Survival Advantage For Women Research Articles

Sex-difference of multifactorial intervention on cardiovascular and mortality risk in DKD: post-hoc analysis of a randomised clinical trial

ObjectiveWomen with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men.Research design and methodsNephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure < 130/80 mmHg, HbA1c < 7%, LDL < 100 mg/dL, and total cholesterol < 175 mg/dL) on cardiovascular and mortality risk in patients with type 2 diabetes. In this post-hoc analysis, we stratified patients by sex to compare the occurrence of MACEs (primary endpoint) and all-cause death (secondary endpoint) between women (104 MT and 105 UC) and men (103 MT and 83 UC).ResultsAchievement of therapeutic goals was similar by sex, with 44% and 47% of women and men in MT achieving at least 3 targets vs. 16% and 20% of women and men in UC. During a median follow-up of 13.0 years, we recorded 262 MACE (48.5% in women) and 189 deaths (53.6% in women). Compared to the UC group, the risk of MACE in the MT group was reduced by 52% in women and by 44% in men (P = 0.11). Conversely, the reduction in mortality risk by MT was greater in women (44% versus 12%, P = 0.019).ConclusionsMT similarly reduces the risk of MACEs in either sex. This therapeutic approach is associated with a survival advantage in women as compared with men and it may represent an important rationale to motivate physicians in overcoming their therapeutic inertia often encountered in female patients as well as to encourage patients of both sexes at improving their adherence to multidrug therapy.

Global Variations According to Sex in Patients Hospitalized for Heart Failure in the REPORT-HF Registry

BackgroundPrevious reports suggest that risk factors, management, and outcomes of acute heart failure (AHF) may differ by sex, but they rarely extended analysis to low- and middle-income countries. ObjectivesIn this study, the authors sought to analyze sex differences in treatment and outcomes in patients hospitalized for AHF in 44 countries. MethodsThe authors investigated differences between men and women in treatment and outcomes in 18,553 patients hospitalized for AHF in 44 countries in the REPORT-HF (Registry to Assess Medical Practice With Longitudinal Observation for the Treatment of Heart Failure) registry stratified by country income level, income disparity, and world region. The primary outcome was 1-year all-cause mortality. ResultsWomen (n = 7,181) were older than men (n = 11,372), were more likely to have heart failure with preserved left ventricular ejection fraction, had more comorbid conditions except for coronary artery disease, and had more severe signs and symptoms at admission. Coronary angiography, cardiac stress tests, and coronary revascularization were less frequently performed in women than in men. Women with AHF and reduced left ventricular ejection fraction were less likely to receive an implanted device, regardless of region or country income level. Women were more likely to receive treatments that could worsen HF than men (18% vs 13%; P < 0.0001). In countries with low-income disparity, women had better 1-year survival than men. This advantage was lost in countries with greater income disparity (Pinteraction < 0.001). ConclusionsWomen were less likely to have diagnostic testing or receive guideline-directed care than men. A survival advantage for women was observed only in countries with low income disparity, suggesting that equity of HF care between sexes remains an unmet goal worldwide.

Abstract 15793: Gender-Specific Pathophysiologic Differences in All-Cause Mortality Among Patients With Atrial Fibrillation

