The Impact of Breast Cancer on the Patient and the Family in Indian Perspective.

PURPOSE: To understand the role played by the immediate family in treatment decision and support in patients diagnosed with breast cancer, the influence of demographic factors on psychosocial roles of women within the family. METHODS: A mixed method design used for data collection on family support, financial arrangement and psychosocial impact of cancer from 378 women with breast cancer recruited at first diagnosis between 2008 and 2012, during multiple counseling sessions. The median follow-up is 7 years with only 2% lost to follow-up. RESULTS: Most patients (99%) had support from family members. 57% of patients met the costs of treatment through personal savings and health insurance. The rest (43%) had difficulty and had to resort to desperate measures such as selling their property or taking on high-interest personal loans. Patients with higher education and urban settings had better financial management. A male member of the family (husband or son) was the main decision maker in half of the cases. Concerns over women's responsibilities within the family varied by the age of the patient. The vast majority of women (90%) experienced social embarrassment in dealing with the disease and its aftermath. CONCLUSION: In India, it is the family that provides crucial support to a woman with breast cancer during her ordeal with the disease and its treatment. This study has implications on the psychosocial support beyond the cancer patients alone, to include the immediate family and consider aspects of finance and social adjustments as critical in addition to the routine medical aspects of the disease.

HR+HER2- breast cancers with growth factor receptor-mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells.

Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor-stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelial-to-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition. A total of 140 primary tumors were sub-divided into groups enriched for the markers of epithelial-to-mesenchymal transition (snail family transcriptional repressor 2 and integrin ß6) versus those with low levels. Within the epithelial-to-mesenchymal transition+ tumors, there was a positive correlation between the transcripts of integrin ß6 and growth factor receptors-human epidermal growth factor receptor 2 and epidermal growth factor receptor. In tumors enriched for epithelial-to-mesenchymal transition markers, patients with tumors with the highest quartile of growth factor receptor transcripts had a shorter disease-free survival compared to patients with low growth factor receptor expression by Kaplan-Meier analysis (log rank, p = 0.03). Epithelial-to-mesenchymal transition was induced in MCF-7 cells by treatment with transforming growth factor beta 1 and confirmed by upregulation of SNAI1 and SNAI2 transcripts, increase of vimentin and integrin ß6 protein, and repression of E-cadherin. Treatment of these cells with the dual-specificity tyrosine-kinase inhibitor lapatinib led to downregulation of epithelial-to-mesenchymal transition as indicated by lower levels of SNAI1 and SNAI2 transcripts, integrin αvß6, and matrix metalloproteinase 9 protein. The results suggest that synergistic interactions between growth factor receptors and integrin ß6 could mediate epithelial-to-mesenchymal transition and migration in a subset of luminal breast cancers and lapatinib might be effective in disrupting this interaction.

Body Image and Sexuality in Women Survivors of Breast Cancer in India: Qualitative Findings.

OBJECTIVES: With increasing rates of breast cancer survivors, psychosocial issues surrounding cancer survivorship have been gaining prominence. The following article reports on body image and sexuality-related issues in aftermath of the diagnosis and its treatment in the Indian context. MATERIALS AND METHODS: Research design was mixed method, cross-sectional, and exploratory in nature. Quantitative sample consisted of fifty survivors while the qualitative sample size included 15 out of the 50 total breast cancer survivors who were recruited from hospitals, nongovernmental organization, and through word-of-mouth. Data was collected using quantitative measures, and in-depth interviews were done using semi-structured interview schedule that was developed for the study. Qualitative data were analyzed using descriptive phenomenological approach. RESULTS: In body image, emerging themes were about identity (womanhood, motherhood, and attractiveness), impact of surgery, hair loss, clothes, and uncomfortable situations. In sexuality, barriers were faced due to difficulty in disclosure and themes were about adjustments made by spouses, role of age, and sexual difficulties due to treatment. CONCLUSIONS: Findings imply need to address the issues of body image and sexuality as it impacts quality of life of survivors.

Posttraumatic Growth in Women Survivors of Breast Cancer.

