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MINDACT Trial Data Reveal Certain Women With Luminal Breast Cancer May Be Undertreated With Tamoxifen Alone

SAN ANTONIO — Among women with hormone receptor (HR)-positive, HER2-negative breast cancer with a high clinical risk (determined by tumor size and histologic grade) and low genomic risk (determined by MammaPrint), those 40 to 50 years old had a greater benefit from chemotherapy than those older than 50, according to data from an unplanned subgroup analysis of the MINDACT trial presented at the 2019 San Antonio Breast Cancer Symposium, held Dec. 10–14.

“Younger women with breast cancer are underrepresented in clinical trials, and treatment decisions are often based on data obtained in older, postmenopausal women,” said Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center/Champalimaud Foundation in Lisbon, Portugal. “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.”

While most patients with HR-positive breast cancer are treated with endocrine therapy, the selection of patients that will derive clinical benefit from the addition of chemotherapy is an area of current research, explained Cardoso.

The goal of the MINDACT trial is to compare the utility of the 70-gene signature commercial diagnostic test MammaPrint with common clinical-pathological criteria (determined by modified

Adjuvant!Online) to select breast cancer patients with zero to three positive nodes for adjuvant chemotherapy. A recent analysis of the TAILORx trial revealed that patients who were 50 years old or younger had an estimated chemotherapy benefit in reducing distant recurrence at nine years if they had an Oncotype DX recurrence score (RS) of 16-20 with high clinical risk, or if they had RS of 21-25, irrespective of clinical risk.

“We conducted this unplanned analysis of the MINDACT trial to determine if the addition of chemotherapy had an age-dependent impact on distant metastasis-free survival (DMFS) among certain breast cancer patients, as was seen recently in an analysis of the TAILORx trial,” said Cardoso.

Cardoso and colleagues evaluated five-year DMFS among HR-positive, HER2-negative breast cancer patients enrolled in the MINDACT trial who had a low genomic risk and a high clinical risk and were randomized to receive chemotherapy based on either clinical or genomic risk.

Because there were only two DMFS events in patients under 40 years old, the researchers restricted their analysis to patients older than 40, resulting in a total population of 1,264 patients.

Among this group, 399 patients were aged 40 to 50, and 865 patients were older than 50. Among patients older than 50, the estimated five-year DMFS was similar between patients who received and who did not receive chemotherapy (95.2 percent versus 95.4 percent, respectively).

However, among patients 40 to 50 years old, the estimated five-year DMFS for patients who received chemotherapy was 96.2 percent versus 92.6 percent for those who did not receive chemotherapy.

“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.

“In both of these trials, the vast majority of women received tamoxifen alone (without ovarian suppression) as adjuvant chemotherapy,” noted Cardoso. “Therefore, we are unable to determine if the results seen in younger women are due to the direct effect of chemotherapy or through chemotherapy-induced ovarian suppression.

“These findings, while hypothesis-generating, are not yet practice-changing as they require confirmation,” continued Cardoso. “However, our results and the TAILORx trial results seem to indicate that younger women with high clinical risk and low genomic risk (per MammaPrint) or with an intermediate RS (per Oncotype DX) may benefit from additional treatment.”

This specific study represents a subset analysis of the MINDACT trial and is therefore only exploratory, representing a limitation of the study, noted Cardoso.

The MINDACT trial was supported by grants from the European Commission Sixth Framework Program, the Breast Cancer Research Foundation, Novartis, F. Hoffmann–La Roche, Sanofi-Aventis, Eli Lilly, Veridex, the National Cancer Institute (U.S.), the European Breast Cancer Council–Breast Cancer Working Group, the Jacqueline Seroussi Memorial Foundation for Cancer Research, Prix Mois du Cancer du Sein, Susan G. Komen for the Cure, Fondation Belge contre le Cancer, Dutch Cancer Society (KWF), the Netherlands Genomics Initiative–Cancer Genomics Center, Association le Cancer du Sein, Parlons-en!, the Brussels Breast Cancer Walk-Run and the American Women’s Club of Brussels, NIF Trust, German Cancer Aid, the Grant Simpson Trust and Cancer Research UK, Ligue Nationale contre le Cancer, and the EORTC Cancer Research Fund. Whole-genome analysis was provided by Agendia without cost.

Cardoso has advisory roles with Amgen, Astellas Pharma/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai Inc., GE Oncology, Genentech, GlaxoSmithKline, MacroGenics, Medscape, Merck-Sharp, Merus, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Seattle Genetics, and Teva Pharmaceutical Industries Ltd.