Lifestyle changes and the risk of developing endometrial and ovarian cancers: opportunities for prevention and management

Figures & data

Table 1 American Cancer Society recommendations for cancer prevention and survivorship

	Cancer prevention	Cancer survivorship
Physical activity	Adopt a physically active lifestyle Engage in at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity each week Limit sedentary behavior, such as sitting down, watching television, or other forms of screen-based entertainment	Adopt a physically active lifestyle Engage in at least 150 minutes of physical activity each week Do strength training exercises at least 2 days each week Avoid inactivity Return to normal activities as soon as possible following diagnosis
Weight management	Achieve and maintain a healthy weight throughout life Be as lean as possible without being underweight Avoid excess weight gain at all ages	Achieve and maintain a healthy weight Limit consumption of high calorie foods and beverages Increase physical activity to promote weight loss if overweight or obese
Diet	Consume a healthy diet, with an emphasis on plant foods Limit consumption of processed meat or red meat Eat at least 2.5 cups of vegetables and fruits each day Choose whole grains over refined grain products Limit alcohol consumption to 1 drink or less per day (for women)	Consume a healthy diet Achieve a diet pattern that is high in vegetables, fruits, and whole grains Follow the American Cancer Society guidelines for diet for cancer prevention

Table 2 Summary of recent meta-analyses on endometrial cancer prevention

	Direction of risk	Relative risk (95% CI)	Studies included
Lifestyle prevention
Obesity (BMI >30)^Citation20	↑	2.54 (2.11–3.06)*	7 cohort, 11 case–control
Physical activity^Citation27	↓	0.77 (0.70–0.85)*	7 cohort
Dairy intake^Citation36	No effect	0.97 (0.93–1.01)a	1 cohort, 8 case–control
Coffee intake^Citation37	↓	0.8 (0.74–0.86)*	13 cohort
Tea intake^Citation38	No effect	Green tea: 0.78 (0.66–0.92)*	Green tea: 1 cohort, 5 case–control
		Black tea: 0.99 (0.79–1.23)	Black tea: 5 cohort, 4 case–control
Red meat intake^Citation36	↑	1.51 (1.19–1.93)*	7 case–control
Alcohol intake^Citation39	No effect	0.83 (0.59–1.18) (cohort analysis)	6 cohort, 14 case–control
		0.89 (0.76–1.05) (case–control analysis)
Smoking^Citation41	↓	0.81 (0.74–0.88)* (cohort analysis)	10 cohort, 24 case–control
		0.72 (0.66–0.79)* (case–control analysis)
Breastfeeding^Citation60	↓	0.77 (0.62–0.96)	14 cohort
Surgical prevention
Bariatric surgery^Citation24	↓	0.4 (0.2–0.79)*	3 cohort
Chemoprevention
Oral contraceptive pills^Citation47	↓	0.69 (0.66–0.73)b,*	15 cohort, 21 case–control
Levonorgestrel intrauterine device^Citation49	↓	0.69 (0.58–0.82)c,*	4 cohort, 14 case–control
Estrogen-only HRT^Citation50	↑	2.3 (2.1–2.5)*	10 cohort, 27 case–control
Combined estrogen–progesterone HRT^Citation50	↓	0.4 (0.2–0.6)*	1 RCT, 3 cohort, 3 case–control
Nonsteroidal anti-inflammatory drugs^Citation53	↓	Overall: 0.87 (0.79–0.96)*	4 cohort, 5 case–control
		Obese: 0.72 (0.58–0.90)*
		Nonobese: 1.08 (0.82–1.43)

Notes:

* Significant at P<0.05.

a Odds ratio shown, per serving of dairy per day.

b 99% CI given.

c Odds ratio shown.

Abbreviations: CI, confidence interval; BMI, body mass index; RCT, randomized controlled trial; HRT, hormone replacement therapy.