Introduction: Although the prevalence of atrial fibrillation (AF) is higher in men than in women, the onset of AF appears to diminish the survival advantage in women. The pathophysiologic factors underlying survival outcome in AF are not well understood. Methods: A cohort of 3480 Olmsted County, Minnesota residents (mean age 72.8±14 years, 51.8% female) with incident AF who underwent transthoracic echocardiography within 30 days of AF diagnosis [median (IQR) 1, 1-6 days] were retrospectively studied. We examined the association of clinical parameters and survival according to gender. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival in males and females. Results: Females were older and slimmer than males and more frequently had hypertension, prior stroke, and had higher CHA 2 DS 2 vasc score, pulse pressure and effective arterial elastance. Women also had smaller LV end diastolic dimension with higher LV ejection fraction, LA volume index, E/e prime ratio, and PASP (43.6±13.8 vs 39.1±13.3; &lt;.001). During a mean follow-up of 7.4±6.2 years (median 6.6 years), 2569 patients died. Women had a lower 5-year survival compared to men. The probability of 1- and 5-year survival rates for women vs men were 80.2% vs 84.1% at 1 year and 54.4% vs 63.7% at 5 years (log-rank P &lt;.001). In multivariable Cox regression analysis, after accounting for potential confounders, the independent predictors of mortality were age (HR 1.07 [95% CI 1.06-1.08]), PASP (per 5 unit increment) (HR 1.11 [95% CI 1.09-1.12]), effective arterial elastance (HR 1.06 [95% CI 1.01-1.12]), previous heart failure (HR 1.34 [95% CI 1.20-1.49]), diabetes (HR 1.33 [95% CI 1.20-1.48]), prior stroke (HR 1.26 [95% CI 1.13-1.41]), smoking (HR 1.13 [95% CI 1.06-1.20]), chronic lung disease (HR 1.32 [95% CI 1.20-1.45]), peripheral arterial disease (HR, 1.32 [95% CI 1.18-1.48]), and chronic kidney disease (HR, 1.52 [95% CI 1.38-1.69]). Conclusions: In a community-based cohort of patients with incident AF, markers of arterial stiffness and diastolic dysfunction were more prevalent in women compared to men and were strongly predictive of mortality. Our findings suggest that vascular stiffness may underlie the increased risk of mortality observed in women after a new diagnosis of AF.

Survival and long-term surgical outcomes after colorectal surgery: are there any gender-related differences?

Colorectal cancer (CRC) incidence and mortality seems to be lower in women than in men. The present study aims to evaluate the impact of gender on CRC diagnosis, treatment, and survival. This is a retrospective cohort study based on a single-center dataset of CRC patients from the University Hospital of Trieste (Italy). Data of 1796 consecutive CRC patients referred to our center from November 11th, 2004, to December 31st, 2017, were analyzed. Right-sided carcinomas are more frequent in women than in men; furthermore, women had a lower surgical complication rate. Men showed a higher 5- and 10-year mortality. This survival benefit for women was observed independently of the tumor localization. The 5-year hazard ratio (HR) for women vs men was 0.776 (p 0.003), and after 10-year 0.816 (p 0.017). Regarding the disease-free survival (DFS), 5 and 10-year HR was 0.759 (p 0.034) and 0.788 (p 0.07), respectively. On multivariable analysis, respecting tumor localization, the odds of female gender were higher than man with right colon disease. Male gender was more independently associated with age at the surgery time. Women survival advantage was higher than men, except for patients older than 80. Surgical outcome and survival after CRC surgical treatment seem to be gender related. For this reason, gender could play an important role in CRC diagnosis and therapy, allowing an earlier diagnosis in women.

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study.

Simple SummaryMelanoma is a malignant form of skin cancer. The overall survival of patients with advanced stages of disease were initially low. Fortunately, in recent years systemic treatment with immunotherapy has prolonged survival. We set out to answer the question whether men and women with advanced melanoma differ in prognostic factors, tumor-response to immunotherapy, and treatment-related adverse events. All patients in the Netherlands were registered between July 2013 and July 2018. We showed that although clinical and tumor characteristics differ, the safety profile of immunotherapy is comparable. Furthermore, overall, a 10% survival advantage for women was seen. Following immunotherapy there was no survival difference.Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013–July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3–4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients ≥60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference.

Four-year mortality in women and men after transfemoral transcatheter aortic valve implantation using the SAPIEN 3.

To investigate 4-year, post-transcatheter aortic valve implantation (TAVI) survival and predictors of survival by sex, in a real-world cohort that underwent transfemoral TAVI with SAPIEN 3 transcatheter heart valve. Previous TAVI investigations of first-generation devices demonstrated an early- to mid-term survival advantage in women compared with men. SOURCE 3 (SAPIEN 3 Aortic Bioprosthesis European Outcome) is a post-approval, multicentre, observational registry. Patients (N = 1,694, 49.2% women, age 81.7 ± 6.7 years) with severe aortic stenosis and high surgical risk (logistic EuroSCORE 17.8%) underwent TAVI between 2014 and 2015. Kaplan-Meier event estimates were used to determine mortality by sex. Predictors of overall mortality were identified using a cox multivariate proportional hazard model. At 4 years, women had lower all-cause mortality than men (36.0 vs 39.7%; p = .0911; HR: 0.87 [95% CI: 0.75-1.02]). No difference was observed for cardiac mortality between women 24.2% and men 24.7% (p = .76; HR: 0.97 [95% CI: 0.79-1.19]). When adjusted for baseline characteristics (age, height, weight, NYHA functional class, renal insufficiency, EuroScore, and tricuspid regurgitation), sex had no impact on mortality. In this large, real-world cohort, all-cause mortality trended lower in women than men at 4 years post TAVI; however, several baseline factors, but not sex, were predictors of mortality. No difference between sexes was observed for cardiovascular mortality.

