Table 2.
Summary of WHI publications on shared outcomes between cardiovascular disease and cancer, focusing on breast cancer.
| Years of study, reference | Study population/design | Main outcome | Study measure | HR, 95% CI | Main conclusion |
|---|---|---|---|---|---|
| 1993-1998; Prentice et al. (35) | N= 48,835 WHI-CT (DM) Age=50-79y Follow-up=16y Design= RCT (as above) |
CHD and overall CVD incidence and mortality (secondary) | Cumulative mortality CHD death CVD death All-cause |
Multivariate HR 0.99 (0.89-1.10) 0.98 (0.91-1.05) 0.99 (0.95-1.03) |
Overall no difference in CHD, total CVD or total mortality in the intervention or post-intervention periods |
| 1993-1998; Park et al. (42) | N=101,916 WHI-OS and CT (all 4) Age=50-79y Follow-up=10.4y (with BC) vs. 15.7 (no BC) |
Incident CVD events, and total and cause-specific death rates | Event (localized BC, age 70-79y) CVD events CVD death Total death |
Multivariate HR 0.84 (0.7-1.00) 0.92 (0.67-1.26) 1.20 (1.04-1.39) |
CVD major contributor to mortality in women 70-79y with localized breast cancer |
| 1993-1998; Chlebowski et al. (46) | N=48,835 WHI-CT (DM) Age=50-79y Follow-up=16.1y Design=RCT |
Annualized rate of death as a result of and after BC | Cumulative outcome (intervention + post-intervention period) Invasive BC incidence Death as a result of BC Death after BC |
Multivariate HR 0.97 (0.9-1.04) 0.91 (0.72-1.15) 0.82 (0.7-0.96) |
Low fat diet led to significantly lower death after BC |
| 1993-1998; Simon et al. (12) | N=8,641 WHI-OS and CT (all 4) Age=50-79y Follow-up=11.3y |
Mortality from BC, CVD and other-cause | Cardiometabolic abnormalities None 1-2 3-4 None 1-2 3-4 None 1-2 3-4 |
Multivariate HR for mortality Breast cancer Ref 1.05 (0.86-1.29) 0.97 (0.65-1.46) CVD Ref 2.06 (1.58-2.69) 3.29 (2.25-4.82) Other-cause Ref 1.39 (1.2-1.61) 1.90 (1.49-2.44) Ptrend <0.001 (for last 2) |
Cardiometabolic risk factors are associated with CVD and other-cause mortality but not BC mortality in early-stage BC |
| 1993-1998; Chlebowski et al. (46) | N=48,835 WHI-CT (DM) Age=50-79y Follow-up=17.7y Design=RCT (same as above) |
Mortality from protocol specified cancers (breast, colorectal, endometrium, ovary) – individual and composite | Death from cancer Breast All protocol-specified Death after cancer Breast All protocol-specified |
Multivariate HR 0.87 (0.7-1.10) 0.94 (0.83-1.08) 0.85 (0.74-0.99) 0.95 (0.85-1.05) |
Low fat diet reduced deaths after BC, but not from or after any other cancer or cancer composite |
| 1993-1998; Chlebowski et al. (51) | N=48,835 WHI-CT (DM) Age=50-79y Follow-up=11.5y Design=RCT (as above) |
BC overall survival | BC overall survival | Multivariate HR 0.78 (0.65-0.94) |
BC overall survival was greater in the dietary intervention group (10y survival 82 vs. 78%) |
| 1993-1998; Sun et al. (53) | N=156,624 WHI-OS and CT (all 4) Age=50-79y Follow-up= 2,811,187 person yrs |
Mortality from all-cause, CVD and cancer | Outcome for normal weight central obesity All-cause mortality CVD mortality Cancer mortality |
Multivariate HR 1.31 (1.20-1.42) 1.24 (1.05-1.46) 1.20 (1.01-1.43) |
Normal weight central obesity associated with higher all-cause, CVD and cancer mortality |
| 1993-1998; Pan et al. (54) | N=48,835 WHI-CT (DM) Age=50-79y Follow-up=19.6y Design=RCT (as above) |
Dietary intervention influence on death from BC | MS score Death from BC None 1-2 3-4 Death after BC None 1-2 3-4 |
Multivariate HR 1.08 (0.63-1.87) 0.8 (0.62-1.02) 0.31 (0.14-.0.69) p=0.01 0.98 (0.7-1.37) 0.86 (0.74-1.01) 0.66 (0.43-1.01) p=0.16 |
3-4 MS components more likely to have reduction in death from BC with low fat diet |
| 1993-2017; George et al. (55) | N=59,388 WHI-OS Age=50-79y Follow-up=18.2y |
Death from all-cause, CVD, cancer, Alzheimer’s dementia and dementia not otherwise specified | HEI-2015 Quintiles All-cause death 1 2 3 4 5 Cancer death 1 2 3 4 5 |