Table 3 Lifestyle interventions in survivors of endometrial cancer

	Study design	Intervention	Results
			Adherence, %	Weight change, physical activity, diet	Quality of life
Completed studies
Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet (SUCCEED trial) von Gruenigen et al^Citation70 McCarroll et al^Citation71	RCT N=75 Overweight or obese stage I or II EC survivors Diagnosed in the past 3 years with no active disease Setting: US clinic	Intervention: education and counseling with 10 weekly and 6 bi-weekly sessions followed by 6 additional months of contact with registered dietician Comparison: usual care Duration: 6 months Follow-up: 6 months	84	Weight change (difference between intervention and comparison): 4.6 kg loss (P<0.001) Physical activity: 100 min/wk increase (6 months, P=0.04), 89 min/wk increase (12 months, P=0.02)	Physical functioning: significant improvement at 6 months (P=0.05) Fatigue: significant improvement at 3 months (P=0.01) Weight loss self-efficacy: significant improvement at 12 months (P<0.001)
Donnelly et al^Citation156	RCT N=33 Stage I–III sedentary ovarian (N=12) and EC survivors (N=11) ≤3 years post-diagnosis Setting: Irish clinic	Intervention: behavior change, moderate intensity physical activity Comparison: usual care Duration: 12 weeks Follow-up: 3 months	88	Body composition: NS Physical activity: NS	Fatigue: significant improvement post-intervention (P=0.05) and at 3-month follow-up (P=0.01) Physical functioning: NS
Loseit! App intervention McCarroll et al^Citation72	Uncontrolled pre–post N=50 Overweight or obese stage I or II breast and EC survivors Diagnosed in the prior 3 years with no active disease Setting: US clinic	Intervention: three in-person counseling visits, diet, lifestyle, and exercise counseling through the Loseit! App. Participants logged daily weight, food choices, and exercise and received real-time feedback through app Duration: 4 weeks Follow-up: immediately post-intervention	70	Weight change: 2.3 kg loss (P<0.001) Physical activity: 182 min/wk increase (P=0.001)	QoL: NS Weight loss self-efficacy: significant improvement (P=0.04)
Steps to Health Basen-Engquist et al^Citation73	Uncontrolled pre–post N=100 Stage I–IIIA EC survivors At least 6 months post-treatment with no evidence of disease and not meeting exercise guidelines Setting: US clinic	Intervention: individualized exercise plan developed from initial laboratory assessment, home-based exercise with daily exercise diary and accelerometer, telephone counseling at weekly to monthly intervals Comparison: none Duration: 6 months Follow-up: immediately post-intervention	NR	Physical activity: 9 min/d increase (P=0.002) Resting heart rate: significant decrease (P=0.047) Systolic blood pressure: significant decrease (P=0.03) VO2 max (aerobic capacity): NS Improvements seen in obese and nonobese survivors	Physical functioning: significant improvement (P<0.001) General health: significant improvement (P<0.001) Mental health: significant improvement (P=0.03)
Upcoming trials
Revving-up Exercise for SustainedWeight Loss by Altering NeurologicReward and Drive (REWARD trial)Nock et al^Citation74	RCT Anticipated accrual: 120 Obese stage I EC survivors Treatment completed >8 weeks and <4 years ago Setting: US clinic	Intervention: “assisted” rate exercise, 3×/wk – mechanical assistance to adjusts participants’ heart rate to a goal Comparison: exercise intervention at “voluntary rate” 3×/wk Both groups receive a dietary behavioral program Duration: 16 weeks Follow-up: 24 weeks	Currently recruiting patients Outcomes: weight change, fitness, body fat, exercise motivation, eating and appetitive behavior measures, QoL, and brain fMRI responses to food

Abbreviations: RCT, randomized controlled trial; EC, endometrial cancer; NS, nonsignificant; QoL, quality of life; NR, not reported; fMRI, functional magnetic resonance imaging; wk, week; App, application.

