Invasive Ductal Carcinoma Research Articles

Upstaging of Invasive Lobular Cancer With FES PET/CT.

A 78-year-old woman diagnosed with left breast invasive lobular carcinoma with left axillary nodal metastasis underwent 18 F-fluoroestradiol (FES) PET/CT imaging for further evaluation of indeterminate right axillary lymph nodes seen on staging 18 F-FDG PET/CT. 18 F-FES PET/CT revealed abnormal 18 F-FES-avid right axillary and bilateral cervical nodes, subsequently biopsy-proven metastases, upstaging the patient from stage II to IV and greatly changing patient management. This case demonstrates the value of 18 F-FES PET/CT in accurately staging metastatic invasive lobular carcinoma at diagnosis, an indication for which 18 F-FES PET/CT "may be appropriate" per current Society of Nuclear Medicine and Molecular Imaging guidelines.

Value of contrast-enhanced ultrasound in differentiating granulomatous mastitis from invasive ductal carcinoma.

This study aims to analyze the imaging manifestations of granulomatous mastitis (GM) and invasive ductal carcinoma (IDC) using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). The objective is to investigate the clinical value of CEUS in differentiating between GM and IDC. We retrospectively enrolled 39 GM patients and 64 IDC patients between January 2020 and June 2023. All diagnoses were confirmed via core needle biopsy or surgical pathology. The characteristics of both conventional US and CEUS in these patients were analyzed to distinguish GM from IDC. Based on CEUS features, GM lesions most commonly presented as hypoechoic areas (43.6%), followed by pseudocysts (28.2%), hypoechoic nodules (15.4%), and honeycomb cysts (12.8%). The diffuse enhancement pattern was an independent characteristic for distinguishing GM from IDC, with the ROC analysis revealing an area under the curve (AUC) value of 0.794. US is the preferred initial examination for GM, and both its conventional and CEUS features can enhance diagnostic accuracy and guide clinical treatment. CEUS demonstrates high differential diagnostic value in distinguishing GM from IDC. This study categorizes GM manifestations on CEUS into four types, each corresponding to different pathological stages of GM. We identified that the diffuse enhancement pattern on CEUS is a distinctive characteristic associated with GM, aiding in its differentiation from IDC.

Immunohistochemical Expression of ROS1 in invasive ductal carcinoma of breast in association with hormonal receptor status and Her2Neu expression

Objective: To determine the frequency of immunohistochemical expression of ROS1 in invasive ductal carcinoma of the breast in relation to hormonal receptor status and HER2 expression. Study Design and Setting: Descriptive cross-sectional study. Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from May 2022 to Dec 2022. Methodology: This study was conducted on a sample size comprising 137 patients diagnosed with invasive breast carcinoma (ductal carcinoma) on histopathological biopsy specimen. Immunohistochemistry was performed using ROS1, estrogen receptor, progesterone receptor and HER2 antibodies on patients’ tissue samples. Results were interpreted by two independent histopathologists. Finally data was analyzed using SPSS version 25. Results: The mean age of sample population was 50.85 ± 12.17 years. 131 patients were women and 6 were men. ROS1 was positive in 54 cases. ROS1 shows weak staining in 41 cases and moderate to strong staining in 13 cases. ER and PR showed no significant statistical correlation with ROS1 expression. HER2 was positive in 37 cases, equivocal in 11 cases and negative in 89 cases. A significant statistical correlation was seen between ROS1 and HER2 as 23 of HER2 positive cases showed ROS1 expression (p=<0.001). Conclusion: Significant number of ROS1 expressing cases in invasive breast carcinoma can be more revealing in the understanding of pathogenesis of breast carcinoma. In addition, it can also lead to use of certain recent tyrosine kinase inhibitors for treatment of this most common carcinoma in females.

