Dietary Modification and Breast Cancer Mortality: Long-Term Follow-Up of the Women's Health Initiative Randomized Trial.
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ABSTRACT: Purpose
Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women's Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence.Methods
In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings.Results
During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02).Conclusion
Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.
SUBMITTER: Chlebowski RT
PROVIDER: S-EPMC7193750 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe Women's Health Initiative (WHI) low-fat (20% kcal) dietary modification (DM) trial (1993-2005) demonstrated a nonsignificant reduction in breast cancer, a nominally significant reduction in ovarian cancer, and no effect on other cancers (mean 8.3 years intervention). Consent to nonintervention follow-up was 83% (n = 37,858). This analysis was designed to assess postintervention cancer risk in women randomized to the low-fat diet (40%) versus usual diet comparison (60%).MethodsRandomized, controlled low-fat diet intervention for prevention of breast and colorectal cancers conducted in 48,835 postmenopausal U.S. women, ages 50 to 79 years at 40 U.S. sites. Outcomes included total invasive cancer, breast cancer, and colorectal cancer, and cancer-specific and overall mortality.ResultsThere were no intervention effects on invasive breast or colorectal cancer, other cancers, or cancer-specific or overall mortality during the postintervention period or the combined intervention and follow-up periods. For invasive breast cancer, the hazard ratios (HR) and 95% confidence interval (CI) were 0.92 (0.84-1.01) during intervention, 1.08 (0.94-1.24) during the postintervention period, and 0.97 (0.89-1.05) during cumulative follow-up. A reduced risk for estrogen receptor positive/progesterone receptor-negative tumors was demonstrated during follow-up. In women with higher baseline fat intake (quartile), point estimates of breast cancer risk were HR, 0.76 (95% CI, 0.62-0.92) during intervention versus HR, 1.11 (95% CI, 0.84-1.4) during postintervention follow-up (Pdiff = 0.03).ConclusionsDietary fat intake increased postintervention in intervention women; no long-term reduction in cancer risk or mortality was shown in the WHI DM trial.ImpactDietary advisement to reduce fat for cancer prevention after menopause generally was not supported by the WHI DM trial.
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Project description:ObjectiveCXCR4 (X4)-tropic HIV-1 was found previously to herald CD4 + cell depletion and disease progression in individuals who were antiretroviral-naive or took combination antiretroviral therapy (cART) for less than 5 years. We updated this finding by investigating whether the deleterious effect of X4-tropic strains is mitigated by long-term cART.DesignWe examined morbidity and mortality in relation to HIV-1 tropism and cART in 529 participants followed up to 18 years in the Women's Interagency HIV Study; 91% were women of color.MethodsPlasma-derived HIV-1 tropism was determined genotypically.ResultsWe categorized participants according to the number of visits reported on cART after initiation. Group 1: three or less visits, 74% of these participants reporting no cART; group 2: at least four visits and less than 70% of visits on cART; group 3: at least 70% of visits on cART. AIDS mortality rates for participants in each group with X4 virus compared with those with R5 virus exclusively were, respectively: 62 vs. 40% ( P = 0.0088); 23% vs. 22% [nonsignificant (NS)]; 7% vs. 14% (NS). Kaplan-Meier curves showed accelerated progression to AIDS death or AIDS-defining illness in participants with three or less cART visits and X4 viruses ( P = 0.0028) but no difference in progression rates stratified by tropism in other groups. Logistic regression found that HIV-1 suppression for at least 10 semiannual visits (≥5 years total) mitigated X4 tropism's deleterious effect on mortality, controlling for maximal viral load, and CD4 + nadir.ConclusionLong-term cART markedly mitigated the deleterious effect of X4 viruses on AIDS morbidity and mortality. Mitigation was correlated with duration of viral suppression, supporting HIV-1 suppression as a crucial goal.
