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4%), and nitric oxide (by≥18.8%). Cellular l-Arginine to medium NOHA ratio was higher, and by at least 6.5-22.5 fold in ER- breast tumor 3D-spheroids, and at least 10-70 fold in ER- ovarian tumor 3D spheroids, than in ER+ and control conditions; and was ≥48% higher in ER- ovarian cancer than in ER- breast cancer 3D-spheroids. The present study shows NOHA as a sensitive and selective indicator differentiating and distinguishing ER- subtypes based on the tumor grade. The present study shows NOHA as a sensitive and selective indicator dif