AIM: The aim of the study was to understand the phenomenon of posttraumatic growth (PTG) in women survivors of breast cancer from an Indian perspective. SETTINGS AND DESIGN: It was a mixed method, cross-sectional, and exploratory design wherein in-depth qualitative data covering a broader area of experiences were gathered from a sub-section of the larger quantitative sample (n = 50). The qualitative sample consisted of 15 Indian women from urban communities of Southern and Eastern India. Sampling method was purposive in nature. SUBJECTS AND METHODS: Semi-structured interview schedule was developed by researchers based on a review of literature. In-depth interviews were audio recorded after their permissions were obtained and carried out at homes and offices of participants. All participants spoke English. Qualitative data were collected until no new phenomenological information emerged through the interviews. DATA MANAGEMENT AND ANALYSIS: Descriptive phenomenological approach was utilized to analyze the interview data. It focuses on understanding one's life experience from the first person's point of view. RESULTS: Consistent with other literature, PTG was evident in varying forms through positive changes in perspective toward life, better understanding of self, closer, and warmer relationships, and richer spiritual dimension of life. CONCLUSIONS: These findings have implications for promoting holistic cancer care and identifying ways to promote PTG through the initial stages of cancer care into survivorship trajectory.

The epigenetic silencing of the estrogen receptor (ER) by hypermethylation of the ESR1 promoter is seen predominantly in triple-negative breast cancers in Indian women.

The proportion of estrogen receptor (ER)-negative and triple-negative (TN) breast cancer in Indian women is higher than that reported in the West, and this difference persists even after their migration to the West. The causes for this significant difference are not entirely clear. Hypermethylation of the ER promoter, an epigenetic alteration, is known to be one of the mechanisms by which the expression of ER is suppressed. Two thirds of breast cancer specimens from an Indian center tested, using the highly sensitive, methylation-specific polymerase chain reaction (MSP) technique, were reported positive. We have used a quantitative assay, the MethyLight, to better assess the extent of methylation in the ESR1 promoter region in 98 breast cancer tumor specimens from Indian women. In addition, the amount of ER transcripts was determined by quantitative reverse transcriptase polymerase chain reaction. Using the stringent cutoff of at least 4% of the target sequence being methylated, 27% of TN tumors were methylated. In addition they demonstrated the highest levels of methylation. In contrast less than 2% ER-positive tumors were hypermethylated. While the proportion of hypermethylated tumors are lower in this study than that estimated using MSP, our results support the notion of increased epigenetic deregulations in ER-negative tumors in general and TN tumors in particular. The development of this assay also permits a rational approach to the selection of patients for clinical trials examining the efficacy of demethylating agents in the treatment of ER-negative breast cancer.

Modified improvised pre-embedding method for core needle biopsies: A clinicopathologic study.

BACKGROUND: An optimal core needle biopsy (CNB) is expected to balance between tissue diagnosis, the accuracy of negative sampling, and concordance with reports from resected specimens to select the appropriate treatment. Though various techniques for CNBs are available, no guidelines exist for processing CNB, with practices varying from lab to lab for transport and processing. This prospective study aims to design a cost-effective, user-friendly pre-embedding method for CNBs to yield intact cores. OBJECTIVE: To compare the outcomes of CNBs by a conventional method with those processed by the modified pre-embedded processing protocol over 2 years. MATERIAL AND METHODS: Presurgical CNBs from SOL in various organs were subjected to the conventional free-floating method in formalin (control) for histopathology diagnosis. CNBs from the corresponding, freshly resected SOLs (test) were taken, inked with coloring inks if multiple, placed between two 2 × 2 cm polyurethane foam meshes fitted inside cassettes, fixed in formalin, and transported to the laboratory. The two CNB groups were coded and scored independently for intactness, tissue processing, ease of embedding, and ease of cutting sections. Data obtained were statistically analyzed. RESULTS: Test CNB cores were better processed, intact, linear, and aligned, compared to control CNBs. With four CNBs in one block, the number of blocks and sections were cut-down by one-fourth. CONCLUSION: CNBs processed using polyurethane foam and coloring inks were superior and economical against conventional free-floating CNBs. This technique can be practiced by surgeons at the bedside.

Recurrent Retroperitoneal Liposarcoma: a Case Report and Literature Review.

This is a case report of a 61-year-old male patient, presented with fifth recurrence of retroperitoneal liposarcoma and operated for six times. Literature review on retroperitoneal liposarcoma biology, recurrence pattern, role of surgery in primary tumor, and recurrent tumor, adjuvant therapy, role of multivisceral resection, and palliative surgery.

Surgical resection for locally invasive renal cell carcinoma: Is it worthwhile?

