Systemic oncological therapy in breast cancer patients on dialysis

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

Comparative Study of the Effect of Shugan Shuru Granule (疏肝舒乳颗粒) on Pathology and p53 Gene Expression in Patients with Hyperplastic Disease of Breast

Objective: To study the effect of Shugan Shuru Granule (疏肝舒乳颗粒,SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG’s effect on HDB on the molecular pathological level. Methods: Sixty-six patients with HDB were allocated in the treated group and the control group,with the former treated with SSG and the latter not. All patients underwent breast operation and their diseased mammary tissues were cut out, sectioned, and observed under microscopy with HE staining and immunohistochemical staining, with ABC method adopted to estimate the degree of hyperplasia and p53 gene expression. The severity of HDB was classified into normal, mild, moderate and severe grades (marked as 0 to Ⅲ), according to the degree of hyperplasia in the mammary gland. Results: Hyperplasia in the control group mostly belonged to grade Ⅰ-Ⅲ before treatment, showing overgrowth of gland and proliferation of glandular epithelial cells, which were high columnar shaped, more stratified, with papillary or substantive dysplasia. While in the treated group, most belonged to grade 0-Ⅰ after SSG treatment, with proliferated gland and dysplasia recovered to normal or disappeared. The positive rate of p53 gene expression in the treated group was 9.09%, and in the control group 39.39%, comparison between the two groups showing significant difference (P<0.01), the intensity in the former was significantly weaker than that in the latter.Conclusion: SSG could not only inhibit the proliferation of mammary duct epithelia and lobuli, but also inhibit the over-expression of P53. Therefore, it could be regarded as an effective remedy for treatment of HDB and prevention of mammary cancer genesis.

The significance of certain factors in the malignant degeneration of fibrocystic disease of breasts．

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Epidemiological Pattern of Breast Diseases among Females in the South-Western Region, Saudi Arabia

Background: Breast diseases cover several conditions. The majority of breast diseases are noncancerous. Some of these lesions are clinically unremarkable, which needed minimal intervention. However, some symptoms may be of clinical value and attract the attention of both the patient and the attending physician, especially when they become persistent. The study aimed to assess the prevalence, pattern, types, and clinical profile of breast diseases among females in the South-western region, during the period from 2018-2020. Methods: A retrospective record-based descriptive approach was used through reviewing medical records of all cases with breast disease attended King Khalid Hospital during the period from January 2018 to January 2020. Data extracted throng pre-structured questionnaire. Results: The study included 211 cases whose ages ranged from 18 to 58 years old with a mean age of 28.9 ± 12.8 years. Breast mass was the most recorded complaint (95.1%) followed with breast pain (32%), skin changes. Benign findings based on the final pathology report were recorded for more than two thirds of the cases, with the most common finding were fibroadenoma. Excisional biopsy and modified radical mastectomy were the most reported surgical interventions. Conclusions: In conclusion, the study revealed that the majority of the cases had benign breast disease (BBD), where fibroadenoma was the most frequent.

STUDIES ON THE HISTOLOGICAL CLASSIFICATION OF PROLIFERATIVE DISEASE OF BREAST AND ITS RELATION WITH BREAST CARCINOMA

Objective: Proliferative disease of breast (PDB)always exists compositely, it is difficult to be classifiedduring pathologic diagnosis. For probe into therelationship between PDB and breast carcinoma in thecyto-biologic level, a new classification method wasstudied.Matcrials and methods: Specimen slices of 439 PDBin females and 176 breast carcinomas were studied incontrast. The degree of fibroplastic proliferation wastaken as the classifying index of the consecutive progressof PDB. Then the PDB cases were divided into three types:the lobular hyperplastic type (LHT), the fibroadenosistype (FAT) and the fibrosclerosis type (FST). Each typewas once again separated into simple and compoundgroups- A part of these slices were stained withmonoclonal immunohistochemical stain to demonstratethe hyperplastic activities of PDB cells as well as theencirclement of periductal myoepithelial cells and basemembrane.Results: PCNA express level was increasedsuccessively along with the progress of pathologic changesin all the three types of PDB. And especially, it was almostparallel with the cancerous express in FST. ASMAstaining showed afrophy and rupture of periductalmyoepithelial cells and base membrane in FST andserious untypical hyperplastic PDB cases.Conclusions: In FST and serious untypicalhyperplastic PDB cases, the ductal epithelial cellsproliferated vigorously, it is closely related with thegrowth of carcinomas. The imcomplete encirclement ofperiductal myoepithelial cells and base membrane arealso a sort of dangerous factor.

