Rowan T Chlebowski

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States

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Publications (412)3995.93 Total impact

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    ABSTRACT: Background: The Breast Cancer Risk Assessment Tool (BCRAT, "Gail model") is commonly used for breast cancer prediction; however, it has not been validated for women age 75 years and older. Methods: We used Nurses' Health Study (NHS) data beginning in 2004 and Women's Health Initiative (WHI) data beginning in 2005 to compare BCRAT's performance among women age 75 years and older with that in women age 55 to 74 years in predicting five-year breast cancer incidence. BCRAT risk factors include: age, race/ethnicity, age at menarche, age at first birth, family history, history of benign breast biopsy, and atypia. We examined BCRAT's calibration by age by comparing expected/observed (E/O) ratios of breast cancer incidence. We examined discrimination by computing c-statistics for the model by age. All statistical tests were two-sided. Results: Seventy-three thousand seventy-two NHS and 97 081 WHI women participated. NHS participants were more likely to be non-Hispanic white (96.2% vs 84.7% in WHI, P < .001) and were less likely to develop breast cancer (1.8% vs 2.0%, P = .02). E/O ratios by age in NHS were 1.16 (95% confidence interval [CI] = 1.09 to 1.23, age 57-74 years) and 1.31 (95% CI = 1.18 to 1.45, age ≥ 75 years, P = .02), and in WHI 1.03 (95% CI = 0.97 to 1.09, age 55-74 years) and 1.10 (95% CI = 1.00 to 1.21, age ≥ 75 years, P = .21). E/O ratio 95% confidence intervals crossed one among women age 75 years and older when samples were limited to women who underwent mammography and were without significant illness. C-statistics ranged between 0.56 and 0.58 in both cohorts regardless of age. Conclusions: BCRAT accurately predicted breast cancer for women age 75 years and older who underwent mammography and were without significant illness but had modest discrimination. Models that consider individual competing risks of non-breast cancer death may improve breast cancer risk prediction for older women.
    No preview · Article · Mar 2016 · JNCI Journal of the National Cancer Institute
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    ABSTRACT: Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.
    No preview · Article · Mar 2016 · JNCI Journal of the National Cancer Institute
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    ABSTRACT: Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p<0.001), and of several site-specific cancers (HR, 1.2-1.4, and up to over 2-fold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p<0.001). There was no overall difference in cancer incidence by diabetes therapy (p=0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 versus 1.45; p=0.007) and for breast cancer (HRs, 0.50 versus 1.29; p=0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · International Journal of Cancer
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    ABSTRACT: In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.
    No preview · Article · Nov 2015 · Breast Cancer Research and Treatment
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    ABSTRACT: For African American or Hispanic women, the extent to which clinical breast cancer risk prediction models are improved by including information on susceptibility single nucleotide polymorphisms (SNPs) is unknown, even though these women comprise increasing proportions of the US population and represent a large proportion of the world's population. We studied 7539 African American and 3363 Hispanic women from the Women's Health Initiative. The age-adjusted 5-year risks from the BCRAT and IBIS risk prediction models were measured and combined with a risk score based on >70 independent susceptibility SNPs. Logistic regression, adjusting for age group, was used to estimate risk associations with log-transformed age-adjusted 5-year risks. Discrimination was measured by the odds ratio (OR) per standard deviation (SD) and the area under the receiver operator curve (AUC). When considered alone, the ORs for African American women were 1.28 for BCRAT, and 1.04 for IBIS. When combined with the SNP risk score (OR 1.23), the corresponding ORs were 1.39 and 1.22. For Hispanic women the corresponding ORs were 1.25 for BCRAT, and 1.15 for IBIS. When combined with the SNP risk score (OR 1.39), the corresponding ORs were 1.48 and 1.42. There was no evidence that any of the combined models were not well calibrated. Including information on known breast cancer susceptibility loci provides approximately 10 and 19 % improvement in risk prediction using BCRAT for African Americans and Hispanics, respectively. The corresponding figures for IBIS are approximately 18 and 26 %, respectively.
    Preview · Article · Nov 2015 · Breast Cancer Research and Treatment
  • Marian L Neuhouser · Rowan T Chlebowski · Garnet L Anderson