Immunohistochemical Expression of Cyclin D1 in Invasive Breast Carcinoma

Objective: This study was conducted to determine the immunohistochemical expression of cyclin D1 in invasive breast carcinoma and its association with already established prognostic parameters like estrogen receptor (ER), progesterone receptor (PR), HER2/Neu, and Ki67 status. Study Design & Setting: Cross sectional Observational. Department of Pathology, Armed Forces Institute of Pathology, Rawalpindi Methodology: The study included 350 cases of invasive breast cancer diagnosed between January 2023 and December 2023. Data collected included patient age, histological subtype, molecular subtypes, tumor size, and the presence of estrogen (ER) and progesterone (PR) receptors, as well as HER2/Neu and Ki67 status. Patients who had undergone chemotherapy, received radiation to the breasts, or experienced relapse were excluded from the study. Immunohistochemistry was conducted using a Cyclin D1 antibody to assess Cyclin D1 expression in tissue samples. The expression levels were categorized as negative, weak, moderate, strong staining in tumor cells. Data analysis was performed using SPSS 29.0, and statistical comparisons were made between Cyclin D1 staining and ER, PR, HER2/Neu, and Ki67 status. Results: Cyclin D1 moderate to strong staining was seen in 173/352 (49.14%) cases of invasive BC. Cyclin D1 expression was slightly statistically significantly associated with ER (x2 = 7.78, P value <0.051) and Ki67 positivity (÷2 = 7.27, P value <0.064). Conclusion: Cyclin D1 has the potential to serve as a prognostic marker. Incorporating it into the routine IHC workup for breast cancer could enhance patient management, especially with the development of new targeted therapies that inhibit the Cyclin D-CDK4/6 axis.

Primary breast lymphoma mimicking triple-negative breast cancer: a case report with clinical and pathological implications

BackgroundPrimary breast lymphoma (PBL) is a rare type of extranodal lymphoma, the diagnostic process for which presents significant challenges owing to an overlap in clinical and pathological features with those observed in triple-negative breast cancer (TNBC). However, the current literature reveals a paucity of information regarding the ramifications of potential diagnostic errors, particularly in the context of emergent therapeutic strategies for TNBC. Thus, we present a unique report of a case of PBL.Case presentationA 76-year-old female with no past medical or family history presented to the hospital with the chief complaint of a mass in the right breast. Two masses were palpated in the right breast: one 56 mm mass (No. 1) located at 10 o'clock, and a 21 mm large, elastic, hard mass (No. 2) at 4 o'clock. Needle biopsy was performed only on the larger 56 mm mass (No. 1). The results showed invasive carcinoma that was negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. The preoperative diagnosis was right breast cancer (T3N0M0 Stage IIB) of the TNBC subtype. The patient refused the preoperative chemotherapy recommended by the treatment team; therefore, right breast mastectomy and sentinel lymph-node biopsy were performed instead. The histopathological diagnosis of the first mass was diffuse large B-cell lymphoma (DLBCL); that of the second mass (No. 2) was an invasive breast carcinoma of no special type. Postoperative treatment consisted of endocrine therapy (letrozole) for breast cancer, while the DLBCL was treated with chemotherapy and three courses of intrathecal chemotherapy. At the time of this report, the patient is still living, and neither tumor had recurred in the 2 years following surgery.ConclusionsOn rare occasions, PBL can preoperatively mimic TNBC. While this case did not lead to serious consequences, because surgery was eventually selected as the first therapy, clinicians should be aware that the diagnosis of PBL is challenging using only a core-needle biopsy and can often be misdiagnosed as TNBC.

Role of bone scan for investigation of breast cancer and its applicability in future management.

Objective: To find out the usefulness of bone scan in all stages of breast cancer. Study Design: Prospective Observation Study. Setting: Surgical Unit I & III Ghulam Muhammad Mahar Medical College Hospital, Sukkur. Period: October 2020 till September 2022. Methods: A total of 300 patients were selected who were newly diagnosed with breast cancer (Biopsy Proven). Data was collected for all these patients which included age, risk factors for breast cancer, findings on local examination, histopathology findings, stage of the cancer and result of the bone scan. Results: In our study, 78% patients were in 4th and 5th decade of life with mean age of 53.46±7.66 years. ‘Age above 40’ was the commonest risk factor for breast cancer followed by positive family history for breast cancer. Tumor size ranged from 2 to 13.2 cm with mean size of 6.06±1.92 cm. In our study, most common type of carcinoma was invasive ductal carcinoma (71.3%) followed by invasive lobar carcinoma (50%). Only 32 (10.67%) out of 300 patients had positive bone scan. Majority of the bone scan positive cases belonged to the Stage IIIB, IIIC and IV. Conclusion: It is concluded in our study that routine use of bone scan in cases of stage 1 and 2 breast cancer is not recommended; only stage 3A or advances cases should undergo bone scan.

