Age Associated With Benefit Derived From Chemotherapy for Women With Luminal Breast Cancer, MINDACT Trial Finds

In a recent analysis of the TAILORx trial, patients who were 50 years of age or younger were shown to have an estimated chemotherapy benefit in reducing distant recurrence at 9 years if they had an Oncotype DX recurrence score (RS) of 16 to 20 with high clinical risk, or if their RS score ranged from 21 to 25 regardless of clinical risk.

This caused researchers, including study author Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center/Champalimaud Foundation, to conduct an unplanned analysis of the MINDACT trial to determine if the addition of chemotherapy did in fact have an age-dependent benefit on distant metastasis-free survival (DMFS) among certain patients with breast cancer, as was seen in the TAILORx trial analysis.

The MINDACT trial compares the utility of the 70-gene signature commercial diagnostic test, MammaPrint, with common clinical-pathological criteria to select patients with breast cancer who have 0 to 3 positive nodes for adjuvant chemotherapy. In the analysis cohort, patients older than 40 were chosen, as there was only 2 DMFS events in patients under 40, attributing to a total population of 1317 patients, 452 aged 40 to 50 and 865 aged older than 50, from the MINDACT trial.

The trial’s inclusion of women aged under 50 served crucial to analyses, as Cardoso noted that younger women with breast cancer are underrepresented in clinical trials, and treatment decisions are often based on data obtained in older, postmenopausal women. “It is important to examine how age impacts treatment efficacy and disease recurrence in patients with breast cancer to determine the best treatment option for each patient,” said Cardoso.

In the analysis, researchers evaluated 5-year DMFS of patients with hormone receptor—positive, HER2-negative breast cancer enrolled in the MINDACT trial who had a low genomic and a high clinical risk. These patients were randomized to receive chemotherapy based on either clinical or genomic risk.

Researchers found that among women at least 50 years of age, estimated 5-year DMFS was similar between patients who received (95.2%) and who did not receive (95.4%) chemotherapy. In patients 40 to 50 years of age, estimated 5-year DMFS for those who received chemotherapy was 96.1% as opposed to 93.1% in those who did not receive chemotherapy. The 3% difference shows evidence similar to the TAILORx trial, but results remain insignificant.

“Similar to the TAILORx trial, we found that women classified as high risk of recurrence by traditional clinical-pathological factors but low risk by MammaPrint had a worse outcome if treated with tamoxifen alone, and that the benefit of chemotherapy may eventually be higher in this group,” said Cardoso.

Tamoxifen treatment alone is common in younger women with only 7% of those in the MINDACT trial also receiving an LHRH analog. This is a trend that the study authors described may suggest that women, presumably premenopausal, might be undertreated with tamoxifen alone.

However, Cardoso noted that results are not confirmed yet, as in both the MINDACT and TAILORx trials, the majority of women received tamoxifen alone (without ovarian suppression) as adjuvant chemotherapy. While researchers are unable to clarify if the results seen in younger women are due to the direct effect of chemotherapy or through chemotherapy-induced ovarian suppression, the growing evidence from the 2 trials indicates that younger women with high clinical risk and low genomic risk, or with an intermediate RS, may benefit from additional treatment.

“The added value of chemotherapy in case of optimal endocrine therapy (i.e. OFS + tamoxifen or aromatase inhibitor) cannot be evaluated in MINDACT nor in TailorX and should be further studied,” said the study authors.

Reference

Piccart MJ, Poncet C, Cardoso F, et al. Should age be integrated together with clinical and genomic risk for adjuvant chemotherapy decision in early luminal breast cancer? MINDACT results compared to those of TAILOR-X. Presented at: San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS4-05.