Relationships between Demographic Variables and Breast Self-Examination among Women in a Rural Community South East of Nigeria

This study examined the relationships between demographic variables of women in a rural community, South East of Nigeria and their practice of Breast Self-Examination (BSE). A descriptive survey design was adopted. The study population of 349 was drawn using system atichousehold sampling technique. Two research questions and three null hypotheses guided the study. The instruments used for data collection were validated structured questionnaire which was interview administered. Demographic information of the women such was also obtained for the study. The result indicated significant correlation between respondents’ educational level and BSE. There was however no significance difference between age, parity and BSE. There was need for community health nurses to reinforce home visits in order to enhance the awareness of breast cancer and needed skill for BSE among the rural populace while liberal education irrespective of age should be instituted by the Government.

Breast Self-Examination (BSE): Association between “Belief in BSE” and “Awareness of BSE” among University Female Students in Uganda

Background: Regular breast self-examination (BSE) has been known to effectively detect breast cancer occurrence early. Are Women who consider BSE effective in detecting breast cancer more likely to be aware of BSE, or vice versa? The present study was an attempt to answer this question. Methods: A cross-sectional study was performed for 259 female University students in Kampala, Uganda. Data were analyzed using SPSS. Univariate and bivariate analyses were carried out. Results: The majority (64.1%) were aware of the BSE technique. Women considering BSE to be effective for early cancer detection were significantly more likely to be aware of the BSE technique. Conclusions: University students who believed in the benefits of BSE were more likely to be aware of BSE than those who did not. More emphasis should be placed on health education for women of younger ages to increase the knowledge of the practice of BSE.

Knowledge, Attitude and Practice of Breast Self-Examination amongst Women in Two Communities of Cameroon

Breast cancer is a major health problem in the world. It is the most common cancer in women and is equally the leading cause of cancer death in women. Though in controversy Breast self-examination (BSE) remains a useful tool in early diagnosis of breast cancer. The aim of this study was to evaluate the knowledge, attitude and practice of BSE amongst women in Yaoundé and Monatele. We carried out a cross sectional study in two communities of Cameron over a period of eight months, targeting females older than 15 years. After obtaining authorization, we randomly interviewed 402 consenting participants, using a pretested questionnaire. Data were entered using CS Pro 7.3 and analysed using SPSS 23. Of a total of 402 participants, 256 (63.7%) in Monatele and 146 (36.3%) in Yaoundé VI, the mean age was 26.55 ± 9.57 years. Exactly 50% (201) had earlier heard of BSE. Health personnel and media represented the main sources of information on BSE. Of the total, 46 (11.4%) knew BSE should be done monthly. Fifty-three percent had poor knowledge and 51.0% had a generally low attitude towards BSE. Out of 402 participants, 65.2% reported not practicing BSE. For those practicing, 71.6% had poor practices. The main reason for not practicing was lack of knowledge. Poor knowledge increased poor practice. In conclusion half of the women had heard about BSE even though the majority had a poor knowledge on BSE and very low overall attitude and practice. Health personnel and media played a key role in passing of information. Increasing the number of health campaigns, multiplying TV shows and health talks about breast self-examination will improve knowledge and hence attitude and practice.

Knowledge and Practice of Breast Self-Examination among Female Undergraduates in South-Eastern Nigeria

Breast disease often presents as palpable masses (lumps), inflammatory lesions, nipple secretion, or mammography abnormalities;and this can be easily treated when discovered early. Breast Self-Examination (BSE) is the quickest and cheapest means of early breast cancer detection. The objective of this study was to determine the knowledge and practice of breast self-examination among female undergraduates in Owerri, south eastern Nigeria. A multi-stage sampling design was used to select participants. Interview using structured questionnaire was conducted on randomly selected respondents in six faculties from each tertiary institution. Questionnaire was prepared in English and was self-administered. Permission to conduct the survey was requested and obtained from the university ethical review board. Informed verbal and written consent was obtained from participants. Confidentiality of information was maintained throughout the study. Knowledge and practice of BSE was examined among 720 randomly selected female undergraduates aged 16 to 28 years. It was found that 98.9 percent have heard of BSE but only 32.5 percent of them performed this examination accurately and monthly as required. There is a statistically significant relationship between knowledge of risk factors for breast cancer and practice of BSE (χ2 = 31.17, P χ2 = 86.75, P χ2 = 75.94, P < 0.001). These female undergraduates had a poor knowledge of the right procedure and practice of BSE;therefore there is need for awareness creation on the risks of breast cancer and benefits of early detection among female undergraduates through breast self-examination.