Table 4 Summary of recent meta-analyses on ovarian cancer prevention

	Direction of risk	Relative risk (95% CI)	Studies included
Lifestyle prevention
Obesity (BMI >30)^Citation81	↑	1.13 (1.06–1.20)a,*	17 cohort, 30 case–control
Physical activity^Citation84	No effect	0.92 (0.84–1.00)	9 cohort, 10 case–control
Vegetable intake^Citation89,Citation90	↓	0.89 (0.81–0.99)*	4 cohort, 4 case–control
Dairy intake^Citation91	No effect	0.925 (0.78–1.09)b	19 case–control
Fish intake^Citation92	No effect	1.04 (0.89–1.22) (cohort analysis)	5 cohort, 10 case–control
		0.90 (0.73–1.12) (case–control analysis)
Coffee intake^Citation93	No effect	1.05 (0.75–1.46)	7 case–control
Tea intake^Citation93,Citation95	No effect	1.07 (0.78–1.45)	6 case–control
Alcohol intake^Citation101	No effect	1.03 (0.96–1.10)	13 cohort
Smoking^Citation105	↑	1.07 (1.03–1.10)a,*	19 cohort, 21 case–control
Breastfeeding^Citation107	↓	0.76 (0.69–0.83)*	5 cohort, 35 case–control
Surgical prevention
Tubal ligation^Citation109	↓	0.7 (0.64–0.75)*	7 cohort, 23 case–control
Chemoprevention
Oral contraceptive pills^Citation112	↓	0.73 (0.70–0.76)*	13 cohort, 32 case–control
Hormone replacement therapy (estrogen only and combined)^Citation123	↑	1.14 (1.10–1.19)*	17 cohort, 35 case–control
Nonsteroidal anti-inflammatory drugs^Citation129	No effect	Aspirin: 0.91 (0.84–0.99)	12 case–control
		NSAIDs: 0.90 (0.77–1.05)
		Acetaminophen: 0.99 (0.88–1.12)

Notes:

* Significant at P<0.05.

a 99% CI given.

b Odds ratio shown is for 13 studies of low-fat/skimmed milk as dairy studies were analyzed by main type of dairy.

Abbreviations: CI, confidence interval; BMI, body mass index; NSAID, nonsteroidal anti-inflammatory drug.

