Abstract GS4-05: 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
Authors: Piccart Martine J , Poncet Coralie , Cardoso Fatima , van't Veer Laura , Delaloge Suzette , Pierga Jean-Yves , Brain Etienne , Vrijaldenhoven Suzan , Neijenhuis P.A. , Aalders Kim , Rutgers Emiel 
Published: March 2020

Background: A secondary analysis of the TAILOR-X trial, based on the integration of a “clinical risk” - as defined in the MINDACT trial - on top of the Oncotype Recurrence Score (RS) revealed that women aged 40 to 50 years with either a RS between 16 and 20 and a high clinical risk (cH) or a RS between 21 and 25, independently from clinical risk, derive non negligible benefits from the addition of chemotherapy to endocrine therapy, in terms of distant recurrence rate at 9 years (J.A. Sparano et al., N Engl J. Med 2019; 380).

Methods: We decided to run a similar (unplanned) analysis of the MINDACT “cH” patients with “luminal” breast cancers (hormone receptor-positive, HER2-negative by local pathology) classified as “low” genomic risk (gL) using the 70 gene signature MammaprintTM (F. Cardoso, N. Engl. J. Med. 2016; 375). Analysis is done as per treatment arm allocated (chemotherapy or no chemotherapy) by randomization. MINDACT primary endpoint was used (5-year distant metastases free survival, DMFS). Of note, the comparison of outcomes with or without chemotherapy was a secondary objective in MINDACT.

Results: Among 6693 enrolled patients, 5402 (81.7%) had luminal breast cancers. Within luminal breast cancers, 1358 (25.1%) had cH/gL risk and were aged &lt;40 (n= 53), 40-50 years old (n= 411), &gt;50 (n = 894). There were too few DMFS events (n = 2) in the &lt;40 year old group to display further results. The analysis population included patients randomized to receive chemotherapy or not (399 patients aged 40-50 and 865 patients &gt;50 years old). Median tumor size was 2.2 cm in both age groups (40-50 years old group: 35.9%/58.4% patients hadT1/T2 tumors, respectively; &gt;50 years old: T1/T2: 41.2%/55.5%). Half of the patients had negative nodal status (40-50 year old: 50.9%; &gt;50 years old: 51.8%). Majority of patients had grade 2 or grade 3 tumors (40-50 years old: 63.9% grade 2 and 26.6% grade 3; &gt;50 year sold: 66.6% grade 2 and 26.9% grade 3).

Luminal cH/gL, 40-50y old patients N = 399Luminal cH/gL &gt; 50y old patients N = 865Events / total5-year Kaplan Meier DMFS estimate (95% CI)Events / total5-year Kaplan Meier DMFS estimate (95% CI)No chemotherapy16/19692.6% (87.7; 95.7)23/44095.4% (92.8; 97.1)Chemotherapy8/20396.2% (91.5; 98.3)23/42595.2% (92.4; 97.0)

Conclusions: While postmenopausal patients primarily received aromatase inhibitors, adjuvant endocrine therapy consisted mostly in tamoxifen in younger women with only 7.0% of them also receiving an LHRH analog.

This unplanned analysis, limited by a small number of events and large confidence intervals, nevertheless shows the same « trend » as seen in Tailor-X and also suggests that women aged 40 to 50, classified cH / gL risk and presumably premenopausal, might be undertreated with tamoxifen alone. It is probable but not proven that this age-dependent chemotherapy effect is due to ovarian function suppression (OFS). 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. Possibly, optimal endocrine therapy, e.g. ovarian ablation in addition to tamoxifene in the 40-50y age group cH could be adequate. This reinforced message is important for practicing oncologists and patients.

Citation Format: Martine J Piccart, Coralie Poncet, Fatima Cardoso, Laura van't Veer, Suzette Delaloge, Jean-Yves Pierga, Etienne Brain, Suzan Vrijaldenhoven, P.A. Neijenhuis, Kim Aalders, Emiel Rutgers. 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 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS4-05.