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Background In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, "local recurrence" may include different components in similar studies.This limits transparency and comparability of results.This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies. Methods The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting. Results Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended. Conclusion This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis. [ABSTRACT FROM AUTHOR]

While ductal carcinoma in situ (DCIS) is known as a precursor lesion to most invasive breast carcinomas, the mechanisms underlying this transition remain enigmatic. DCIS is typically diagnosed by the mammographic detection of microcalcifications (MC). MCs consisting of non-stoichiometric hydroxyapatite (HA) mineral are frequently associated with malignant disease, yet it is unclear whether HA can actively promote malignancy. To investigate this outstanding question, we compared phenotypic outcomes of breast cancer cells cultured in control or HA-containing poly(lactide- co- glycolide) (PLG) scaffolds. Exposure to HA mineral in scaffolds increased the expression of pro-tumorigenic interleukin-8 (IL-8) among transformed but not benign cells. Notably, MCF10DCIS.com cells cultured in HA scaffolds adopted morphological changes associated with increased invasiveness and exhibited increased motility that were dependent on IL-8 signaling. Moreover, MCF10DCIS.com xenografts in HA scaffolds displayed evidence of enhanced malignant progression relative to xenografts in control scaffolds. These experimental findings were supported by a pathological analysis of clinical DCIS specimens, which correlated the presence of MCs with increased IL-8 staining and ductal proliferation. Collectively, our work suggests that HA mineral may stimulate malignancy in preinvasive DCIS cells and validate PLG scaffolds as useful tools to study cell-mineral interactions. [ABSTRACT FROM AUTHOR]