Clinicopathological significance of immunohistochemical expression of Filamin A in breast cancer.

BACKGROUND: Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy. MATERIALS AND METHODS: One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A. RESULTS: Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. CONCLUSION: No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients.

Post-traumatic necrotising fasciitis of the breast: a case study with literature review.

Necrotising fasciitis is a rare infection of the skin and underlying soft tissue. It primarily involves the extremities and rarely the breast. Primary necrotising fasciitis of the breast in a non-lactating, healthy female is rarer still. The authors present the case report of a patient presenting with primary necrotising fasciitis of the breast after sustaining a penetrating injury. The patient was managed successfully with serial debridement and negative pressure wound therapy (NPWT). To our knowledge only 19 such cases have been reported in the indexed literature so far. This is also the eighth case globally of primary necrotising fasciitis of the breast in a non-lactating female without any associated immunosuppression, which is the basis of reporting this case.

Psychosocial well-being and quality of life in women with breast cancer in foothills of North India.

Introduction: Breast cancer remains a leading cause of unintended death among Indian women. Cancer treatment-induced pain, fatigue, nausea/vomiting, body image, and sexual problems could affect the patient psychosocial well-being and quality of life (QOL). The study aims to determine the QOL and psychosocial well-being among women with breast cancer. Materials and Methods: A cross-sectional survey completed by 244 women with breast cancer at a tertiary level teaching hospital. The European Organisation for Research and Treatment of Cancer QOL Questionnaire C30, the Breast Module (QLQ-BR23), and the Hospital Anxiety and Depression Scale (HADS) is used to measure the QOL, and psychological well-being, respectively. Appropriate descriptive and inferential statistics are applied to compute the results. Results: The total number of women with breast cancer interviewed was 244, with a mean age of 45.06 (standard deviation ± 11.17) years. The mean global health score was 70.97 ± 15.63. As per the QLQ-C30 scale, "physical functioning" scored the highest (70.54 ± 22.00), and "role functioning" reported the lowest (49.45 ± 36.15) mean score. Further, on the QLQ-C30 symptoms scale, "appetite loss" (45.09 ± 35.09) was the worst reported symptom, followed by "nausea and vomiting" (34.97 ± 38.39). On the BR-23 scale, body image said (68.42 ± 22.28) higher score than other domains and experience of arm-related problems (43.80 ± 26.06) were more frequently reported symptom in women. As per the HADS scale, 24.6% and 36.1% of women were in moderate anxiety and depression, respectively. The mean HADS score was 14.39 ± 5.82. Findings on predictors for the individual patient remained the same as that earlier published literature. Conclusions and Recommendations: Women with breast cancer have an overall good QOL and poor psychosocial well-being. However, using a holistic approach, including identifying psychological problems and their time management, signifies the need for the studied population.

Detecting Human Epidermal Growth Factor Receptor 2 (HER2) Amplification: Proof of Concept of an Alternative Approach.

BACKGROUND: There are multiple genes that are co-amplified along with human epidermal growth factor receptor 2 (HER2) in chromosome 17. GRB7 and PGAP3 are two such genes. We hypothesize that the protein products of these genes may serve as immunohistochemistry (IHC) markers for detecting HER2 amplification in breast cancer. METHODS: Tissue sections from one hundred and thirty-five primary breast carcinoma cases were subjected to immunohistochemical staining for antibodies against HER2, GRB7, and PGAP3 and graded on a scale of 1 to 3. Both membranous staining and cytoplasmic staining were assessed for GRB7 and PGAP3. For equivocal HER2 IHC positivity, fluorescent in situ hybridization was performed to get the final HER2 status. RESULTS: IHC staining for GRB7 and PGAP 3 was a moderate to strong predictor for HER2 status (area under the curve (AUC) of 0.768, 0.868,0.754, and 0.790 for GRB7 membranous staining, GRB7 cytoplasmic staining, PGAP3 membranous staining, and PGAP3 cytoplasmic staining respectively). A combination of GRB7 cytoplasmic and PGAP3 membranous staining resulted in an AUC of 0.905 (95% CI 0.855-0.954), while a combination of GRB7 and PGAP3 cytoplasmic staining resulted in an AUC of 0.902 (95% CI 0.851-0.953). CONCLUSION: The point estimates for the AUC of GRB7 and combined GRB7 and PGAP3 in predicting the AUC suggest a strong predictive ability of these markers to predict HER2. With further refinement in technique, cytoplasmic staining and membranous IHC staining for GRB7 and PGAP3 have potential to serve as surrogate markers for HER2 status. The strategy of using protein products of co-amplified genes of HER2 is likely to be successful in technical validation.

