Adding an assessment of a woman’s clinical risk to Genomic Health‘s genomic test Oncotype DX to estimate the likelihood of breast cancer recurrence may spare more young women from having to undergo chemotherapy after surgery than originally thought.
These findings come from a secondary analysis of the landmark study TAILORx, which also revealed that combining the two assessments can help identify young women who are likely to benefit from more effective anti-estrogen hormonal therapy.
Based on TRIALx results, the American Society of Clinical Oncology (ASCO) updated its recommendations to highlight the advantages of using Oncotype DX to help physicians determine which women should or should not undergo adjuvant chemotherapy for early-stage, hormone receptor (HR)-positive, node-negative breast cancer.
The new analysis, titled “Impact of clinical risk category on prognosis and prediction of chemotherapy benefit in early breast cancer (EBC) by age and the 21-gene recurrence score (RS) in TAILORx,“was recently presented by Joseph A. Sparano, MD, the researcher who led the study, at the 2019 ASCO meeting in Chicago.
Sparano is the associate director of clinical research at Albert Einstein Cancer Center and Montefiore Health System and vice chair of the ECOG-ACRIN.
The work is also described in detail in the report, “Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer,” published in the New England Journal of Medicine.
TAILORx was a Phase 3 clinical trial (NCT00310180) to investigate the best individual therapy for women with node-negative, estrogen receptor-positive breast cancer by using the Oncotype DX test.
Oncotype DX is a molecular diagnostic test that analyzes the activity of 21 genes in the tumor tissue. The test output is a recurrence score (RS) that helps estimate how likely a women’s breast cancer is to come back within 10 years, and if she would benefit from adjuvant chemotherapy after breast surgery. Scores can range between zero and 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy.
In the present study, the researchers did a secondary analysis of TRIALx data to evaluate whether including information about clinical risk provides additional prognostic or predictive information to Oncotype DX scores.
For that, the researchers classified the clinical risk of recurrence as low or high on the basis of the tumor size and histologic grade in 9,427 women enrolled in TAILORx who had an Oncotype DX test. They then used statistical models to weigh the benefit of adding clinical risk into the test’s predictions.
Of the participants, 70.2% met the criteria for low clinical risk and 29.8% for high risk. The data showed that adding clinical risk recurrence estimations did in fact provide additional prognostic information across all recurrence scores.
However, there was no chemotherapy benefit for those with an intermediate RS of 11 to 25, regardless of their clinical risk. At nine years, the rate of women in this group living without disease or cancer recurrence at a distant site was similar regardless of whether or not they had received chemotherapy, and whether they had a low or high clinical risk.
In fact, clinical risk alone was not predictive of chemotherapy benefit, both in the overall population and in women older than 50. This showed that categorizing patients by clinical risk “provided additional prognostic information to the 21-gene RS, but not prediction of chemotherapy benefit in the overall TAILORx population or those [older than 50 years],” the researchers wrote.
Researchers also studied in more detail the chemotherapy benefit for younger women (50 or younger) who had a score of 16 to 25. This was a particularly relevant group because it was previously suggested that chemotherapy may be beneficial for these women.
They found that chemotherapy brought no significant benefit to younger women with a score of 16 to 25 and at a low clinical risk.
Another aspect explored was if integrating RS with clinical information could help identify premenopausal women from this same group (RS 16–25) who would benefit from more effective anti-estrogen hormonal therapy.
From the original trial data, it was unclear if the modest chemotherapy benefit seen in this group was due to cell toxic effects or a castration effect inducing premature menopause from chemotherapy, or both.
Integrating RS and clinical risk supported the use of adjuvant chemotherapy in women ages 46 to 50 who were premenopausal, but not for those who had already been through menopause.
For those ages 40 or younger, who are less likely to develop early menopause from the treatment, chemotherapy also did not bring a significant benefit.
These study results demonstrate that “clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy,” the researchers wrote.
“Last year’s TAILORx results gave clinicians high-quality data to inform personalized treatment recommendations for women,” Sparano said in press release.
“With this new analysis, it is clear that women ages 50 or younger with a Recurrence Score result between 16 and 20 and at low risk, clinically, do not need chemotherapy. Furthermore, the integration of the Recurrence Score with clinical risk information could identify premenopausal women with higher clinical risk who may benefit from ovarian function suppression and more aggressive anti-estrogen therapy,” he added.