Table 5 Lifestyle interventions in survivors of OC

	Study design	Intervention	Results
			Adherence, %	Weight change, physical activity, diet	Quality of life
Completed studies
Ovarian Nutrition Education (ONE) study Paxton et al^Citation147	RCT N=51 Stage II–IV OC survivors Setting: US clinic	Intervention: weekly to monthly telephone calls with dietitian advising diet with ≥5 vegetable servings/d, 16 ounces of vegetable juice/d, ≥3 fruit servings/d, ≥30 grams of fiber, and ≤20% energy from fat Comparison: weekly to monthly telephone calls with dietitian advising diet with ≥5 fruit and/or vegetable servings/d, ≥25 grams of fiber, ≤20% energy from fat, four fruit and vegetable capsules, and a soy-based beverage supplementation Duration: 6 months Follow-up: immediately post-intervention	11–33	Weight: NS Serum albumin: NS CA-125: NS Dietary: significant increase in juice, intake (P=0.02), NS for energy, vegetable, fat, or fiber intake	QoL: NS Fatigue: NS Pain: NS
Moonsammy et al^Citation144	Controlled pre–post N=19 women Intervention: seven newly diagnosed epithelial ovarian, fallopian, or primary peritoneal cancer Comparison: 12 women previously treated for ovarian, fallopian tube, or peritoneal cancer Setting: Canadian clinics	Intervention: individualized home-based exercise program and equipment (stability ball, yoga mat, resistance bands), biweekly telephone-based cognitive behavior therapy Comparison: surveillance, biweekly telephone-based cognitive behavior therapy Duration: 24 weeks Follow-up: immediately post-intervention	NR	Body composition: significant increase in body fat (P=0.03) and waist circumference (P=0.02) VO2 max (aerobic capacity): significant improvement (P=0.008) HR: NS Blood pressure: NS	QoL: NS Anxiety: NS
Hwang et al^Citation143	Controlled pre–post N=40 OC survivors s/p hysterectomy, oophorectomy, and chemotherapy In remission for 0.5–3 years Setting: Korean hospital	Intervention: 1-hour weekly health education and support group, home exercise (three 60-min sessions/wk), relaxation therapy (three 15-min sessions/wk) for 8 weeks Comparison: usual care Follow-up: immediately post-intervention	92	Distance walked: significant improvement (P=0.005) Muscle strength: significant improvement (P=0.001)	QoL: significant improvement (P=0.004)
von Gruenigen et al^Citation145	Uncontrolled pre–post N=27 Ovarian, fallopian tube, or peritoneal cancer patients Receiving at least six cycles of adjuvant chemotherapy Setting: US clinic	Intervention: 30-minute dietary and exercise counseling at each chemotherapy session, pedometer Comparison: none Duration: six chemotherapy cycles Follow-up: immediately post-intervention	92	Physical activity: NS Fruit and vegetable intake: NS	QoL: significant improvement (P=0.001) Fatigue: NS
Newton et al^Citation146	Uncontrolled pre–post N=17 Newly diagnosed OC In chemotherapy Setting: Australian hospital	Intervention: educational booklet, individualized weekly walking prescription, weekly counseling with exercise physiologist (in-person or by phone, depending on participant distance from hospital) Comparison: none Duration: 11–21 weeks (length of active chemotherapy) Follow-up: immediately post-intervention	76	Physical functioning (measured with a 6-minute walk test): significant improvement (P=0.01)	Physical well-being: significant improvement (P=0.01), NS for other QoL measures Symptoms: NS Anxiety, depression: NS
Mizrahi et al^Citation139	Uncontrolled pre–post N=30 Recurrent OC On second or third line chemotherapy Setting: Australian clinic	Intervention: individualized 90 min/wk prescribed exercise, weekly telephone call Comparison: none Duration: 12 weeks Follow-up: 12 weeks	81	BMI: NS Heart rate: NS Blood pressure: NS Physical activity: significant improvement (8.8 METs × hour per week, P=0.003) Physical fitness: significant improvement in upper and lower body strength and balance (P=0.002) VO2 max (aerobic capacity): NS	QoL: significant improvement (P=0.001) Fatigue: NS Symptoms: significant improvement in sleep (P=0.04) and mental function (P=0.001)
Upcoming RCTs
Lifestyle Interventionfor oVarian cancer Enhanced Survival (LIVES) Gynecologic Oncology Group 225^Citation148	1,070 women Stage II, III, or IV of epithelial OC, fallopian tube, or primary peritoneal carcinoma at diagnosis Completed treatment within past 6 weeks to 6.5 months No clinical evidence of persistent or recurrent disease	Intervention: in-person diet counseling, telephone counseling (twice a week to bimonthly), exercise diaries Comparison: telephone check-ins Duration: 12 months Follow-up: 5 years	Currently recruiting patients Outcomes: weight, exercise adherence, and QoL

Abbreviations: RCT, randomized controlled trial; OC, ovarian cancer; NS, nonsignificant; QoL, quality of life; NR, not reported; HR, hazard ratio; BMI, body mass index; MET, metabolic equivalent of task; wk, week.

ZhangYLiuHYangSZhangJQianLChenXOverweight, obesity and endometrial cancer risk: results from a systematic review and meta- analysisInt J Biol Markers2014291e21e2924170556

 PubMed Web of Science ®Google Scholar

VoskuilDWMonninkhofEMEliasSGVlemsFAvan LeeuwenFETask Force Physical Activity and CancerPhysical activity and endometrial cancer risk, a systematic review of current evidenceCancer Epidemiol Biomarkers Prev200716463964817416752

 PubMed Web of Science ®Google Scholar

BanderaEVKushiLHMooreDFGifkinsDMMcCulloughMLConsumption of animal foods and endometrial cancer risk: a systematic literature review and meta-analysisCancer Causes Control200718996798817638104

