Joseph A. Sparano, MD, on Long-Term Breast Cancer Recurrence and Survival Data from TAILORx
2022 San Antonio Breast Cancer Symposium
Joseph A. Sparano, MD, of the Tisch Cancer Center at Mount Sinai Health System, discusses long-term clinical outcomes data that continue to show many women with early breast cancer can safely forgo chemotherapy, when guided by the 21-gene recurrence score result. The longer follow-up also showed that recurrences of breast cancer continue to occur years after the original diagnosis, although these recurrences were not prevented by chemotherapy use. Racial disparities were not explained by inequities in social determinants of health or treatment adherence, with Black women at higher risk of early recurrence within the first 5 years of diagnosis, but not later recurrence after 5 years (Abstract GS1-05).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
At this meeting I presented a 12-year update of the results of the TAILORx trial. TAILORx was a phase three trial that integrated the 21 gene recurrent score assay into clinical decision-making for patients with estrogen receptor positive, HER2-negative node negative breast cancer. For patients who had a low recurrent score of zero to 10 or high recurrent score of 26 to a 100, they were assigned to treatment with either endocrine therapy alone or chemotherapy plus endocrine therapy respectively based on information that we had at the time that that was the appropriate choice for them.
For the two-thirds of patients who had a recurrent score in the mid-range of 11 to 25, they were randomized to either chemotherapy plus endocrine therapy, the standard arm or endocrine therapy alone, which we considered the experimental arm. All of these patients met NCCN guidelines for either recommending or considering chemotherapy.
At the time of the original analysis after a median followup of seven and a half years, we conclusively demonstrated that endocrine therapy was non-inferior to chemotherapy plus endocrine therapy. At this meeting, we reported a 12-year event rates with a median follow up of 11 years. In other words, three and a half more years of follow up. And we came to the following conclusions after analyzing the data.
First of all, our primary conclusion of non-inferiority of endocrine therapy compared with chemo endocrine therapy did not change, indicating that we can effectively spare chemotherapy in the majority of patients with early stage breast cancer. Secondly, for patients who were 50 or under and premenopausal at the time of diagnosis, some of those patients did benefit from chemotherapy, namely those who had a recurrent score of 21 to 25, or those with a recurrent score of 16 to 20 and high clinical risk features.
At this analysis, we found that those trends continued, although the largest difference was in those patients who had the highest recurrent score of 21 to 25 within this range. And additionally, we did find that with continued follow-up relapses continued to occur, and in fact, late relapses occurring more than five years after diagnosis, which is a typical course of adjuvant endocrine therapy, now exceeded early relapse.
And finally, when we examined outcomes by race and ethnicity, we found that Black women had a higher recurrence rate despite comparable clinical characteristics, recurrence scores, treatment administration, insurance status, and other social determinants of health. However, we specifically found that Black women were at increased risk for early recurrence within the first five years of diagnosis.
The take home clinical implications of this are that with continued follow up, the main conclusions derived from the TAILORx trial remain unchanged. That chemotherapy can be effectively spared in the majority of women with ER positive, HER2-negative breast cancer, who have a recurrent score of zero to 10 or have a recurrent score of 11 to 25, including all postmenopausal women with a score of 11 to 25 who are node negative, and in addition, women 50 or under who have a recurrent score of up to 15 or 16 to 20 and low clinical risk.
There is a follow-up study that is planned by another group, the NRG, that will address the areas where equipoise exists or continues to exist after TAILORx. That trial will be coordinated by the NRG. It will be an NCI sponsored trial where women with one to three positive nodes in a recurrent score of zero to 25, or a woman with node negative breast cancer, and this of course is estrogen receptor positive, HER2-negative breast cancer and a recurrent score of 21 to 25 or 16 to 20 and high clinical risk will be randomized to receive either chemotherapy plus ovarian function suppression and an aromatase inhibitor or ovarian function suppression and an aromatase inhibitor without chemotherapy.
The reason for doing this trial is because it's believed that the chemotherapy benefit that was seen in premenopausal women, 50 or under in TAILORx may have been driven entirely by an effect of chemotherapy in inducing early menopause. A similar effect was also seen in the RxPONDER trial in patients with one to three positive nodes, which provides a basis for addressing this lingering question.
The ASCO Post Staff
Per Karlsson, MD, PhD, of Sweden’s University of Gothenburg and the Sahlgrenska Comprehensive Cancer Center, discusses results from the POLAR study, which was a meta-analysis of three clinical trials of breast-conserving surgery with or without radiotherapy. POLAR is the first genomic classifier that appears not only to be prognostic for locoregional recurrence, but also predictive of radiotherapy benefit. Although patients with breast cancer who had a high POLAR score benefited from radiotherapy, patients with a low score did not, and may be candidates for omission of radiotherapy after breast-conserving surgery (Abstract GS4-03).
The ASCO Post Staff
Andrea De Censi, MD, PhD, of Italy’s E.O. Ospedali Galliera, discusses phase III findings showing that low-dose tamoxifen (so-called babytam) given for 3 years still significantly prevents recurrences from noninvasive breast cancer after a median of 7 years from treatment cessation. Babytam at 5 mg/d for 3 years significantly lowered recurrence from noninvasive breast cancer at 10 years without “excess” adverse events (Abstract GS4-08).
The ASCO Post Staff
Erica L. Mayer, MD, PhD, of Dana-Farber Cancer Institute, discusses findings from the PACE study of patients with endocrine- and CDK4/6 inhibitor–pretreated estrogen receptor–positive/HER2-negative metastatic breast cancer who were randomly assigned to fulvestrant alone; fulvestrant and palbociclib; or fulvestrant, palbociclib, and avelumab. Combining palbociclib with fulvestrant beyond disease progression on a prior CDK4/6 inhibitor regimen did not improve progression-free survival compared with fulvestrant alone. A longer progression-free survival when a PD-L1 inhibitor was added to fulvestrant and palbociclib deserves further study. A baseline circulating tumor DNA analysis suggests that the potential benefit of palbociclib after progression on a prior CDK4/6 inhibitor may be influenced by ESR1 or PIK3CA status (Abstract GS3-06).
The ASCO Post Staff
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, discusses results from the POSITIVE trial, which showed that a temporary interruption of endocrine therapy in women with hormone-responsive breast cancer in order to attempt pregnancy, does not affect short-term disease outcomes. The study found that 74% of women had at least one pregnancy, most (70%) within 2 years. Birth defects were low (2%) and were not clearly associated with treatment exposure. Dr. Partridge explains that these data stress the need to incorporate patient-centered reproductive health care in the treatment and follow-up of young women with breast cancer (Abstract GS4-09).
The ASCO Post Staff
Marleen Kok, MD, PhD, of the Netherlands Cancer Institute, discusses the most important advances in early breast cancer treatment during the past year for patients with triple-negative, HER2-positive, and estrogen receptor–positive disease. Dr. Kok also addresses long-term treatment toxicities and quality of life.