RESUMEN
Background: World over, less than a quarter of breast cancer diagnoses are in premenopausal women. However, in India premenopausal women constitute half of all women with breast cancer in most hospital case series. Most of these women present at advanced stages with aggressive subtypes of disease and hence the high mortality.The role and utility of detecting androgen receptor (AR) expression in the different sub-types of breast cancer, especially the ones without hormone receptor expression is yet to be firmly established. Evidence from previous studies is suggestive of its beneficial role in hormone receptor positive (HR+) breast cancer. The biological function of AR on the mammary epithelium is determined by the Estrogen receptor (ER) context, in that, it is found to be anti-proliferative in ER positive tumors while it is thought to promote growth in the absence of ER activity. An interesting approach to representing this interplay is as a ratio between AR/ER expressions. As expected, the ratio has been shown to be positively correlated with better outcomes in hormone receptor cancers, mostly in postmenopausal women. The effect of a high ratio in ER negative tumors seems more complicated. In this study, we have evaluated the AR/ER ratio specifically in patients younger than 50 years in whom the estrogenic influence is dominant due to their premenopausal status. Materials and Methods: Tumor samples from patients 50 years or younger were chosen from a larger cohort of 275 patients with median follow up of 72 months. Expression of ER and AR proteins were detected by immunohistochemistry (IHC), and the transcript levels of ESR1 and AR were determined by quantitative PCR. Relative normalized units of their gene expression were used to calculate the AR/ER ratio. A cut-off at the 3rd quartile was used to divide tumors into categories of high and low ratios. Clinical characteristics were compared between the low and high ratio groups along with IHC subtype distribution (HR+, HER2+ and Triple negative (TNBC)). Kaplan Meier curves was used for survival analysis and Cox proportional hazard analysis model was used to calculate the hazard ratio (HR). The results were validated in METABRIC dataset. Results: Eighty-eight (32%) patients were <50 years with a mean age of 43 years. AR/ER ratio ranged between 0.6 to 3.5 with a mean of 1.5. Sixty-six tumors were categorized as low and 22 were high based on the 3Q cut off (1.7). Clinical characters such as age, tumor size, grade, stage of disease was not different between the high and low ratio categories. Distribution of IHC subtypes among each group showed high ratio category had 64% TNBC tumors (p<0.0001). Tumors with high ratio had poor disease-free survival, (HR-2.6(95% CI-1-6.9) p-0.03). Trends in the METABRIC dataset was similar with 411(21%) patients <50 years. Ninety-seven patients with high ratio had significantly poor disease-free survival (HR-1.95 (95% CI-1.3-2.7) p-0.000). Conclusion: Interaction between AR and ER is known to influence the AR activity and our results reiterate prognostic ability of AR/ER ratio even in young patients of breast cancer. Our results suggest androgenic influences on clinical progression of breast cancer in this age group mediated through AR, has to be examined by its level in relation to the activity of ER, particularly in hormone receptor negative breast cancers. Even more importantly, examining these influences in the context of the menopausal status might help identify subgroups of patients most likely to benefit from interventions targeted at AR.
RESUMEN
OBJECTIVES: This study compares the effects of an integrated yoga program with brief supportive therapy on distressful symptoms in breast cancer outpatients undergoing adjuvant radiotherapy. MATERIALS AND METHODS: Eighty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to their radiotherapy treatment. Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days during the course of their adjuvant radiotherapy. Assessments included Rotterdam Symptom Check List and European Organization for Research in the Treatment of Cancer-Quality of Life (EORTC QoL C30) symptom scale. Assessments were done at baseline and after 6 weeks of radiotherapy treatment. RESULTS: A GLM repeated-measures ANOVA showed a significant decrease in psychological distress (P = 0.01), fatigue (P = 0.007), insomnia (P = 0.001), and appetite loss (P = 0.002) over time in the yoga group as compared to controls. There was significant improvement in the activity level (P = 0.02) in the yoga group as compared to controls. There was a significant positive correlation between physical and psychological distress and fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, and constipation. There was a significant negative correlation between the activity level and fatigue, nausea and vomiting, pain, dyspnea, insomnia, and appetite loss. CONCLUSION: The results suggest beneficial effects with yoga intervention in managing cancer-and treatment-related symptoms in breast cancer patients.
