Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial | Breast Cancer | JAMA | JAMA Network
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1.
Freedman LS, Clifford C, Messina M. Analysis of dietary fat, calories, body weight and the development of mammary tumors in rats and mice: a review.  Cancer Res. 1990;50:5710-57192203521Google Scholar
2.
Prentice RL, Sheppard L. Dietary fat and cancer: consistency of the epidemiologic data and disease prevention that may follow from a practical reduction in fat consumption.  Cancer Causes Control. 1990;1:81-972102280Google ScholarCrossref
3.
Howe GR, Hirohata T, Hislop TG.  et al.  Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies.  J Natl Cancer Inst. 1990;82:561-5692156081Google ScholarCrossref
4.
Hunter DJ, Spiegelman D, Adami HO.  et al.  Cohort studies of fat intake and the risk of breast cancer: a pooled analysis.  N Engl J Med. 1996;334:356-3618538706Google ScholarCrossref
5.
Boyd NF, Stone J, Vogt KN, Connelly BS, Martin LJ, Minkin S. Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature.  Br J Cancer. 2003;89:1672-168514583769Google ScholarCrossref
6.
Heitmann BL, Lissner L. Dietary underreporting by obese individuals: is it specific or non-specific.  BMJ. 1995;311:986-9897580640Google ScholarCrossref
7.
Subar AF, Kipnis V, Troiano RP.  et al.  Using intake biomarkers to evaluate the extent of dietary misreporting in a large sample of adults: the OPEN study.  Am J Epidemiol. 2003;158:1-1312835280Google ScholarCrossref
8.
Day NE, McKeown N, Wong MY, Welch A, Bingham S. Epidemiologic assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium.  Int J Epidemiol. 2001;30:309-317Google ScholarCrossref
9.
Bingham SA, Luben R, Welch A, Wareham N, Khaw KT, Day N. Are imprecise methods obscuring a relation between fat and breast cancer.  Lancet. 2003;362:212-21412885485Google ScholarCrossref
10.
Insull W, Henderson MM, Prentice RL.  et al.  Results of a randomized feasibility study of a low-fat diet.  Arch Intern Med. 1990;150:421-4272405805Google ScholarCrossref
11.
Coates RJ, Bowen DJ, Kristal AR.  et al.  The Women's Health Trial Feasibility Study in minority populations: changes in dietary intakes.  Am J Epidemiol. 1999;149:1104-111210369504Google ScholarCrossref
12.
Prentice R, Thompson D, Clifford C, Gorbach S, Goldin B, Byar D. Dietary fat reduction and plasma estradiol concentration among healthy postmenopausal women.  J Natl Cancer Inst. 1990;82:129-1342294222Google ScholarCrossref
13.
Rose DP, Connolly JM, Chlebowski RT, Buzzard IM, Wynder EL. The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients.  Breast Cancer Res Treat. 1993;27:253-2628312583Google ScholarCrossref
14.
Rock CL, Flatt SW, Thompson CA.  et al.  Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer.  J Clin Oncol. 2004;22:2379-238715197199Google ScholarCrossref
15.
Wu AH, Pike MC, Stramm DO. Meta-analysis: dietary fat intake, serum estrogen levels, and risk of breast cancer.  J Natl Cancer Inst. 1999;91:529-53410088623Google ScholarCrossref
16.
World Cancer Research Fund.  Food, Nutrition and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 1997
17.
Smith-Warner SA, Spiegelman D, Yaun SS.  et al.  Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies.  JAMA. 2001;285:769-77611176915Google ScholarCrossref
18.
Gandini S, Merzenich H, Robertson C, Boyle P. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and Vegetable consumption and the intake of associated micronutrients.  Eur J Cancer. 2000;36:636-646Google ScholarCrossref
19.
Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk.  Am J Clin Nutr. 2003;78:(suppl 3)  559S-569S12936950Google Scholar
20.
Working IARC Group on the Evaluation of Cancer-Preventive Strategies.  Fruit and vegetables In: IARC Handbooks of Cancer Prevention: Vol. 8. Lyon, France: International Agency for Research on Cancer; 2003
21.
Chatenoud L, Tavani A, La Vecchia C.  et al.  Whole grain food intake and cancer risk.  Int J Cancer. 1998;77:24-289639389Google ScholarCrossref
22.
Jacobs DR, Marquent L, Slavin J, Kischi LH. Whole grain intake and cancer: an expanded review and meta-analysis.  Nutr Cancer. 1998;30:85-969589426Google ScholarCrossref
23.
Nicodemus KK, Jacobs DR Jr, Folsom AR. Whole and refined grain and risk of incident postmenopausal breast cancer (United States).  Cancer Causes Control. 2001;12:917-92511808711Google ScholarCrossref
24.
Kipnis V, Midthune D, Freedman LS.  et al.  Empirical evidence of correlated biases in dietary assessment instruments and its implications.  Am J Epidemiol. 2001;153:394-40311207158Google ScholarCrossref
25.
Women's Health Initiative Study Group.  Design of the Women's Health Initiative clinical trial and observational study.  Control Clin Trials. 1998;19:61-1099492970Google ScholarCrossref
26.
