Steroidal dihydrotriazines 4a–c proved to be more active against MCF-7 cancer cells compared to steroidal fused pyrimidines. Androstene derivative 4c bearing the dihydrotriazine moiety at C-2 had the IC50 value of 14.8 μM, while the IC50 value for compound 4b modified at 16-C reached 11.2 μM. The 16-C dihydrotriazine-modified estrane 4a was shown to be the most active derivative. Moreover, only steroidal dihydrotriazines 4a, 4b, and 4c were active against ERα-negative MDA-MB231 cells; their IC50 values vary in the range of 12.2–19.1 μM.