RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Standardizing R-E-NSM Surgical Protocols: A Critical Appraisal for Breast Cancer Patients

To the editors:We read with interest the article by Jiao ZHOU et al,which introduces a novel technique of reverse-sequence endoscopic nipple-sparing mastectomy(R-E-NSM)with direct-to-implant breast reconstruction(DIBR)for breast cancer patientsll.While the study presents a promising approach,the interpretation of its findings warrants careful consideration owing to several methodological and clinical aspects:(1)Table 1 presents the lymph node status following propensity score matching but does not detail the total number of lymph nodes resected.

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

Tumor deposits in axillary adipose tissue in patients with breast cancer:Do they matter?

Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Prognostic factors of breast cancer brain metastasis

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

Identifying microRNA-Target Gene Pairs in Luminal B Breast Cancer Using Integrated Analysis of miRNA and Transcriptome Profiles

Dysregulation of post-transcriptional regulation of gene expression has been found to influence various human disorders. Aberrant miRNA-based regulation of gene expression has been found to be associated with different cancers, including breast cancers. Very little information is available on the effect of dysregulation of miRNA-mediated regulation on luminal B breast cancer. This study was aimed at comprehending the regulation of gene expression through miRNA in luminal B breast cancers by comprehensive analysis of miRNA and mRNA expression data together. Negatively regulated miRNA-target gene pairs were identified, and the target genes were functionally enriched to identify critical pathways associated with luminal B breast cancer. Further, the prognostic significance of these miRNAs and target gene pairs was assessed to identify genes with prognostic value in luminal B breast cancer. A total of 266 differentially expressed miRNAs and 164 dysregulated miRNA-target gene pairs were identified. Four genes, including SRP9, DSN1, RACGAP1, and SLC10A6, and one miRNA, hsa-mir-421, showed significant influence on the prognosis of patients with luminal B breast cancer. Through additional experimental examination of these findings, a deeper comprehension of miRNA-based post-transcriptional regulation in luminal B breast tumors will be possible.

Breast Cancer in a Supernumerary Breast at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital: About a Case

Accessory or ectopic breast tissue is an anomaly in the development of the breast. It is a rare condition that occurs along the embryological mammary line. In less than 1% of all breast cancers, supernumerary breast cancer is reported, with the axillary location being the most common in 60% to 90% of cases. Cancerous degeneration of this supernumerary breast tissue can pose a dual diagnostic and therapeutic problem. We report the case of locally advanced adenocarcinoma in a right supernumerary breast. This is a 75-year-old, grand-multiparous, postmenopausal, and known hypertensive patient on treatment. Family history was remarkable for brain cancer in her sister and oesophageal cancer in her mother. She consulted for a mass in the right axillary cavity on supernumerary breast evolving for a year. Clinical examination revealed a large, fixed, budding and haemorrhagic-ulcerated mass of the right axilla, with long axis measuring about 15 cm. There was as wella supernumerary breast on the left, but without particularity. A soft tissue ultrasound showed a large hypoechoicmass in the right axillary region of 116 mm with areas of central necrobiosis. Morphologically, the breasts were normal. A breast MRI revealed a subcutaneous mass in the right axillary cavity with skin ulceration and satellite lymphadenopathy. The extension assessment revealed liver metastases, and a biopsy of the mass revealed a breast adenocarcinoma. The case was the subject of a multidisciplinary consultation meeting following which a wide excision of the mass was indicated. The histo-pathology analysis results of the surgical specimen were in favour of a triple negative papillary adenocarcinoma. After a post-operative multidisciplinary consultation meeting, adjuvant chemotherapy was indicated. The development of supernumerary breasts depends on hormones, just like normal breasts. Breast cancer in accessory breast tissue is quite rare with the incidence being 6%. The most common pathology is invasive carcinoma (50% - 75%). It is usually located in the armpit (60% - 70%) although it can be present in other less common locations such as the inframammary region (5% - 10%) and rarely the thighs, perineum, groin and the vulva. Since accessory axillary breast tissue is not considered during breast screening examination, it is necessary for clinicians to be aware of this entity and associated pathologies. Their preventive excision in women at high risk can also be considered.