Ritenbaugh C, Patterson R, Chlebowski RT.  et al.  The Women's Health Initiative Dietary Modification Trial: overview and baseline characteristics of participants.  Ann Epidemiol. 2003;13:(9S)  S87-S9714575941Google ScholarCrossref
27.
Hays J, Hunt JR, Hubbell FA.  et al.  The Women's Health Initiative recruitment methods and results.  Ann Epidemiol. 2003;13:(9S)  S18-S7714575939Google ScholarCrossref
28.
Writing Group for the Women's Health Initiative Investigators.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.  JAMA. 2002;288:321-33312117397Google ScholarCrossref
29.
Women's Health Initiative Steering Committee.  Effects of conjugated equine estrogen in postmenopausal women with hysterectomy.  JAMA. 2004;291:1701-171215082697Google ScholarCrossref
30.
Patterson RE, Kristal AR, Tinker LF.  et al.  Measurement characteristics of the Women's Health Initiative food frequency questionnaire.  Ann Epidemiol. 1999;9:178-18710192650Google ScholarCrossref
31.
Tinker L, Burrows E, Henry H, Patterson R, Rupp J, Van Horn L. The Women's Health Initiative: overview of the nutrition components. In: Krummel DA, Kris-Etherton PM, eds. Nutrition in Women's Health. Gaithersburg, Md: Aspen Publishers; 1996:510-549
32.
 Nutrition and Your Health: Dietary Guidelines for Americans. 3rd ed. Washington, DC: US Dept of Health and Human Services; 1990
33.
Curb JD, McTiernan A, Heckbert SR.  et al.  Outcomes ascertainment and adjudication methods in the Women's Health Initiative.  Ann Epidemiol. 2003;13:(9S)  S122-S12814575944Google ScholarCrossref
34.
Cox DR. Regression analysis and life tables.  J R Stat Soc B. 1972;34:187-220Google Scholar
35.
Robins JM, Finkelstein DM. Correcting for noncompliance and dependent censoring in an AIDS clinical trial with inverse probability of censoring weighted (IPCW) log-rank tests.  Biometrics. 2000;56:779-78110985216Google ScholarCrossref
36.
Piegorsch WW, Weinberg CR, Taylor JA. Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies.  Stat Med. 1994;13:153-1628122051Google ScholarCrossref
37.
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. 2nd ed. New York, NY: John Wiley & Sons Inc; 2002:255
38.
O’Brien PC, Fleming RT. A multiple testing procedure for clinical trials.  Biometrics. 1979;35:549-556497341Google ScholarCrossref
39.
Freedman L, Anderson G, Kipnis V.  et al.  Approaches to monitoring the results of long-term disease prevention trials: examples from the Women's Health Initiative.  Control Clin Trials. 1996;17:509-5258974210Google ScholarCrossref
40.
Women's Health Initiative Study Group.  Dietary adherence in the Women's Health Initiative Dietary Modification Trial.  J Am Diet Assoc. 2004;104:654-65815054353Google ScholarCrossref
41.
Chlebowski RT, Blackburn GL, Elashoff RE.  et al.  Dietary fat reduction in postmenopausal women with primary breast cancer: phase III Women's Intervention Nutrition Study (WINS) [abstract].  Proc Am Soc Clin Oncol. 2005;23:(16S)  3SAbstract 10Google Scholar
42.
Fung TT, Hu FB, Holmes MD.  et al.  Dietary patterns and the risk of postmenopausal breast cancer.  Int J Cancer. 2005;116:116-12115756679Google ScholarCrossref
43.
Early Breast Cancer Trialists' Collaborative Group.  Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomized trials.  Lancet. 2005;365:1687-171715894097Google ScholarCrossref
44.
Smith IE, Dowsett M. Aromatase inhibitors in breast cancer.  N Engl J Med. 2003;348:2431-244212802030Google ScholarCrossref
45.
Romond EH, Perez EA, Bryant J.  et al.  Trastuzumab plus adjuvant chemotherapy for operable HER-2 positive breast cancer.  N Engl J Med. 2005;353:1673-168416236738Google ScholarCrossref
46.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B.  et al. Herceptin Adjuvant (HERA) Trial Study Team.  Trastuzumab after adjuvant chemotherapy in HER-2 positive breast cancer.  N Engl J Med. 2005;353:1659-167216236737Google ScholarCrossref
47.
Rouzier R, Perou DM, Symmans WF.  et al.  Breast cancer molecular subtypes respond differently to preoperative chemotherapy.  Clin Cancer Res. 2005;11:5678-568516115903Google ScholarCrossref
48.
ATAC Trialist Group.  Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years of adjuvant treatment for breast cancer.  Lancet. 2005;365:60-6215639680Google ScholarCrossref
49.
Lawlor DA, Smith GD, Ebrahim S. Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women's Heart and Health Study.  Cancer Causes Control. 2004;15:267-27515090721Google ScholarCrossref
50.
Toniolo P, Bruning PF, Akhmedkhanov A.  et al.  Serum insulin-like growth factor-I and breast cancer.  Int J Cancer. 2000;88:828-83211072255Google ScholarCrossref
51.
Patterson RE, Kristal A, Rodabough R.  et al.  Changes in food sources of dietary fat in response to an intensive low-fat dietary intervention: early results from the Women's Health Initiative.  J Am Diet Assoc. 2003;103:454-46012669007Google Scholar
Original Contribution
February 8, 2006

Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial

Author Affiliations
 

Author Affiliations: Fred Hutchinson Cancer Research Center, Seattle, Wash (Drs Prentice, Patterson, Anderson, LaCroix, and Henderson); Kaiser Permanente Division of Research, Oakland, Calif (Dr Caan); Harbor-UCLA Research and Education Institute, Torrance, Calif (Dr Chlebowski); University of Pittsburgh, Pittsburgh, Pa (Dr Kuller); University of Massachusetts/Fallon Clinic, Worcester (Dr Ockene); University of Minnesota, Minneapolis (Dr Margolis); University of Florida, Gainesville/Jacksonville (Dr Limacher); Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (Dr Manson); University of Miami, Miami, Fla (Dr Parker); Ohio State University, Columbus (Drs Paskett and Jackson); Emory University, Atlanta, Ga (Dr Phillips); University of California at Davis, Sacramento (Dr Robbins); National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Rossouw); University of Wisconsin, Madison (Dr Sarto); University of Alabama, Birmingham (Dr Shikany); Stanford Prevention Research Center, Stanford, Calif (Dr Stefanick); University of Arizona, Tucson/Phoenix (Dr Thomson); Northwestern University, Chicago/Evanston (Dr Van Horn); Wake Forest University School of Medicine, Winston-Salem, NC (Dr Vitolins); State University of New York, Buffalo (Dr Wactawski-Wende); University of Iowa, Iowa City/Davenport (Dr Wallace); Albert Einstein College of Medicine, Bronx, NY (Dr Wassertheil-Smoller); Kaiser Permanente Center for Health Research, Portland, Ore (Dr Whitlock); Pacific Health Research Institute, Honolulu, Hawaii (Dr Yano); MedStar Research Institute and Howard University, Washington, DC (Dr Adams-Campbell); Brown University, Providence, RI (Dr Assaf); University of Washington, Seattle (Dr Beresford); Rush University Medical Center, Chicago, Ill (Dr Black); University of Nevada, Reno (Dr Brunner); University of Texas Health Science Center, San Antonio (Dr Brzyski); National Cancer Institute, Bethesda, Md (Dr Ford); University of Cincinnati, Cincinnati, Ohio (Dr Gass); Baylor College of Medicine, Houston, Tex (Dr Hays); University of California, Los Angeles (Dr Heber); University of North Carolina, Chapel Hill (Dr Heiss); Wayne State University School of Medicine and Hutzel Hospital, Detroit, Mich (Dr Hendrix); George Washington University, Washington, DC (Dr Hsia); University of California, Irvine (Dr Hubbell); University of Tennessee Health Science Center, Memphis (Dr Johnson); Medical College of Wisconsin, Milwaukee (Dr Kotchen); State University of New York, Stony Brook (Dr Lane); University of California at San Diego, LaJolla/Chula Vista (Dr Langer); University of Medicine and Dentistry of New Jersey, Newark (Dr Lasser).

JAMA. 2006;295(6):629-642. doi:10.1001/jama.295.6.629
Abstract

Context The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.

Objective To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.

Design and Setting A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.

Participants A total of 48 835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.

Interventions Women were randomly assigned to the dietary modification intervention group (40% [n = 19 541]) or the comparison group (60% [n = 29 294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.

Main Outcome Measure Invasive breast cancer incidence.

Results Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.

Conclusions Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.

Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00000611

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