Pectoralis major muscle sarcoma masquerading breast lesion: A rare case report with review of literature.

Pectoralis major muscle sarcomas are extremely rare and can mimic breast lesion clinically. We report a case of poorly differentiated sarcoma of the pectoralis major muscle in a 63-year-old woman of south east Asian ethnicity presenting with a progressively increasing right breast lump. Mammography, ultrasonography (US), contrast-enhanced computed tomography, and biopsy were done to make the final diagnosis. Complete surgical excision was planned but deferred due to pulmonary metastasis, and the patient was treated with palliative chemotherapy. Clinical examination may be confusing but radiological and pathological investigations provide detailed information about the location and the extent of the disease and a definitive tissue diagnosis can only be made on histopathology which will be helpful in preoperative planning and further treatment of the patient.

Study of Diagnostic Delay among Symptomatic Breast Cancer Patients in Northern India: A Mixed-Methods Analysis from a Dedicated Breast Cancer Centre.

OBJECTIVE: We conducted this study to understand the factors that contribute to the delay in diagnosis of symptomatic breast cancer patients. METHODOLOGY: We did a prospective analytical study with both quantitative and qualitative components over 14 months. The total delay in diagnosis of breast cancer from first symptom onset was defined as diagnostic delay. Presentation delay was defined as the time duration between the first symptom and the first visit to a health care provider. Provider delay was defined as the time duration between the presentation to a health care provider and the final diagnosis. Three hundred female breast cancer patients with a diagnostic delay of at least 3 months were interviewed using a pre-tested semi-structured questionnaire. RESULTS: We found that more than 50% of patients with delayed presentation were between 30-50 years of age. Painless breast lump was the most common initial symptom. More than 70% of patients presented with locally advanced and metastatic disease. The patient-related delay was more common than provider delay. Breast cancer awareness (p = 0.040) and reasons for delay (p = 0.014) were found to significantly influence the delay. More than 70% of patients reported their symptoms to male members of their families. CONCLUSION: Breast cancer awareness is the single most important determinant influencing diagnostic delay among symptomatic patients.

Utility of Axillary Reverse Mapping (ARM) and Incidence of Metastasis in Arm Draining Lymph Nodes in Patients with Breast Cancer.

Objective Lymphedema of the upper limb is the most common complication in patients with breast cancer, who require axillary lymph node (LN) dissection. Proposition of identifying upper limb draining LN and preserving it, during axillary dissection can reduce significant postoperative morbidity, but it has the risk of inadequate oncological resection. This study was planned to find out metastatic rate in axillary reverse mapping (ARM) nodes in our population. Materials and Methods Lymphoscintigraphy (LSG) was performed using intradermal injection of 99m Tc Sulfur Colloid into ipsilateral second and third interdigital web spaces of hand in patients with breast cancer. Planar, single-photon emission computed tomography-computed tomography images were acquired followed by intraoperative localization of arm draining LNs using Gamma Probe. All identified ARM nodes were dissected and sent for histopathological examination to confirm metastatic involvement. Results Twenty eligible patients were prospectively analyzed. The identification rate of arm draining LN with LSG was 90% (18/20). Among 14 eligible patients included in the study, ARM node metastasis was seen in two patients. A total of 64 ARM nodes were dissected from 14 patients, 4/64 nodes (2 patients) were positive for metastases (6.25%). Of the six patients excluded from the study, in 1 patient ARM node could not be identified on Gamma Probe, in two cases, it could not be retrieved surgically, in next two cases ARM could not be identified on LSG and remaining one case was removed because of previous surgical intervention. Conclusion In the current study, LSG showed the identification rate of 90% for ARM nodes in patients with carcinoma breast and metastatic involvement was seen in 6.25% (4/64) of these nodes in 2/14 (14.2%) patients, which is in agreement with previously published data. Oncological safety of preserving ARM nodes needs to be evaluated in the larger population.

Evaluation of an Interventional Health Education Project: Screening of Breast Cancer and Health Education (SHE).