The Influence of Progesterone Gel Therapy in the Treatment of Fibrocystic Breast Disease

The effect of progesterone therapy on E2/P ratio changes during the luteal phase, and its consequences are on mastalgia and cyst, within a fibrocystic breast disease (FBD). Fifty women with FBD were included. Information for mastalgia and mastodynia were checked with a questionnaire. All women had (E2) and (P) concentration checked before and during the therapy on the 21st and 24th day of a cycle, ultrasound measured size and number of cysts before and during the therapy. T-test, X2-test, McNemar test, Wilcoxon test and Friedman test were used for statistics. There was a decrease E2/P relation during the therapy vs. before the treatment p < 0.01, as well as the decrease of E2 level on the 24th day during the therapy vs. same day of E2 level, before the therapy (p = 0.164). There was an increase of p level on the 24th day vs. on 24th day before the therapy (p < 0.001). During the therapy, it was found decrease in pain and tension (p < 0.001), and the number and size of the cysts (p < 0.001). Mastalgia and mastodynia significantly decreased during the local p gel therapy, and there was a significantly lower number and size of the cysts in patients with FBD.

乳腺Paget's病的影像学特征分析

目的:通过分析乳腺Paget's病的影像学特征,提高对本病的检出率和认识。方法:回顾性分析68例三家三甲医院自2000年1月至2022年6月期间病理学确诊为Paget's病的患者,采用描述性统计分析其临床特征、X线、超声、磁共振成像(MRI)和病理学特征。结果:59例乳腺Paget's病患者纳入研究,59例累及乳头乳晕,8例累及皮肤,55例有乳内病变,15例出现腋下淋巴结转移者。乳内病变包含导管原位癌19例,浸润性导管癌16例,浸润性导管癌合并原位癌20例。分子分型包括Luminal A型12例,Luminal B型9例,人表皮生长因子受体2(HER2)过表达型32例,三阴型2例。X线对钙化灶的探测较显优势;超声对肿块、乳头乳晕侵犯和淋巴结的评估较有优势;MRI对乳头乳晕侵犯、非肿块病变的评估较有优势。结论:临床特征、X线、超声、MRI结合对诊断乳腺Paget's病具有较高的临床价值。

Can trastuzumab emtansine be replaced by additional chemotherapy plus targeted therapy for HER2-overexpressing breast cancer patients with residual disease after neoadjuvant chemotherapy?

Human epidermal growth factor receptor 2(HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis,and can easily metastasize and recur.Currently,chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients.Given that neoadjuvant chemotherapy(NAC)has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits,many patients,especially those with more advanced tumors,prefer NAC and generally will not receive additional chemotherapy after surgery,irrespective of the pathological response.However,achieving pathological complete response to NAC is strongly correlated with prognosis,especially in triple-negative and HER2-overexpressing breast cancer.Therefore,postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes.The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC.In addition,chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions.Therefore,can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer?At present,no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer.The KATHERINE study revealed that trastuzumab emtansine(T-DM1)can reduce the risk of recurrence or death by 50%compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy.T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine,and thus,to an extent,T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy.However,high cost and low accessibility limit its use especially in low-and middle-income countries and regions.Hence,we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1.Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable.However,further clinical research on the selection of chemotherapeutic agents is warranted.

Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

Objective： To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases. Methods： The expression of VEGF and MVD count in 115 cases breast benign diseases （including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining （SP-method）. Results： The positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%（25/115）, 31.58.% （6/19）and 53.13%（17/32） respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups （P〈0.05）. The MVD count of the three groups were 14.41 ± 2.59, 18.89± 4.47 and 21.13 ± 4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually （P〈0.05）. In VEGF positive group, MVD count was 19.41 ±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group （P〈0.05）. Conclusion： The results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Primary Screening for Breast Diseases among 17618 Women in Wufeng Area, a Region with High Incidence of Cervical Cancer in China

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50–60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, P<0.05). It was shown that the occurrence of breast diseases was concentrated in women aged 20–40 years, while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40. Compared with the patients elder than or equal to 40 years old (n=3289, 27.46%), the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases, 47.18%; P<0.001). However, there was no significant difference in the morbidity of breast diseases between the age group of 20–29 years and that of 30–39 years (P=0.453), and both of them were high. There was no significant association between the morbidity of breast diseases and cervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Role of FDG PET-CT in evaluation of locoregional nodal disease for initial staging of breast cancer