Sex Differences in Care Need and Survival in Patients Admitted to Nursing Home Poststroke.

Women are more likely to be admitted to nursing home after stroke than men. Differences in patient characteristics and outcomes by sex after institutionalization are less understood. We examined sex differences in the characteristics and care needs of patients admitted to nursing home following stroke and their subsequent survival. We identified patients with stroke newly admitted to nursing home between April 2011 and March 2016 in Ontario, Canada, with follow-up until March 2018 using linked administrative data. We calculated prevalence ratios and 95% confidence intervals (CIs) for the primary outcomes of dependence for activities of daily living, cognitive impairment, frailty, health instability, and symptoms of depression or pain, comparing women to men. The secondary outcome was all-cause mortality. Among 4831 patients, 60.9% were women. Compared to men, women were older (median age [interquartile range, IQR]: 84 [78, 89] vs. 80 [71, 86]), more likely to be frail (prevalence ratio 1.14, 95% CI [1.08, 1.19]), have unstable health (1.45 [1.28, 1.66]), and experience symptoms of depression (1.25 [1.11, 1.40]) or pain (1.21 [1.13, 1.30]), and less likely to have aggressive behaviors (0.87 [0.80, 0.94]). Overall median survival was 2.9 years. In a propensity-score-matched cohort, women had lower mortality than men (hazard ratio 0.85, 95% CI [0.77, 0.94]), but in the age-stratified survival analysis, the survival advantage in women was limited to those aged 75 years and older. Despite lower subsequent mortality, women admitted to nursing home after stroke required more care than men. Pain and depression are two treatable symptoms that disproportionately affect women.

376P - Multidisciplinary treatments increase overall survival in patients with newly diagnosed stage IV breast cancer: An analysis of 2010–2014 SEER data

BackgroundPrimary treatments for stage IV breast cancer are chemotherapy and endocrine therapy. We sought to determine whether multidisciplinary therapy provides a survival advantage for women with metastatic breast cancer. MethodsWe conducted a population-based cohort study by using the 2010-2014 Surveillance, Epidemiology, and End Results (SEER) program data. By use of the log-rank test and multivariate cox regression models, overall survival in patients was compared between women who underwent different combination modes of surgery, radiotherapy and chemotherapy, controlling for potential confounding demographic, tumor- and treatment-related variables, and propensity scores. ResultsOf 17191 SEER patients with de novo stage IV breast cancer, 29.4% underwent surgery, 32.3% received radiotherapy and 49.6% received chemotherapy. The median follow-up was 28.0 months for all patients. The median survival time of combined surgery, chemotherapy and radiotherapy(SCRT), combined surgery and radiotherapy(SRT),combined surgery and chemotherapy(SC), combined chemotherapy and radiotherapy (CRT), surgery alone, chemotherapy alone, radiotherapy alone and no therapy were 51.0m (95%CI, NR), 46m (95%CI, 39.7-52.3), 37.0m (95%CI, 33.4-40.6), 22.0m (95%CI, 20.0-24.0), 29.0m (95%CI, 25.3-32.7), 26.0m (95%CI, 24.5-27.5), 22.0m (95%CI, 19.9-24.1) and 13.0m (95%CI, 11.8-14.2), respectively (p<0.001). After controlling for potential confounding variables and propensity scores, patients who underwent surgery, radiotherapy and chemotherapy were less likely to die compared with patients who did not undergo surgery, radiotherapy and chemotherapy,respectively (HR=0.32, 95% CI, 0.30-0.34, p<0.001, HR=0.40, 95%CI, 0.38-0.43, p<0.001 and HR=0.51, 95%CI, 0.48-0.54, p<0.001). There was no statistically significant difference among patients with different breast cancer subtype. ConclusionsAnalysis of 2010-2014 SEER data indicated that multidisciplinary approach is especially important in the management of newly diagnosed metastatic breast cancer to consider all potential treatment options for optimal outcomes. Legal entity responsible for the studyJian Zhang. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Two decades of the Eurotransplant Senior Program: the gender gap in mortality impacts patient survival after kidney transplantation.