BACKGROUND: Many patients with renal cell carcinoma (RCC) present with disease involving the adjacent viscera. Although survival in such patients is poor, surgery remains the only proven modality of treatment. We describe our experience with radical nephrectomy for locally invasive RCC over a five-year period. STUDY DESIGN: A retrospective analysis of the records of all patients who had undergone surgery for locally invasive RCC between January 1999 and December 2004 at our institute. MATERIALS AND METHODS: During the study period, 102 patients with RCC underwent surgery at our institute, out of which 18 (17.6%) patients had adjacent organ involvement. The survival and outcomes in terms of symptom relief are described. STATISTICAL ANALYSIS: The survival rates were calculated by the Kaplan-Meier method using EGRET statistical software package. RESULTS: Of the 18 patients, two patients had inoperable disease. Fifteen out of the 18 patients succumbed to their disease after a median period of 7.5 months. Three patients are still alive, having survived for 13, 16 and 25 months. Most patients derived considerable benefit with respect to relief of symptoms, which was long-lasting. CONCLUSION: For selected patients with locally invasive RCC, radical nephrectomy with en bloc resection of involved organs may provide the opportunity for long-term survival. In others, it may provide considerable symptomatic relief.

Metaplastic Carcinoma of Breast and Neurofibromatosis 1: A Rare Association.

Neurofibromatosis 1 (NF1) patients are generally at higher risk of developing common malignant tumors such as brain and soft tissue tumors. These patients are 5-fold increased the risk of developing breast cancer by the age of 50 years after that the risk remains the same. The most common reported cancer is infiltrating duct carcinoma. We report a case of 61-year-old female with NF1 presented with pain and breast lump for the past 2 months. On mammography, a retroareolar solid cystic lesion measuring 32 mm × 30 mm × 30 mm was noted which was definitive for malignancy. Right-modified radical mastectomy with axillary lymph node dissection was done which revealed a neoplasm composed of glandular and squamous components. Immunohistochemically, these cells were triple negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-neu and expressed markers of basal cell differentiation. The final pathological staging was T2N0M0. This is the fourth case report in the English literature with such association. In this case report, we discussed the importance of breast cancer screening in such patients along with a review of the literature.

Cutaneous Squamous Cell Carcinoma in Lupus Vulgaris Caused by Drug Resistant Mycobacterium Tuberculosis.

Tuberculosis (TB) is still a major public health problem in the world, with many factors contributing to this burden, including poor living conditions, overcrowding, poverty, malnutrition, illiteracy, and rapid spread of human immunodeficiency virus infection. Cutaneous tuberculosis is a less common form of extrapulmonary tuberculosis, and in this paucibacillary form the diagnosis depends on histopathology, tuberculin positivity, and response to treatment. The diagnosis is even more difficult in cases with drug resistant Mycobacterium tuberculosis due to lack of awareness and lack of facilities to diagnose drug resistant tuberculosis. In this article, we describe an unusual case of multidrug resistant lupus vulgaris (LV), in a 34-year-old male who responded to anti-tubercular treatment (ATT) initially, but developed recurrent disease which failed to respond to standard four-drug ATT; subsequently, tissue culture showed growth of multidrug resistant M. tuberculosis. Subsequently, he also developed cutaneous squamous cell carcinoma. This article aims to exemplify a grave complication that can occur in long-standing case of LV, the limitations faced by clinicians in developing countries where tuberculosis is endemic, and classical methods of proving drug resistance are generally unavailable or fail.

Histological Surprises in Benign Cytologies after Lymph Node Biopsy-Surgeon's Knife Improving Patient Care.

