[Clinical application of endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants].

Objective: To 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. Results: The 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.

MGP+ and IDO1+ tumor-associated macrophages facilitate immunoresistance in breast cancer revealed by single-cell RNA sequencing.

Immunotherapy is widely applied for the treatment of breast cancer, but to which some patients respond poorly or develop resistance. Therefore, the mechanism needs to be further studied. Transcriptomic data of 31 breast cancer patients treated with anti-programmed death receptor 1 (PD-1) was downloaded from the VIB-KULeuven Center for Cancer Biology to analyze the changes in myeloid cells in tumor tissues before and after immunotherapy. And 24 cell populations that may be immune-related were further identified. Representative cell populations were also screened and validated through cellular and animal experiments to evaluate the relevant molecular expression and pathways of tumor-associated macrophages (TAMs) in the tumor microenvironment. The results demonstrated that MGP+ TAMs and IDO1+ TAMs influenced the efficacy of immunotherapy in breast cancer patients. After anti-PD-1 treatment, Increased numbers of MGP+ TAMs and IDO1+ TAMs in breast cancer patients upregulated pro-tumorigenic factors associated with resistance to immunosuppressive therapy. This study provides new biomarkers for immunotherapy to predict therapeutic responses and overcome potential resistance to immunotherapy. It is an important complement to the immunosuppression caused by TAMs after immunotherapy for breast cancer.

CD63+ cancer-associated fibroblasts confer CDK4/6 inhibitor resistance to breast cancer cells by exosomal miR-20.

Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) have rapidly received Food and Drug Administration (FDA) approval as a new type of therapy for patients with advanced hormone receptor-positive breast cancer. However, with the widespread application of CDK4/6i, drug resistance has become a new challenge for clinical practice and has greatly limited the treatment effect. Here, the whole microenvironment landscape of ER+ breast cancer tumors was revealed through single-cell RNA sequencing, and a specific subset of cancer-associated fibroblasts (CD63+ CAFs) was identified as highly enriched in CDK4/6i resistant tumor tissues. Then, we found that CD63+ CAFs can distinctly promote resistance to CDK4/6i in breast cancer cells and tumor xenografts. In addition, it was discovered that miR-20 is markedly enriched in the CD63+ CAFs-derived exosomes, which are used to communicate with ER+ breast cancer cells, leading to CDK4/6i resistance. Furthermore, exosomal miR-20 could directly target the RB1 mRNA 3'UTR and negatively regulate RB1 expression to decrease CDK4/6i sensitivity in breast cancer cells. Most importantly, we designed and synthesized cRGD-miR-20 sponge nanoparticles and found that they can enhance the therapeutic effect of CDK4/6i in breast cancer. In summary, our findings reveal that CD63+ CAFs can promote CDK4/6i resistance via exosomal miR-20, which induces the downregulation of RB1 in breast cancer cells, and suggest that CD63+ CAFs may be a novel therapeutic target to enhance CDK4/6i sensitivity.