Objective To investigate the differences in clinicopathological characteristics and prognostic survival of human epidermal growth factor receptor 2 (HER2) high expression, HER2 low expression and HER2 negative breast cancer. MethodWe retrospectively collected 1 560 female breast cancer patients who underwent surgical treatment at the Department of Breast and Thyroid Surgery in Renmin Hospital of Wuhan University between January 8, 2010 and December 31, 2015, and divided them into high expression group, low expression group and negative group according to HER2 expression, to compare the differences in clinicopathological characteristics among the three groups of breast cancer patients and to explore the factors influencing prognosis. Results The proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, TNM stage Ⅲ, Ki67 high expression, and hormone receptor negative expression were higher in the high expression group than those in the low expression group and negative group (P<0.050); the proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, and TNM stage Ⅲ were higher in the low expression group than those in the negative group (P<0.050). However, the proportions of Ki67 high expression and hormone receptor negative expression were lower than those of the negative group (P<0.050). The 5-year disease-free survival rate were 85.6%, 80.3% and 74.5% for the high expression, low expression and negative group, respectively, and the 5-year overall survival rate were 90.4%, 86.0% and 80.7%, respectively. The results of multivariate Cox proportional hazard model showed that patients with high histological grade, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year disease-free survival (P<0.050); patients with older age, high histological grade, lymph node metastasis, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year overall survival (P<0.050). Conclusions The intensity of HER2 expression affects the 5-year disease-free survival and overall survival of breast cancer patients, and the higher the intensity of HER2 expression, the better the 5-year disease-free survival and overall survival, while the weaker the HER2 expression, the worse the 5-year disease-free survival and overall survival.
ObjectiveTo investigate whether Osteoglycin (OGN) gene inhibits the proliferation of Luminal breast cancer cells by up-regulating the expression of estrogen receptor (ER). Methods① Ualcan online database was used to analyze the expression of OGN in the breast cancer, and Kaplan-Meier Plotter was used to analyze the effect of OGN on the prognosis of patients with breast cancer. The median OGN mRNA expression level was taken as the cut-off point for high or low OGN expression. ② The expression of OGN mRNA in the Luminal breast cancer tissue of clinical case was examined using real time quantitative PCR (qRT-PCR). ③ Up-regulation of OGN expression in the Luminal breast cancer cell lines MCF-7 and T47D cells by transfection of overexpressing OGN plasmid, the expressions of OGN and ER were detected by qRT-PCR and Western blot, respectively. CCK8 assay and colony formation assay were applied to detect the cell proliferation and colony formation of Luminal breast cancer cells. ④ siRNA transfection was used to interfere with the expression of ER (ESR1) of breast cancer cells in the overexpressing OGN of breast cancer cells, then the CCK8 assay was used to detect the proliferation ability of the breast cancer cell lines after down-regulating the expression of ER in the overexpressing OGN patients. Results① The results of Ualcan online database showed that the expression of OGN mRNA in the breast cancer tissues of different types of breast cancer was lower than that in the normal breast tissues (P<0.001), and which was highest in the Luminal breast cancer tissues (P<0.001). The Kaplan-Meier Plotter prognosis analysis showed that in all breast cancer or Luminal breast cancer patients, the prognosis of patients with high OGN expression was better than those with low OGN expression (P=0.000 14, P=0.001 80). ② The OGN mRNA expression was decreased in the 30 Luminal breast cancer samples as compared with the corresponding adjacent normal breast tissues (t=4.774, P=0.000 019). ③ The expressions of OGN and ER in the MCF-7 and T47D cells were up-regulated after transfection of overexpressing OGN plasmid (P=0.000 002, P=0.000 001). The cell proliferation was inhibited (P<0.05) and the number of cell clones was decreased significantly (P<0.05). ④ After transient transfection of siRNA interfered with breast cancer cell lines of overexpressing OGN, ER mRNA level decreased (P<0.05), and cell proliferation ability increased significantly (P<0.05). Conclusion OGN could exert a tumor suppressor effect in Luminal breast cancer by mediating expression of ER.
