Introduction: In spite of rapid urbanization and modernization the family remains central in the socio-cultural structure of India. The individuals are enmeshed into this unit and tend to be interlinked financially, emotionally and socially. The head of this family unit tends to be a male more often than not. As is well known, despite recent attempts by the governments at the state and centre at providing health coverage for cancer through regional cancer centres, a majority have to raise the money for cancer care by themselves. We have examined the role of the family in treatment decision making and in the strategies employed to raise the money and cope with the financial stress imposed by a diagnosis of breast cancer. Method: 378 women with breast cancer were enrolled into a longitudinal study at first diagnosis between the years 2008-2012, at two tertiary care hospitals in Bangalore, India. The median follow up as of May 31st 2017 is 78 months with only 2% loss to follow-up over the past 8 years. Follow-up was maintained by frequent meetings between a counselling psychologist (AA) and the patient and/or a family member. The frequency of meetings was monthly during the initial treatment and then quarterly over the next 5 years. Information on demographics was collected during the treatment phase and information on the psychosocial aspects was collected in non-structured interactions subsequently. This information included details of support structure, decision making, and financial arrangements. Results: This is a predominantly urban cohort with 80% being urban. The median age of patients at first diagnosis was 55 years. Almost all of our patients (99%) had the support of one or more family members. We analysed the pattern of decision making for treatment and in half of all cases either the husband or the son were the decision makers. In an additional 15% daughters and other relatives were the primary decision makers. Approximately a third of women made the decision concerning treatment themselves, and these women tended to be college educated (51% vs 16%) and employed (53% vs 12%). 30% of the patients met the costs incurred through medical insurance plans purchased by the family. Another quarter of patients were able to meet the costs from their savings. 45% had difficulty in finding the money for treatment and 15% took personal loans while 30% had to sell land/gold ornaments or take loans against assets of these sorts. Only (3%) discontinued the treatment due to financial difficulties. As in the case of decision making those who had the financial resources tended to be more educated (41% vs 11%), and were employed (31% vs 21%). Conclusion: The data from a predominantly urban cohort of breast cancer enrolled between 2008-2012, supports the general belief that in India the family remains the fulcrum of an individual during crises, and not surprisingly education and employment lead to both psychological and economic emancipation of women. Citation Format: Alexander A, Kaluve R, Prabhu JS, Korlimarla A, BS S, Manjunath S, Patil S, KS G, Sridhar TS. Treatment decision making, and strategies for coping with financial stress in Indian women diagnosed with breast cancer and their families [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-12.
e22219 Background: Triple-negative (ER-negative, PR-negative, HER2/neu negative) breast cancer has distinct clinical and pathologic features, and is a clinical problem because of its typically high grade, relatively poor prognosis, aggressive behavior and lack of targeted therapies leaving chemotherapy as the mainstay of treatment. This study envisaged to analyse the influence of triple negativity status on survival and disease free survival in prospective cohort of breast cancer patients. Methods: Breast tumors of 215 women aged 30–75, diagnosed from 2004 were tested for ER, PR and HER2 positivity by immunohistochemistry and correlated with clinical outcomes such as recurrence, disease free survival and overall survival using Kaplan Meiers Survival analysis and Coxs regression analysis. The study cohort was followed up for 60 months or until death whichever was earlier. Results: Triple negativity significantly influenced disease free survival (46 ± 3, 41, 52) vs. non triple negative cohort (mean ± SE; 95%CI, 37 ± 2; 32, 40) and log rank = 2.1, p = 0.04. However triple negativity did not influence overall survival in months (56 ± 0; 55, 56) vs. non triple negative cohort (43 ± 1; 42, 45), (log rank = 1.78, p = 0.16). However, the mean disease free survival was (45 ± 7; 32, 58) months for patients >40 years age vs (37 ± 4; 33, 39) for patients < 40 years of age (log rank = 2.87, p =0.02). Stage of disease, node status, grade and menopausal status did not influence disease free survival significantly. However, Cox regression analysis did not predict significant effects of triple negativity on overall survival or disease free survival when controlled for confounding factors such as age, node status, stage etc Conclusions: Our observations suggest that triple negativity can significantly affect progression of breast cancer in Indian breast cancer patients and longer follow up is necessary (10 years) to determine its effects on survival. No significant financial relationships to disclose.