Assessment of Breast Cancer Prevention Practices among Women Attending Primary Health Care in Abha City, Aseer Region, Saudi Arabia

Cancer is a leading cause of death worldwide, with breast cancer being the most common (2.26 million new cases and 685,000 deaths). In Saudi Arabia, breast cancer ranked the first among females in 2014, accounting for 15.9% of all cancers reported among Saudi nationals and 28.7% of all cancers reported among females of all ages. Early detection of breast cancer could decrease the risks, have a better prognosis, and have better outcomes/more successful treatments. Prevalence of breast cancer reached more than 25% of all diagnosed cancer in the kingdom among women. Aim: This study aims to assess the knowledge and performance of women attending primary care centers about breast self-examination and mammogram screening for prevention and early detection of breast cancer in Abha city primary healthcare centers, Kingdom of Saudi Arabia. Research Method: cross sectional design was conducted by using questionnaire, which was distributed to primary care center nurses. The collected data was statistically analyzed using the Statistical Package for Social Sciences, version 25. Results: The study found that participants had poor awareness and knowledge about breast self-examination, risk factors for breast cancer, and trends and practices in early diagnosis of breast cancer. Conclusion and Recommendations: It recommends increasing awareness campaigns and providing educational programs to improve knowledge and practices.

Clinical Study of Double Contrast-Enhanced Ultrasound Combined with Dye Method and Marker Placement to Identify and Locate Sentinel Lymph Nodes in Patients with Breast Cancer

Objective: To explore the value of percutaneous ultrasonography combined with transvenous ultrasonography for accurate localization of sentinel lymph nodes and diagnosis of metastatic lymph nodes in patients with breast cancer. Methods: 18 cases of patients with breast cancer attending the Hainan General Hospital from May 2022 to June 2024 who were proposed to undergo axillary lymph node dissection were selected, and the ultrasonographic agent was injected subcutaneously through the areola on the 1st day before the operation, and the marker localization of the manifestation of the Sentinel lymph nodes and draw the lymphatic vessel alignment for drainage on the body surface, and record the manifestation of SLN by conventional ultrasound and dual ultrasonography. At the time of surgery, intraoperative melphalan localization was used to identify the SLN, the difference between the number of ultrasound and melphalan localization was observed, and resection was performed for pathological examination to determine whether they were metastatic or not. Results: There were 8 metastatic lymph nodes and 18 non-metastatic lymph nodes among 31 SLN. A total of 62 SLN were localized by intraoperative melphalan, of which 31 were consistent with ultrasound localization and 31 were not identified by ultrasound. The diagnostic sensitivity of SLN metastasis diagnosed by transcutaneous ultrasonography was 62.50%, specificity was 91.30%, positive predictive value was 71.43%, negative predictive value 87.50%, accuracy was 83.87%, and the AUC was 0.769;the diagnostic sensitivityof transvenous ultrasonography diagnosed was 75.00%, specificity was 75.00%, and the accuracy was 83.87%, 75.00%, specificity 91.30%, positive predictive value 75.00%, negative predictive value 91.30%, accuracy 87.10%, AUC 0.832;dual ultrasonography diagnostic sensitivity 87.50%, specificity 91.30%, positive predictive value 77.78%, negative predictive value 95.45%, accuracy 90.32%. The AUC was 0.894. Conclusion: Transcutaneous ultrasonography combined with transvenous ultrasonography can accurately localize sentinel lymph nodes and improve the sensitivity and accuracy of the diagnosis of metastatic SLN.

Comparative Study of Gut Microbiota in Breast Cancer Patients versus Controls in Abidjan, Côte d’Ivoire

Context: The gut microbiota represents a complex ecosystem encompassing all unicellular microorganisms residing in the digestive tract, primarily bacteria, fungi, archaea, and even viruses. The relationship between the host and the microbiota is symbiotic: bacteria benefit from a stable environment, while the host gains numerous capabilities in terms of digestion, metabolism, nutrition, and immunity. However, numerous studies suggest that the gut microbiota plays a crucial role in various non-communicable diseases, including obesity, chronic inflammatory bowel diseases, allergic and immune disorders, behavioral disorders, and even certain cancers. The objective of our study was to characterize the gut microbiota of a group of breast cancer patients by comparing it to that of control subjects in Côte d’Ivoire, using a metagenomic approach. Method: A case-control study was conducted from May 2020 to September 2023. A total of 85 women (39 cases and 46 controls) were recruited, and stool samples were collected from both breast cancer patients and healthy women. Among these, ten (10) samples from patients and ten (10) samples from healthy women were randomly selected for the study of the gut microbiota. The gut microbiota was characterized by sequencing the V4 region of 16S rRNA using metagenomic NGS technology, and bioinformatic analysis was performed using the mothur pipeline. Results: In women with breast cancer, we observed a reduction in the relative abundance of the phyla Firmicutes and Bacteroidetes, as well as an increase in the phyla Actinobacteria and Verrucomicrobia. Additionally, their microbiota exhibited lower Chao1 and Sobs diversities compared to the control women (p < 0.05). Molecular variance analysis (AMOVA) revealed a significant difference between the case and control groups (p < 0.001). This study has highlighted a significant difference in the relative abundance of major phyla within the gut microbiota of cases compared to healthy controls. It will contribute to enriching African and global data, thus promoting a better understanding of the role of gut microbiota in breast cancer.