ObjectiveTo summarize the mechanism of action of programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, the application in breast cancer in recent years and the advances in the study of their bio-markers of effects. MethodRelevant literatures on PD-1/PD-L1 inhibitors and the study in the field of breast cancer were reviewed and summarized.ResultsIn recent years, the monotherapy of immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors or in combination with other therapies had brought new hope for patients with breast cancer especially triple-negative breast cancer (TNBC). However, only a small number of patients could benefit from breast cancer immunotherapy. The current researchers think that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), high level of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR).ConclusionBreast cancer can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, but formulating personalized medicine model, finding biomarkers that can predict efficacy and selecting patients with breast cancer who can benefit from it for targeted therapy are the new requirements in the new era of breast cancer immunotherapy.
ObjectiveTo synthesize recent advances in surgical management of breast cancer, focusing on five key issues: axillary surgery de-escalation, margin control in breast-conserving surgery (BCS), prophylactic surgery for BRCA1/2 gene mutation carriers, local therapy for oligometastasis, and intraoperative radiotherapy (IORT), aiming to guide individualized clinical decisions. MethodsA comprehensive analysis of high-quality evidence (RCTs, prospective cohorts and multicenter studies) was conducted, comparing efficacy and safety across strategies. ResultsFor patients with positive sentinel lymph nodes (SLN) undergoing BCS, axillary lymph node dissection (ALND) can be safely omitted if they present with clinical stage cT1–2, cN0 disease, have not received preoperative chemotherapy, exhibit 1–2 positive SLNs, and are planned for whole-breast radiotherapy. The Memorial Sloan Kettering Cancer Center nomogram quantitatively predicts non-SLN metastasis risk by integrating features like tumor size and SLN metastatic burden. Omission of ALND is particularly safe for SLN micrometastasis (≤2 mm), demonstrating a 5-year overall survival rate of approximately 97.5%. In patients achieving clinically node-negative (ycN0) status post-neoadjuvant therapy, techniques such as dual-tracer mapping or pre-treatment marking of suspicious nodes reduce the false negative rate of SLN biopsy. Treatment decisions for elderly patients require multidisciplinary assessment of surgical risks versus benefits. The integration of multiparametric MRI, artificial intelligence with intraoperative ultrasound significantly reduces positive margin rates in BCS from 25% to 8%–15%, markedly decreasing reoperation rates. For BRCA1/2 mutation carriers, prophylactic mastectomy reduces breast cancer risk by 90%–95%, while prophylactic bilateral salpingo-oophorectomy (PBSO) reduces ovarian cancer risk by 80%–90%; the timing of PBSO is stratified by genotype (BRCA1: 35–40 years; BRCA2: 40–45 years) and integrated with fertility plans and psychological assessment. Local therapy provides clear survival benefits for oligometastatic breast cancer patients with hormone receptor positive disease and bone/soft tissue metastases, with stereotactic body radiotherapy being preferred for low-burden metastases. IORT for early breast cancer is strictly limited to low-risk patients, achieving long-term survival rates equivalent to conventional radiotherapy but necessitating stringent patient selection. ConclusionsPrecision surgery is evolving through axillary de-escalation, real-time margin assessment, risk-adapted prophylactic surgery, selected local therapy for oligometastasis, and strict patient selection for IORT. Multidisciplinary integration is essential for future optimization.