Novel Delivery Systems of Raloxifene Hydrochloride for Improved Bioavailability and Therapeutic Efficacy: A Review

Raloxifene hydrochloride belongs to the selective estrogen receptor modulator category. Initially, US FDA approved its use for the prevention and treatment of osteoporosis in postmenopausal women. Later, raloxifene hydrochloride was also approved for the prevention of invasive breast carcinoma in post-menopausal women under the high-risk category. Despite its immense and diverse therapeutic potential, the oral bioavailability of raloxifene hydrochloride is only ~ 2%. The factors responsible for the poor bioavailability of raloxifene hydrochloride include its amphiphobic nature, para-glycoprotein pump-mediated efflux in the intestine, and high pre-systemic glucuronidation. In the past two decades, multiple novel delivery systems, viz. lipid-based nanocarriers, polymeric nanoparticles, polymer-lipid hybrid nanoparticles, micelles, and mixed micelles, have been developed to overcome its drawbacks. Moreover, inclusion complex, phospholipid complex, and solid dispersion have also been developed to improve its solubility and dissolution rate. Further, some research groups successfully explored non-peroral routes like nasal and transdermal for augmenting the raloxifene hydrochloride bioavailability and its therapeutic efficacy. Hence, the principal objective of this review paper is to critically analyze all the delivery systems developed for raloxifene hydrochloride with their advantages and limitations. In addition, a detailed discussion of the physicochemical and pharmacokinetic parameters of raloxifene hydrochloride has been included in this paper. An in-depth understanding of these parameters will assist formulation scientists in developing efficient delivery systems in the future. In conclusion, the literature review revealed that the nanoparticulate systems successfully augmented the raloxifene hydrochloride bioavailability and therapeutic efficacy in pre-clinical experiments. However, future clinical trials should be conducted to assess their safety and therapeutic efficacy for rapid preclinical to clinical translation.

9218 Highly Multiplexed Mapping of the Ductal Carcinoma In Situ Ecosystem to Predict Disease Outcome

Abstract Disclosure: G.M. Wilson: None. T.B. Doan: None. B.J. Guild: None. N. Pathmanathan: None. J.D. Graham: None. Mammographic screening programs have resulted in remarkable improvements in breast cancer survival due to early-stage detection. However, this has resulted in a dramatic increase in the detection of non-invasive ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive ductal carcinoma (IDC), which is confined to the ducts and surrounded by a normal myoepithelial cell layer. Many DCIS cases will not progress to IDC within the lifetime of the patient. However, there are limited tools to accurately predict progression, thus virtually all DCIS is surgically removed, and most patients receive adjuvant radiotherapy as it halves recurrence rates. This likely represents overtreatment for a majority of patients. Emerging evidence has revealed that the adjacent microenvironment becomes progressively altered in DCIS and IDC compared to normal tissue, and this is correlated with disease outcome. The objective of this study was to investigate changes to the DCIS microenvironment during disease progression and identify disease states that predict patient outcome. We used immunohistochemistry and imaging mass cytometry with a well-annotated cohort of DCIS, with or without adjacent IDC, to measure a panel of 40 phenotypic and functional markers that allowed us to distinguish the diverse cell populations present in the tissues. We observed striking changes to almost all cell types within the DCIS tissue when comparing pure DCIS cases to DCIS adjacent to IDC. In particular, there were considerable changes to tissue-resident immune populations, with differences observed in the type, location and population size of a variety of immune cell subsets, in IDC-associated DCIS compared with DCIS-only cases. Computational mapping of cell type communities in pure and IDC-adjacent DCIS tissues revealed specific differences that could be used to predict the emergence of invasive disease, informing clinical management of this good prognosis malignancy and potentially avoiding over-treatment. Presentation: 6/3/2024