Fluorodeoxyglucose positron emission tomography/computed tomography(FDG PET/CT) is not indicated or recommended in the initial staging of early breast cancer. Although it is valuable for detecting distant metastasis, providing prognostic information, identifying recurrence and evaluating response to chemotherapy, the role of FDG PET/CT in evaluating locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. FDG PET/CT has high specificity but compromised sensitivity for identifying axillary nodal disease in breast cancer. Positive axillary FDG PET/CT is a good predictor of axillary disease and correlates well with sentinel lymph node biopsy(SLNB). FDG PET/CT may help to identify patients with high axillary lymph node burden who could then move directly to axillary lymph node dissection(ALND) and would not require the additional step of SLNB. However, FDG PET/CT cannot replace SLNB or ALND due to unsatisfactory sensitivity. The spatial resolution of PET instruments precludes the detection of small nodal metastases. Although there is still disagreement regarding the management of internal mammary node(IMN) disease in breast cancer, it is known that IMN involvement is of prognostic significance, and IMN metastasis has been associated with higher rates of distant metastasis and lower overall survival rates. Limited clinical observationssuggested that FDG PET/CT has advantages over conventional modalities in detecting and uncovering occult extra-axillary especially IMN lesions with upstaging the disease and an impact on the adjuvant management.

Management of inflammatory bowel disease in the pregnant patient

Inflammatory bowel disease (IBD) is a chronic disorder affecting young adults in their reproductive years. Many young women with IBD express concern about the effect their disease will have on fertility, pregnancy course and fetal development. This article presents an approach to management of IBD in the pregnant patient, including counseling and investigation, and summarizes existing data on the safety of medications used to treat IBD in pregnancy and breastfeeding.

Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine-induced killer cells in 294 patients

Objective: To examine the efficacy and safety of a sequential combination of chemotherapy and autologous cytokine-induced killer(CIK) cell treatment in triple-negative breast cancer(TNBC) patients.Methods: A total of 294 post-surgery TNBC patients participated in the research from January 1, 2009 to January 1, 2015. After adjuvant chemotherapy, autologous CIK cells were introduced in 147 cases(CIK group), while adjuvant chemotherapy alone was used to treat the remaining 147 cases(control group). The major endpoints of the investigation were the disease-free survival(DFS) and overall survival(OS). Additionally, the side effects of the treatment were evaluated.Results: In the CIK group, the DFS and OS intervals of the patients were significantly longer than those of the control group(DFS:P = 0.047;OS: P = 0.007). The multivariate analysis demonstrated that the TNM(tumor-node-metastasis) stage and adjuvant CIK treatment were independent prognostic factors for both DFS [hazard ratio(HR)= 0.520, 95% confidence interval(CI):0.271-0.998, P = 0.049;HR = 1.449, 95% CI:1.118-1.877, P = 0.005, respectively] and OS(HR=0.414, 95% CI:0.190-0.903, P = 0.027;HR= 1.581, 95% CI:1.204-2.077, P = 0.001, respectively) in patients with TNBC. Additionally, longer DFS and OS intervals were associated with increased number of CIK treatment cycles(DFS: P = 0.020;OS: P = 0.040). The majority of the patients who benefitted from CIK cell therapy were relatively early-stage TNBC patients.Conclusion: Chemotherapy in combination with adjuvant CIK could be used to lower the relapse and metastasis rate, thus effectively extending the survival time of TNBC patients, especially those at early stages.

The Therapeutic Ways for Chronic Liver Diseases Accompanied by Diseases of the Endocrine and Mammary Glands

It is discovered by the authors of this article thatchronic hepatitis and hepatocirrhosis (hereinafterchronic hepatopathy for short) are often accompaniedby some diseases of endocrine and mammary glands.The authors have studied the pathogenesis andtreatment of the complications as presented in thefollowing.

Reirradiation of recurrent breast cancer with proton beam therapy:A case report and literature review

BACKGROUND Locoregional recurrence of breast cancer is challenging for clinicians,due to the various former treatments patients have undergone.However,treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities,particularly radiation-induced cardiovascular disease.Reirradiation by proton beam therapy(PBT)enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor.This technology is expected to improve the overall outcome of recurrent breast cancer.CASE SUMMARY A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer.Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy,the patient was treated with PBT BE total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions.Follow-up computed tomography showed a partial remission,without evidence of newly emerging metastasis.At 19 mo after the PBT,the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea,which were successfully treated by drainage and corticosteroid.Cytological analysis of the puncture fluid showed no malignancy,and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions.The patient remains free of progression to date.CONCLUSION PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.

