Contents lists available at ScienceDirect Journal of Forensic and Legal Medicine journal homepage: www.elsevier.com/locate/yj flm Research Paper The appearance of breast cancer metastases on dry bone: Implications for forensic anthropology Lucie Biehler-Gomez * , Gaia Giordano, Cristina Cattaneo LABANOF, Laboratorio Di Antropologia E Odontologia Forense, Sezione Di Medicina Legale, Dipartimento Di Scienze Biomediche per La Salute, Università Degli Studi Di Milano, Milan, Italy ARTICLE INFO Keywords: Forensic anthropology Breast cancer Bone pathology Bone metastases ABSTRACT Breast carcinoma is a major cause of morbidity and mortality in women. The study of bone pathologies presents considerable potential in anthropology, paleopathology, forensic science and medicine. In this paper, we present and discuss metastatic lesions found in the skeletons of known individuals from the CAL Milano Cemetery Skeletal Collection, clinically diagnosed with breast cancer during life. Fourteen skeletons from a contemporary and identified collection were macroscopically studied and metastases were identified by comparison with clinical literature. As a result, bone metastases were observed in 43% of the study sample. They were located most commonly on the ribs (28.1%), pelvic girdle (19.8%), vertebrae (15.6%), skull (15.6%), scapulae (10.2%) as well as proximal segment of the femora (8.4%) and humeri (2.4%) respectively, favoring sites of high vas- cularization. The majority of the lesions were osteolytic, although osteoblastic and mixed metastases did occur. Osteolytic metastases appear as coalescent porosity or round to oval perforating lesions on bones with denti- culated margins and pitted surrounding bone, whereas osteoblastic metastases thickened the existing trabecula (spongiosclerosis). Mixed metastases were perforating lytic lesions exposing the osteoblastic activity in the underlying trabecular bone. These results, consistent with the data from the literature, strengthen the diagnostic criteria for metastases and illustrate the aspect of bone metastases in breast carcinoma. 1. Introduction Breast carcinoma is the leading cause of death in women aged 40–59, the first cause of cancer-related deaths in female sex and the most common cancer diagnosed in women. 1,2 It has been estimated that the lifetime probability of developing invasive breast cancer in the United States of America is 1 in 8 women. 1 Although male breast cancer may occur, it is extremely rare and represents less than 1% of all breast cancer cases. 3 Breast and prostate cancers are the most common solid tumors to metastasize to bone with an incidence at autopsy of bone metastases ranging from 65 to 75%, 4–6 making it the first site of me- tastasis for these cancer primaries. 7,8 In 1889, Stephen Paget postulated his “seed and soil” theory that presupposes that metastatic growth (seed) is dependent upon the fa- vorable microenvironment provided by the bone matrix (soil). 9,10 The bone microenvironment is a storage of immobilized growth factors re- leased during bone resorption that will attract tumor cells and stimulate their proliferation. This disastrous loop of tumor growth and bone re- sorption or “vicious cycle” is the mechanism responsible for osteolytic metastases. In short, breast tumor cells secrete osteoblastic and osteo- clastic factors that will promote the phenotypic differentiation of bone cells to osteoblasts (bone forming cells) and osteoclasts (bone re- modeling cells) and their activation. Bone forming cells synthetize growth factors kept within the bone matrix until the osteoclastic ac- tivity releases them, promoting the proliferation of tumor cells and attracting new ones. 7,11–18 Bone metastases are classically divided into three types: osteolytic (when the osteoclastic activity predominates), osteoblastic (when bone formation overcomes bone resorption) or mixed (with both osteoclastic and osteoblastic activities). However, both components are generally expressed and bone metastases range from mostly lytic to mostly blastic. Breast carcinoma is predominantly osteolytic (80–90% of me- tastases) but osteoblastic metastases may occur (10–20%). 2,8,12,13 Through naked eye observation, osteolytic metastases materialize as coalescent porosity or perforations of the bone cortex. Perforating le- sions are round to oval destructive bone lesions of various size with well-defined denticulated or scalloped margins, but the greatest extent of the lesion is located in the trabecular bone, often dissimulated from https://doi.org/10.1016/j.jflm.2018.10.007 Received 21 June 2018; Received in revised form 2 October 2018; Accepted 22 October 2018 * Corresponding author. LABANOF, Laboratorio di Antropologia e Odontologia Forense, Sezione di Medicina Legale, Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Via Mangiagalli 37, 20133, Milan, Italy. E-mail address: lucie.biehler@unimi.it (L. Biehler-Gomez). Journal of Forensic and Legal Medicine 61 (2019) 5–12 Available online 25 October 2018 1752-928X/ © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved. T