9218 Highly Multiplexed Mapping Of The Ductal Carcinoma In Situ Ecosystem To Predict Disease Outcome

Abstract Disclosure: G.M. Wilson: None. T.B. Doan: None. B.J. Guild: None. N. Pathmanathan: None. J.D. Graham: None. Mammographic screening programs have resulted in remarkable improvements in breast cancer survival due to early-stage detection. However, this has resulted in a dramatic increase in the detection of non-invasive ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive ductal carcinoma (IDC), which is confined to the ducts and surrounded by a normal myoepithelial cell layer. Many DCIS cases will not progress to IDC within the lifetime of the patient. However, there are limited tools to accurately predict progression, thus virtually all DCIS is surgically removed, and most patients receive adjuvant radiotherapy as it halves recurrence rates. This likely represents overtreatment for a majority of patients. Emerging evidence has revealed that the adjacent microenvironment becomes progressively altered in DCIS and IDC compared to normal tissue, and this is correlated with disease outcome. The objective of this study was to investigate changes to the DCIS microenvironment during disease progression and identify disease states that predict patient outcome. We used immunohistochemistry and imaging mass cytometry with a well-annotated cohort of DCIS, with or without adjacent IDC, to measure a panel of 40 phenotypic and functional markers that allowed us to distinguish the diverse cell populations present in the tissues. We observed striking changes to almost all cell types within the DCIS tissue when comparing pure DCIS cases to DCIS adjacent to IDC. In particular, there were considerable changes to tissue-resident immune populations, with differences observed in the type, location and population size of a variety of immune cell subsets, in IDC-associated DCIS compared with DCIS-only cases. Computational mapping of cell type communities in pure and IDC-adjacent DCIS tissues revealed specific differences that could be used to predict the emergence of invasive disease, informing clinical management of this good prognosis malignancy and potentially avoiding over-treatment. Presentation: 6/3/2024

8770 Highly Multiplexed Mapping of the Ductal Carcinoma In Situ Ecosystem to Predict Disease Outcome

Abstract Disclosure: G.M. Wilson: None. T.B. Doan: None. B.J. Guild: None. N. Pathmanathan: None. J.D. Graham: None. Mammographic screening programs have resulted in remarkable improvements in breast cancer survival due to early-stage detection. However, this has resulted in a dramatic increase in the detection of non-invasive ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive ductal carcinoma (IDC), which is confined to the ducts and surrounded by a normal myoepithelial cell layer. Many DCIS cases will not progress to IDC within the lifetime of the patient. However, there are limited tools to accurately predict progression, thus virtually all DCIS is surgically removed, and most patients receive adjuvant radiotherapy as it halves recurrence rates. This likely represents overtreatment for a majority of patients. Emerging evidence has revealed that the adjacent microenvironment becomes progressively altered in DCIS and IDC compared to normal tissue, and this is correlated with disease outcome. The objective of this study was to investigate changes to the DCIS microenvironment during disease progression and identify disease states that predict patient outcome. We used immunohistochemistry and imaging mass cytometry with a well-annotated cohort of DCIS, with or without adjacent IDC, to measure a panel of 40 phenotypic and functional markers that allowed us to distinguish the diverse cell populations present in the tissues. We observed striking changes to almost all cell types within the DCIS tissue when comparing pure DCIS cases to DCIS adjacent to IDC. In particular, there were considerable changes to tissue-resident immune populations, with differences observed in the type, location and population size of a variety of immune cell subsets, in IDC-associated DCIS compared with DCIS-only cases. Computational mapping of cell type communities in pure and IDC-adjacent DCIS tissues revealed specific differences that could be used to predict the emergence of invasive disease, informing clinical management of this good prognosis malignancy and potentially avoiding over-treatment. Presentation: 6/3/2024