Women’s Performance of Breast Cancer Screening (Breast Self-Examination, Clinical Breast Exam and Mammography)

Background: Breast cancer is the most common malignancy among women in Saudi Arabia. Despite the availability of early detection methods to diagnose breast cancer, a huge number of women are still unaware about these methods. This study was conducted to identify the attitude of women in Medina toward breast cancer screening methods, including breast self-examination (BSE), clinical breast examination (CBE) and mammography. Methods and Materials: A cross-sectional survey has been conducted on 124 women aged from 39 and older, who attended Taibah Medical Center for cancer screening either by doctor’s recommendation, family or friends advice, or by herself. Face to face questionnaire was used to collect data. All data were analyzed by statistical analysis system software. Results: The results showed only 35.5%, 27.4% and 37.8% of participants reported that they practiced BSE, CBE and annual mammography, respectively. Only 27.3% of women practiced BSE once per month, and 8.8% visited doctor annually for CBE. Both educational level (p = 0.004) and family history (p = 0.01) were significantly related to BSE. 57.7% of the participants who had positive family history practiced BSE, and 56.0% of the participants who practiced BSE were highly educated. Lacking awareness about BSE is the most important barrier in not practicing BSE, while not having a breast lump was the reason for not undergoing either clinical breast examination (38.7%) or periodic mammography (54.9%). Conclusion: This study emphasized the need for massive health education program to increase awareness, and improve the attitude of women toward breast cancer screening methods.

Practice of breast self-examination among high risk Chinese women in Hong Kong

Background The incidence of breast cancer in Hong Kong is increasing and breast serf-examination (BSE)as a screening tool is becoming mere popular,especially among first-dsgree relatives (FDR) of breast cancer victims. BSE may be mere applicable to Chinese women as their breast size is smaller. This study explores the BSE practice in this group of women.Methods A cross sectional study was conducted by sending questionnaires to 330 FDR of breast cancer patients treated in the Department of Surgeory,Univeisity of Hong Kong. BSE behavior was studied with respect to its frequency,awareness,completeness and confidence of practice.Results 110 subjects returned the questionnaires with a response rate of 33%.The mean age of the respondent was 37 years. Only 57 women (52%)were practicers. The practicers have a stronger BSE awareness (p＜0.01) and a lower mean score on thought barriers (P=0.002) than the non-practicers.40% of the practicers gain their BSE knowledge through clinicians and their mean period of practica was 3.2 yeara. 68% of the practicers performed BSE completely.The overall confidence rate was 35%, but the rate was 43% among those who performled complete BSE.Thirteen factors possibly related to the completeness and rate of confidence of BSF examination were studied.The only factor that significantly deternined completenass was the time spent for each examination (P=0.002).The complete practicers required a longer time than the incomplete practicers(6.60 and 2.96 min,respectively).Women with a stronger BSE intention (P=0.001)and a lower mean score on thought barrers(P=0.001)performed the examination confidently.Conclusions Slightly over half of the FDR practice BSE.The majority perform a complete BSE but they are not confident in finding abnormalities. Women spending more time on BSE are associated with a higher rate of completeness. However,only those with a stronger DSE: intention and lesser thought barriers are more confident in their practice.