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Project description:Purpose Earlier Women's Health Initiative Dietary Modification trial findings suggested that a low-fat eating pattern may reduce breast cancers with greater mortality. Therefore, as a primary outcome-related analysis from a randomized prevention trial, we examined the long-term influence of this intervention on deaths as a result of and after breast cancer during 8.5 years (median) of dietary intervention and cumulatively for all breast cancers diagnosed during 16.1 years (median) of follow-up. Patients and Methods The trial randomly assigned 48,835 postmenopausal women with normal mammograms and without prior breast cancer from 1993 to 1998 at 40 US clinical centers to a dietary intervention with goals of a reduction of fat intake to 20% of energy and an increased intake of fruits, vegetables, and grains (40%; n = 19,541) or to a usual diet comparison (60%; n = 29,294). Results In the dietary group, fat intake and body weight decreased (all P < .001). During the 8.5-year dietary intervention, with 1,764 incident breast cancers, fewer deaths occurred as a result of breast cancer in the dietary group, which was not statistically significant (27 deaths [0.016% per year] v 61 deaths [0.024% per year]; hazard ratio [HR], 0.67; 95% CI, 0.43 to 1.06; P = .08). During the same period, deaths after breast cancer (n = 134) were significantly reduced (40 deaths [0.025% per year] v 94 deaths [0.038% per year]; HR, 0.65; 95% CI, 0.45 to 0.94; P = .02) by the dietary intervention. During the 16.1-year follow-up, with 3,030 incident breast cancers, deaths after breast cancer also were significantly reduced (234 deaths [0.085% per year] v 443 deaths [0.11% per year]; HR, 0.82; 95% CI, 0.70 to 0.96; P = .01) in the dietary group. Conclusion Compared with a usual diet comparison group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer.
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Project description:BackgroundThe past years have witnessed dramatic changes in the population admitted to the intensive care unit (ICU). Older and sicker patients are now commonly treated in this setting due to the newly available sophisticated life support. However, the short- and long-term benefit of this strategy is scarcely studied.MethodsThe Critically Ill patients' mortality by age: Long-Term follow-up (CIMbA-LT) was a multicentric, nationwide, retrospective, observational study addressing short- and long-term prognosis of patients admitted to Portuguese multipurpose ICUs, during 4 years, according to their age and disease severity. Patients were followed for two years after ICU admission. The standardized hospital mortality ratio (SMR) was calculated according to the Simplified Acute Physiology Score (SAPS) II and the follow-up risk, for patients discharged alive from the hospital, according to official demographic national data for age and gender. Survival curves were plotted according to age group.ResultsWe included 37.118 patients, including 15.8% over 80 years old. The mean SAPS II score was 42.8 ± 19.4. The ICU all-cause mortality was 16.1% and 76% of all patients survive until hospital discharge. The SAPS II score overestimated hospital mortality [SMR at hospital discharge 0.7; 95% confidence interval (CI) 0.63-0.76] but accurately predicted one-year all-cause mortality [1-year SMR 1.01; (95% CI 0.98-1.08)]. Survival curves showed a peak in mortality, during the first 30 days, followed by a much slower survival decline thereafter. Older patients had higher short- and long-term mortality and their hospital SMR was also slightly higher (0.76 vs. 0.69). Patients discharged alive from the hospital had a 1-year relative mortality risk of 6.3; [95% CI 5.8-6.7]. This increased risk was higher for younger patients [21.1; (95% CI 15.1-39.6) vs. 2.4; (95% CI 2.2-2.7) for older patients].ConclusionsCritically ill patients' mortality peaked in the first 30 days after ICU admission. Older critically ill patients had higher all-cause mortality, including a higher hospital SMR. A long-term increased relative mortality risk was noted in patients discharged alive from the hospital, but this was more noticeable in younger patients.
