An NCI-designated Comprehensive Cancer Center
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Rowan Chlebowski, M.D., Ph.D.

Research Professor, Department of Medical Oncology & Therapeutics Research
Research Focus
  • Breast cancer

Research Teams

  • Medical Oncology & Therapeutics Research
Rowan Chlebowski, M.D., Ph.D., is one of the most influential breast cancer researchers in the world. As a clinical breast oncologist with a Ph.D. in reproductive biology, he has a credentialed clinical and research interest in breast cancer therapy and prevention, menopausal hormone therapy influences on cancer and chronic disease, and lifestyle influences on breast cancer incidence and outcome. He is best known for studying breast cancer issues in the Women's Health Initiative (WHI). He has published widely and led reports in well-cited journals such as JAMA, New England Journal of Medicine, Lancet, Lancet Oncology, Journal of Clinical Oncology, Journal of the National Cancer Institute and JAMA Oncology.
 
Dr. Chlebowski has received accolades and awards from the American Society of Clinical Oncology, the American Association for Cancer Research and other distinguished societies. He was one of 13 named WHI investigators awarded the "2016 AACR Team Science Award" for groundbreaking work in the women's health area. Based on his body of publications, Dr. Chlebowski has been on the Thomson Reuters "Most Influential Scientific Minds" for the last two years, which is based on the highest number of highly cited papers over the most recent decade, defined as the top 1 percent most cited in the area of clinical medicine. He is one of only 14 breast oncologists on the worldwide list.
 
Chlebowski RT, Aragaki AK, Thomson CA, Anderson GL, Manson JE, Simon MS, Rohan TE, Snetselaar L, Barrington W, Vitolins M, Womack C, Qi L, Hou L, Thomas F, Prentice RL. Low-fat dietary pattern and breast cancer mortality in the Women’s Health Initiative (WHI) randomized controlled trial.  J Clin Oncol 2017 Jun 27:JCO2016720326. DOI: 10.1200/JCO.2016.72.0326. [Epub ahead of print]

ABSTRACT
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, 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 during 16.1 years (median) of follow-up.

Patients and Methods
The trial randomly assigned 48,835 postmenopausal women with normal mammograms 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<0.001). During the 8.5 year dietary intervention, fewer deaths occurred as a result of breast cancer in the dietary group, which was not statistically significant (hazard ratio [HR], 0.67; 95% CI, 0.43 to 1.06; P=0.08). During the same period, deaths after breast cancer were significantly reduced (HR 0.65; 95% CI, 0.45-0.94; P=0.02) by the dietary intervention. During the 16.1 year follow-up, with deaths after breast cancer also were significantly reduced (HR 0.82; 95% CI, 0.70 to 0.96; P=0.01) 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.

Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, Manson JE, Stefanick ML, Ockene J, Sarto GE, Ravdin PM, Schenken R, Hendrix SL, Rajkovic A, Rohan TE, Yasmeen S, Prentice RL. Influence of estrogen plus progestin on breast cancer incidence and mortality. JAMA 2010; 304(15):1684-1692.

CONTEXT: in the Women’s Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy.

OBJECTIVE: To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality.

DESIGN, SETTING, AND PARTICIPANTS: A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill.

MAIN OUTCOME MEASURES: Invasive breast cancer incidence and breast cancer mortality.

RESULTS: In intention-to-treat analyses, estrogen plus progestin was associated with more invasive breast cancers compared with placebo. There were more deaths directly attributed to breast cancer (HR 1.96; 95% CI, 1.00-4.04; P=0.049) as well as more deaths from all causes occurring after a breast cancer diagnosis (HR 1.57; 95% CI, 1.01-2.48; P=0.045) among women who received estrogen plus progestin compared with women in the placebo group.

CONCLUSIONS: Estrogen plus progestin was associated with greater breast cancer incidence. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.
 
Chlebowski RT, Kuller L, Prentice RL, Stefanick M, Manson J, Gass M, Aragaki A, Ockene J, Lane D, Sarto G, Schenken R, Hendrix S, Ravdin P, Rohan T, Yasmeen S, Anderson G. Breast cancer after estrogen plus progestin use in postmenopausal women. N Engl J Med 2009; 360(6):573-587.

BACKGROUND
Following the release of the 2002 report of the Women’s Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.

METHODS
We analyzed the results of the WHI randomized clinical trial – in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo – and examined temporal trends in breast cancer diagnoses.

RESULTS
In the clinical trial, an increase in breast cancer diagnoses was seen in the group receiving estrogen plus progestin over the course of the 5.6 year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography.

CONCLUSIONS
The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.

Chlebowski RT, Blackburn G, Thomson CA, Nixon DW, Shapiro A, Hoy MK, Goodman MT, Giuliano AE, Karanja N, McAndrew P, Hudis C, Butler J, Merkel D, Kristal A, Caan B, Michaelson R, Vinciguerra V, Del Prete S, Winkler M, Hall R, Simon M, Winters BL, Elashoff RM. Dietary fat reduction and breast cancer outcome: Interim efficacy results from the Women’s Intervention Nutrition Study (WINS) J Natl Cancer Inst 98(24):1767-76, 2006.

BACKGROUND: Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management.

METHODS: A total of 2,437 women were randomly assigned dietary intervention (n=975) or control (n=1462). Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided.

RESULTS: Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, P<0.001) (corresponding to a statistically significant P=0.005), 6 pounds lower mean body weight in the intervention group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI, 0.60-0.98, P=0.77 for stratified log rank and P=0.034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status.

CONCLUSIONS: A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management.
 
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