Multivariate HR Ref 0.94 (0.88-1.0) 0.88 (0.83-0.94) 0.84 (0.78-0.9) 0.82 (0.76-0.87) Ref 0.92 (0.82-1.02) 0.86 (0.77-0.96) 0.86 (0.77-0.97) 0.79 (0.7-0.88) |
Higher HEI-2015 scores associated with 18% lower risk of all-cause and 21% lower risk of cancer death; but not CVD deaths |
| 1993-1998; Pan et al. (56) | N=22,837 WHI-OS and CT (all 4) Age=50-79y Follow-up=18.9y |
Cancer-specific and all-cause mortality | HOMA-IR quartiles Cancer-specific 0.05-1.09 >1.09-1.77 >1.77-3.03 >3.03-402.99 All-cause 0.05-1.09 >1.09-1.77 >1.77-3.03 >3.03-402.99 |
Multivariate HR Ref 1.11 (0.97-1.27) 1.14 (0.98-1.31) 1.20 (1.02-1.40) Ptrend =0.03 Ref 1.08(1.01-1.16) 1.10(1.02-1.18) 1.42 (1.32-1.53) Ptrend <0.001 |
High insulin resistance associated with higher risk of cancer-specific and all-cause mortality |
| 1993-1998; Yuan et al. (57) | N=544 WHI-OS and CT (all 4) Age=50-79y Follow-up=19.9y |
Mortality after triple-negative BC (TNBC) – BC-specific and BC overall mortality | MS components BC-specific mortality None 1-2 3-4 BC-overall mortality None 1-2 3-4 |
Multivariate HR Ref 0.86 (0.53-1.4) 1.13 (0.5-2.55) Ref 1.41 (1.01-1.98) 2.13 (1.22-3.71) Ptrend =0.006 |
TNBC with 3-4 MS components had higher BC-specific (non-significant) and overall mortality |
| 1993-1998; Simon et al. (11) | N=12,076 WHI-OS and CT (all 4) Age=50-79y Follow-up=10y |
All-cause, CVD, cancer-specific and other-cause mortality from obesity-related cancers (breast, colorectal, endometrial, kidney, pancreatic, ovarian, stomach, liver, non-Hodgkin lymphoma) | Mortality by Cardiometabolic risk factors All-cause None 1-2 3-4 Cancer-specific None 1-2 3-4 CVD None 1-2 3-4 Other-cause None 1-2 3-4 |
Multivariate HR Ref 1.5 (1.36-1.65) 1.99 (1.73-2.30) Ref 1.29 (1.12-1.48) 1.37 (1.10-1.72) Ref 2.52 (1.95-3.26) 4.01 (2.88-5.57) Ref 1.45 (1.23-1.70) 2.14 (1.7-2.69) Ptrend <0.001 (for all) |
Cardiometabolic risk factors before any obesity-related cancer diagnosis significantly associated with higher all-cause, cancer-specific, CVD and other cause mortality in early-stage cancer; but not BC-mortality specifically |
| 1993-1998; Chen et al. (59) | N=96,831 WHI-OS and CT (all 4) Age=50-79y Follow-up=18.9y |
Incident CVD, and all-cause and cause-specific mortality | Dietary cholesterol quartile Incident CVD Q1 Q2 Q3 Q4 Q5 Cancer mortality Q1 Q2 Q3 Q4 Q5 |
Multivariate HR Ref 1.04 (0.96-1.10) 1.05 (0.96-1.12) 1.10 (1.02-1.19) 1.12 (1.03-1.21) Ptrend <0.001 Ref 0.94 (0.86-1.03) 0.98 (0.9-1.08) 1.03 (0.93-1.13) 1.03 (0.93-1.14) Ptrend =0.16 |
High dietary cholesterol and egg consumption associated with higher risk of incident CVD and all-cause mortality; but not cancer mortality |
| 1993-1998; Dieli-Conwright et al. (63) | N=161,308 WHI-OS and CT (all 4) Age=50-79y Follow-up=9.5y |
BC-specific and overall mortality | Physical activity level (all women) All-cause mortality 0 >0-2.9 3-8.9 ≥9 BC mortality 0 >0-2.9 3-8.9 ≥9 |
Multivariate HR Ref 0.96 (0.84-1.10) 0.80 (0.72-0.90) 0.86 (0.78-0.95) Ptrend <0.001 Ref 1.0(0.76-1.31) 0.92 (0.74-1.15) 0.85 (0.7-1.04) Ptrend =0.09 |
Higher physical activity associated with lower all-cause mortality, which did not differ by cardiometabolic risk factor number in early-stage BC |
WHI, Women’s Health Initiative; OS, Observational Study; CT, Clinical Trial; DM, Dietary modification; CHD, Coronary heart disease; CVD, Cardiovascular disease; HR, Hazard ratio; CI, Confidence interval; RCT, Randomized controlled trial; BC, Breast cancer; MS, Metabolic syndrome; HEI-2015, Healthy Eating Index 2015; HOMA-IR, Homeostasis model assessment of insulin resistance; TNBC, Triple-negative breast cancer; HFpEF, Heart failure with preserved ejection fraction; HFrEF, Heart failure with reduced ejection fraction.