Unusual Presentation of a Rare Giant Fibroadenoma of the Breast

Giant fibroadenomas are exceptional in pregnancy and in most of cases, diameter doesn’t reach more than 15 cm. However, our case is a rare one that reached 18 cm in a 23-year-old female referred post-partum for evaluation of a huge left breast mass. On the other hand, there is a persistent debate regarding the best modality of the surgical approach to giant tumors;most of the experts recommend the enulceation of the tumor after delivery while others argue that extirpation during pregnancy is the best since we have to exclude malignancy. In our patient, the whole tumor was excised at the postpartum period and the pathology did not show any sign of malignancy. Even if our case does not clearly reveal the long term result of the postpartum excision of a giant fibroadenoma, the short term result we have had after this approach was satisfying. Further studies are important to be published in order to confirm pros and cons of the postpartum approach.

Paget's Disease is Associated with Eleven Cancerous Regions:a Case Report and Therapeutic Strategy

Paget＇s disease of the breast is an uncommon disorder that accounts＇for 1% to 3% of all mammary tumors. The incidence of underlying carcinoma associated with Paget＇s disease has been reported in 82% to 100% of cases. The finding of underlying carcinoma reaches almost 100% when a palpable lump is also present. In this rare case, we described a patient presenting with Paget＇s disease but no palpable lump. However, we found 11 independent regions which were all invasive ductal carcinoma after the operation. Considering this patient, we should pay more attention to a multifocal and multicentric breast carcinoma associated with Paget＇s disease. Furthermore, we believe the mammography examination and a modified radical mastectomy are the most appropriate treatments for this population in clinical practice.

Correlation of radiotherapy with prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping

Objective: The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone receptor-positive early breast cancer.Methods: A retrospective analysis of 327 patients aged ≥65 years, with stage I-II, hormone receptor-positive breast cancer who underwent breast-conserving surgery and received endocrine therapy(ET) or radiotherapy plus endocrine therapy(ET+RT) was performed. Both groups were divided into luminal A type and luminal B type subgroups. Evaluation criteria were 5-year disease-free survival(DFS), local relapse rate(LRR), overall survival(OS), and distant metastasis rate(DMR).Results: There were significant differences in 5-year DFS [hazard ratio(HR)=1.59, 95% confidence interval(95% CI), 1.15-2.19;P=0.005] and LRR(HR=3.33, 95% CI, 1.51-7.34;P=0.003), whereas there were no significant differences in OS and DMR between ET group and ET+RT group. In luminal A type, there was no significant difference in 5-year DFS, LRR, OS and DMR between ET group and ET+RT group. In luminal B type,there were statistically significant differences in 5-year DFS(HR=2.19, 95% CI, 1.37-3.49;P=0.001), LRR(HR=5.45, 95% CI, 1.65-17.98;P=0.005), and OS(HR=1.75, 95% CI, 1.01-3.05;P=0.048) between ET group and ET+RT group. In the ET group, there were significant differences between luminal A type and luminal B type in5-year DFS(HR=1.84, 95% CI, 1.23-2.75;P=0.003) and OS(HR=1.76, 95% CI, 1.07-2.91;P=0.026).Conclusions: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly patients, whereas luminal A type elderly patients do not benefit from radiotherapy.Without radiotherapy, luminal A type patients have better DFS and OS than luminal B type patients.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis

Background:Programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)inhibitors have become integral elements within the current landscape of breast cancer treatment modalities;however,they are associ-ated with interstitial lung disease(ILD),which is rare but potentially fatal.Notably,only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors.Therefore,this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors.We also reported three cases of ILD after PD-1 inhibitor treatment.Methods:We comprehensively searched PubMed,EMBASE,and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer.Pooled overall estimates of incidence and risk ratio(RR)were calculated with a 95%confidence interval(CI),and a mirror group analysis was per-formed using eligible studies.Results:This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment.A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors(0.05 vs.0.02).The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors(RR=2.34,95%CI,1.13-4.82,P=0.02).Conclusion:Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors.These findings are instrumental for clinicians in treatment deliberations,and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Determinants of Malignant Transformation in Fibrocystic Disease of Breast

Background: Fibrocystic disease of the breast in one of the commonest diseases in women above 30 years of age. The assumption of it being innocuous and benign is questionable with increased incidence of malignancies developing in these women. Introduction: Understanding the pathophysiology of fibrocystic disease is essential for identifying determinants of malignant change. Case Report: A case of carcinoma of breast developing in a longstanding and recurrent fibrocystic disease is reported. Discussion: The pathological changes including the influence of hormones on the natural history of the disease arediscussed to identify the determinants of malignant transformation. Conclusion: Breast cyst fluid, patterns of cellular lining of the cysts, multiplicity, recurrence and patterns of cellular morphology are important determinants of malignant change.