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Project description:BackgroundBy contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort.MethodsBetween 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50-79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611.FindingsAfter a median follow-up of 11·8 years (IQR 9·1-12·9), the use of oestrogen for a median of 5·9 years (2·5-7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62-0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61-1·02) and post-intervention phase effects (0·75, 0·51-1·09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13-0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39-0·97; p=0·04).InterpretationOur findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.FundingUS National Heart, Lung, and Blood Institute; Wyeth.
| S-EPMC3412626 | biostudies-literature
Project description:BackgroundThe Women's Health Initiative Dietary Modification (DM) Randomized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence, with breast cancer and colorectal cancer as primary outcomes. The trial protocol also listed ovarian cancer and endometrial cancer as outcomes that may be favorably affected by the intervention.MethodsA total of 48,835 postmenopausal women were randomly assigned during 1993-1998 to a DM intervention (n = 19,541) or comparison (usual diet; n = 29,294) group and followed up for an average of 8.1 years. The intervention goal was to reduce total fat intake to 20% of energy and to increase consumption of vegetables, fruits, and grains. Cancer outcomes were verified by pathology report review. We used weighted log-rank tests to compare incidence of invasive cancers of the ovary and endometrium, total invasive cancer, and invasive cancers at other sites between the groups. All statistical tests were two-sided.ResultsOvarian cancer risk was lower in the intervention than in the comparison group (P = .03). Although the overall ovarian cancer hazard ratio (HR) was not statistically significantly less than 1.0, the hazard ratio decreased with increasing intervention duration (P(trend) = .01). For the first 4 years, the risk for ovarian cancer was similar in the intervention and control groups (0.52 cases per 1000 person-years in the intervention group versus 0.45 per 1000 person-years in the comparison group; HR = 1.16, 95% confidence interval [CI] = 0.73 to 1.84); over the next 4.1 years, the risk was lower in the intervention group (0.38 cases per 1000 person-years in the intervention group versus 0.64 per 1000 person-years in the comparison group; HR = 0.60, 95% CI = 0.38 to 0.96). Risk of cancer of the endometrium did not differ between the groups (P = .18). The estimated risk of total invasive cancer was slightly lower in the intervention group than in the control group (HR = 0.95, 95% CI = 0.89 to 1.01; P = .10).ConclusionsA low-fat dietary pattern may reduce the incidence of ovarian cancer among postmenopausal women.
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Project description:BackgroundLymphopenia is associated with adverse prognosis in chronic disease states that are related to immune dysregulation. We aimed to determine the association between lymphopenia and mortality in patients presenting to coronary angiography and investigate whether elevated red blood cell distribution width (RDW), an established cardiovascular prognostic marker, further refines risk stratification.MethodsRetrospective analysis of patients undergoing coronary angiography for evaluation or treatment of coronary artery disease between 2003 and 2018. Mortality risk associated with relative (1000-1500/μL) or severe ( < 1000/μL) lymphopenia was analyzed using adjusted Cox proportional hazards regression models.ResultsOverall, 15,179 patients aged 65 ± 12 years underwent coronary angiography. During a median follow-up of 8 years, 4253 patients died. Compared to normal lymphocyte count, the adjusted hazard ratio (HR) for mortality was 1.31 (95% confidence interval [CI] 1.21-1.41) and 1.97 (95% CI 1.75-2.22) for relative and severe lymphopenia, respectively. The increase in mortality associated with severe lymphopenia was significant in patients presenting in the non-acute setting (HR 2.18, 95% CI 1.74-2.73), ST-segment elevation myocardial infarction (STEMI) (HR 1.59, 95% CI 1.15-2.21), or unstable angina/non-STEMI (HR 2.00, 95% CI 1.70-2.34); p-value for interaction 0.626. The association of lymphopenia with mortality remained significant after additional adjustment to RDW. High RDW ( > 14.5%) was associated with reduced survival, and it improved the predictive accuracy of lymphocytes count with an increase in Harrell's Concordance statistic from 0.634 (SE = 0.005) to 0.672 (SE = 0.005), p < 0.001.Conclusionslymphopenia is associated with increased risk of mortality during long-term follow-up in patients undergoing coronary angiography, regardless of the coronary presentation. High RDW may enhance the predictive ability of lymphopenia.
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