The concepts and techniques of surgical treatment for breast cancer have been innovated for more than 100 years and the development can be divided into four stages: radical resection, function preservation, organ reconstruction and minimally invasive treatment. Currently, clinical treatment of breast cancer is a process in which these four stages overlap and continuously progress. This evolution not only embodies the deepening of the treatment concept, shifting from radical disease elimination to organ and function protection in breast cancer surgery, but also mirrors the continuous progress in physiological and psychological care for patients. With the help of advanced technical equipment,clinical problems are constantly being solved,highlighting the specialty features of breast surgery. However, the following issues still impede the further development of breast surgery: lack of breakthroughs in the etiology of major breast diseases, few updates on guiding theories for breast surgery, slow development of key surgical techniques in breast cancer and limited successful cases using modern technology in clinical practice and few techniques related to sensory restoration during breast reconstruction. Among these, a major theoretical breakthrough of surgical techniques in breast cancer is a key point at present. This article put forward,for the first time,the treatment concept of non-radical breast cancer surgery, aiming to construct the theoretical and technical system of non-radical breast cancer surgery and analyze its theoretical basis and clinical feasibility. Moreover, it systematically summarized the current development of non-radical breast cancer surgery and its potentials as an alternative to classic radical surgery, and explored the research directions and related topics required to establish a new clinical treatment theory in breast cancer, hoping to draw the attention and spark discussions among the academic community.
Whether applying adjuvant treatment including radiotherapy, chemotherapy and endocrine therapy after traditional surgery, or performing neoadjuvant therapy to achieve debulking, breast and axillary lymph node conservation, surgery is always primary treatment for breast cancer. In recent years, an increasing number of researches have focused on precision surgical treatment, in order to realize minimal surgical incision and maximal clinical benefit at the same time. Therefore, this article summarized the top ten hot issues in surgical treatment of breast cancer, including concept innovation of breast conservation, definition of breastconserving surgery margins, breast conservation of germline BRCA mutation patients, breast-conserving surgery after neoadjuvant therapy, feasibility of surgery exemption after neoadjuvant therapy, exemption of sentinel lymph node biopsy, treatment of low-burden metastases in sentinel nodes, de-escalation therapy of axillary nodes after neoadjuvant therapy, local treatment of newly diagnosed stage Ⅳbreast cancer and minimally invasive surgery such as endoscopic and Da Vinci-assisted robotic surgery, in order to provide a refence for precision and standardization of surgical treatment in the future.
The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, also known as the PAM signaling pathway, influences breast cancer development and progression through various mechanisms and plays a critical role in therapeutic resistance.Breast cancer patients with aberrant PAM signaling pathway activation typically have worse prognosis compared with those with normal signaling. In recent years, targeted therapies focusing on the PAM signaling pathway,including PI3K inhibitors, AKT inhibitors, mTOR inhibitors and dual PI3K/mTOR inhibitors, have achieved significant progress in breast cancer treatment, particularly in improving the prognosis of hormone receptorpositive, HER-2-negative advanced breast cancer patients. This review systematically summarized key clinical studies on PAM signaling pathway inhibitors across different molecular subtypes of breast cancer, discussed the challenges in PAM pathway detection and safety management of targeted therapy, and predicted future directions in this field. Through precise detection of PAM signaling pathway and rational application of related inhibitors, more optimized treatment strategies for breast cancer patients are expected.
To compare one-step nucleic acid amplification (OSNA) technique and the frozen section (FS) method in intraoperative detection of sentinel lymph node (SLN) metastasis in breast cancer patients, and evaluate the diagnostic performance of OSNA.
Methods
A prospective study was conducted on clinical data of 116 patients with primary breast cancer admitted to the General Hospital of the Northern Theater Command from November 2021 to April 2023. Each patient underwent sentinel lymph node biopsy, and 287 identified SLNs were subjected to both OSNA and FS testing. Postoperative pathological examination served as the gold standard for diagnosis. Diagnostic concordance rates, sensitivity, specificity,positive predictive value (PPV) and negative predictive value (NPV) were calculated for both OSNA and FS.Kappa test was used to assess the consistency of OSNA and FS with the postoperative pathological result (gold standard). McNemar’s test was employed to compare the sensitivity and specificity of OSNA and FS,as well as the serial and parallel combinations of the two methods. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to compare the diagnostic efficacy of different methods. Chi-squared tests and Mann-Whitney U tests clinicopathological features between lymph node metastasis group and non-metastasis group.
Results
Vascular invasion and total tumor burden were associated with SLN metastasis (χ2 =16.454,P<0.001;Z=-8.876,P<0.001). For the 116 patients, the diagnostic concordance rate of OSNA with postoperative pathology was 93.1% (108/116), with a sensitivity of 95.8%(23/24), specificity of 92.4% (85/92), PPV of 76.7% (23/30), and NPV of 98.8% (85/86). The kappa value was 0.808 (P<0.001) and the AUC was 0.941 (95%CI: 0.885-0.997, P<0.001). The sensitivity of OSNA and FS showed no statistically significant difference (95.8% vs 87.5%,χ2=0.500,P=0.500). For the 287 SLNs, the diagnostic concordance rate of OSNA was 94.8% (272/287), with a sensitivity of 93.8% (30/32), specificity of 94.9% (242/255), PPV of 69.8% (30/43), and NPV of 99.2% (242/244). The kappa value was 0.771 (P <0.001) and the AUC was 0.961 (95%CI: 0.911-1.000, P<0.001). The sensitivity showed no significant difference between OSNA and FS (93.8% vs 90.6%, χ2 = 0.333,P= 1.000). The sensitivity of OSNA combined with FS in series of the 116 patients was 87.5% (21/24), specificity 92.4%(85/92), PPV 75%(21/28), and NPV 96.6%(85/88). The sensitivity indicated a significant difference compared with OSNA alone (χ2 = 7.111,P= 0.004). For the parallel combination of OSNA and FS, the sensitivity was 95.8% (23/24), specificity 92.4% (85/92), PPV 76.7% (23/30), and NPV 98.8% (85/86). The detection rate of positive case was the same as that of OSNA alone, indicating no statistical significance.