 PubMed Web of Science ®Google Scholar

ZhouQLuoM-LLiHLiMZhouJ-GCoffee consumption and risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studiesSci Rep201551341026302813

 PubMed Web of Science ®Google Scholar

ZhouQLiHZhouJ-GMaYWuTMaHGreen tea, black tea consumption and risk of endometrial cancer: a systematic review and meta-analysisArch Gynecol Obstet2015293114315526138307

 PubMed Web of Science ®Google Scholar

SunQXuLZhouBWangYJingYWangBAlcohol consumption and the risk of endometrial cancer: a meta-analysisAsia Pac J Clin Nutr201120112513321393120

 PubMed Web of Science ®Google Scholar

ZhouBYangLSunQCigarette smoking and the risk of endometrial cancer: a meta-analysisAm J Med20081216501.e508.e18501231

 PubMed Web of Science ®Google Scholar

WangLLiJShiZAssociation between breastfeeding and endometrial cancer risk: evidence from a systematic review and meta-analysisNutrients2015775697571126184301

 PubMed Web of Science ®Google Scholar

UpalaSAnawinSBariatric surgery and risk of postoperative endometrial cancer: a systematic review and meta-analysisSurg Obes Relat Dis201511494995525620433

 PubMed Web of Science ®Google Scholar

Collaborative Group on Epidemiological Studies on Endometrial CancerEndometrial cancer and oral contraceptives: an individual participant meta-analysis of 27,276 women with endometrial cancer from 36 epidemiological studiesLancet Oncol20151691061107026254030

 PubMed Web of Science ®Google Scholar

FelixASGaudetMMLa VecchiaCIntrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer ConsortiumInt J Cancer20151365E410E42225242594

 PubMed Web of Science ®Google Scholar

GradyDGebretsadikTKerlikowskeKErnsterVPetittiDHormone replacement therapy and endometrial cancer risk: a meta-analysisObstet Gynecol19958523043137824251

 PubMed Web of Science ®Google Scholar

NeillASNagleCMProtaniMMObermairASpurdleABWebbPMAspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysisInt J Cancer201313251146115522777678

 PubMed Web of Science ®Google Scholar

von GruenigenVFrasureHKavanaghMBSurvivors of uterine cancer empowered by exercise and healthy diet (SUCCEED): a randomized controlled trialGynecol Oncol2012125369970422465522

 PubMed Web of Science ®Google Scholar

McCarrollMLArmbrusterSFrasureHESelf-efficacy, quality of life, and weight loss in overweight/obese endometrial cancer survivors (SUCCEED): a randomized controlled trialGynecol Oncol2014132239740224369301

 PubMed Web of Science ®Google Scholar

DonnellyCMBlaneyJMLowe-StrongAA randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivorsGynecol Oncol2011122361862421689848

 PubMed Web of Science ®Google Scholar

McCarrollMLArmbrusterSPohle-KrauzaRJFeasibility of a lifestyle intervention for overweight/obese endometrial and breast cancer survivors using an interactive mobile applicationGynecol Oncol2015137350851525681782

 PubMed Web of Science ®Google Scholar

Basen-EngquistKCarmackCBrownJResponse to an exercise intervention after endometrial cancer: differences between obese and non-obese survivorsGynecol Oncol20141331485524680591

 PubMed Web of Science ®Google Scholar

NockNLDimitropoulosARaoSMRationale and design of REWARD (revving-up exercise for sustained weight loss by altering neurological reward and drive): a randomized trial in obese endometrial cancer survivorsContemp Clin Trials201439223624525139726

 PubMed Web of Science ®Google Scholar

KotsopoulosJBaerHJTworogerSSAnthropometric measures and risk of epithelial ovarian cancer: results from the nurses’ health studyObesity20101881625163120035276

 PubMed Web of Science ®Google Scholar

CanniotoRAMoysichKBEpithelial ovarian cancer and recreational physical activity: a review of the epidemiological literature and implications for exercise prescriptionGynecol Oncol2015137355957325797080

