Abstract: Analyzing the guiding and foreseeing role of systemic theory in the multifactorial study of breast cancer prognosis clarifies that consciously and actively using the scientific method of systemic theory in clinical scientific research can expand research ideas and provide new methods for the treatment of breast cancer; it also suggests that the reduction method is only one of the basic methods of systemic theory research, but not the only method. The reductionist and holistic approaches should be organically combined in the systematics-based research. Breast cancer is the most common malignant tumor among women in western countries, and in China breast cancer has been ranked the first malignant tumor among women, and the incidence rate is increasing year by year. There are many factors affecting the prognosis of breast cancer, and although the current research has reached a consensus in some aspects, there seems to be controversies and contradictions. This requires a systems theory to find a way out. Broadly speaking, philosophy includes ontology and methodology. Among them, the study of methodology has received much attention because of its role in guiding and anticipating scientific research. Methodology has undergone a development from reductionism to systematics. In this paper, we try to analyze the guiding and foreseeing role of system theory in the study of breast cancer prognosis multifactors, and clarify that the conscious and active use of the scientific method of system theory in clinical research can expand research ideas and lead breast cancer treatment to a new leap. The reductionist approach refers to the metaphysical view of reducing the higher forms of motion of matter to lower forms of motion and replacing the laws of higher forms of motion with the laws of lower forms of motion. Reductionism refers to simplification, reduction, lowering, and subsumption, a method of study that breaks down a higher (complex) level into a lower (simpler) level. Reductionism is both related to and qualitatively different from reductionism. Reduction as a method is necessary and effective for scientific research, but it is not sufficient for the understanding of things; reductionism is a philosophical idea formed by the unrestricted expansion of the cognitive function of reductionism. So far, medical research guided by reductionist philosophy has achieved brilliant achievements and given birth to corresponding disciplines, such as molecular biology. The same is true for the study of multiple factors in breast cancer prognosis. By decomposing several factors affecting breast cancer prognosis, such as age, pathological type, tumor size, lymph node metastasis, estrogen receptor (ER) and progesterone receptor (PR) status, scholars have conducted single-factor studies on their respective prognostic effects on breast cancer, and then, under the guidance of reductionism, they have studied each factor separately. The results were then simply summed under the guidance of reduction theory, which in turn guided treatment and prognosis and significantly improved patient survival. For example, Guan Yin et al [4] showed through a univariate analysis of 128 breast cancer patients with more than 10 lymph node metastases that the number of lymph node metastases was greater than 20, the ratio of metastatic lymph nodes was greater than 0.8, disease-free survival and overall survival were poorer in those with vascular tumor emboli; overall survival was poorer in those with negative receptors; and radiotherapy improved disease-free survival. Reductionism has played an important role in multifactorial studies of breast cancer prognosis, but has its own inevitable limitations. For example, univariate analysis found that chemotherapy is highly valuable in patients with invasive breast cancer, but multifactorial study found that age factor should be considered together with chemotherapy, and there are significant differences in the effect of chemotherapy in different age groups. 2. The current status of multifactorial study of breast cancer prognosis with system theory approach By system theory, we mean the idea and method of treating and understanding the problem according to the system characteristics and system laws by treating the research object as a system (including several interacting elements with definite performance). System properties and system laws include the principles of wholeness, connectedness, orderliness, dynamics, and overall optimality. It is based on this methodology that systems biology has been developed. Similarly, in multifactorial studies of breast cancer prognosis, it has been found that the outcome of multiple factors acting together is not simply the sum of the effects of each factor. For example, in univariate studies, the effect of hormone receptor status on the prognosis of breast cancer is clearer, with a poorer prognosis in those with ER(-), while the effect of different chemotherapy regimens (adriamycin, cyclophosphamide, docetaxel, ACT and cyclophosphamide, adriamycin, fluorouracil, CAF) on prognosis is controversial, leading to multifactorial studies of both. berry et al [5] retrospectively analyzed 6644 cases with ER(-) and ER(+) patients benefited more from postoperative adjuvant chemotherapy and had 50% lower recurrence and mortality rates with the ACT regimen than with the CAF regimen. It is clear that there is an interaction between