Conclusion
OSNA is a reliable method for detecting SLN metastasis in breast cancer patients.
To explore the effect of mogroside (MO) on autophagy and apoptosis in human breast cancer cells.
Methods
MDA-MB-231 and SK-BR-3 cells in the logarithmic growth phase were randomly divided into control group (C group) and treatment groups (MO-treated groups,treated with 10, 20,40 and 80 μmol/L of MO, respectively). The MTT assay was employed to evaluate the cell proliferation rate,and a real-time cell electronic sensing system was utilized to measure the cell doubling time. Acridine orange(AO) staining was used to detect autophagy and a flow cytometer was applied to analyze apoptosis. Western blotting was performed to determine the expression levels of autophagy-related proteins (LC3β, p62),apoptosis-related proteins (BAX, Bcl-2), as well as PI3KCA and AKT1. One-way analysis of variance was used to compare the cell proliferation rate, doubling time, relative autophagosome content, apoptosis rate, and protein expression among groups, and pairwise comparisons were carried out using the LSD-t test.
Results
There were significant differences in the proliferation rate and doubling time of MDA-MB-231 and SK-BR-3 cells between the C group and different MO-treated groups (F=102.570,110.256,85.238,79.014;P<0.001). Specifically, the cell proliferation rates in the MO-treated groups were significantly lower than those in the C group, while the doubling times were significantly longer (P<0.050). The relative autophagosome content in all MO-treated groups was significantly higher than that in the C group (P<0.050), and it increased with the elevation of MO concentrations (P<0.050 for all pairwise comparisons). Significant differences in apoptosis rates were also noted among groups (F=161.327,151.304;P<0.001). The apoptosis rates in all MOtreated groups were significantly higher than those in the C group, and they increased as the MO concentrations rose (P<0.050 for all pairwise comparisons). Moreover, significant differences were detected in the expression levels of LC3β, p62, BAX, Bcl-2, PI3KCA, and AKT1 in MDA-MB-231 and SK-BR-3 cells among groups(F=97.150,101.254,81.578,83.336,78.541,85.233,68.435,71.332,163.576,152.673,138.107,143.188;P<0.001). The expression levels of LC3β, BAX, PI3KCA, and AKT1 in the MO-treated groups were significantly higher than those in the C group, while the expression levels of p62 and Bcl-2 were significantly lower (P<0.050). With the increase of MO concentrations,the expression levels of BAX,PI3KCA,and AKT1 showed an upward trend, and the Bcl-2 expression showed a downward trend, with all pairwise comparisons being statistically significant (P<0.050).
Conclusions
MO is a potential inhibitor of triple-negative breast cancer and HER-2-positive breast cancer. Its mechanism might be related to targeting the PI3K/AKT signaling pathway to induce autophagy and apoptosis in breast cancer cells.
To investigate the application of the 21-gene recurrence risk score (RS) in patients with early breast cancer, and analyze its correlation with clinicopathological characteristics and the prognosis.
Methods
Based on the inclusion and exclusion criteria, a total of 122 patients with early breast cancer who underwent surgical treatment and 21-gene testing in the Department of Breast Surgery, the Second Affiliated Hospital of Dalian Medical University from January 2019 to December 2023 were enrolled in this retrospective study. The RS was calculated according to the results of 21-gene testing. All patients were categorized into low-risk group (RS<11), intermediate-risk group (11≤RS<26), and high-risk group (RS≥26). All patients were followed up until May 1, 2024 or until the occurrence of recurrence and metastasis.Information regarding postoperative adjuvant treatment, recurrence, and metastasis was collected. The relationships between RS classification and clinicopathological characteristics, the selection of adjuvant chemotherapy, recurrence, and metastasis were analyzed. For multi-group comparisons of count data, χ2 test or Fisher’s exact test was utilized, while rank data was analyzed using the non-parametric test(Kruskal-Wallis H test) for multiple independent samples. Pair-wise comparisons among multiple groups were corrected by the Bonferroni method. Survival analysis was carried out using the Kaplan-Meier method and Log-rank test.
Results
Among the 122 patients,19 cases were in the low-risk group,69 cases were in the intermediate-risk group, and 34 cases were in the high-risk group, among which 1, 12 and 30 patients received adjuvant chemotherapy. A total of 112 patients (91.8%) had no axillary lymph node metastasis,while 10 patients (8.2%)had axillary lymph node metastasis. Statistically significant differences were observed in age and menstrual status among the three groups (χ2=8.936, 12.738; P=0.011, 0.002). Among the 112 patients with negative lymph nodes, 19 were in the low-risk group, 64 were in the intermediate-risk group, and 29 were in the highrisk group. There were statistically significant differences in age (χ2= 8.916, P=0.012), menstrual status(χ2=12.773, P=0.002), and PR status (P=0.035) among the three groups. The median follow-up time was 26 (12, 36) months. Local recurrence occurred in three cases, all of which were in the high-risk group as determined by 21-gene testing. The recurrence rate of the high-risk group was 8.8% (3/34), and no distant metastasis or death events were recorded. Survival analysis of the 122 patients revealed that there was no statistically significant difference in the DFS curves among the low-risk group, intermediate-risk group, and high-risk group (P = 0.059).
Conclusions
The RS classification based on 21-gene testing can offer a relatively reliable basis for treatment decision-making in patients with early breast cancer.