Lymphadenopathy can be due to multitude of causes. Owing to the high prevalence of infectious diseases in India, and malignancy being a life threatening cause for lymphadenopathy; accurate diagnosis is important in preventing delay or misdiagnosis and in improving patient care, thereby increasing longevity with quality. Fine needle aspiration cytology (FNAC) is the first line investigation commonly done. Should the doctor be contented with the benign FNAC or is a lymph node biopsy needed in this age? The aims of this study are the following: (1) to study the spectral pattern of lymph node biopsies done in a surgical oncology unit of tertiary care centre, (2) to assess the yield of malignant cases from lymph node biopsy and (3) to compare the reliability of benign FNAC with lymph node biopsy. Cross-sectional study of 114 cases that underwent lymph node biopsy during the year 2014, at the Surgical Oncology Department of St. John's Medical College Hospital, Bangalore. Lymph node biopsies were done in the outpatient department (OPD) under local anaesthesia or in the operation theatre under local anaesthesia/monitored anaesthesia care based on the clinical condition of the patient. Regional lymph node dissections, central node biopsy, patients with known case of malignancy were excluded. Specimen sent for histopathological study and immunohistochemistry (IHC) done when needed. 58.8% were males among study population, age ranging from 15 to 80 years, 57% cervical and 29.8% axillary lymph node biopsies done. Sixty-seven percent (67%) of biopsies done in OPD. Thirty-three percent (33%) of biopsies in the operation theatre among which 60.5% under local anaesthesia only. 35.1% cases were reactive hyperplasia, 24.6% lymphomas with non-Hodgkin's lymphoma being the commonest, 13.2% metastatic disease with adenocarcinoma being the commonest. 72.7% of the supraclavicular nodes were malignant. 47.4% of subjects had prior FNAC of the lymph node. Twenty-five percent (25%) of the reactive hyperplasia's on FNAC (p < 0.0001), 33.3% of inadequate FNAC (p = 0.003) and 75% of atypical cells in FNAC turned to be malignant on lymph node biopsy with a discordance rate of 20.3%. Lymph node size didn't correlate with neoplasm. In our study, benign cytologies were malignant on biopsy and statistically significant. Lymph node biopsies are reliable in detecting malignancy and subtyping of the disease. In the presence of strong clinical suspicion, lymph node biopsy is essential even when the FNAC is promisingly benign in a country with limited resources. Lymph node biopsy can be safely done in OPD under local anaesthesia at a lower cost, resulting in a reliable diagnosis thereby improving patient care.

Feasibility of Axillary Reverse Mapping and Clinicopathological Features Predicting ARM Node Metastasis in Breast Cancer-a Pilot Study.

The axillary reverse mapping (ARM) technique has been described as an attempt to map and preserve the upper extremity lymphatic drainage during axillary lymph node dissection (ALND) and/or SLNB. This technique is based on the hypothesis that the lymphatic pathway from the upper extremity is not involved by metastasis from primary breast cancer. The ARM node/s however, has been found, in various studies, to be involved with metastatic foci in patients with extensive axillary lymph node metastases. Therefore, the oncological safety of this procedure has not yet been determined. In this pilot study, we assessed the ARM node intraoperatively for various parameters and compared it to final HPR, to try and determine the oncologic safety of preserving the ARM node. Seventy-two breast cancer patients were screened for this prospective pilot study which was planned to recruit 20 patients. The study was initiated on May 2014, 20 patients were recruited till July 2015. Eligibility criterion was as follows: patients requiring primary axillary lymph node dissection based on a clinically positive axilla. Forty-five patients were ineligible because they had either received neoadjuvant chemotherapy or underwent previous axillary surgery or axillary radiation (exclusion criteria). Seven patients refused to give consent. ARM node identification rate was 75%. The most common location of the ARM node was lateral to the latissimus dorsi pedicle (42.10%), none of them being malignant. None of the oval or firm nodes were malignant. Tumor deposits were identified in 13%. Fine-needle aspiration cytology (FNAC) had 100% specificity, 94.4% negative predictive value, 100% positive predictive value, and 50% sensitivity. ARM is feasible using blue dye alone, with an acceptable identification rate. Location, consistency, and intraoperative FNAC of the ARM node, put together, may be reliable parameters to predict involvement of the ARM node with metastasis.

Dissecting the Biological Heterogeneity within Hormone Receptor Positive HER2 Negative Breast Cancer by Gene Expression Markers Identifies Indolent Tumors within Late Stage Disease.

Hormone receptor positive (HR+) breast cancers are a heterogeneous class with differential prognosis. Although more than half of Indian women present with advanced disease, many such patients do well. We have attempted identification of biologically indolent tumors within HR+HER2- tumors based on gene expression using histological grade as a guide to tumor aggression. 144 HR+HER2- tumors were divided into subclasses based on scores derived by using transcript levels of multiple genes representing survival, proliferation, and apoptotic pathways and compared to classification by Ki-67 labeling index (LI). Clinical characters and disease free survival were compared between the subclasses. The findings were independently validated in the METABRIC data set. Using the previously established estrogen receptor (ER) down stream activity equation, 20% of the tumors with greater than 10% HR positivity by immunohistochemistry (IHC) were still found to have inadequate ER function. A tumor aggression probability score was used to segregate the remainder of tumors into indolent (22%) and aggressive (58%) classes. Significant difference in disease specific survival was seen between the groups (P = .02). Aggression probability based subclassification had a higher hazard ratio and also independent prognostic value (P<.05). Independent validation of the gene panel in the METABRIC data set showed all 3 classes; indolent (24%), aggressive (68%), and insufficient ER signaling (7%) with differential survival (P = .01). In agreement with other recent reports, biologically indolent tumors can be identified with small sets of gene panels and these tumors exist in a population with predominantly late stage disease.