 PubMed Web of Science ®Google Scholar

ChandranUBanderaEVWilliams-KingMGHealthy eating index and ovarian cancer riskCancer Causes Control201122456357121286802

 PubMed Web of Science ®Google Scholar

HuJHuYHuYZhengSIntake of cruciferous vegetables is associated with reduced risk of ovarian cancer: a meta-analysisAsia Pac J Clin Nutr201524110110925740748

 PubMed Web of Science ®Google Scholar

HanBLiXYuTCruciferous vegetables consumption and the risk of ovarian cancer: a meta-analysis of observational studiesDiagn Pathol20149724444040

 PubMed Web of Science ®Google Scholar

LiuJTangWSangLMilk, yogurt, and lactose intake and ovarian cancer risk: a meta-analysisNutr Cancer2014671687225298278

 PubMed Web of Science ®Google Scholar

JiangPJiangZShenKYueYFish intake and ovarian cancer risk: a meta-analysis of 15 case-control and cohort studiesPLoS One201494e9460124732053

 PubMed Web of Science ®Google Scholar

GosvigCFKjaerSKBlaakærJHøgdallEHøgdallCJensenACoffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: results from a Danish case-control studyActa Oncol (Madr)201554811441151

 PubMed Web of Science ®Google Scholar

KingMGOlsonSHPaddockLSugary food and beverage consumption and epithelial ovarian cancer risk: a population-based case-control studyBMC Cancer2013139423442818

 PubMed Web of Science ®Google Scholar

TworogerSSGertigDMGatesMAHechtJLHankinsonSECaffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancerCancer200811251169117718213613

 PubMed Web of Science ®Google Scholar

FaberMTKjærSKDehlendorffCCigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studiesCancer Causes Control2013245989100423456270

 PubMed Web of Science ®Google Scholar

FengL-PChenH-LShenM-YBreastfeeding and the risk of ovarian cancer: a meta-analysisJ Midwifery Womens Health201459442843725066743

 PubMed Web of Science ®Google Scholar

MarchettiCDe FeliceFPalaiaIRisk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriersBMC Womens Health20141415025494812

 PubMed Web of Science ®Google Scholar

RossouwJEAndersonGLPrenticeRLRisks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trialJAMA2002288332133312117397

 PubMed Web of Science ®Google Scholar

CookNRLeeI-MGazianoJMLow-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trialJAMA20052941475515998890

 PubMed Web of Science ®Google Scholar

PaxtonRJGarcia-PrietoCBerglundMA randomized parallel-group dietary study for stages II-IV ovarian cancer survivorsGynecol Oncol2012124341041622119991

 PubMed Web of Science ®Google Scholar

MoonsammySHGugliettiCLSanta MinaDA pilot study of an exercise & cognitive behavioral therapy intervention for epithelial ovarian cancer patientsJ Ovarian Res2013612123557323

 PubMed Web of Science ®Google Scholar

HwangK-HChoO-HYooYSThe effect of comprehensive care program for ovarian cancer survivorsClin Nurs Res Epub20141126

 Web of Science ®Google Scholar

von GruenigenVEFrasureHEKavanaghMBLernerEWaggonerSECourneyaKSFeasibility of a lifestyle intervention for ovarian cancer patients receiving adjuvant chemotherapyGynecol Oncol2011122232833321600635

 PubMed Web of Science ®Google Scholar

NewtonMJHayesSCJandaMSafety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer: a pilot studyBMC Cancer20111138921899778

 PubMed Web of Science ®Google Scholar

MizrahiDNaumannFBroderickCSamaraJRyanMFriedlanderMQuantifying physical activity and the associated barriers for women with ovarian cancerInt J Gynecol Cancer201525457758325628105

 PubMed Web of Science ®Google Scholar

ThomsonCAE CraneTWertheimBCDiet quality and survival after ovarian cancer: results from the Women’s Health InitiativeJ Natl Cancer Inst201410611dju31425335480

 PubMedGoogle Scholar