8770 Highly Multiplexed Mapping Of The Ductal Carcinoma In Situ Ecosystem To Predict Disease Outcome

Abstract Disclosure: G.M. Wilson: None. T.B. Doan: None. B.J. Guild: None. N. Pathmanathan: None. J.D. Graham: None. Mammographic screening programs have resulted in remarkable improvements in breast cancer survival due to early-stage detection. However, this has resulted in a dramatic increase in the detection of non-invasive ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive ductal carcinoma (IDC), which is confined to the ducts and surrounded by a normal myoepithelial cell layer. Many DCIS cases will not progress to IDC within the lifetime of the patient. However, there are limited tools to accurately predict progression, thus virtually all DCIS is surgically removed, and most patients receive adjuvant radiotherapy as it halves recurrence rates. This likely represents overtreatment for a majority of patients. Emerging evidence has revealed that the adjacent microenvironment becomes progressively altered in DCIS and IDC compared to normal tissue, and this is correlated with disease outcome. The objective of this study was to investigate changes to the DCIS microenvironment during disease progression and identify disease states that predict patient outcome. We used immunohistochemistry and imaging mass cytometry with a well-annotated cohort of DCIS, with or without adjacent IDC, to measure a panel of 40 phenotypic and functional markers that allowed us to distinguish the diverse cell populations present in the tissues. We observed striking changes to almost all cell types within the DCIS tissue when comparing pure DCIS cases to DCIS adjacent to IDC. In particular, there were considerable changes to tissue-resident immune populations, with differences observed in the type, location and population size of a variety of immune cell subsets, in IDC-associated DCIS compared with DCIS-only cases. Computational mapping of cell type communities in pure and IDC-adjacent DCIS tissues revealed specific differences that could be used to predict the emergence of invasive disease, informing clinical management of this good prognosis malignancy and potentially avoiding over-treatment. Presentation: 6/3/2024

8042 A Rare Case of Papillary Thyroid Carcinoma in a Patient with Li-Fraumeni Syndrome

Abstract Disclosure: K.M. Bakhtawar: None. G. Jaiswal: None. Li-Fraumeni syndrome (LFS) is an autosomal dominant syndrome with a high lifetime probability of cancer at an early age. The spectrum of cancers primarily includes osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, leukemia, and Adenoid cystic carcinoma. Prior studies have estimated the cumulative cancer risk to be about 50% by age 40 and as high as 90% by age 60. As screening for TP53 mutations has improved and more patients are identified, the LFS cancer spectrum has expanded to include thyroid cancer. However, the occurrence of thyroid cancer in LFS has not been extensively assessed in the literature. A recent study examined cancer patients carrying the Brazilian p.R337H TP53 mutation which demonstrated that out of 101 patients, 11 had thyroid cancer (10.9%). In our case, a 45-year-old female with a past medical history of Li-Fraumeni syndrome, Von Willebrand disease, Pulmonary embolism, HER-2 positive invasive ductal carcinoma of the left breast status post chemotherapy, and bilateral mastectomy presented for evaluation of papillary thyroid carcinoma (PTC). An enlarged thyroid was initially identified on physical exam by the PCP with a follow-up thyroid ultrasound showing bilateral nodules. The right upper pole 1.9 x 1.3 x 1.6 cm nodule was biopsied revealing PCT. Following neck ultrasound demonstrated mildly enlarged lymph nodes on the right side, level 2A 1.5 cm and level 3 1.6 cm. The patient subsequently underwent total thyroidectomy and lymph node dissection. The pathology report revealed a 1.4 cm PTC in the upper right pole, a 0.9 cm PCT in the isthmus, and a 0.8 cm PTC in the left midpole. 4/62 lymph nodes were positive with the largest deposit of 1 cm. All margins were negative for carcinoma with no angioinvasion or lymphatic invasion. She was staged as T1bN1bM0. We are awaiting post-operative Thyroglobulin level to assess the need for Radioactive iodine. BRAFV600E and P53 mutation was identified. The patient carries known heterozygous mutation p.R1755H in the TP53 gene with an estimated lifetime cancer risk of 93%. This particular mutation has not been associated with thyroid cancer in prior studies. Although thyroid cancer is an uncommon manifestation of LFS, this case begs the importance of further studies to explore this association which may then lead to early screening and treatment of thyroid cancer in individuals with founder TP53 mutations. Presentation: 6/1/2024

Immunoglobulin A-dominant membranoproliferative glomerulonephritis-like pattern of injury as a possible paraneoplastic nephropathy in a breast cancer patient.

