Earlier this month, the long-awaited results of the TAILORx clinical trial were announced.
The findings from this study are important for early stage breast cancer patients with hormone receptor-positive breast cancer. The study results are expected to assist many patients in this group in determining whether chemotherapy should be part of their treatment.
The TAILORx findings are also interesting when viewed as part of a developing trend in treatment for early stage breast cancer away from a one-size-fits all approach toward more personalized care.
The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) and also published in the New England Journal of Medicine (NEJM).
Background and Purpose of TAILORx Study
Chemotherapy has long been a part of standard treatment for early stage breast cancer. As the NEJM article notes, studies in the 1980s and 1990s found that adjuvant chemotherapy reduces the risk for recurrence, particularly in younger women. Based on those findings, chemotherapy has been recommended for most patients because there was little information that could reliably distinguish patients who would benefit from it from those who would not.
That began to change with the creation of the Oncotype DX genetic test. Oncotype DX is a 21-gene assay that is used to measure gene activity and related risk for recurrence. The test assigns a recurrence risk score between 0 and 100.
The purpose of the TAILORx clinical trial was to learn how Oncotype DX’s risk scores aligned with whether or not a patient would benefit from chemotherapy to reduce recurrence risk. About 10,000 women who were between 18 and 75 years old signed up for TAILORx between 2006 and 2010. All had hormone receptor-positive, HER2-negative breast cancer with no lymph node involvement.
In the trial, women who had very low risk scores (10 or lower) received hormone therapy only (tamoxifen or an aromatase inhibitor). Those with “high-risk” scores (26 or higher) received chemotherapy and hormone therapy. And those who had “midrange” scores (11 to 25) were randomized to receive either hormone therapy alone or chemotherapy plus hormone therapy.
A first set of results from TAILORx were reported in 2015. Those results showed that women with a low risk score could safely avoid chemotherapy. This was true despite other factors, such as the size of their tumor, that would have typically suggested they should receive chemotherapy. Those findings confirmed results from earlier trials.
What Did the TAILORx Study Find?
Almost 70 percent of women with hormone receptor-positive early stage breast cancer fall into the midrange risk group, with scores of 11 to 25 on the Oncotype DX text. The new TAILORx results are understood to provide strong evidence that most women with midrange scores will not benefit from chemotherapy and do not need it. This is what the study found for patients in the midrange risk group over the 9-year timeframe of the trial:
- survival without a distant recurrence was almost the same in both treatment groups (95% for those receiving chemotherapy and hormone therapy and 94.5% for those receiving just hormone therapy)
- overall survival was nearly identical for both treatment groups (93.9% for the chemotherapy plus hormone therapy group and 93.8% for the hormone therapy alone group)
Subgroup analyses suggested a somewhat different result for patients 50 years old or younger with scores at the higher end of the midrange (i.e. 16-25). For these patients, particularly those with risk scores of 21-25, there was some benefit from chemotherapy. The study authors weren’t sure whether this effect was from the chemotherapy itself or from early menopause induced by the chemotherapy and its effect in suppressing estrogen.
Since breast cancer can sometimes recur after many years, I wondered whether the timespan of the trial was long enough to take into account any possible longer-term benefits of chemotherapy. In a webinar with patient advocates, Steven Shak, medical director of Genomic Health (which makes the Oncotype DX test), explained that various studies have shown that the benefits of chemotherapy are seen early–within the first 5-6 years after treatment. Therefore, he said, we can be assured that longer follow-up (which will be done) will not show different results.
Implications and Ongoing Research
These study results will help personalize treatment decisions for patients with hormone receptor-positive early stage breast cancer. The findings are expected to lead to adjusted guidelines on when patients in this group need chemotherapy.
While many patients will not need chemotherapy, other studies have demonstrated that chemotherapy is an effective treatment for patients at higher risk for recurrence. Harold Burstein, a breast cancer specialist at Dana-Farber Cancer Institute, told the Washington Post: “You want to bring the right amount of treatment to the tumor based on its biology.”
Other related research is still in process. In particular, the patients who participated in TAILORx all had stage I breast cancer with no lymph node involvement–what about patients who have a small number of positive lymph nodes? The ongoing RxPONDER clinical trial is investigating whether patients with hormone receptor-positive breast cancer who have one to three positive lymph nodes–and a recurrence score of 25 or less–benefit from chemotherapy. Results from that trial are expected in four to five years.
Given the implications of genomic tests such as the Oncotype DX test, these tests need to be available and accessible for all patients who can benefit from them. This issue came up in the patient advocate webinar with Steven Shak, who explained that although the Oncotype DX test is covered by most major forms of health insurance, it’s not being used as often as had been thought. He noted that overall, four out of ten women who could benefit are not being tested, and that the test’s use varies widely across geographic regions.
For More Information
Here are some resources for additional information about the TAILORx trial and what it’s findings mean for patients:
- “Many Breast Cancer Patients Can Safely Skip Chemo, Large Trial Confirms” by Dr. Elaine Schattner in Forbes
- “Tailoring Chemotherapy Decisions – TAILORx Study Results” by Dr. Deanna Attai
- “TAILORx: Most Women With Early-Stage Breast Cancer Can Forgo Chemotherapy When Guided by a Diagnostic Test” in The ASCO Post
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