ObjectiveTo investigate the effectiveness of endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants. Methods The clinical data of 138 female patients with breast cancer who met the selection criteria between April 2019 and December 2023 were retrospectively analyzed. The mean age of the patients was 43.8 years (range, 27-61 years). The maximum diameter of the tumors ranged from 1.00 to 7.10 cm, with an average of 2.70 cm. Pathological examination showed that 108 cases were positive for both estrogen receptor and progesterone receptor, and 40 cases were positive for human epidermal growth factor receptor 2. All patients underwent endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants. The operation time, intraoperative blood loss, prosthesis size, and occurences of nipple-areola complex (NAC) ischemia, flap ischemia, infection, and capsular contracture were recorded. The Breast-Q2.0 score was used to evaluate breast aesthetics, patient satisfaction, and quality of life (including the social mental health score, breast satisfaction score, and chest pain score). Patients were divided into two groups based on the time of operation after the technique was implemented: group A (within 1 year, 25 cases) and group B (after 1 year, 113 cases). The above outcome indicators were compared between the two groups. Furthermore, based on the postoperative follow-up duration, patients were classified into a short-term group (follow-up time was less than 1 year) and a long-term group (follow-up time was more than 1 year). The baseline data and postoperative Breast-Q2.0 scores were compared between the two groups. ResultsThe average operation time was 120.76 minutes, the average intraoperative blood loss was 23.77 mL, and the average prosthesis size was 218.37 mL. Postoperative NAC ischemia occurred in 21 cases (15.22%), flap ischemia in 30 cases (21.74%), infection in 23 cases (16.67%), capsular contracture in 33 cases (23.91%), and prosthesis removal in 2 cases (1.45%). The operation time of group A was significantly longer than that of group B (P<0.05), and there was no significant difference in intraoperative blood loss, prosthesis size, and related complications between the two groups (P>0.05). All patients were followed up 3-48 months (mean, 20 months). There were 33 cases in the short-term group and 105 cases in the long-term group. There was no significant difference in baseline data such as age, body mass index, number of menopause cases, number of neoadjuvant chemotherapy cases, number of axillary lymph node dissection cases, breast cup size, degree of breast ptosis, and postoperative radiotherapy constituent ratio between the two groups (P>0.05). At last follow-up, the breast satisfaction score in the patients’ Breast-Q2.0 score ranged from 33 to 100, with an average of 60.9; the social mental health score ranged from 38 to 100, with an average of 71.3; the chest pain score ranged from 20 to 80, with an average of 47.3. The social mental health score of the long-term group was significantly higher than that of the short-term group (P<0.05); there was no significant difference in breast satisfaction scores and chest pain scores between the two groups (P>0.05). No patient died during the follow-up, and 2 patients relapsed at 649 days and 689 days postoperatively, respectively. The recurrence-free survival rate was 98.62%. Conclusion Endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants has fewer complications and less damage, and the aesthetic effect of reconstructed breast is better.
ObjectiveTo analyze the factors influencing axillary pathological complete response (pCR) after neoadjuvant therapy (NAT) and to provide the possibility of exempting axillary surgery for patients with better pathological efficacy of primary breast lesions after NAT. MethodsAccording to the inclusion and exclusion criteria, the patients with breast cancer admitted to the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from January 1, 2020 to June 30, 2022 were retrospectively analyzed. All patients were diagnosed with ipsilateral axillary lymph node metastasis of breast cancer and the NAT cycle was completed according to standards. All patients underwent axillary lymph node dissection (ALND) after NAT. The therapeutic effect of primary breast lesions was evaluated by Miller-Payne (MP) grading system. The axillary pCR was judged according to whether there was residual positive axillary lymph nodes after ALND. The unvariate and multivariate logistic regressions were used to analyze the risk factors affecting the axillary pCR. At the same time, the possibility of exempting axillary surgery after NAT in the MP grade 5 or in whom without ductal carcinoma in situ (DCIS) was evaluated. The ALND was considered to exempt when the negative predictive value was 90% or more and false negative <10% or almost same. ResultsA total of 111 eligible patients with breast cancer were gathered in the study, 64 of whom with axillary pCR. There were 43 patients of MP grade 5 without DCIS after NAT, 41 of whom were axillary pCR. The univariate analysis results showed that the estrogen receptor and progesterone receptor statuses, molecular type, NAT regimen, and MP grade were associated with the axillary pCR after NAT, then the logistic regression multivariate analysis results showed that the MP grade ≤3 and MP grade 4 decreased the probability of axillary pCR as compared with the MP grade 5 [OR=0.105, 95%CI (0.028, 0.391), P=0.001; OR=0.045, 95%CI (0.012, 0.172), P<0.001]. There were 51 patients of MP grade 5 after NAT, 46 of whom were axillary pCR. The negative predictive value and the false negative rate of MP grade 5 on predicting the postoperative residual axillary lymph nodes were 90.2% [95%CI (81.7%, 98.6%)] and 10.6% [95%CI (1.5%, 19.8%)], respectively, which of MP grade 5 without DCIS were 95.3% [95%CI (88.8%, 101.9%)] and 4.3% [95%CI (–1.7%, 10.2%)] , respectively. ConclusionsThe probability of axillary pCR for the patient with higher MP grade of breast primary after NAT is higher. It is probable of exempting axillary surgery when MP grade is 5 after NAT.