A middle-aged woman was found to have proteinuria during a health check-up. About sixteen months later, she was diagnosed with stage IIA invasive ductal carcinoma of the right breast. Her proteinuria progressed to nephrotic syndrome with significant hematuria. Hormone therapy was initiated for her estrogen and progesterone receptor-positive breast cancer. A kidney biopsy performed 47days after starting the therapy revealed an IgA-dominant membranoproliferative glomerulonephritis-like pattern of injury. Electron microscopy showed subendothelial-dominant electron-dense deposits (EDD), with small amounts of mesangial EDD and a single occurrence of subepithelial hump-like EDD, along with occasional mesangial interpositions. Similar pathology can be caused by IgA vasculitis with nephritis, IgA-dominant infection-associated glomerulonephritis, and liver disease-associated glomerulopathy, but all of these were ruled out. The deposited IgA was found to be galactose-deficient IgA1. Thus, IgA nephropathy with glomerular capillary IgA deposition was considered. She underwent a right partial mastectomy and sentinel lymph node biopsy in the right axilla 75days after starting hormone therapy, followed by adjuvant radiation. Proteinuria and hematuria tended to decrease after the treatment, and this trend continued even after corticosteroid therapy for glomerulonephritis, which was administered 156days after starting hormone therapy. Approximately 15months after starting hormone therapy, her proteinuria had reduced to around 1.0g/g of creatinine, and her hematuria was negative. IgA nephropathy with glomerular capillary IgA deposition is known to be resistant to corticosteroid therapy. The favorable clinical course of the rare glomerulopathy following breast cancer treatment suggested a diagnosis of paraneoplastic glomerulopathy secondary to breast cancer in our patient.

Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes

BackgroundDuctal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.ResultsWe identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.ConclusionsWe identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

The Association of Neuroendocrine Differentiation with MicroRNA 21 and MicroRNA let7f Expression and the Clinicopathological Parameters in Primary Invasive Breast Carcinomas with Neuroendocrine Features.

MiRNAs have been reported as biomarkers with diagnostic, prognostic, and predictive value for many different diseases. Therapeutic agents targeting some miRNAs are currently being developed. We aimed to compare BC-NEFs (carcinoma of the breast with neuroendocrine features) with IDC (invasive ductal carcinoma) cases without neuroendocrine features in terms of the level of miRNA expression known to show the oncogenic (miR-21) and tumor-suppressor effects (miR-let7f) and the clinicopathological features. A total of 29 patients with a diagnosis of BC-NEFs (15 cases with neuroendocrine differentiation >50% of the whole section of tumor and 14 cases with neuroendocrine differentiation 10-50% of the tumor) and 30 patients with a diagnosis of IDC (no neuroendocrine differentiation) were retrospectively re-evaluated. Expression levels of miR-21 and miR-let7f were determined by the qRT-PCR method in paraffin tissue blocks. MiR-21 expression was significantly higher in the IDC group than in the group with BC-NEFs. miR-let7f expression was significantly lower in the group with BC-NEFs compared to the IDC group. A high expression level of miR-21 was found to be associated with progesterone receptor (PR) negativity. Our findings show that the presence of NEFs in breast carcinomas makes a significant difference in the expression levels of the investigated oncogenic (miR-21) and tumor-suppressor (miR-let7f) miRNAs. These findings suggest that miRNAs may be a potential biomarker in BC-NEFs and would benefit from targeted therapy.

Pleomorphic Lobular Carcinoma In Situ Composed of Signet-Ring Cells Mimicking Ductal Carcinoma In Situ with A Papillary Pattern: A Case Report.