    No preview · Article · Nov 2015
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    ABSTRACT: Introduction: In the Women's Health Initiative (WHI) estrogen plus progestin trial, after 5.6 years' intervention and 8 years' median follow-up, more women died from lung cancer in the hormone therapy group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.16-2.52; P = .01). Now after 14 years' median follow-up, we reexamined combined hormone therapy effects on lung cancer mortality. Patients and methods: In the WHI placebo-controlled trial, 16,608 postmenopausal women aged 50 to 79 years and with an intact uterus were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Incidence and mortality rates for lung cancer were assessed from multivariant proportional hazard models. Results: After 14 years' cumulative follow-up, there were 219 lung cancers (0.19% per year) in the estrogen plus progestin group and 184 (0.17%) in the placebo group (HR, 1.12; 95% CI, 0.92-1.37; P = .24). While there were more deaths from lung cancer with combined hormone therapy (153 [0.13%] vs. 132 [0.12%], respectively), the difference was not statistically significant (HR, 1.09; 95% CI, 0.87-1.38; P = .45). The statistically significant increase in deaths from lung cancer observed during intervention in women assigned to estrogen plus progestin was attenuated after discontinuation of study pills (linear trend over time, P = .042). Conclusion: The increased risk of death from lung cancer observed during estrogen plus progestin use was attenuated after discontinuation of combined hormone therapy.
    No preview · Article · Oct 2015 · Clinical Lung Cancer
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    ABSTRACT: Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited. In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided. The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%. These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity-breast cancer relation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Sep 2015 · Journal of the National Cancer Institute
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    ABSTRACT: Estrogens are important immunomodulators, exerting significant effects on cell proliferation, apoptosis, cytokine production and differentiation of hematopoietic cells. Estrogen receptors are expressed on normal B and T lymphocytes, bone marrow and in leukemia and lymphoma cell lines. Epidemiologic evidence for the association of menopausal hormone use with risk of non-Hodgkin's lymphoma (NHL) has been mixed; however, all of the investigations have been observational. We analyzed the data from Women's Health Initiative hormone therapy trials where conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n=16654) or CEE alone (women with prior hysterectomy) (n=10685) were tested against placebos and the intervention lasted a median of 5.6 years in the CEE + MPA trial and 7.2 years in the CEE alone trial. During 13 years of follow-up through September 20, 2013 383 incident NHL cases were identified. We used the intent-to-treat approach to calculate incidence rates of NHL, hazards ratios (HR) and 95% confidence intervals (CI) by treatment group. Incidence of NHL was virtually the same in the treatment and placebo groups. The HR was 1.02 (95%CI 0.74-1.39) for CEE alone, 0.98 (95% CI 0.76-1.28) for CEE+MPA, and 1.00 (95% CI 0.82-1.22) for both combined. There were no specific NHL subtypes associated with either type of the treatment, except a marginally decreased risk of plasma cell neoplasms (HR= 0.53 95% CI 0.27-1.03) in the CEE-alone group. These results do not support a role of estrogen alone or combined with progestin in the development of NHL among postmenopausal women. This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2015 · International Journal of Cancer
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    ABSTRACT: The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis. Women (n=2833) with centrally confirmed invasive breast cancer in the Women's Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality. Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23-2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86-2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality. Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality.British Journal of Cancer advance online publication: 9 July 2015; doi:10.1038/bjc.2015.249 www.bjcancer.com.
    No preview · Article · Jul 2015 · British Journal of Cancer
  • Rowan T Chlebowski · Aaron K Aragaki · Garnet L Anderson
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    ABSTRACT: The Woman's Health Initiative has conducted 2 full-scale, placebo-controlled clinical trials to determine the influence of menopausal therapy on breast cancer incidence and outcome. Estrogen plus progestin use in postmenopausal women with a uterus increases breast cancer incidence and deaths from breast cancer. Despite a short-term reduction in risk after stopping estrogen plus progestin use, an increase in breast cancer risk persists postintervention. Estrogen-alone use in postmenopausal women with prior hysterectomy reduces breast cancer incidence and reduces deaths from breast cancer. The reduced breast cancer risk persists for several years after stopping estrogen-alone use but is lost in late postintervention. These findings suggest recalibration of breast cancer risk and benefit consideration for both regimens, with estrogen plus progestin use associated with greater risk and estrogen-alone use associated with greater benefit. Use of either regimen in clinical practice requires careful consideration of all clinical risks and benefits. Copyright © 2015 by the National Comprehensive Cancer Network.
    No preview · Article · Jul 2015 · Journal of the National Comprehensive Cancer Network: JNCCN
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    ABSTRACT: Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women’s Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32–1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13–0.86, p trend = 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18–1.03, p trend = 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.
    Full-text · Article · Jun 2015 · Journal of Cancer Epidemiology
  • Rowan T Chlebowski

