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Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.

ABSTRACT: More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer.To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women's Health Initiative (WHI) clinical trials.The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67?142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed.Height and weight were measured at baseline, and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history, and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators.Women who were overweight and obese had an increased invasive breast cancer risk vs women of normal weight. Risk was greatest for obesity grade 2?plus?3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2?plus?3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P?=?.02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P?=?.06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P?=?.05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P?

SUBMITTER: Neuhouser ML

PROVIDER: S-EPMC5070941 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.

Neuhouser Marian L ML Aragaki Aaron K AK Prentice Ross L RL Manson JoAnn E JE Chlebowski Rowan R Carty Cara L CL Ochs-Balcom Heather M HM Thomson Cynthia A CA Caan Bette J BJ Tinker Lesley F LF Urrutia Rachel Peragallo RP Knudtson Jennifer J Anderson Garnet L GL

JAMA oncology 20150801 5

<h4>Importance</h4>More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer.<h4>Objective</h4>To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women's Health Initiative (WHI) clinical trials.<h4>Design, setting, and participants</h4>The WHI clinical trial protocol incorporated measured height and weight, baseline a ...[more]

PMID: 26182172

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Project description:ObjectivesWe evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials.DesignThe hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6.SettingThe Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States.ParticipantsThe trials enrolled 27,347 postmenopausal women, aged 50-79 y.InterventionsWe randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo.Outcome measuresMyocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial.ResultsHazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified.ConclusionsUse of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results.

Project description:Background: The association between thyroid disorders and breast cancer remains controversial, in part, due to small cohort sizes and inconsistent findings. We investigated this association in postmenopausal women to determine whether hyper- or hypothyroidism is associated with the risk of developing breast cancer and to determine whether menopausal hormone therapy (MHT) further modifies the risk. Methods: We conducted a prospective cohort study of multiethnic U.S. postmenopausal women aged 50 to 79 years enrolled in both clinical trial and observational study arms between 1993 and 1998 and followed up through February 28, 2017. Development of invasive breast cancer after enrollment was recorded and a history of hyper- or hypothyroidism before the diagnosis of breast cancer was identified. The effect modification by MHT in both study arms was analyzed. All statistical tests were two sided. Results: Among a total of 134,122 women who were included in our study, 8137 participants developed invasive breast cancer during the follow-up period. There was a significant inverse association of invasive breast cancer among women with a history of hypothyroidism (hazard ratio [HR] 0.91, confidence interval [95% CI] 0.86-0.97) and among women who had taken levothyroxine [HR 0.89, 95% CI 0.82-0.96]. Evaluating effect modification by MHT use, the inverse association between hypothyroidism treated with thyroid replacement medications and breast cancer risk was strongest in non-MHT users [HR 0.80, 95% CI 0.69-0.93]. The results did not significantly differ by race/ethnicity. Although a history of hyperthyroidism was associated with an increased risk of invasive breast cancer [HR 1.11, 95% CI 0.91-1.35], this finding did not reach statistical significance. We did not see significant differences in the breast cancer Surveillance, Epidemiology, and End Results stages, histologic types, morphologic grades, or receptor status (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) according to thyroid disorder status. Conclusions: Compared with women with no history of thyroid disorder, hypothyroidism was associated with a lower risk of breast cancer. This was mainly seen among those who received thyroid replacement therapy and had never used MHT. Among the treatment options for hypothyroidism, levothyroxine had the strongest inverse association with breast cancer risk.

Project description:ObjectivesTo determine associations between postmenopausal change in body weight and incidence of fracture and associations between voluntary and involuntary weight loss and risk of fracture.DesignPost hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials.Setting40 clinical centers in the United States.Participants120,566 postmenopausal women, aged 50-79 at baseline (1993-98), followed through 2013 (mean fracture follow-up duration 11 years from baseline).ExposuresAnnualized percentage change in measured body weight from baseline to year 3, classified as stable (<5% change), weight loss (≥ 5%), or weight gain (≥ 5%). Self assessment of whether weight loss was intentional or unintentional. Cox proportional hazards regression models were adjusted for age, race/ethnicity, baseline body mass index (BMI), smoking, alcohol intake, level of physical activity, energy expenditure, calcium and vitamin D intake, physical function score, oophorectomy, hysterectomy, previous fracture, comorbidity score, and drug use.Main outcomesIncident self reported fractures of the upper limbs, lower limbs, and central body; hip fractures confirmed by medical records.ResultsMean participant age was 63.3. Mean annualized percent weight change was 0.30% (95% confidence interval 0.28 to 0.32). Overall, 79,279 (65.6%) had stable weight; 18,266 (15.2%) lost weight; and 23,021 (19.0%) gained weight. Compared with stable weight, weight loss was associated with a 65% higher incidence rates of fracture in hip (adjusted hazard ratio 1.65, 95% confidence interval 1.49 to 1.82), upper limb (1.09, 1.03 to 1.16), and central body (1.30, 1.20 to 1.39); weight gain was associated with higher incidence rates of fracture in upper limb (1.10, 1.05 to 1.18) and lower limb (1.18, 1.12 to 1.25). Compared with stable weight, unintentional weight loss was associated with a 33% higher incidence rates of hip fracture (1.33, 1.19 to 1.47) and increased incidence rates of vertebral fracture (1.16, 1.06 to 1.26); intentional weight loss was associated with increased incidence rates of lower limb fracture (1.11, 1.05 to 1.17) and decreased incidence of hip fracture (0.85, 0.76 to 0.95).ConclusionsWeight gain, weight loss, and intentional weight loss are associated with increased incidence of fracture, but associations differ by fracture location. Clinicians should be aware of fracture patterns after weight gain and weight loss.

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Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.

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Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.

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