Experiences of Breast Cancer Survivors with Oncology Settings in Urban India: Qualitative Findings.

The experience of diagnosis and treatment of cancer leads to significant changes within an individual. In the course of survivorship trajectory, very often cancer survivors are left with the sense, improvements could be done to enhance the quality of cancer care. This article focuses on experiences of breast cancer survivors with oncology setting in urban India. Data was collected from 15 women in South and East India using in-depth interview method. Qualitative interview data was analysed using descriptive phenomenology method. Areas of importance that emerged broadly included informational and emotional categories. Findings reveal quality of cancer care in India can be improved through developing an orientation towards patient-centred style rather than doctor/disease centred approach which has major influence on physical and mental health outcomes. This would require further research and increased emphasis on training of medical as well as paramedical professionals.

Identification of BRCA1 Deficiency Using Multi-Analyte Estimation of BRCA1 and Its Repressors in FFPE Tumor Samples from Patients with Triple Negative Breast Cancer.

PURPOSE: Apart from germ-line BRCA1-mutated breast cancers, a significant proportion of women with sporadic triple negative breast cancer (TNBC) sub-type are known to harbour varying levels of BRCA1-dysfuction. There is currently no established diagnostic method to identify these patients. METHODS: The analysis was performed on 183 primary breast cancer tumor specimens from our longitudinal case-series archived as formalin-fixed-paraffin-embedded (FFPE) blocks comprising 71 TNBCs and 112 Hormone receptor positive HER2 negative (HR+HER2-) tumors. Transcript levels of BRCA1 and two of its repressors ID4 and microRNA182 were determined by TaqMan quantitative PCR. BRCA1 protein was detected immunohistochemically with the MS110 antibody. RESULTS: The representation of BRCA1 and its repressor ID4 as a ratio led to improved separation of TNBCs from HR+HER2- compared to either measure by itself. We then dichotomised the continuous distribution of each of the three measurements (Protein, MIRNA and transcript:repressor ratio) into categories of deficient (0) and adequate (1). A composite BRCA1 Deficiency Score (BDS) was computed by the addition of the score for all three measures. Samples deficient on 2 or more measures were deemed to be BRCA1 deficient; and 40% of all TNBCs met this criterion. CONCLUSION: We propose here a simple multi-level assay of BRCA1 deficiency using the BRCA1:ID4 ratio as a critical parameter that can be performed on FFPE samples in clinical laboratories by the estimation of only 3 bio-markers. The ease of testing will hopefully encourage adoption and clinical validation.

High expression of integrin ß6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.

Integrin αvß6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin ß6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvß6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin ß6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvß6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15.

Mixed exocrine-endocrine pancreatic carcinoma in childhood.

A 7-year-old boy with mixed exocrine-endocrine pancreatic cancer is presented. This may be the second reported case of such a tumor in childhood.

An unusual presentation of thyroid cancer.

Well-differentiated thyroid cancers can present with nodal metastasis that have undergone cystic degeneration. Rarely, mediastinal nodes may undergo cystic changes and pose a diagnostic dilemma, especially if the primary lesion is occult. We describe the case of a patient who presented with a large mediastinal cystic lesion which turned out to be metastasis from thyroid cancer.

Dedifferentiated chondrosarcoma: an aggressive variant of chondrosarcoma.

Dedifferentiated chondrosarcomas are a rare and aggressive subtype of chondrosarcoma with a bimorphic pattern on histopathology. Rib is a rare site of dedifferentiated chondrosarcoma. Diagnosis of this subtype preoperatively can be challenging. Treatment options for dedifferentiated chondrosarcoma are limited because they are chemoresistant, and therefore adequate surgery forms the main stay of treatment. We present our experience with a dedifferentiated chondrosarcoma of the rib, and discuss the management of this rare entity.

Biliary Ascariasis Mimicking Colonic Tumor Infiltration of the Biliary System.

Ascariasis is a common problem in developing countries with poor hygiene and sanitation. It is endemic in India and usually seen in the northern states. Biliary ascariasis is an uncommon cause of obstructive jaundice. We present a case of carcinoma of hepatic flexure of colon in which the patient developed biliary ascariasis and posed a diagnostic challenge as it mimicked tumor infiltration of the biliary system.