BackgroundLong-term outcomes of the Eurotransplant Senior Program (ESP) are urgently needed to improve selection criteria and allocation policies in the elderly. MethodsWe analysed patient and allograft outcomes of 244 ESP-kidney transplant recipients (KTRs) between 1999 and 2019 and assessed quality of living compared with 82 ESP-waitlisted dialysis patients using standardized short form-8. ResultsWe observed 1-, 5- and 10-year patient survival of 91.7, 66.3 and 38.0%, respectively. Mortality risk factors included male gender (P = 0.006) and T-cell-mediated rejection (P < 0.001). Median patient survival of male ESP-KTRs was 80 versus 131 months for female ESP-KTRs (P = 0.006). 1-, 5- and 10-year death-censored allograft survival was 93.3, 82.6 and 70.4%. Risk factors included high body mass index (P < 0.001) and T-cell-mediated rejection (P < 0.001). After re-initiation of dialysis median patient survival was 58 months. Change of estimated glomerular filtration rate showed a mean decline of 2.3 and 6.8 mL/min at 5 and 10 years. Median physical and mental component scores of ESP-KTRs were 40.2 and 48.3, significantly higher compared with dialysis patients (P < 0.05). Of ESP-KTRs, 97.5% who underwent transplantation would again do so. ConclusionsLong-term outcomes of ESP-KTRs ultimately support the effectiveness of an age-matched allocation system. Our data suggest that the survival advantage of women is maintained after kidney transplantation and calls for gender-specific care.

Transcatheter Aortic Valve Replacement: What Really Matters for Women?

The prevalence of senile calcific aortic stenosis, a degenerative disease, mirrors the portion of the population that survives other processes to reach an advanced age. Thus, because of longer life expectancy, increasing numbers of women are candidates for aortic valve replacement (AVR). In current cardiovascular medicine, transcatheter AVR (TAVR) has proved to be suitable in the elderly and in those otherwise at high risk for surgical AVR (SAVR).Early TAVR trials appeared to harbor a recruitment bias against women—related, in part, to the use of large-profile devices, which precluded insertion in smaller femoral arteries. Even so, sex-specific examination of TAVR in early cohorts suggested distinct profiles of outcome for men and women, including an apparent survival advantage for women.In the Partner high-risk trial, sex-specific all-cause mortality rates at 2 years were reported.1 The investigators concluded that early and late mortality rates in women were better with TAVR than with SAVR; in contrast, there was no late survival benefit with TAVR in men, although their general clinical outcomes from both methods were similar. Thus, in the high-risk cohort, late mortality rates with TAVR were lower in women than in men, especially in women who underwent transfemoral TAVR.In a patient-level meta-analysis that included 47,188 subjects, women who underwent TAVR had more strokes, major bleeding, vascular complications, and need for transfusion within 30 days than did men, but lower mortality rates at one year.2 Likely factors contributing to complications were older age, lower body surface area, and vessels of smaller diameter. Increased occurrences of bleeding and vascular complications in women did not negatively affect their long-term survival benefit. Women had a lower risk of permanent pacemaker placement after TAVR; however, their increased 30-day risk of stroke and transient ischemic attack remained significantly higher after one year.The investigators2 concluded that women had better one-year and long-term survival prospects (mean follow-up duration, 3.28 ± 1.4 yr) than did men, despite more risk of early (30-d) postoperative bleeding and vascular complications and a greater long-term risk of stroke. The long-term survival advantage in women was consistently observed in multiple sensitivity and subgroup analyses of the cohorts, vascular access methods, geographic variations, and valve types.Smaller annular size in the women probably reduced the incidence of prosthesis undersizing. In comparison, the men tended to receive undersized valves, which resulted in more paravalvular leaks. In addition, the men had markedly worse baseline vascular disease and comorbidities than did the women, including hypertension, diabetes mellitus, coronary artery disease, prior revascularization, lower left ventricular ejection fraction, and higher risk scores. Of note, women's hearts may exhibit more favorable remodeling when hemodynamically stressed by aortic stenosis, mainly through less fibrosis and collagen deposition, thus enabling the reversal of cardiac remodeling after TAVR.One-year outcomes were recently reported in the Women's International Transcatheter Aortic Valve Implantation Registry.3 The investigators noted that baseline characteristics differ in men and women who undergo TAVR, and that these can affect short- and long-term events. Women have smaller peripheral vessels and aortic valve annuli, lower origins of the coronary arteries, more prevalent osteoporosis and frailty, greater risk of bleeding, and more prevalent concomitant valve disease and heart failure.Composite TAVR efficacy in women at one year was reported.3 The rate of all-cause death, and of all stroke, myocardial infarction, and hospitalizations for valvular symptoms or worsening congestive heart failure or valve-related dysfunction, was 16.5%. The rate for composite all-cause death or stroke was 13.9%; for death alone, 12.5%; and for stroke, 2.2%. EuroScore I, baseline atrial fibrillation, and prior percutaneous coronary intervention (PCI) were independent predictors of one-year death or stroke. Independent predictors of the Valve Academic Research Consortium-2 efficacy endpoint were EuroScore I and prior PCI or coronary artery bypass grafting.3Other investigators studied sex-related outcome differences with the use of lower-profile devices, specifically the Edwards Sapien 3 valve (Edwards Lifesciences) in intermediate and high-risk cohorts.4 At one year, the rates of death, disabling stroke, and repeat hospitalization were 22.4% in women and 20.9% in men. Even so, the one-year all-cause mortality rate slightly favored the women (9.4% vs 10.4%).Like the outcomes in earlier patient cohorts, these recent trial results continue to suggest a slight survival advantage for women after TAVR, especially when devices compatible with their physical characteristics are implanted.

