Aparna Keshaviah

Bio: Aparna Keshaviah is an academic researcher from Harvard University. The author has contributed to research in topics: Breast cancer & Letrozole. The author has an hindex of 31, co-authored 49 publications receiving 6286 citations. Previous affiliations of Aparna Keshaviah include Brigham and Women's Hospital.

A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer

Abstract: Background The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. Methods The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. Results A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. Conclusions In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.)

Five Years of Letrozole Compared With Tamoxifen As Initial Adjuvant Therapy for Postmenopausal Women With Endocrine-Responsive Early Breast Cancer: Update of Study BIG 1-98

Abstract: Purpose Previous analyses of the Breast International Group (BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results. Patients and Methods Four thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point. Results At a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women re...

Complicated grief and related bereavement issues for DSM‐5

Abstract: Bereavement is a severe stressor that typically incites painful and debilitating symptoms of acute grief that commonly progresses to restoration of a satisfactory, if changed, life. Normally, grief does not need clinical intervention. However, sometimes acute grief can gain a foothold and become a chronic debilitating condition called complicated grief. Moreover, the stress caused by bereavement, like other stressors, can increase the likelihood of onset or worsening of other physical or mental disorders. Hence, some bereaved people need to be diagnosed and treated. A clinician evaluating a bereaved person is at risk for both over-and under-diagnosis, either pathologizing a normal condition or neglecting to treat an impairing disorder. The authors of DSM IV focused primarily on the problem of over-diagnosis, and omitted complicated grief because of insufficient evidence. We revisit bereavement considerations in light of new research findings. This article focuses primarily on a discussion of possible inclusion of a new diagnosis and dimensional assessment of complicated grief. We also discuss modifications in the bereavement V code and refinement of bereavement exclusions in major depression and other disorders.

Molecular Markers in Ductal Carcinoma in Situ of the Breast

Abstract: Gene expression patterns in ductal carcinoma in situ (DCIS), and in invasive, and metastatic breast tumors were determined using serial analysis of gene expression (SAGE). We used mRNA in situ hybridization to examine gene expression at the cellular level and immunohistochemistry on tissue microarrays to determine association between gene expression patterns and histopathologic characteristics of the tumors. We found that that the most dramatic transcriptome change occurs at the normal to DCIS transition, while there is no clear universal "in situ" or "invasive" tumor molecular signature. From the 16,430 transcripts analyzed, we identified only 5 and 11 that were preferentially up-regulated in DCIS and invasive tumors, respectively. The majority of invasive cancer specific SAGE tags correspond to novel genes. The genes we identified may define biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease.

Impact of a Mixed Strength and Endurance Exercise Intervention on Insulin Levels in Breast Cancer Survivors

Abstract: Purpose Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors. Methods One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks. Results Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 μU/mL in the exercise group (P = .03), with no significant change in the control group (decrease of 0.27 μU/mL, P = .65). The change in insulin levels in the exercise group seemed ...

Diagnostic and statistical manual of mental disorders, fifth edition

Abstract: Binge eating disorder (BED) is characterized by recurrent episodes of binge eating and, subsequently, significant psychological distress (e.g., shame, guilt). Recently recognized by the American Psychiatric Association (APA) as a distinct eating disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), BED is considered a significant public health problem independently and for its impact on obesity and diabetes. The related problem, loss-of-control (LOC) eating, describes recurrent binge-like eating behavior in individuals who cannot meet full criteria for BED such as post-bariatric surgery patients and children. LOC eating has detrimental psychological and physical health effects, including significant distress and symptoms of depression, as well as excess weight gain in children and suboptimal weight loss and weight regain in post-bariatric patients. Table 1 lists the diagnostic criteria for BED (as defined in the current DSM-5 and earlier, in the DSM, Fourth Edition [DSM-IV]) and frequently-used definitions of LOC eating.

American College of Sports Medicine roundtable on exercise guidelines for cancer survivors.

Abstract: to physical functioning and quality of life are sufficient for the recommendation that cancer survivors follow the 2008 Physical Activity Guidelines for Americans, with specific exercise programming adaptations based on disease and treatment-related adverse effects. The advice to ‘‘avoid inactivity,’’ even in cancer patients with existing disease or undergoing difficult treatments, is likely helpful.