally, there was a gray, intermediate zone, where the magnitude of benefit for chemotherapy was unclear, creating practical decision-making challenges for patients and clinicians.
The results are clear. For almost all women who have tumors with recurrence scores less than 25, there will be no role for chemotherapy. There will be discussion for the small group of women aged younger than 50 years who have intermediate-range recurrence scores in the order of 20 or 25 as to whether they need chemotherapy or whether using an alternative endocrine therapy can accomplish the same goals.
This isn’t so much about de-escalation. The goal of the study is not to just use less treatment, but to tailor treatment, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different therapy based on biology. This is extraordinary data for breast cancer doctors and for women with breast cancer. It allows us to individualize treatment based on extraordinary science that now has tremendous prospective validation.
There will be questions moving forward. But, for today and the weeks to come, it is a very powerful finding.
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