There is an increasing incidence of breast cancer in India, especially among younger women. The study's main objective was to create awareness related to breast cancer and breast self-examination by community health workers and assess the effectiveness of improving knowledge and practice. Secondary objective was to conduct clinical breast examination (CBE) of women and prompt referral. METHODS: An outcome evaluation of the Educational Interventional project was conducted in a hilly district of Uttarakhand. Twenty Accredited Social Health Activists (ASHA) were identified and trained in breast cancer awareness, the procedure of breast self-examination, and screening methods. These ASHA's further created awareness among study participants (women above 30 years). A structured questionnaire on knowledge and practice was administered before and after educational intervention by ASHA workers. Clinical Breast Examination (CBE) camps were held for women at high risk for breast cancer who were referred to the Division of Breast Surgery, AIIMS Rishikesh, for further management. RESULT: One thousand sixty-one females participated in health education sessions by ASHAs. There was an improvement in knowledge and practice regarding Breast Self-examination after health education intervention. A low prevalence of risk factors for breast cancer was found among attendees of the CBE camp. 3.2% of participants had abnormalities on breast examination needing further workup. CONCLUSION: In the pre-test assessment, we found a low awareness and practice regarding breast cancer which increased significantly among women after behavioral change intervention. The prevalence of risk factors for breast cancer was very low. Trained community health workers were found to be effective in raising awareness, selective screening, and prompt referral.

Axillary vascular malformation visualized on mammogram: A case report.

Chest wall lesions can mimic masses on mammograms and can cause diagnostic difficulty in interpretation. Here, we report a case of an axillary and retro-pectoral vascular malformation visualized on mammography in a 67-year-old patient presenting with fullness in the right axilla and right supraclavicular region. Mammography, ultrasonography (US), and computed tomography (CT) angiography of the patient were done to make the final diagnosis.

Expression of Programmed Cell Death-1 (PD-1) and Its Ligand (PD-L1) in Breast Cancers and Its Association with Clinicopathological Parameters.

Introduction Cancer immunotherapy targeting the programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) axis has revolutionized cancer therapy. PD-L1 also serves as a predictive marker for such therapy. To assess the potential of such therapy in any cancer, the positivity of PD-1 and PD-L1 in such cancers needs to be assessed. However, such studies for breast cancer are lacking in South Asia. We aimed to estimate the positivity of PD-L1 and PD-1 receptors in breast cancer and its various clinicopathological groups in our patient population. Materials and Methods We studied the immunoexpression of PD-1 and PD-L1 in 103 histologically proven invasive carcinoma breast cases from October 2018 to April 2019. The percent positivity of PD-1 and PD-L1 with 95% confidence intervals (CI) was estimated for all the cases as well as groups defined by stage, grade, molecular subtype, hormone receptor status, K i -67, and age. Results PD-1 positivity was seen in 72 (69.9%) cases (95% CI: 60.1-78.6). PD-L1 immunoexpression was seen in 61 (59.2%) cases (95% CI: 49.1-68.8) in immune cells and in 39 (37.9%) cases (95% CI: 28.5-50.0) in tumor cells. No significant association was found between PD-1, PD-L1 and age, overall clinical stage, grade, size, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and K i -67. Moderate-to-high PD-1 and PD-L1 immunopositivity was seen in all subtypes of breast cancer. Conclusion PD-1 and PD-L1 is expressed in all subgroups of breast carcinoma. Patients in all such groups are amenable to immunotherapy, provided they are found suitable otherwise.

Relationship of Tubule Formation, Indian File Pattern and Apocrine Change With Estrogen and Progesterone Receptors and HER2 Immunostaining.

OBJECTIVES: In breast carcinomas, histomorphological features like low-grade and lobular differentiation are associated with estrogen receptor (ER) and progesterone receptor (PR) expression. Apocrine carcinoma is associated with human epidermal growth factor receptor 2 (HER2) positivity. Studies have not emphasized the association between other histological features like tubule formation, Indian file pattern and apocrine change (which may be found in all grades of tumors or as a part of a mixed pattern of no special type) and immunohistochemistry (IHC). The study was designed to find the association between these morphological factors and ER, PR and HER2 status. MATERIALS AND METHODS: The presence or absence of tubule formation, Indian file pattern and apocrine change was correlated with ER, PR and HER2 expression in core biopsies of 102 invasive breast carcinomas. STATISTICAL ANALYSIS: Fisher exact test with median unbiased odds ratio was used. RESULTS: Tubule formation and/or Indian file pattern were significantly associated with ER in all tumors (P-value <0.001), as well as separately for grade II, grade III, HER2-negative and HER2-positive tumors. Comparable results were obtained for their association with PR. Apocrine change was significantly associated with HER2 in all tumors (P-value <0.001), as well as separately for grade III, ER-positive and ER-negative tumors. CONCLUSION: These histomorphological patterns are modest predictors of IHC status in breast carcinomas, even in tumors of higher grade. Knowledge of these morphological correlates of ER, PR and HER2 in breast cancer may serve as an aid in the quality management of breast carcinoma reporting.

