Factors associated with mammographic breast density among women in Karachi Pakistan

Background There are no studies done to evaluate the distribution of mammographic breast density and factors associated with it among Pakistani women. Methods Participants included 477 women, who had received either diagnostic or screening mammography at two hospitals in Karachi Pakistan. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System. In person interviews were conducted using a detailed questionnaire, to assess risk factors of interest, and venous blood was collected to measure serum vitamin D level at the end of the interview. To determine the association of potential factors with mammographic breast density, multivariable polytomous logistic regression was used. Results High-density mammographic breast density (heterogeneously and dense categories) was high and found in 62.4% of women. There was a significant association of both heterogeneously dense and dense breasts with women of a younger age group < 45 years (OR 2.68, 95% CI 1.60–4.49) and (OR 4.83, 95% CI 2.54–9.16) respectively. Women with heterogeneously dense and dense breasts versus fatty and fibroglandular breasts had a higher history of benign breast disease (OR 1.90, 95% CI 1.14–3.17) and (OR 3.61, 95% CI 1.90–6.86) respectively. There was an inverse relationship between breast density and body mass index. Women with dense breasts and heterogeneously dense breasts had lower body mass index (OR 0.94 95% CI 0.90–0.99) and (OR 0.81, 95% CI 0.76–0.87) respectively. There was no association of mammographic breast density with serum vitamin D levels, diet, and breast cancer. Conclusions The findings of a positive association of higher mammographic density with younger age and benign breast disease and a negative association between body mass index and breast density are important findings that need to be considered in developing screening guidelines for the Pakistani population.

Granular Cell Tumor of the Breast: Clinical Presentation, Pathological Diagnosis and Treatment

Introduction: Granular cell tumor is a rare neoplasm of soft tissue and only in 1% of cases, it can shows a malignant behaviour. It is presumed to be a tumor originating from perineural or putative Schwann cells of peripheral nerves. Materials and Methods: We reviewed five patients affected by Granular cell tumor of the breast treated between January 2011 and January 2021 at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome, Italy. Results: All of the granular cell tumors presented as solitary, painless and firm lump, highly suggestive of malignancy. The radiological findings were heterogeneous and non-specific. All lesions presented as masses, more clearly evident on ultrasound as hypoechoic lesions, with irregular shape, blurred contours and borderline features. The tumors were composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small, central nuclei, being immunohistochemically positive for S100, Vimentin (with variable staining), CD56; negative for HMB45, MelanA, AE1/AE3, EMA, and Desmin. Conclusion: Granular cell tumor is a rare, usually benign breast disease that can have very similar characteristics to breast cancer both clinically and radiologically. Treatment of choice consists in wide resection or lumpectomy with margin assessment (no ink on tumor).

LncRNA SRA gene polymorphisms and risk of gynecological pathology development among Ukrainian women with proliferative type of benign breast disease without atypia

Benign breast disease is a group of all noncancerous mammary lesions with a risk of breast cancer (BC) development. BC is the most common cancer in the world; therefore, it is necessary to find new biomarkers and targets for early diagnosis, treatment, prediction of prognosis and survival. Long non-coding RNA SRA could play this role, thus further studies of its impact on the precancerous lesion pathogenesis are needed. The aim. To analyze the association between SRA1 rs801460 and rs10463297 SNPs and the occurrence of gynecological pathology among Ukrainian women with the proliferative type of benign breast disease without atypia. Materials and methods. This study included 115 patients with proliferative type of benign breast disease without atypia: 55 – with gynecological pathology and 60 – without it. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for polymorphism genotyping. Hematoxylin and eosin, toluidine blue and van Gieson’s picrofuchsin methods were applied for staining of sections. Statistical analysis was carried out using Statistical Package for the Social Sciences software (SPSS, version 25.0, Chicago, IL, USA). Results. Significant differences were found in the rs10463297 frequency of alleles (P = 0.032), but not in the rs801460 (P > 0.05), in groups with and without gynecological pathology, while the distribution of both single nucleotide polymorphism (SNPs) genotypes was similar between these groups (P > 0.05). Statistically significant association was detected between SRA1 rs10463297 polymorphism and gynecological pathology occurrence in both dominant (Pa = 0.023; ORa = 2.638, 95 % CI = 1.145–6.076) and additive (Pa = 0.034; ORa = 2.489, 95 % CI = 1.069–5.794) models of inheritance. No association was found between SRA1 rs801460 SNP and gynecological pathology development among Ukrainian women with proliferative type of benign breast disease without atypia (P > 0.05). Conclusions. It was revealed that SRA1 rs10463297 TT carriers had 2.6 times higher risk of gynecological pathology development than C allele carriers and 2.48 times than TC carriers.

Isolated eosinophilic mastitis: a rare breast disease mimicking malignancy

Eosinophilic mastitis is a rare benign breast pathology which presents with lump breast and can mimic malignancy. So far eight reported cases have been found in literature review. All cases were associated with peripheral eosinophilia and systemic involvement except one. Isolated eosinophilic mastitis in the absence of peripheral eosinophilia or systemic involvement is a very rare presentation. Being one of the rare cases, prompted us to take up this case in our present study. A 40-year-old lady presented with progressively enlarging, slightly painful swelling in left breast of 15 days duration with no other relevant past and family history. The clinical differential diagnosis of mastitis and carcinoma was suggested. Aspiration cytology was reported as benign breast disease- fibroadenosis. Imaging studies undertaken were inconclusive. Case managed surgically with wide local excision. Post-surgical tissue specimen was subjected to histopathology examination and was diagnosed as eosinophilic mastitis. A prolonged follow-up revealed no recurrence.