Awareness, Practice and Intention to Practice Testicular Self-Examination among Professional Working Males in Ghana

Background: The aetiology of Testicular Cancer (TC) is still unknown to researchers but many of the associated risk factors have been identified. These include family history, age, racial origin, cryptorchidism, urogenital malformations, testicular atrophy, and infertility. Given the lack of scientific data on the causes of the disease, it has been asserted in previous studies that the promotion of awareness and early detection are prerequisites to mitigating risks of metastasis as well as improving survival. This study is to assess the awareness, practice, and intention to practice testicular self-examination among professional working males in Accra. Methods: A quantitative cross-sectional design with a structured research instrument was used to collect data from respondants. The purposive and convenience sampling techniques were used to collect data from 300 men at Accra in Ghana. The study was conducted at two (2) Universities and a Senior High school at Accra in Ghana. The data was then analysed using descriptive statistics, logistic regression, multiple linear regression, and structural equation modeling. Results: From the study findings, 37% of male participants rated their knowledge of testicular self-examination and related symptoms as good, 28% of participants practised testicular self-examination monthly, while 65% of respondents expressed their intention to practice monthly testicular self-examination. The findings from logistic regression demonstrated that level of education, age, and marital status of participants had a significant influence on testicular self-examination. Additionally, the multiple linear regression results revealed knowledge and self-efficacy significantly predict testicular self-examination intention. The path coefficient results from the structural equation model are consistent with results from the regression models. Conclusion: This research is the first to investigate testicular self-examination among men in Ghana. The findings revealed awareness and practice of TSE are low among participants. Therefore, the research findings would improve the expertise of physicians and nurses in providing counsel, intervention, and support for patients at risk of testicular cancer.

Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast cancer.It is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone.Although cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation.Despite recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative approach.Since CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented.Nevertheless,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone metastases.Thus,surgical removal of breast CS does not necessarily ensure patient’s long-term recovery.Moreover,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is limited.Nevertheless,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone.The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread.Clinical features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

Moderating Effect of Perceived Threat of Breast Cancer on Relation between Knowledge and Breast Self Examination

Estimated at more than 2.2 million cases worldwide,most breast cancer cases and deaths from breast cancer occur in low and middle-income countries.In Cameroon,many studies have underlined the effect of knowledge of breast cancer on screening measures such as self-examination and,to a lesser extent,the perception of the threat of this disease.This research aims to assess according to the Health Belief Model(HBM),the moderating effect of perceived threat of breast cancer on the relation between knowledge and breast self-examination.A questionnaire survey was conducted among 517 Cameroonian women to assess their general knowledge about breast cancer(risk factors and screening measures),their level of the perceived threat of breast cancer through Perceived susceptibility and severity,and the prevalence of breast self-examination amongst them.A regression analysis using the Macro Process for moderation indicates the main effect of Perceived threat(b=0,29;t(517)=2,36;p=0,02)of breast cancer and knowledge(b=0,02;t(517)=4,29;p<0,001)on breast self-examination.Results also confirm that the perceived threat of breast cancer moderates the effect of knowledge on breast self-examination.While the low level of perceived threat highlights the effect of knowledge on breast self-examination(b=0,02;t(517)=3,49;p<0,001),the high level of perceived threat cancels that effect(b=0,01;t(517)=1,97;p=0,01).A woman who perceives severity and susceptibility to breast cancer is more inclined to perform breast self-examination.This result suggests the importance of taking into account,in a context where knowledge of breast cancer is limited,relevant factors of the health belief model in preventive measures against breast cancer in general and the practice of breast self-examination in particular.

Application effect of safety hazard self-examination mode in nursing risk management in hepatobiliary surgery

Objective:To explore the application effect of safety hazard self-examination mode in nursing risk management in hepatobiliary surgery.Methods:Sixty patients underwent hepatobiliary surgery in two tertiary hospitals in Shandong Province from May 2021 to October 2021.According to the different implementation time,they were divided into 30 cases in the observation group and 30 cases in the control group.The control group adopts routine risk assessment,and the observation group adopts the self-examination mode of potential safety hazards on the basis of routine risk assessment to compare the incidence of nursing risk between the two groups.Results:The observation group had a significantly lower incidence of safety hazards in terms of missing surgical instruments,lack of aseptic operation,and postoperative pressure injuries than the control group(P<0.05).Conclusion:The appropriate hazard self-examination mode in the hepatobiliary operation room is of positive significance to improve the safety awareness of operating staff and the comprehensive ability of operating room nurses.

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.

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.

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.

Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

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.

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.

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.

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.