TUMOR PLASTICITY AND PHENOTYPIC SWITCHING AS DRIVERS OF THERAPEUTIC RESISTANCE IN BREAST CANCER

Breast cancer remains one of the most extensively treated yet persistently recurrent malignancies in oncology, and much of that persistence traces back to a single unresolved problem: tumors that respond to therapy often find a way back. For decades the dominant explanation was genetic, resistance following classic Darwinian logic as mutations accumulate and the fittest clone survives. That is true, but it is not the whole story. Breast cancer cells can also survive treatment by changing what they are, temporarily, without changing their genetic material. They can adopt mesenchymal features, slip into stem-like states, enter a dormant drug-tolerant condition, lean on a supportive tissue environment, or rewire how they generate energy. This review brings together evidence on these five reversible mechanisms in breast cancer, arguing that they represent facets of one underlying phenomenon, a flexible tumor cell state that treatment pushes cells across, and sometimes back over. Therapies aimed only at a genetic target may be treating the wrong problem, and future strategies may need to address timing and cell state, not just molecular targets.

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