Background <p>Hormone receptor–positive breast cancer frequently develops resistance to conventional therapies, highlighting the need for novel preclinical approaches targeting calcium homeostasis and metabolic stress.</p> Materials and methods <p>ER-positive MCF-7 breast cancer cells were treated with increasing concentrations of fatty acid anti-orbital ionic calcium (AIC-FA) and liquid anti-orbital ionic calcium stealth glucose (AIC-SG) (150–9.125&#xa0;µg/mL) for 0–72&#xa0;h. Cell viability was assessed using the MTT assay, and apoptosis and necrosis were analyzed by Annexin V/Propidium Iodide flow cytometry.</p> Results <p>Both AIC-FA and AIC-SG reduced cell viability at 24, 48, and 72&#xa0;h compared with the control group (<i>p</i> &lt; 0.05), with more pronounced effects observed at later time points. No significant differences were detected at the 0-hour time point. Flow cytometry showed changes in Annexin V/PI-defined cell death populations, with AIC-FA associated with increased early apoptotic-like and necrotic-like populations (<i>p</i> &lt; 0.05), whereas AIC-SG showed a greater tendency toward necrotic-like populations. Both compounds significantly reduced the proportion of live cells (<i>p</i> &lt; 0.05).</p> Conclusion <p>AIC-FA and AIC-SG reduced cell viability in MCF-7 breast cancer cells and were associated with partially different Annexin V/PI-defined cell death profiles. These findings support further investigation of the cytotoxic effects of these compounds in preclinical breast cancer models.</p>