**1. Introduction**

Fibroadenoma is one of the commonest benign female breast diseases. Histologically, it is a well-circumscribed homogeneous biphasic solid lump with distinct imaging features made up of epithelial and stromal tissues [1]. Definitive diagnostic techniques include ultrasound, mammography, magnetic resonance imaging or stereotactic guided needle biopsy [2]. Their sizes are normally small (<2.5 cm), but can become giant juvenile tumors (>10 cm) during puberty or pregnancy [3] causing considerable pain and cosmetic deformity of the breast. Although it accounts for 25% of all breast masses in women [4], the numbers are higher in adolescents: 68% of all breast masses and 44–94% of biopsied breast lesions [5,6]. Furthermore, available data seem to suggest that incidence and recurrence rates are common in black race [7–9], who are more likely to develop breast cancer at a younger age [10].

Management of fibroadenomas can take two forms: observation and therapy. For fibroadenomas that cause pain, deform the breast, persist without any regression and are histologically complex, therapy is warranted [2]. Available options include open surgical excision as well as several modern minimally invasive probe-based thermal therapies including cryotherapy, radiofrequency ablation (RFA), microwave ablation (MWA), focused ultrasound (FUS) and laser-induced thermotherapy (LITT) [11,12]. On the other hand, observation, which involves yearly breast imaging, is usually recommended when the tumor is asymptomatic, small and not rapidly increasing in size to cause cosmetic deformity and pain. However, there are situations when patients who qualify for observation agitate due to the fear of malignancy leading to significant anxiety [12]. Furthermore, a recent study reported a 41% increase in cancer risk for women diagnosed with fibroadenomas compared to those without them [13]. Issues related to superficial skin burns, hemorrhage and hematoma, cost and complexity of technique that are associated with options stated earlier limit their use for small-sized fibroadenoma [11,14]. An ideal treatment will be one that is noninvasive with no side-effects. Recent advances in nanomedicine offer the opportunity for the design of smart strategies that can potentially overcome drawbacks with conventional techniques to reduce invasiveness and complexity.

Nanomedicine involves the use of nanomaterials—metallic and ceramic (iron-oxide) nanoparticles (NPs)—for theranostic purposes in living organisms. Photothermal therapy (PTT) is an emerging localized cancer treatment whereby NPs embedded in the tumor convert near-infrared light, which is minimally absorbed by biological tissue, to heat leading cell death. Traditionally, metallic NPs such as gold, silver, copper as well as carbon-nanotubes or graphene have been used for PTT [15]. Although several promising results have been reported in the literature for both in-vitro (cells) and in-vivo (animals), issues related to NP biocompatibility and stability have limited their progression to the clinics [15]. Unlike their metallic counterparts, ceramic NPs—Fe3O4 and *γ*-Fe2O3—have been used in human trials for magnetic hyperthermia treatment of brain [16] and prostate [17] cancers. Furthermore, these ceramic NPs have very recently been tested for photothermal therapy in both in-vitro and in-vivo studies. Chu et al. [18] showed that various shapes of Fe3O4 nanoparticles (NPs) were able to kill cancer cells and tumors in in-vitro (esophageal cancer cell) and in-vivo (mouse esophageal tumor) models, respectively. In another study, Espinosa and co-workers [19], demonstrated the ability of the iron-oxide NPs to act as magnetic and photothermal agents simultaneously—so called magnetophotothermal approach—and showed their unprecedented heating powers and remarkable heating efficiencies (up to 15-fold amplifications).

Here, we describe an integrated approach composed of experiments for NP characterization and models for optical property predictions and computational treatment planning. Our long term goal is to develop a noninvasive but highly efficacious treatment method for the destruction of fibroadenomas. The feasibility of such integrated approaches for photothermal therapies have been previously reported for different application in the literature [20,21]. We characterized the material properties and quantified the photothermal heat generation of Fe3O4 NPs by experimental measurements, obtained their optical absorption coefficient via experimentally guided Mie scattering theory and integrated it into a computational—finite element method (FEM)—model to predict in-vivo thermal damage of a NP-embedded tumor located in a multi-tissue breast model during irradiation by a near-infrared (NIR) 810 nm laser. Using a temperature-controlled parametric study, we explored the feasibility of NP-mediated photothermal therapy for the destruction of fibroadenomas and the influence of tumor size on parameters such as NP concentration, treatment duration and irradiation protocols (laser power and duration). The implications of the results are discussed for the development of an integrated strategy for photothermal therapy for the destruction of fibroadenomas.
