SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 266,120 new cases of invasive breast cancer will be diagnosed in 2018 and about 40,920 women will die of the disease. Approximately 50% of all breast cancers are Estrogen Receptor (ER) positive, HER2-negative, axillary node-negative tumors. Patients with early stage breast cancer often receive adjuvant chemotherapy. The Oncotype DX breast cancer assay, is a multigene genomic test that analyzes the activity of a group of 21 genes and is able to predict the risk of breast cancer recurrence and likelihood of benefit from systemic chemotherapy, following surgery, in women with early stage breast cancer. Chemotherapy recommendations for early stage, hormone receptor positive, HER negative, early stage breast cancer patients, are often made based on tumor size, grade, ImmunoHistoChemical (IHC) markers such as Ki-67, nodal status and Oncotype DX Recurrence Score (RS) assay.
Oncotype Dx assay categorizes patients on the basis of Recurrence Scores into Low risk (less than 18), Intermediate risk (18-30), and High risk (31 or more). It has been unclear whether patients in the Intermediate risk group benefited from the addition of chemotherapy to endocrine therapy. TAILORx was specifically designed to address this question and provide a very definitive answer. In this study, the Intermediate risk Recurrent Score (18-30) was changed to 11-25, to account for exclusion of higher-risk patients with HER2-positive disease and to minimize the potential for under treatment.
TAILORx ((Trial Assigning Individualized Options for Treatment) is a phase III, randomized, prospective, non-inferiority trial, and is the largest breast cancer treatment trial ever conducted, and the first precision medicine trial ever done, according to the authors. In this study, 10,273 women, 18-75 years of age, with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer were enrolled. Patients had tumors 1.1-5.0 cm in size (or 0.6-1.0 cm and intermediate/high grade). Patients were divided into three groups based on their Recurrence Score. Women with a Low Recurrence Score of 0-10 received endocrine therapy alone and those with a High Recurrence Score of 26-100 received endocrine therapy in combination with standard adjuvant chemotherapy. Patient with Intermediate Recurrence Score of 11-25 (N=6711) were randomly assigned to receive endocrine therapy alone or endocrine therapy and adjuvant chemotherapy. The Primary endpoint was invasive Disease Free Survival, defined as recurrence of cancer in the breast, regional lymph nodes, and/or distant organs, a second primary cancer in the opposite breast or another organ, or death from any cause.
At a median follow-up of 7.5 years, the study met its Primary endpoint, and it was noted that that endocrine therapy alone was non-inferior to chemotherapy plus endocrine therapy, in patients with Intermediate Recurrence Score of 11-25. At 9 years, patients with Intermediate Recurrence Scores receiving endocrine therapy or chemotherapy in combination with endocrine therapy showed similar invasive Disease Free Survival rates (83.3% vs 84.3%), distant Recurrence Free Interval (94.5% vs 95.0%), Recurrence Free Interval (92.2% vs 92.9%) and Overall Survival (93.9% vs 93.8%) respectively. These findings suggested that there was no benefit from adding chemotherapy to endocrine therapy, for this patient group.
The authors also conducted an exploratory analysis of patients in the Intermediate Risk group to determine which patients would benefit from added chemotherapy. They noted that there was no significant interaction between menopause, tumor size or grade, with Recurrence Score. There was however an interaction between age and Recurrence Score. In women 50 years or younger with a Recurrence Score of 16-20, there were 2% fewer distant recurrences, and in those with a recurrence score of 21-25, there were 7% fewer distant recurrences with the addition of chemotherapy, suggesting that younger women with a Recurrence Score of 16-25 had some benefit with the addition of chemotherapy to endocrine therapy.
It was concluded that women older than 50 years with hormone receptor-positive, HER2-negative, node-negative breast cancer and a Recurrence Score of 0-25, as well as women 50 years or younger with hormone receptor-positive, HER2-negative, node-negative breast cancer and a Recurrence Score of 0-15, could be spared from chemotherapy, based on this study. This study showed that chemotherapy could be avoided in about 70% of these patients, by allowing this test to tailor treatment. Further, this prospective study reflects outcomes with current modern chemotherapy and endocrine therapy regimens. The authors recommended that any patient 75 years or younger with early-stage breast cancer should therefore be offered Oncotype DX assay test, for guidance regarding chemotherapy recommendations after surgery. TAILORx: phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score. Sparano JA, Gray RJ, Wood WC, et al. J Clin Oncol. 2018;36(suppl; abstr LBA1).