Objective To evaluate the effect of neoadjuvant chemotherapy (NAC) on breast conserving surgery and the outcomes of treatment for women with operable breast cancer. Methods We searched The Cochrane Library (Issue 1, 2007), CENTRAL (1970 to 2007), PUBMED (1978 to March 2007), CBM (1978 to 2006), CNKI (1994 to 2007), CMCC (1994 to May 2007) and other relevant databases and journals. We identified randomized controlled trials (RCTs) comparing NAC plus breast conserving therapy (BCT) or mastectomy versus BCT or mastectomy plus postoperative chemotherapy in women with operable breast cancer. Two reviewers independently assessed trial quality and extracted data. Meta-analyses were performed for homogenous studies by using The Cochrane Collaboration’s RevMan 4.2.10. Results Three eligible studies involving 2 391 women were included. The median follow-up in the studies ranged from 17 to 137 months. The methodological quality of the three RCTs was high. Meta-analyses showed that NAC had no significant effect on overall survival (OS) (RR 0.99, 95%CI 0.92 to 1.07), disease-free survival (RR 1.04, 95%CI 0.94 to 1.15) and ipsilateral breast cancer recurrence (RR 1.34, 95%CI 0.84 to 2.13). Two RCTs revealed that NAC significantly increased the rate of BCT in operable breast cancer patients, but the other RCT reported similar rates of BCT in both groups. One RCT indicated that NAC did not increase the incidence of surgery-related local complications. Conclusions NAC is safe for the treatment of women with operable breast cancer, which may increase the rate of BCT and help to evaluate chemosensitivity. There is insufficient evidence to assess the effect of NAC on conserving surgery procedure and survival rate in operable BCT patients. More large-scale RCTs are needed to define further the role of NAC in the treatment of operable breast cancer patients.
ObjectiveTo summarize the progress of diagnosis and treatment in male breast cancer. MethodsThe literatures about the research progress of diagnosis and treatment in male breast cancer were reviewed. ResultsThe diagnosis of male breast cancer relied mainly on clinical manifestations and imaging manifestations, the main treatment of male breast cancer was modified radical operation, combining with radiotherapy, chemotherapy, endocrine therapy, and targeted therapy. ConclusionsThe treatment of male breast cancer is mainly reference the treatment of female breast cancer, which is lack of a clear standard of treatment. Indepth study on the molecular genetic level will provide more accurate care decisions for the treatment of male breast cancer.
ObjectiveTo explore advances in clinical applications of circulating tumor DNA (ctDNA) for early diagnosis of breast cancer.MethodReviewed on the latest literatures about studies of advances in clinical applications of ctDNA for early diagnosis of breast cancer.ResultsctDNA was a cell-free DNA generated by tumor cells that contained tumor-associated mutations and could dynamically reflect the entire picture of the tumor genome. It was a very important potential tumor biomarker. ctDNA had been widely used in a variety of tumors for early diagnosis, curative effect assessment, and prognosis evaluation due to its advantages such as small trauma and real-time monitoring, and its role in breast cancer had attracted more and more attention.ConclusionEarly diagnosis is critical to improve the breast cancer patients’ overall survival rate and ctDNA plays an important role in early diagnosis and early detection of recurrence and metastasis of breast cancer.
ObjectiveTo summarize the latest advances in copper and cuproptosis in the field of breast cancer, and to provide a reference for clinical treatment decisions. MethodThe literatures related to copper and cuproptosis in recent years were read and summarized, and the research progress on the role of copper in breast cancer, the application of cuproptosis in the diagnosis and treatment of breast cancer were reviewed. ResultsCuproptosiswas a novel form of programmed cell death, which occurred via direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle, this resulted in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, leading to proteotoxic stress and ultimately cell death. Cuproptosis induced proliferation and migration of breast cancer cell , mediated personalized immunotherapy, and participated in endocrine and chemotherapeutic drug resistance. ConclusionExploring the mechanism of cuproptosis provides potential applications for subsequent immunotherapy, endocrine therapy, and chemotherapy for breast cancer, leading to new effective strategies for patients.