Women live longer than men even during severe famines and epidemics

Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors.

Influence of marital status on risk of mortality for 23,493 cases of triple negative breast cancer for four mutually exclusive race/ethnicities.

1098 Background: Marital status has been associated with better breast cancer survival. However, breast cancer is a heterogeneous disease and it has not been determined whether marital status is a survival advantage for women with triple negative breast cancer (TNBC) and if this advantage holds for all race/ethnicities. The purpose of this study was to determine if being unmarried resulted in an increased risk of mortality for TNBC for four mutually exclusive race/ethnicities. Methods: We identified 23,493 cases of TNBC from the California Cancer Registry 2000-2014. Marital status at time of diagnosis was defined as: 1) married, 2) single, never married; 3) separated; 4) divorced; 5) widowed. Race/ethnicity was defined as white (n = 13,241), black (n = 2,775), Hispanic (n = 5,059), and Asian/Pacific Islander (API) (n = 2,418). Kaplan-Meier Survival Analysis and Cox Regression were used to assess the risk of mortality associated with marital status using married as the reference category. Marital status was considered a risk for mortality and hazard ratios (HR) and 95% confidence intervals reported if the Wald χ2 was statistically significant (p &lt; 0.05). Models were adjusted for AJCC stage, age, grade, socioeconomic status, and treatment. Separate analyses were conducted for each race/ethnicity. Results: For allraces, single women had statistically significantly worse unadjusted survival (p &lt; 0.05) than married women. However adjusted analyses showed that single (HR = 1.13; 1.01-1.27) and widowed (HR = 1.43; 1.27-1.61) white women had increased mortality when compared with married women. Single (HR = 1.50; 1.14-1.96) and divorced (HR = 1.75; 1.23-2.48) API women had an increased risk of mortality compared with married women. For black and Hispanic women, marital status was not associated with risk of mortality. Conclusions: Being married at the time of diagnosis of TNBC is a survival advantage only for white and API women but not for black and Hispanic women.

Abstract P1-10-01: Utilization and outcomes of post-mastectomy radiotherapy in women with 1-3 positive axillary nodes following neoadjuvant chemotherapy: A multiply-imputed, propensity-adjusted National cancer database analysis