Introduction Although endocrine therapy has improved the survival of patients with hormone receptor (HR) positive breast cancer considerably, patients with weaker HR expression tend to have poorer outcomes. There exists significant intra tumoral heterogeneity of ER expression and a recent study suggested that patients with high intra tumoral heterogeneity of ER had an increased long term risk of recurrence (Lindstrom et al JNCI 2018). Multiple reports have supported a role for alterations in microRNA levels having a role in promoting tumor invasion and metastasis. In this study we have explored the epigenetic regulation of ER by microRNA hsa-miR-18a-5p and its role as a prognostic marker in ER positive tumors. Methods 123 surgically excised specimens of ER positive primary breast cancers were analyzed. Samples were segregated into high and low ER positive groups using 50% positivity as the cut-off. Relative abundance of hsa-miR-18a-5p in these samples was assessed using a TaqMan qRT-PCR. hsa-miR-18a-5p was over-expressed in MCF7 cells using a synthetic mimic and downstream changes in gene and protein expression were assessed using q-RT PCR, immunofluorescence and western blot. Migratory and proliferative ability was assessed using wound healing and MTT assay respectively. Microarray based global gene expression analysis of hsa-miR-18a-5p over-expressing cells was performed. Disease free survival analysis was done using Kaplan-Meier survival analysis. Result We estimated the relative abundance of hsa-miR-18a-5p in 123 ER positive primary breast cancers and found the distribution of this miRNA to be highest in the lower ERgroup (p<0.05). hsa-miR-18a-5p also correlated negatively with ESR1 and PGR (p<0.05).To further probe the role of miR-18a-5p in invasion and metastasis, we over-expressed this microRNA using a synthetic mimic in a luminal cell line MCF7. Microarray analysis revealed an increase in the expression of ECM associated genes, and the Cadherin signalling pathway. We observed a decrease in the expression of luminal genes (PGR, TFF1, GREB1; p<0.05), loss of Tff1 and increase in the levels of basal cytokeratin 14 at the protein level in addition to an increase in proliferative rate of upto 35% (p<0.05). Further, we observed a 15 % (p<0.05) increase in the invasive ability by wound healing assay with a significant loss in the levels of E-cadherin protein. In order to study the prognostic importance of hsa-miR-18a-5p, we performed Kaplan-Meier survival analysis and found that stratification of the ER+ve tumor samples by hsa-miR-18a-5p levels produced significant separation of the groups based on disease-free survival (log rank p <0.05). The prognostic value was also validated with multivariate Cox-proportional hazard analysis (Hazard Ratio (HR)of 3.18 (1.07-9.42); p=0.03). Conclusion The results from the over-expression of miR-18a-5p in MCF7 cells support the existence of an epigenetic pathway of repression of the luminal phenotype and increased acquisition of traits associated with basal-like and mesenchymal characteristics. It is possible that the over-expression of miR-18a-5p plays a role in patients with poorer outcomes. Citation Format: Nair MG, Prabhu JS, Korlimarla A, Hari P, Rajarajan S, Kaul R, Alexander A, Raghavan RS, Rakesh S, Correa M, Prasad M, Srinath B, Tirumalai SS. Epigenetic regulation of ER through miR-18a shows ECM activation and identifies poor prognostic subtype within ER+ve HER2-ve breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-05.
This abstract was withdrawn by the authors. Citation Format: Chakladar M, Nair MG, Prabhu JS, Cohen S, Srinivas ST, Lingadahalli SS. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-09-05.
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