This title is part of UC Press's Voices Revived program, which commemorates University of California Press's mission to seek out and cultivate the brightest minds and give them voice, reach, and ...impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1994.
There is growing public health interest in understanding and promoting successful aging. While there has been some exciting empirical work on objective measures of physical health, relatively little ...published research combines physical, cognitive, and psychological assessments in large, randomly selected, community-based samples to assess self-rated successful aging.
In the Successful AGing Evaluation (SAGE) study, the authors used a structured multicohort design to assess successful aging in 1,006 community-dwelling adults in San Diego County, ages 50-99 years, with oversampling of people over 80. A modified version of random-digit dialing was used to recruit subjects. Evaluations included a 25-minute telephone interview followed by a comprehensive mail-in survey of physical, cognitive, and psychological domains, including positive psychological traits and self-rated successful aging, scaled from 1 (lowest) to 10 (highest).
The mean age of the respondents was 77.3 years. Their mean self-rating of successful aging was 8.2, and older age was associated with a higher rating, despite worsening physical and cognitive functioning. The best multiple regression model achieved, using all the potential correlates, accounted for 30% of the variance in the score for self-rated successful aging and included resilience, depression, physical functioning, and age (entering the regression model in that order).
Resilience and depression had significant associations with self-rated successful aging, with effects comparable in size to that for physical health. While no causality can be inferred from cross-sectional data, increasing resilience and reducing depression might have effects on successful aging as strong as that of reducing physical disability, suggesting an important role for psychiatry in promoting successful aging.
Sexual health and function is an important yet understudied aspect of overall health and well-being in older adults. There are limited data on the relative strength of associations between various ...aspects of sexual health with the physical, emotional, and cognitive function in older adults. Additionally, there is little information on how these associations differ by age and sex.
In this Successful Aging Evaluation (SAGE) study, 606 community-dwelling adults in San Diego County, aged 50-99 years and who had a partner, were included in the analysis. Evaluations included a phone-based cognitive screening followed by a comprehensive mail-in survey including rating scales of sexual health, depression, anxiety, and physical function.
The mean age of the sample was 75.2 years. Over 80% of respondents had engaged in sexual activity in the past year, over 70% engaged in sexual activity weekly or more than once a week, and over 60% were somewhat or very satisfied with their sex lives. No sex differences were evident on dimensions of sexual health except for a higher rate of rejection of sexual overtures by women. Depressive symptoms were negatively associated with all assessed aspects of sexual health, even after adjusting for age, physical functioning, anxiety, cognitive ability, or perceived stress in both men and women.
In this population-based study older men and women who had a partner reported frequent engagement in and satisfaction with sexual activity. Depressive symptoms were broadly associated with worse sexual health, more so than physical function, anxiety or stress, or age itself.
Background
The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely ...determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status.
Methods
The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18–90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) tumors.
Results
MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%;
p
= 0.64) or High-Risk tumors (14.5% vs. 11.5%;
p
= 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype.
Conclusion
Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.
As more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to ...benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET.
1091 patients with early-stage breast cancer scheduled to receive neoadjuvant therapy were prospectively enrolled into NBRST, and a sub-analysis of 67 patients treated with NET was performed. Patients received standard of care genomic testing using the 70-gene and 80-gene signatures and were treated with NET, per physician's discretion. The primary endpoint was pathologic partial response (pPR) and secondary endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Clinical benefit was defined as having a pPR or stable disease (SD) with NET.
Overall, 94.4% of patients with genomically (g) Luminal A-Type (50.0% pPR and 44.4% SD) and 95.0% with Luminal B-Type tumors (55.0% pPR and 40.0% SD) exhibited clinical benefit. At 5 years, patients with gLuminal B tumors had significantly worse DMFS (75.6%, 95% CI 50.8–89.1) than patients with gLuminal A (91.1%; 95% CI 74.8–97.1; p = 0.047), with a similar trend for OS, albeit not significant (81.0%, 95% CI 56.9–92.4 and 91.1%, 95% CI 74.8–97.1, respectively; p = 0.13).
Genomic assays offer a broader understanding of the underlying tumor biology, which adds precision to pathology as a preoperative risk classifier. Patients with 70-gene signature Low Risk, gLuminal A tumors treated with endocrine therapy alone have excellent 5-year outcomes. Most patients with genomically-defined Luminal A- and B-Type tumors respond well to NET, suggesting these patients may be safely treated with NET, while those with gLuminal B tumors will also require post-operative chemotherapy or CDK4/6 inhibitors to improve long-term outcomes. Overall, these findings demonstrate that genomic classification, defined by the combined 70- and 80-gene signatures, is associated with tumor response and prognostic of long-term outcomes.
•MammaPrint and BluePrint are prognostic for patients treated with NET.•BluePrint Luminal tumors respond well to NET and may safely delay surgery.•MammaPrint Low Risk tumors have excellent 5-year outcomes with NET.•MammaPrint High Risk, Luminal B tumors would benefit from adjuvant chemotherapy.•Genomic stratification adds precision to IHC and better corresponds with outcomes.
The 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive ER+, human epidermal growth factor ...receptor 2-negative HER2-) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.
Neoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC).
80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34%
38%;
= .52), and significantly higher pCR than ER+/Luminal A (2%;
< .001) and ER+/Luminal B (6%;
< .001) tumors. The 5-year DMFS (%, 95% CI) was significantly lower for patients with ER+/Basal tumors (66% 52.6 to 77.3), compared with those with ER+/Luminal A tumors (92.3% 85.2 to 96.1) and ER+/Luminal B tumors (73.5% 44.5 to 79.3). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR.
Significant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.
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