Abstract Background: Use of post-mastectomy radiotherapy (PMRT) following neoadjuvant chemotherapy (NAC) varies widely. The combined analysis of NSABP B1724 studies suggests a higher risk of locoregional recurrence for women with persistently positive lymph nodes following NAC. The impact of PMRT on survival in the subset of patients with 1 to 3 positive nodes after NAC is not clear and the goal of the current study is to evaluate practice patterns and the impact of PMRT on survival in this subset of patients. Methods: The National Cancer Database was queried for women who underwent NAC followed by mastectomy and had 1-3 persistent axillary lymph nodes with or without adjuvant PMRT. A propensity score was generated to account for indication bias under two circumstances: one with the original dataset and one following a multiple imputation to complete the dataset to allow for a more accurate propensity score generation. Factors impacting utilization of PMRT were calculated with backwards-selection binary regression. Kaplan-Meier with log-rank test and Cox-regression analyses were used for survival. Results: Within the queried cohort of 14,895 women from 2006-2012, 70% of women received PMRT following NAC with 1-3 positive axillary lymph nodes. One lymph node was positive in 56%, 2 in 25.9%, and 3 in 18.1%. PMRT was utilized in 67.3% of women with 1 node positive, 71.5% with 2 nodes positive, and 76.2% with 3 nodes positive. Factors associated with the usage of PMRT were: residence on the east coast in a highly populated region with proximity to the treatment center, later year of diagnosis (71% of women in 2012), younger age, non-African American race, non-Hispanic descent, private insurance, higher clinical stage, triple negative/high grade histology, pathologic T4, greater number of axillary node positive, positive margins or LVSI, greater number of nodes examined, and use of adjuvant hormonal therapy (all p&amp;lt;.05). Median follow up was 40.1 months (range: 2.6-106.9 months). Prior to multiple imputation, a propensity score was generated which accounted for 28.7% of cases. PMRT did not have an impact on survival within the limited analysis. In a pooled propensity-adjusted Cox analysis following multiple imputation to complete the dataset, PMRT was found to have an OS HR of 0.878 (95%CI 0.806-0.957, p=.003). Five year overall survival rates with and without PMRT were 77.6% and 75.4% (p&amp;lt;.001). For 1-3 positive nodes respectively, 5-year overall survival rates with and without PMRT were: 79.7% vs. 79.1% (p=.041), 77.3% vs. 70.8% (p&amp;lt;.001), and 71.8% vs. 68.0% (p=.004). Conclusions: In a population-based analysis of women who underwent neoadjuvant chemotherapy prior to mastectomy, post-mastectomy radiotherapy appears to confer a survival advantage in women with 1-3 residual axillary lymph nodes. There continues to be a wide variation in practice nation-wide with a significant number of women with persistently positive 1-3 axillary lymph nodes not receiving PMRT. Citation Format: Horne ZD, Gebhardt BJ, Balasubramani GK, Beriwal S. Utilization and outcomes of post-mastectomy radiotherapy in women with 1-3 positive axillary nodes following neoadjuvant chemotherapy: A multiply-imputed, propensity-adjusted National cancer database analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-01.

Survival and its predictors from age 75 to 85 in men and women belonging to cohorts with marked survival differences to age 75: a comparative study in three Nordic populations

While predictors of survival in older people have been examined in depth in a large number of studies, a literature search revealed no cross-national comparative prospective cohort studies on this issue. This study investigated survival and its predictors from age 75 to 85 among three local Nordic populations using survival data on national cohorts as background information. The data were derived from national registers and from samples of 75-year old living in Denmark, Sweden, and Finland. The subjects were invited to take part in interviews and examinations focusing on different domains of health, functional capacity, and physical and social activities. The proportion of survivors to age 75 was markedly smaller among the Finnish men and women than Danish or Swedish subjects. In the local population no marked differences in survival from age 75 to 85 were observed between the groups of men, while women survived longer than men and longer in Göteborg than in Glostrup or Jyväskylä. Univariate models revealed 12 predictors of survival. In the multivariate models, the significant predictors among men related to physical fitness, whereas among women they pertained to social activities and morbidity. Despite great differences in the proportions of survivors to age 75, and excepting the survival advantage of women, only minor differences were present in the subjects' further survival to age 85. In the univariate analyses, many of the factors predictive of survival from age 75 to 85 were the same in the examined populations, whereas in the multivariate analyses differences between the sexes emerged.

Survival advantage of women in localized melanoma mainly relies on clinical-pathological differences by sex. A retrospective study of 1,607 patients in Valencia, Spain.

