The trial’s results, “Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer,” were published in the New England Journal of Medicine.
Women with early stage breast cancer long have been treated with aggressive therapies, such as chemotherapy, in addition to hormone therapy. But in the past few years, many researchers have come to understand that not all patients benefit from chemotherapy.
The development of Oncotype DX Breast Recurrence Score test has changed the standard of care for many breast cancer patients. The test consists of a tumor biopsy that looks at 21 tumor genes associated with a high likelihood of recurrence, giving it a score from one to 100 for its risk of spreading elsewhere and returning.
In 2004, a study called NSABP B-20 showed this test could successfully predict not only cancer recurrence, but also the benefit from adjuvant chemotherapy in women with early-stage breast cancer. Women with low recurrence scores (0-10) showed little to no benefit from chemotherapy, while those with high recurrence scores (26 or more) clearly benefited from it.
Since then, women with a low score typically receive hormone therapy alone and those with a high score receive hormone therapy and chemotherapy.
However, most women with early-stage breast cancer fall between these two points, with an intermediate risk (a score of 11-25), where the benefits of chemotherapy are still uncertain and treatment decisions are more challenging.
To clarify whether these patients (with intermediate scores) would benefit from adjuvant chemotherapy after surgery, the ECOG-ACRIN Cancer Research Group designed and led a Phase 3 clinical trial called Trial Assigning Individualized Options for Treatment (Rx), or TAILORx (NCT00310180).
TAILORx, sponsored by the National Cancer Institute (NCI), enrolled 10,253 women with the most common form of early breast cancer hormone-receptor positive, HER2-negative cancer that had not spread to the axillary lymph nodes — in more than 1,200 trial sites from six countries, being the largest breast cancer treatment trial ever conducted.
The Oncotype DX Breast Recurrence Score test was performed in all patients, and of the 9,719 eligible patients with follow-up information, 6,711 (69%) had a mid-range recurrence score of 11-25. These patients were randomly assigned to receive hormone therapy alone, or hormone therapy and chemotherapy and followed-up for a median of nine years.
Nine years after initial treatment, 83.3% of those treated with hormone therapy alone, and 84.3% in the combination therapy group, were cancer-free. Also, 93.9% of those in the single therapy group and 93.8% percent of those treated with combination therapy were alive.
These results showed no benefit from adding chemotherapy to hormone therapy in women with an intermediate recurrence score.
“These findings, showing no benefit from receiving chemotherapy plus hormone therapy for most patients in this intermediate-risk group, will go a long way to support oncologists and patients in decisions about the best course of treatment,” Jeffrey Abrams, associate director of NCI’s Cancer Therapy Evaluation Program, said in a press release.
However, some benefit of chemotherapy was found in women 50 years or younger with a recurrence score of 16-25, which means that subsequent chemotherapy may be considered in these cases.
Women with low scores (0-10) received hormone therapy alone and had very low cancer recurrence after nine years (3%), supporting previous findings showing that chemotherapy adds no benefit in these patients.
On the other hand, women with a score of 26-100 were treated with both hormone therapy and chemotherapy, and showed a distant recurrence rate of 13%, indicating the need to develop more effective therapies for women with a high risk of recurrence.
According to the investigators, the results of the TAILORx study suggest that chemotherapy may be avoided in about 70% of women with this type of early-stage breast cancer, including those with a score of 0-10 (16%), those 50 years old or younger with a recurrence score of 11-15 (8%), and those older than 50 with a recurrence score of 11-25 (45%).
“These data confirm that using a 21-gene expression test to assess the risk of cancer recurrence can spare women unnecessary treatment if the test indicates that chemotherapy is not likely to provide benefit,” added Joseph A. Sparano, the study’s lead author and vice chair of the ECOG-ACRIN Cancer Research Group.
The TAILORx results were presented earlier this month at the 2018 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.