Somatic mutations in benign breast disease tissues and association with breast cancer risk

Background Benign breast disease (BBD) is a risk factor for breast cancer (BC); however, little is known about the genetic alterations present at the time of BBD diagnosis and how these relate to risk of incident BC. Methods A subset of a long-term BBD cohort was selected to examine DNA variation across three BBD groups (42 future estrogen receptor-positive (ER+) BC, 36 future estrogen receptor-negative (ER−) BC, and 42 controls cancer-free for at least 16 years post-BBD). DNA extracted from archival formalin fixed, paraffin-embedded (FFPE) tissue blocks was analyzed for presence of DNA alterations using a targeted panel of 93 BC-associated genes. To address artifacts frequently observed in FFPE tissues (e.g., C>T changes), we applied three filtering strategies based on alternative allele frequencies and nucleotide substitution context. Gene-level associations were performed using two types of burden tests and adjusted for clinical and technical covariates. Results After filtering, the variant frequency of SNPs in our sample was highly consistent with population allele frequencies reported in 1 KG/ExAC (0.986, p < 1e−16). The top ten genes found to be nominally associated with later cancer status by four of 12 association methods(p < 0.05) were MED12, MSH2, BRIP1, PMS1, GATA3, MUC16, FAM175A, EXT2, MLH1 and TGFB1, although these were not statistically significant in permutation testing. However, all 10 gene-level associations had OR < 1 with lower mutation burden in controls compared to cases, which was marginally statistically significant in permutation testing (p = 0.04). Comparing between the three case groups, BBD ER+ cases were closer to controls in mutation profile, while BBD ER− cases were distinct. Notably, the variant burden was significantly higher in controls than in either ER+ or ER− cases. CD45 expression was associated with mutational burden (p < 0.001). Conclusions Somatic mutations were more frequent in benign breast tissue from women who did not develop cancer, opening questions of clonal diversity or immune-mediated restraint on future cancer development. CD45 expression was positively associated with mutational burden, most strongly in controls. Further studies in both normal and premalignant tissues are needed to better understand the role of somatic gene mutations and their contribution to future cancer development.

A Diagnostic Analysis Workflow to Optimal Multiple Tumor Markers to Predict the Nonmetastatic Breast Cancer from Breast Lumps

Objective. To assess the diagnostic performance of clinically common single markers and combinations to distinguish nonmetastatic breast cancer and benign breast tumor. A predictive model with a better diagnostic ability for nonmetastatic breast cancer was established by using the diagnostic process. Methods. A total of 222 patients with nonmetastatic breast cancer and 265 patients with benign breast disease were enrolled in this study. CEA, Ca 15-3, Ca 125, Ca 72-4, CYFRA 21-1, FERR, AFP, and NSE were measured by an electrochemiluminescent immunoenzymometric assay on the Elecsys system. There are four key steps for our diagnostic workflow, that is, feature selection, algorithm selection, parameter optimization, and outer test data was used to validate the optimal algorithm and markers. Results. CEA, Ca 15-3, CYFRA 21-1, AFP, and FERR were selected using the t-test in our inner development set. The optimal algorithm among logical regression, decision tree, support vector machine, random forest, and gradient boost machine was selected by 10-fold cross-validation, and we found that random forest and logistic regression are the better classification. The outer test data was used to validate the best markers and classification. The random forest with CEA, Ca 15-3, CYFRA 21-1, AFP, and FERR showed the optimal combination for distinguishing breast cancer and benign breast disease. The AUC value was 0.888, the cut-off point was 0.484, and sensitivity and specificity were 78.9% and 90.1%. Conclusions. No single marker of these eight markers was good at identifying nonmetastatic breast cancer from benign tumors. But a diagnostic analysis workflow was established to develop a predictive model with better diagnostic capability for nonmetastatic breast cancer. This workflow is also applicable to the optimization of other disease markers and diagnostic models. The predictive model showed good diagnostic performance, and it could be gradually incorporated as a support method for the diagnosis of nonmetastatic breast cancer.

An Unusual Breast Mass in a 13-year-old Girl: a Case Report

BackgroundIn puberty breast intraductal papilloma was rare, but the pathological changes of intraductal papilloma combined with intraductal fibroadenoma in the duct lumen were even less reported. Herein we reported a case of adolescent benign breast disease that contained the two features of neoplasm in the same duct and discussed its clinical course.Case presentationA 13-year-old adolescent female presented to our hospital with spontaneous bloody discharge of the left nipple. On clinical examination, a 2.5cmx1.5cm mass could be palpable under the left nipple, and a single-hole bloody discharge could be seen by squeezing the mass. Surgical resection of the mass and part of the breast duct was confirmed by postoperative pathology as intraductal papilloma and intracanalicular type fibroadenoma, with cystic changes of ductal epithelium hyperplasia. After 15 months of follow-up, there was no evidence of recurrence.ConclusionsIntraductal fibroadenomatosis may be a new pathological subtype in which multiple histologic characteristics can be seen in the same duct. Surgical resection is the only effective treatment. Its etiology is still unknown, and it remains to be accumulated more cases for further exploration.