Among melanoma patients, women have a better prognosis than men but the differences might be due to a different presentation of melanoma. The aim of this study was to identify differences in clinical presentation and survival in cutaneous melanoma between men and women in a Spanish population stratified by age. In total, 1,607 consecutive patients with localized cutaneous melanoma and complete clinical and pathological information were evaluated. Average follow-up was 5 years. Patients were stratified by age into three groups: ≤ 45 years, 46-60 years, and >60 years. Disease-free survival, overall-survival and disease-specific survival were generated using the Kaplan-Meier method. Multivariate survival analyses were evaluated using Cox modelling. Melanoma presented more frequently in the trunk in male patients and in the lower extremities and acral location in female patients. Men presented thicker tumors than women. However, for histological type, mitotic rate and ulceration there were no significant differences between the sexes. In the univariate survival analyses, women showed better disease-free, overall and disease-specific survival in the younger age group, compared with males of the same group. After adjusting for anatomical site, Breslow thickness, mitotic rate and presence of ulceration, there were no differences between males and females in any of the three age groups. The superior survival for women over men did not persist after adjusting for multiple prognostic variables such as anatomical site, Breslow thickness, mitotic rate and ulceration.

Zoledronic acid induces an immune response through increased central memory and effector memory gamma/delta T cells in early and metastatic breast cancer patients

Introduction: Zoledronic acid (ZA) in combination with endocrine therapy (ET) and ovarian ablation yielded a disease-free survival and overall survival advantage in women with estrogen receptor+ early stage breast cancer (EBC). Evidence from preclinical studies suggests that ZA increases gamma/delta T cells (GDT). Materials and Methods: We examined immune responses following ZA in 24 BC patients by collecting peripheral blood mononuclear cells at day 0, 1, 7, and 28. GDT population and cytokine responses were assayed using flow cytometry and multi-analyte profiling beads (Luminex), respectively, and relative changes from baseline were analyzed using the Wilcoxon signed-rank test. Results: In total, 18 (75%) patients had metastatic breast cancer (MBC), 6 (25%) had EBC, 18 (75%) received ET, 4 (17%) chemotherapy (C), and 2 (8%) no concurrent therapy. Following ZA, an increase in both effector (CD3+/Vdelta2+/CD45RA−/CD27−) ( P = 0.0005) and central memory GDT (CD3+/Vdelta2+/CD45RA−/CD27+) ( P = 0.006), as well as a decrease in naive GDT (CD3+/Vdelta2+/CD45RA+/CD27+) ( P = 0.003) were observed at day 7. Cytokines, including interleukin-1 (IL-1) receptor antagonist ( P P P P P Conclusion: In both EBC and MBC patients, ZA appears to induce a significant change in GDTs and cytokines associated with cell-mediated immunity offering a possible biologic mechanism for ZA's anticancer activity. Further studies are necessary to determine which BC patients might achieve clinically meaningful anticancer benefits from ZA.

Immunohistochemical Expression of Hormone Receptors in Melanoma of Pregnant Women, Nonpregnant Women, and Men

The survival advantage of women over men with cutaneous melanoma and the reports of accelerated progression of melanoma during pregnancy have led to studies of the effect of hormones and hormone receptors on the development and progression of melanoma. However, the results are inconclusive. We therefore evaluated the expression of estrogen receptor α, estrogen receptor β, and androgen receptor in melanomas of stage- and age-matched pregnant women, nonpregnant women, and men by immunohistochemical analysis of formalin-fixed, paraffin-embedded archival tissues. In addition, we also assessed the mitotic rate using the antiphosphohistone H3 antibody by immunohistochemistry. Our data showed a trend of more frequent expression of estrogen receptor β in the melanomas of pregnant patients than in the melanomas of male patients, without a significant difference observed between pregnant and nonpregnant women. However, no association between the expression of estrogen receptor β and survival was observed. The small cohort may have limited the statistical power of the study, and large-scale studies are needed to elucidate the potential role of estrogen receptor β as a prognostic marker of melanoma.

Age-specific effect of gender on upper tract urothelial carcinoma outcomes

The research is to evaluate the age-specific differential effects of gender on outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Between August 1998 and October 2010, we retrospectively reviewed the data from 285 (67.7%) men and 136 (32.3%) women treated with RNU for UTUC at our two institutions. Kaplan-Meier survival estimates the age-specific effect of gender on cancer-specific survival (CSS). Cox proportional hazards regression analyses were used to address the effect of gender on CSS. No significant sex-related differences were found in age and diagnosis, clinicopathologic features, and treatment (all P values >0.05). Women had a 18.7% increased risk of death from UTUC than men (hazard ratio [HR] 1.187; 95% confidence interval [95% CI] 1.017-1.893; P = 0.021). The survival disadvantage was only present in patients aged 59 years and older (P < 0.001). Conversely, the survival advantage for women was found in women aged 42 to 58 years (P = 0.011) and in the age group <42 years (P = 0.019). On multivariable Cox regression analyses that adjusted for the effects of clinicopathologic features, the female gender was associated with decreased CSS (P = 0.036). In conclusion, the impact of gender on UTUC outcomes after RNU is age-specific. Females who aged 59 years and older experienced worse outcomes than their male counterparts, while women in the age group <42 years and 42-58 years have better outcomes than men. Further research is needed to elucidate the molecular mechanisms underlying the age-specific differential effect of gender on UTUC outcomes.

