MINDACT: Long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients.

Abstract

506 Background: The 70-gene signature MammaPrint has been shown to identify breast cancer patients for whom adjuvant chemotherapy (CT) could be safely omitted even in the presence of unfavorable standard clinical-pathological criteria. The MINDACT primary endpoint at 5 years median follow-up was met in 2016 (Cardoso et al, NEJM 2016) with a distant metastasis free survival (DMFS) rate at 5 years of 94.7% (95% CI: 92.5-96.2) in clinical high (C-High) / genomic low (G-Low) risk patients who received no CT. Longer follow-up is now available. Methods: 6693 patients were enrolled in the prospective phase III randomized MINDACT study (EORTC 10041/BIG3-04) between 2007-2011. We assessed the DMFS rate at 5 years in the primary test (PT) population of C-High / G-Low patients who were randomized to receive no CT (n = 644). As secondary analysis, we evaluated DMFS and overall survival (OS) in the intention to treat (ITT) population of the C-High / G-Low group randomized to CT vs no CT (n = 749 and 748 respectively). Comparisons between CT and no CT groups are low-powered. We used Kaplan-Meier estimates for time to event endpoints and hazard ratios (HR) with 95% CI from cox-regression models adjusted for stratification factors used for the randomization. Results: The median follow-up is 8.7 years, resulting in an updated 5-year DMFS rate for the PT population of C-High / G-Low patients with no CT of 95.1% (95% CI 93.1-96.6). The updated outcomes of the ITT population of C-High / G-Low patients are shown in the table. Further analyses will update the suggested age-dependent effect of CT omission for luminal breast cancer seen at 5 years in pre- versus post-menopausal women as in Tailor-X (Piccart et al, SABCS 2019). Conclusions: The primary DMFS endpoint at 5 years continues to be met in CT untreated C-High / G-Low risk women, confirming MINDACT as a positive de-escalation study. With longer follow-up and in line with the natural history of luminal breast cancer, more distant relapses do occur but the estimated gain of 2.6% for CT administration in C-High / G-Low patients remains small in light of CT harmful effects. The level IA evidence for the clinical utility of the 70-gene signature for adjuvant CT decision making is maintained. Clinical trial information: NCT00433589 . [Table: see text]

Clinical utility of genomic signatures in young breast cancer patients: a systematic review

“…This observation is hard to reconcile especially in light of the trial by Poorvu et al 21 who did not observe a benefit from chemotherapy use in terms of DRFS at 6 years for YWBC with an intermediate risk for recurrence (i.e., [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. On the other hand, in the MINDACT trial patients aged ≤50 years with CH/GL risk appeared to derive more benefit of chemotherapy 28,45 , which was also different to the main results taking into account data from all patients 26 .…”

Update Breast Cancer 2020 Part 3 – Early Breast Cancer

“…The primary analysis was confirmed with the more mature data. The metastasis-free 5-year survival was 95.1% (95% CI: 93.1 – 96.6%) 68 .…”

“…Mit den nun reiferen Daten konnte die primäre Analyse bestätigt werden. Die metastasenfreie 5-Jahres-Überlebensrate lag bei 95,1% (95%-KI: 93,1 – 96,6%) 68 .…”

“…HER2: humaner epidermaler Wachstumsfaktor-Rezeptor 2; HR: Hormonrezeptor; TNBC: triple-negativer Brustkrebs. Modifiziert nach 68 .…”

Long-Term MINDACT Results Affirm Excellent Prognosis for Clinically and Genetically Low-Risk Early Breast Cancer

“…MammaPrint is a 70-gene signature assay used to calculate the risk of breast cancer recurrence at 5 and 10 years. The phase III MINDACT trial was designed to evaluate whether genetic risk category could be used to identify which patients with early breast cancer could safely deescalate chemotherapy without adversely affecting their long-term risk of recurrence [1][2][3]. Laura van't Veer, Ph.D., of the University of California at San Francisco, presented updated long-term findings from the trial [3].…”