Correlation Analysis between Self-Disclosure and Social Support in Patients with Breast Cancer

Objective: Describe the status quo of self-disclosure and social support in breast cancer patients and analyze the correlation between them. Methods: General data questionnaire, distress disclosure Index scale and Chinese version of medical social support scale were used to investigate the correlation between self-disclosure and social support in breast cancer patients by Pearson correlation analysis. Results: 1) The total self-disclosure score was (38.75 ± 9.18);the total score of social support was (70.57 ± 14.04) scores, including emotional information support dimension (28.39 ± 6.06) scores, practical support dimension (15.62 ± 3.31) scores, elastic support dimension (14.85 ± 3.23) scores, and emotional support dimension (11.70 ± 2.56) scores. 2) Self-disclosure was positively correlated with social support (r = 0.433, p Conclusion: Breast cancer patients had a moderate level of self-disclosure, and the higher the level of self-disclosure, the better the social support. It is suggested that improving the self-disclosure level of breast cancer patients can help them obtain more social support.

Nursing Care and Causative Analysis of Grade IV Capsular Contracture Following Breast Cancer Expander Implantation

Objective: By observing the treatment and nursing care of a patient with Grade IV capsular contracture following breast cancer expander implantation and subsequent Stage II reconstruction, we aim to analyze the reasons for the formation of capsular contracture after Stage I expander implantation and prevent its recurrence following Stage II reconstruction. Methods: In May 2020, the patient noticed an increase in the size of a breast mass. In August, she underwent AC-THP neoadjuvant chemotherapy, followed by a “right breast-conserving nipple-areolar subglandular excision + right axillary lymph node dissection + expander implantation” surgery in November 2020. Radiation therapy began in January 2021. During radiation therapy, the patient experienced severe breast hardening, distortion, tenderness, and was diagnosed with Grade IV capsular contracture. To relieve the capsular contracture, the patient underwent a “contracted capsule incision and release procedure + removal of the right breast expander + right breast implantation” surgery in July 2021. Postoperatively, measures were taken to prevent incision infection, emphasizing aseptic techniques, ensuring smooth negative pressure drainage, reducing skin flap tension, monitoring skin flap blood supply, actively preventing subcutaneous effusion and hematoma, and applying appropriate compression dressings. Results: The patient was discharged after the removal of the drainage tube. During the postoperative follow-up at 3 and 6 months, there was no recurrence of capsular contracture, and the breast appeared full, upright, and relatively soft. There were no complications such as hematoma, infection, breast implant rupture, breast sagging, or displacement. The patient had a good outcome without additional financial or surgical burdens. Conclusion: The occurrence of Grade IV capsular contracture in the patient is generally related to infection after Stage I expander implantation, improper compression dressing, excessive saline injection causing content infiltration, and radiation therapy. Therefore, it is recommended to enhance the intraoperative and postoperative prophylactic use of antibiotics after Stage I expander implantation. Intermittent saline injection after surgery, with the amount of saline gradually increasing rather than filling all at once, is advisable. This helps the breast tissue gradually adapt to expansion, reducing the risk of capsular contracture. Postoperatively, patients should be instructed to wear pressure garments and breast elastic bandages while intensifying breast monitoring during radiation therapy and increasing postoperative follow-up.

Personalized Perioperative Care for a Patient with a 10-Year-Old Postpartum Old Thrombus after Neoadjuvant Therapy for Breast Cancer

Breast cancer is one of the most common malignant tumors in women, and has become the main cause threatening women’s health. A case of breast cancer with neoadjuvant chemotherapy was discharged after active treatment and nursing.

Assessment and Visualization of Ki67 Heterogeneity in Breast Cancers through Digital Image Analysis

The Ki67 index (KI) is a standard clinical marker for tumor proliferation;however, its application is hindered by intratumoral heterogeneity. In this study, we used digital image analysis to comprehensively analyze Ki67 heterogeneity and distribution patterns in breast carcinoma. Using Smart Pathology software, we digitized and analyzed 42 excised breast carcinoma Ki67 slides. Boxplots, histograms, and heat maps were generated to illustrate the KI distribution. We found that 30% of cases (13/42) exhibited discrepancies between global and hotspot KI when using a 14% KI threshold for classification. Patients with higher global or hotspot KI values displayed greater heterogenicity. Ki67 distribution patterns were categorized as randomly distributed (52%, 22/42), peripheral (43%, 18/42), and centered (5%, 2/42). Our sampling simulator indicated analyzing more than 10 high-power fields was typically required to accurately estimate global KI, with sampling size being correlated with heterogeneity. In conclusion, using digital image analysis in whole-slide images allows for comprehensive Ki67 profile assessment, shedding light on heterogeneity and distribution patterns. This spatial information can facilitate KI surveys of breast cancer and other malignancies.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.