Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine.

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Cold atmospheric plasma has emerged as a novel oncotherapeutic approach that has undergone a fast growth in the past few years. However, there is no quantitative assessment of the factors influencing its anti-tumor efficacy and the mechanism driving its activity remains mysterious. Through the use of 18 orthogonal experiments followed by linear model construction, we identified four deterministic parameters, that is, "treatment time," "liquid surface area," "thickness of medium," and "number of cells," which play deterministic roles on the anti-tumor efficacy of plasma. We propose "Reactive Species Diffusion Model" and "Signal Transduction Model" to explain the mechanics determining the activity of plasma treated medium and its celldeath induction efficacy. We, in addition, proposed the use of deterministic parameters in defining plasma dose in the liquid form to more objectively reflect its multi-modality nature. Our study contributes in elucidating plasma activity and efficacy in a quantitative way, which guides other plasma related investigations and accelerates plasma clinical applications as a type of precision oncotherapy. K E Y W O R D S cold atmospheric plasma, plasma activated medium, quantitative modeling, triple-negative breast cancer Xiaoyu Xu and Xiaofeng Dai contributed equally to this study.