While some forms of invasive or in situ carcinoma of the breast may be partly composed of signet-ring cells, signet-ring cells rarely become a prominent feature of pleomorphic lobular carcinoma in situ (LCIS). We report a rare example of pleomorphic LCIS composed predominantly of signet-ring cells with a papillary pattern mimicking ductal carcinoma in situ (DCIS). A 58-year-old woman presented with a mass in the left breast detected by ultrasonography. Fourteen years previously, the patient underwent right breast-conserving surgery for invasive breast carcinoma of no special type. Ultrasonography revealed an irregular parallel, angular hypoechoic mass measuring 1.5 cm in the left breast. An ultrasound-guided core needle core biopsy was conducted. Microscopically, the lesion was composed of epithelial cells supported by a fibrovascular stroma. The majority (> 70%) of the lesional cells between the fibrovascular stalks showed signet-ring cell features. Some of the nuclei of the signet-ring cells showed intermediate-grade atypia. A mucicarmine stain showed intracytoplasmic mucin in the signet-ring cells. Immunohistochemistry for E-cadherin was negative in the tumor cells. After surgical excision, the final diagnosis was a pleomorphic LCIS. To our knowledge, there have been no previous reports of pleomorphic LCIS consisting primarily of signet-ring cells with a papillary pattern.

Epidemiological and Histological Profile of Breast Cancer in the Ghrab Chrarda Bni Hsein Region, Morocco

Introduction Breast cancer is the most common cancer, accounting for 38.9% of all cancers diagnosed, it is also the most fatal among Moroccan women. The aims of this study were to draw up an epidemiological profile of breast cancer and to establish the link between patient characteristics and the histological types of cancer observed. Methods This was a retrospective study including 877 patients with histologically confirmed breast cancer. The study was conducted at the Reproductive Health Reference Center in the province of Kénitra (Morocco). It covered the period 2013 - 2018. Results The median age of patients at diagnosis was 50 years (Q1-Q3: 42 - 58 years). Most patients were aged 40 years or older (84.04%) and married (67.32%). They were nulliparous in 18.61% of cases. The average number of live children (LVC) was 3.5 LVC (Q1- Q3: 2 - 5 LVC). Approximately 10.22% of patients had a family history of invasive carcinoma (96.58%). The median tumour size was 25 mm (Q1 - Q3: 20 - 36 mm). The predominant histological type was invasive ductal carcinoma. The most common Scarff- Bloom-Richardson (SBR) grade was SBR II (63.64%). High histological grade correlated with large tumour size. Histological type showed a significant association with time to consultation (p<0.05) and age at first pregnancy (p<0.05). Conclusion All the contextual factors need to be taken into account to improve the assessment of the risk of developing breast cancer, and even of dying from it. Research, awareness-raising and ongoing education are essential if we are to develop more effective prevention strategies and treatments. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1129-1136

Comparative Analysis of Vitamin D, Folic Acid, and Trace Minerals Levels in Various Stages of Invasive Ductal Breast Cancer.

Invasive ductal carcinoma (IDC) is one of the most commonly diagnosed subtypes of breast cancer, representing the majority of breast cancer cases. This study investigates the levels of vitamin D, folic acid, and antioxidant minerals (zinc (Zn), copper (Cu), and magnesium (Mg)) in IDC patients across different disease stages to explore their potential roles in disease progression. We analyzed a cohort of 150 female patients with IDC, aged between 30 and 67 years (51 ± 15.5 years). Blood samples were collected to measure levels of vitamin D, folic acid, Cu, Mg, and Zn. Patients were categorized into Stage1 to Stage 4 of cancer. Variations in nutrient levels across these stages were statistically assessed using ANOVA and post-hoc tests. The study results revealed varying levels of key nutrients across different stages of the disease. Vitamin D levels averaged 17.7 ng/mL, with higher concentrations in early-stage patients, indicating a possible correlation with disease severity. Folic acid levels had a mean of 12.2 ng/mL, showing a decline in later stages, potentially linking it to cancer progression. Copper levels averaged 161.3μg/dL, peaking at 170μg/dL in Stage 3, suggesting a connection with cancer aggressiveness. Magnesium levels, with an average of 1.4 mg/dL, dropped notably to 0.6 mg/dL by Stage 4, highlighting its possible involvement in disease progression. Zinc levels averaged 69.4 μg/dL, with a significant decrease in advanced stages, emphasizing its importance for immune function and cellular health. The study demonstrates significant variations in the levels of vitamin D, folic acid, and antioxidant minerals across different stages of IDC. These nutrients may influence cancer progression, underscoring the potential benefits of nutritional assessments and interventions in managing IDC.