Keratin cyst as a diagnostic pitfall in aspiration cytology of phyllodes tumor.

BACKGROUND: Phyllodes tumor (PT) is a fibroepithelial lesion of breast known for presence of a heterogenous stroma. However occurrence of a keratin cyst within PT is a rare incidence. An inadequate sampling during fine needle aspiration (FNA) of such lesions may result in an erroneous cytological diagnosis. CASE REPORT: In the present case, ultrasound guided FNA smears from the breast lump in a 31-year-old lady with a clinical suspicion of malignancy, were repeatedly interpreted as an epidermal inclusion cyst, which was ultimately reported as a borderline PT on mastectomy. CONCLUSION: The case report aims at highlighting the importance of a diligent FNA technique keeping in mind the possibility of the various uncommon lesions especially while dealing with such a heterogenous tumor as phyllodes.

Impact of COVID-19 On Breast Cancer Management: A Radiological Prespective from A Tertiary Centre.

OBJECTIVE: The coronavirus-2019 (COVID-19) pandemic caused delaying breast cancer management, increasing time interval in chemotherapy cycles and surgery. This has implications on radiological manifestation of cancer. Further, we evaluated changes observed in mammography. MATERIALS AND METHODS: This case control study was conducted from March 25th, 2020 to August 15th, 2020 at the Integrated Breast Care Centre, All India Institute of Medical Science Rishikesh (AIIMS), Rishikesh. Sonomammography was performed on follow-up patients who were on chemotherapy and were scheduled for surgery. Moreover, duration of delay from the last neoadjuvant chemotherapy (NACT) cycle was recorded. Similar data in the pre-COVID-19 period from November 4th, 2019 to March 24th, 2020 was compared with post-COVID-19 data and was analyzed by SPSS Version 23. RESULTS: The study included 54 patients who presented between March 25th, 2020 and August 15th, 2020. Furthermore, the delay in NACT cycles has been shown to be associated with disease progression (p = 0.045). Subgroup analysis of treatment duration with various parameters revealed significant correlation between size, appearance of ulceration, and response evaluation (p<0.05). However, no significant association was found between duration of delay and the histological subtype of lesion (p>0.05). A substantial difference was seen in the evaluation of NACT response in pre- and post-COVID-19 time, with partial response (n = 39, 58.24%) seen as the most common response in pre-COVID-19 time and progressive disease (n = 28, 51.9%) as the most common response in post-COVID-19 time (p<0.001). CONCLUSION: The coronavirus pandemic has severe impact on breast cancer management. A delay in NACT causes progression in cancer. This can be seen in ultrasound and mammogram.

Accuracy of the International Academy of Cytology Yokohama system of breast cytology reporting for fine needle aspiration biopsy of the breast in a dedicated breast care setting.

BACKGROUND: The International Academy of Cytology (IAC) Yokohama system is a recently proposed system for reporting breast cytology by fine needle aspiration biopsies (FNAB). Multiple studies are needed to confirm the risk of malignancy (ROM) of the various reporting categories of this system. The present article studies the accuracy of the IAC Yokohama system in our center. METHODS: Over a period of 1 year (September 2018-August 2019), all cases of breast masses assessed by FNAB and histological correlation were studied retrospectively. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) and overall accuracy of the IAC Yokohama system for diagnosing malignancy were assessed. The rates of malignancy (ROM) of each diagnostic category were also estimated. RESULTS: Three hundred and twenty-one FNABs had cyto-histological correlation. The percent sensitivity (with 95% Confidence Intervals) when the atypical, suspicious of malignancy and the malignant categories were regarded as positive for malignancy were 98.2% [95.5%, 99.5%], 96.0% [92.5%, 98.2%], and 86.7% [81.5%, 90.8%] respectively. The percent specificity (with 95% Confidence intervals) for the same categories in the same order were 59.5% [47.4%, 70.7%], 91.9% [83.2%, 97.0%], and 100% [95.1%, 100%] respectively. The area under curve (AUC) for diagnosing malignancy was 0.981[0.963, 0.993]. The ROM for the benign, atypical, suspicious of malignancy and malignant category were 8.3% [2.3%, 20.0%], 17.2% [5.8%, 35.8%], 77.8% [57.7%, 91.4%], and 100% [98.1%, 100%] respectively. CONCLUSION: The IAC Yokohama system is suitable for accurately reporting breast lesions on FNAB.