Adjuvant Photodynamic Therapy, Mediated via Topical Versus Systemic Administration of 5‐Aminolevulinic Acid for Control of Murine Mammary Tumor after Surgical Resection†

Abstract Treatment de‐escalation is sought in the management of precursor lesions of early stage breast cancer, driving the appeal of adjuvant modalities to lumpectomy that reduce toxicity and minimally detract from patient quality of life. We investigate photodynamic therapy (PDT), with the photosensitizing prodrug, 5‐aminolevulinic acid (ALA), as adjuvant therapy to complete resection of murine mammary tumor (propagated from TUBO cells). ALA was delivered either systemically (oral, 250 mg kg−1) at 5 h before 632 nm illumination or topically (20% solution) to the resection site at 10 min before light delivery to 135 J cm−2. Treatment with either oral‐ALA‐PDT (oALA‐PDT) or topical‐ALA‐PDT (tALA‐PDT) to the mammary fat pad after TUBO complete resection (CR) produced long‐term tumor control with 90‐day complete response rates of 21% and 32%, respectively, compared to control rates of 0–5% in mice receiving only CR. Thus, CR/tALA‐PDT was equipotent to CR/oALA‐PDT despite ~10‐fold lower levels of ALA‐induced protoporphyrin XI as photosensitizer after topical versus oral‐ALA administration. CR/oALA‐PDT produced more vascular damage, greater proportion of tissue‐resident neutrophils and stronger inflammation when compared to CR/tALA‐PDT. Collectively, these data provide rationale for ongoing investigation of ALA‐PDT as adjuvant therapy after lumpectomy for increased probability of local control in the treatment of breast cancer.