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Preinvasive breast carcinoma cells that proliferate and accumulate within the nonvascular, closed intraductal niche are under severe hypoxic and metabolic stress. Understanding the survival mechanisms used by these cells has revealed therapeutic strategies for killing preinvasive neoplasms. We have found that autophagy (‘self-eating’) is a major survival strategy used by preinvasive carcinoma and breast cancer stem-like cells. Based on this finding, we have opened a clinical trial that is exploring neoadjuvant oral chloroquine antiautophagy therapy for ductal carcinoma in situ. We envision that antiautophagy therapy can be administered in combination with other treatments such as those that elevate intracellular calcium, to create a state of intolerable stress for preinvasive neoplastic cells, and thereby stop breast cancer before it starts.

Attacking Breast Cancer at the Preinvasion Stage by Targeting Autophagy