Clinical, histological and receptor profiles of invasive breast cancer and ductal carcinoma in situ in females with germline pathogenic variants in PTEN and implications for germline testing

PTEN hamartoma tumour syndrome (PHTS) is an autosomal dominant hereditary cancer syndrome, caused mostly by germline pathogenic variants in PTEN. Female carriers have an up to 80% lifetime risk of breast cancer. Pathologic features of breast cancer in PHTS have seldom been reported.In a collaboration between all histopathology laboratories in our state and our statewide familial cancer service, we tracked the breast biopsies of 12 females with known PTEN pathogenic or likely pathogenic variants (Jan 1990 to Jan 2018). Two further cases were added by a Victorian cancer genetics unit.Breast cancer, inclusive of invasive cancer or ductal carcinoma in situ (DCIS), was diagnosed in 12 of 14 cases (85.7%). One case had a family history of PHTS and six a family history of breast cancer. The mean age at first breast cancer diagnosis was 41.6 years (range 27-63). Six cases developed more than one breast cancer. Five (42%) developed contralateral breast cancer. Ten of the 12 invasive cancers were of no special type, two were reported as lobular carcinomas. None were grade 1. When reported, all cancers were hormone receptor positive and HER2 negative. All were associated with DCIS. The DCIS spanned all grades.The two cases without breast cancer still required surgery for exuberant benign changes, including papillomas, fibroadenomatoid change, florid ductal epithelial hyperplasia, adenosis and stromal fibrosis.We note that the morphology and receptor profiles of breast cancer in individuals with P/LP PTEN variants are not distinctive. Contrary to prevalent beliefs, these cancers do not conform to the contemporary definition of apocrine breast carcinoma. Greater familiarity of healthcare professionals with the overall clinical and pathologic findings in PHTS and the validated Cleveland Clinic PTEN calculator (http://www.lerner.ccf.org/gmi/ccscore) would improve the recognition of female PHTS individuals with breast cancer. Earlier identification of their cancer predisposition syndrome would benefit these patients and their families who are at high risk of a range of cancers.

The implementation and outcome of a breast cancer genetic counselling service at Potchefstroom Hospital: a model for outreach

Aim Breast cancer is the most prevalent cancer in South African females, making up 27.1% of all histologically diagnosed cancers in 2020. Although genetic technology and awareness of genetic counselling have improved, genetic counselling services in South Africa remain largely inaccessible. Clinical genetic services are only formally available in four South African provinces and few outreach programmes exist for small towns and cities. Until 2019, genetic counselling services were unavailable in the North West province; however, since then, genetic counsellors from the National Health Laboratory Service and the University of the Witwatersrand have provided genetic counselling services to patients at the Breast Clinic at Potchefstroom Hospital regularly each year. Method The aim of this pilot study was to perform a retrospective file review and report on the implementation and outcomes of the genetic counselling service at the Breast Clinic at Potchefstroom Hospital, from its inception in 2019, until November 2022. Fifty-two patients attended a genetic counselling consultation during that period. Results The majority of patients (83.7%) were diagnosed with an invasive ductal carcinoma, and 57.7% of the patients had a family history of cancer. A total of 62.8% of patients had a histologic grade 3 tumour. A total of 25.5% (12/47) of patients tested positive for a pathogenic variant in BRCA1 or BRCA2. A total of 45 at-risk first-degree relatives were identified who could benefit from predictive testing. Conclusions This study highlights the benefit of offering clinical genetics services through outreach clinics. Being able to offer this service is not only beneficial for the management of the affected individuals, but also for their at-risk relatives. The initiative serves as a positive example of how limited resources can be extended to benefit patients.