The effect of gender and age on kidney cancer survival: Younger age is an independent prognostic factor in women with renal cell carcinoma

ObjectiveGender-specific differences in incidence of renal cell carcinoma (RCC) and its outcome have previously been reported. We used age as a surrogate to test whether this might be hormone-related in a large international RCC cohort. Methods and MaterialsThis study included patients treated by nephrectomy at 10 international academic centers. Clinicopathologic features were assessed using chi-square and the Student t-tests. Kaplan-Meier survival estimates and Cox proportional hazards models addressed the effect of gender and age on disease-specific survival. ResultsOf the 5,654 patients, 3,777 (67%) were men and 1,877 (33%) were women. Generally, women presented at lower T stages (P<0.001), had fewer metastases (P<0.001), and had lower-grade tumors (P<0.001). Women more frequently had clear-cell (87% vs. 82%) and less frequently had papillary RCC (7% vs. 12%) than men (P<0.001). Women had a 19% reduced risk of death from RCC than men (hazard ratio 0.81, 95% confidence interval 0.73–0.90, P<0.001). The survival advantage for women was present to the greatest degree in the age group<42 years (P = 0.0136) and in women aged 42 to 58 years (P<0.001), but was not apparent in patients aged 59 years and older (P = 0.248). Age was an independent predictor of disease-specific survival in women (hazard ratio 1.011, 95% confidence interval 1.004–1.019, P = 0.004), but not in men. ConclusionsAs a group, women present with less advanced tumors, leading to a 19% reduced risk of RCC-specific death compared with men. This survival difference is present only in patients aged<59 years. Because this gender-based survival difference is not related to pathologic features, the role of hormonal effects on the development and progression of RCC needs to be investigated.

Stage IV breast cancer in the community hospital setting: Primary tumor extirpation effect on overall survival.

90 Background: Publications from academic centers and national cancer databases suggest a survival advantage for women who undergo primary tumor extirpation in the setting of known distant disease. We asked if similar findings exist in a community hospital setting. Methods: 15,887 patients entered in a longitudinally maintained breast cancer database (encompassing a system network of 13 community hospitals) during 1985-2009 were analyzed for those diagnosed with stage IV disease upon initial presentation. The cohort was divided into those who underwent primary tumor resection, and those who did not. The two subgroups were compared for patient demographics, tumor characteristics, sites of distant metastases, systemic treatment, and overall survival (OS). Results: 643 (4.05%) presented with an intact primary breast malignancy and synchronous distant metastasis. Median age at diagnosis: 66 years (range 22-96). Median OS: 15 months (range 0-249). 264 (41.1%) patients underwent primary tumor resection as part of first course treatment. On Kaplan-Meier univariate analysis, patients who underwent surgical extirpation of the primary tumor demonstrated improved median OS compared to those who did not (26 vs 10 months; p&lt;0.0001, HR 0.52). Age at diagnosis &lt;50 (p=0.0003, HR 0.65) and oligometastasis to bone (p=0.0002, HR 0.72) were statistically significant predictors of improved OS. Race, primary tumor size, and ER status alone did not influence OS. Those ER+ patients who underwent primary tumor excision in addition to chemotherapy and/or hormonal therapy fared significantly better than those treated with systemic therapy alone (32 vs 17 months; p&lt;0.0001). Chemotherapy 16+ weeks prior to surgery improved OS compared to those who had surgery &lt;16 weeks after starting chemotherapy. While there was no difference with regards to type of resection (partial vs simple vs modified radical mastectomy), clear margins were imperative to optimize OS. Conclusions: Patients with stage IV breast cancer treated at community hospitals also demonstrate improved OS after primary tumor extirpation, especially in the context of a multimodality approach combining chemotherapy and/or hormonal therapy preceding surgery.