hormone receptor status and chemotherapy regimen, and that hormone receptor status has a role in the prognostic impact of chemotherapy regimens on breast cancer, and that the prognostic impact of these two factors is not simply additive. Other multifactorial studies such as these include the effect of Human Epidermal growth factor Receptor-type 2 (HER2) status and chemotherapy regimen on breast cancer prognosis.Pritchard KI et al [6] in the Mammary 5 randomized controlled study, looked at 710 patients with HER2 gene amplification in tumor tissue in premenopausal breast cancer cases with lymph node metastasis, and when evaluated based on recurrence-free survival, the cyclophosphamide, epothilone, and fluorouracil (CEF) regimen was superior to the cyclophosphamide, methotrexate, and fluorouracil (CMF) regimen, as was the outcome of the overall survival evaluation. CEF did not improve recurrence-free survival or overall survival in those without HER2 amplification in the tumor tissue. The corrected ORs for the interaction between treatment and HER2 amplification were 1.96 for recurrence-free survival and 2.02 for overall survival, respectively. it is evident that there is an interaction between HER2 amplification status in breast cancer cells and chemotherapy regimens containing anthracycline anticancer drugs, and that HER2 amplification status has a role in the effect of chemotherapy regimens on breast cancer prognosis, and the effect of these two factors on prognosis is not simply cumulative. It can be seen that consciously and actively using the scientific method of system theory in the study of multifactorial breast cancer prognosis can expand the new ideas of research and solve some long-standing doubts. The development of systemic theory in breast cancer multifactorial research The current systemic theory approach to breast cancer prognostic multifactorial research is mainly based on the reduction method and further study of its interaction, which is still divided first and then combined, only realizing that the combination is not simple addition, and realizing that “the whole is greater than the sum of its parts”. But we must understand that from the phylogenetic point of view, there are two systems: the combinatorial system and the differentiated system. For the combinatorial system, we can certainly study the system by reduction. But in the case of differentiated systems, they cannot be partitioned or partitioned in such a way that they completely change the inherent characteristics of the system itself and can no longer be called “systems”. A systems theory approach based on the reductionist approach is not feasible and may lead to wrong conclusions. It can be seen that the reduction method is only one of the basic methods of system theory research, but not the only method, and the system theory-based research method should combine the reduction method and the holistic method organically. For some differentiated systems, the whole cannot be partitioned, and if partitioning is forced, the partitioned part may be completely different from the original whole and result in wrong findings. For example, in a multifactorial study of breast cancer prognosis, the hormone receptor status and endocrine therapy of breast cancer are inseparable and have statistical covariance, so they should be studied as a whole. Similarly, for some other combined systems, each of their combined parts can be divided into combined subsystems and differentiated subsystems, and the whole can only be partly divided, then they must be studied by a combination of reduction and holistic methods. For example, in the multifactorial study of breast cancer prognosis, the prognostic outcome and the time of occurrence of the prognostic outcome are indivisible, and it is influenced by multiple factors, some of these factors can be divided and can be studied by reduction method; some of them must be done as a whole study. Whereas there may be no interaction between the influencing factors, there may be synergistic or antagonistic effects. The proportional risk model proposed by British statistician Cox is based on such systematic methodological considerations. However, the Cox proportional risk model is not widely used in China at present, and because of the inability to recognize the interaction between factors, it often fails to include the factor product phase to explore its interaction, but simply does linear summation of the factors, which is one of the reasons that hinder multifactorial studies. Thus, it is necessary and effective to use a systemic approach combining holistic and reductive methods in the multifactorial study of breast cancer prognosis. In conclusion, reductionism has played a great role in the multifactorial study of breast cancer prognosis, but with the rise of biological science and complexity science, the limitations of reductionism have gradually emerged as a stumbling block to scientific progress, so that transcending reductionism has become a common goal of scientific development [7], and thus system theory was born. In clinical medical science research, the conscious and active use of dialectical thinking and the scientific method of systematics can expand the thinking and provide the best solution for the diagnosis and treatment of diseases, which is of great importance to promote and guide clinical treatment. The holistic approach should be combined organically.