The continuous improvement of modern medical level has reduced the mortality of BC to a certain extent, but the annual increase in the incidence of BC has prompted people to pay more attention to BC, especially LABC with its unique nature. This study started with the common surgical methods of T1 LABC, and established the COX regression prediction model to provide reference value for predicting the 5-year OS and BCSS survival probability of BCS and TM, so as to provide clinicians with a general understanding of the survival rate after the selection of surgical methods and help to provide the optimal treatment plan for patients.
The difference in survival between BCS and TM has always been a hot topic. Previous studies had confirmed that the survival rate of BCS was better than that of TM[6][7], which was consistent with the results of this study. The study by Rosenberg SM's team, based on the quality of life and psychosocial aspects of postoperative patients with BCS and TM, concluded that the long-term body image, sexual health and anxiety of BCS patients were better than those of TM patients. In recent years, the conjecture that BCS is superior to TM have also been increasing. On the one hand, the wide use of neoadjuvant therapy has made the indications of BCS more widely, which has promoted clinicians to increase the selectivity of patients to a certain extent. On the other hand, the cancer components of tumor cells can interact with their surrounding stromal cells and Inflammatory cells to form the Inflammatory tumor microenvironment (TME). The cells in TME are highly plastic. It can affect the tumor process by changing its phenotypic and functional characteristics [9]. Cancer associated fibroblasts (CAF) in TME can affect the growth, metastasis and remodeling of tumor cells due to their heterogeneity [10]. Fibroblast subsets increase the survival of CD4+ /CD25 + T lymphocytes by attracting T lymphocytes. Thus, immunosuppression is achieved [11]. A study had proposed the breast tumor homing hypothesis based on two special types of cells, Disseminated tumor cells (DTCs) and Circulating tumor cells (CTCs). This hypothesis points out that in the process of breast tumor development, cancer cells can not only enter the whole body along the blood or lymphatic system, but also have the ability to return to the primary site [12]. After treatment, DTCs and CTCs exist in the peripheral blood or bone marrow in a dormant form for a long time [13]. And the epithelial-mesenchymal transition (EMT) program that is formed by relying on the TME to provide good inducing conditions can cause DTC and CTCs to exit the dormant state [14]. Active tumor cells that enter the body under the regulation of various cell and gene functions in the TME will re-proliferate and grow. Compared to the "new environment" of TM, the TME of the original tumor site in BCS provides a more suitable environment for the rapid proliferation of DTCs and CTCs, laying the foundation for local recurrence, which also to some extent explains why the survival rate of TM is inferior to that of BCS [15].
Age has always occupied an irreplaceable position in BC. Previous studies have shown that the choice of LABC surgical methods was related to age, and with the rise of the trend of young BC, more and more young patients took TM and contralateral prophylactic mastectomy [16]. Several studies had pointed out that young BC patients had a higher risk of recurrence and more aggressive disease compared with older patients with similar disease characteristics [17][18]. This study found that age was an independent influencing factor of BCS and TM, and age was negatively correlated with OS of BCS and TM. And this was inconsistent with the results of previous studies. We suspect that the previous studies did not fully consider the condition of elderly patients when comparing the correlation between age and prognosis. These patients may be undertreated or overtreated due to the imperfect management system and the lack of evidence-based data to guide treatment, thus delaying their condition [19]. In addition to the above reasons, the underlying diseases that may exist in elderly patients themselves can also affect OS. For example, Diabetes mellitus (DM) will not only increase the incidence of autoimmune diseases, but also damage the innate and adaptive immune systems [20]. As an important cause of death or disability in the world, hypertension has always occupied an irreplaceable position in medicine. The activation of innate and adaptive immune cells leads to hypertension. In the continuous state of hypertension, it will induce stroke, heart failure, renal failure and other diseases, and the risk of damage cannot be reduced even if the blood pressure is reduced to normal [21]. The irreversible damage caused by chronic diseases can lower the tolerance and immunity of elderly patients, whether it is the initial surgical treatment during the treatment period, or the subsequent chemotherapy and maintenance treatment. In addition, some chemotherapy drugs have different side effects, some of which can cause irreversible damage to the body. And this may lead to reduced selectivity of treatment options or ineligibility for existing treatment options. Although these results provide some speculation for the reasons why younger patients have better OS than elderly patients, more prospective studies are needed to explore and confirm the specific reasons and mechanisms.
BCS + RT has become an internationally recognized treatment mode for BC. The first case of BC treated with radiation was initiated by Emil Grubbe in 1896 [22]. In the following 30 years, the use of radiation therapy in BC had been favored by medical researchers. Geoffrey Keynes found that the survival rate after BCS plus radium treatment was equivalent to that after radical mastectomy for BC [23]. With the rapid development of medicine today, the treatment mode of RT after BC is not only suitable for most BC, but also continues to improve in terms of breast RT dose and target volume [24]. For patients with positive sentinel lymph node (SLN) biopsy, the traditional treatment is routine axillary lymph node dissection (ALND). And the AMAROS trial and the ACOSOG Z011 trial offer the possibility of exempting these patients from ALND [25][26]. The follow-up study of AMAROS trial also found that combined with the incidence of complications after treatment, axillary radiotherapy (ART) had a better axillary recurrence rate (ARR) than ALND for cT1-2 BC patients with positive SLN [27]. All the above data indicate that the treatment mode of surgery + RT can increase the survival rate of BC, and ART can be used to replace ALND for patients who receive BCS or TM and 3 or less positive SLNS.
Metaplastic breast carcinoma (MBC) is a special type of invasive carcinoma in BC, accounting for less than 1% of all types of BC [28], but it has always made medical workers a bit of a jerk due to its highly invasive characteristics. Although it often appears as Triple negative breast cancer (TNBC), its prognosis is worse than that of TNBC due to its genetic heterogeneity and somatic mutations.
A research had compared the protein profiles of MBC and TNBC proteomics, showing that the MBC proteome had a higher level of EMT phenotype and inflammatory response, but the active extracellular matrix (ECM) and Oxidative phosphorylation (OXPHOS) were decreased [29]. As mentioned above, the EMT program can lead to the proliferation and growth of tumor cells under the regulation of various cells and genes in the organism, which is consistent with the fact that MBC may lead to a more aggressive phenotype than TNBC. This study found that MBC was negatively correlated with the 5-year OS of TM, which might be related to the highly aggressive characteristics of MBC. However, due to its genetic complexity, it is not a simple project to truly understand the cause of MBC. Further exploration of the cause may help to improve the quality of life and survival time of patients with MBC in the future.
The advantages and disadvantages of BCS and TM have always been a hot topic for medical workers to discuss. And various guidelines and relevant expert consensus also have certain indications for the selection of BCS and TM procedures.
Medicine is a discipline developing in a spiral of constant affirmation, denial and affirmation. Precision medicine is the stage goal of this discipline. In order to achieve this goal, it is particularly important to provide effective treatment plans. The emergence of clinical prediction model is an important node of medical progress. It integrates, analyzes and verifies different types of data, and then summarizes the probability value of an event in a specific scenario. Finally, it is presented in the way of data visualization to provide help for doctors to diagnose or predict the prognosis of diseases, so as to provide reference for clinical decision-making. The aim of this study was to compare the 5-year OS between BCS and TM in patients with T1 LABC, and to found out the risk factors of OS in different surgical procedures, so as to provide a basis for clinicians to individualized treatment.