    No preview · Article · Jun 2015 · The Lancet Oncology
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    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 < .001). Women with a baseline BMI of less than 25.0 who gained more than 5% of body weight over the follow-up period had an increased breast cancer risk (HR, 1.36; 95% CI, 1.1-1.65), but among women already overweight or obese we found no association of weight change (gain or loss) with breast cancer during follow-up. There was no effect modification of the BMI-breast cancer relationship by postmenopausal hormone therapy, and the direction of association across BMI categories was similar for never, past, and current hormone therapy use. Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention. clinicaltrials.gov Identifier: NCT00000611.
    No preview · Article · Jun 2015
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    ABSTRACT: The use of menopausal hormone therapy (HT) continues in clinical practice, but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use. To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women's Health Initiative (WHI) randomized clinical trials. A total of 27 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010. A total of 16 608 women with a uterus were randomized to conjugated equine estrogens (0.625 mg/d [estrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) (E + P) or placebo with a median intervention duration of 5.6 years, and 10 739 women with prior hysterectomy were randomized to conjugated equine estrogens alone (0.625 mg/d) or placebo with a median intervention duration of 7.2 years. Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials. In the E + P trial, hazard ratios (HRs) for the influence of combined HT on breast cancer were lower than 1 for 2 years (HR, 0.71; 95% CI, 0.47-1.08) and steadily increased throughout intervention, becoming significantly increased for the entire intervention phase (HR, 1.24; 95% CI, 1.01-1.53). In the early postintervention phase (within 2.75 years from intervention), there was a sharp decrease in breast cancer incidence in the combined HT group, though the HR remained higher than 1 (HR, 1.23; 95% CI, 0.90-1.70). During the late postintervention phase (requiring patient re-consent), the HR for breast cancer risk remained higher than 1 through 5.5 years (median) of additional follow-up (HR, 1.37; 95% CI, 1.06-1.77). In the estrogen alone trial, the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase (HR, 0.79; 95% CI, 0.61-1.02) and remained lower than 1 in the early postintervention phase (HR, 0.55; 95% CI, 0.34-0.89), but risk reduction was not observed during the late postintervention follow-up (HR, 1.17; 95% CI, 0.73-1.87). Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials. In the E + P trial, the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase, but a higher breast cancer risk remained during the late postintervention follow-up. In the estrogen alone trial, the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up.
    No preview · Article · Jun 2015
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    ABSTRACT: In an invited editorial, Dr Shapiro proposes that vaginal bleeding leading to unblinding and subsequent detection bias explains the breast cancer increase seen with estrogen plus progestin in the Women's Health Initiative (WHI) clinical trial (1) . In the context of a uniform detection program of protocol-mandated annual mammography and breast examinations, such a proposal is medically implausible. Dr Shapiro suggests detection bias would identify a larger number of 'slowly growing tumors that would otherwise remain clinically silent'. The findings of more advanced cancers with increased deaths from breast cancer in the estrogen plus progestin group refute this conjecture. During early post-intervention phases of both WHI hormone therapy trials, when breast cancer detection bias is asserted by Dr Shapiro because participants had been informed of randomization assignment, breast cancer incidence rates were lower (rather than higher) than during intervention. Thus, Dr Shapiro's claims are directly refuted by findings from the WHI randomized clinical trials. Health-care providers should be aware that randomized clinical trial evidence supports estrogen plus progestin increasing breast cancer incidence and deaths from breast cancer. In contrast, among women with prior hysterectomy, randomized clinical trial evidence supports estrogen alone reducing breast cancer incidence and deaths from breast cancer.
    No preview · Article · Jun 2015 · Climacteric

  • No preview · Article · May 2015 · Cancer Research

  • No preview · Article · May 2015 · Cancer Research
  • Rowan T Chlebowski · George L Blackburn

    No preview · Article · May 2015 · Cancer Research
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    ABSTRACT: BACKGROUND The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer.METHODS The WHI study was a randomized, double-blind, placebo-controlled trial involving 10,739 postmenopausal women with prior hysterectomy. Participants were assigned to conjugated equine estrogen at 0.625 mg/d (n = 5279) or a matching placebo (n = 5409). Rates of colorectal cancer diagnoses and deaths from and after colorectal cancer were assessed throughout the study.RESULTSColorectal cancer rates in the estrogen-alone and placebo groups were comparable: 0.14% and 0.12% per year, respectively (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.83-1.58; P = .43). Bowel screening examinations were comparable between the 2 groups throughout the study. The grade, stage, and location of colorectal cancer did not differ between the randomization groups. There were more colorectal cancer deaths in the estrogen-alone group (34 [0.05%] vs 24 [0.03%]; HR, 1.46, 95% CI, 0.86-2.46; P = .16), but the difference was not statistically significant. The colorectal cancer incidence was higher for participants with a history of colon polyp removal in the estrogen-alone group (0.23% vs 0.02%; HR, 13.47; nominal 95% CI, 1.76-103.0; P < .001).CONCLUSIONS The use of estrogen alone in postmenopausal women with prior hysterectomy does not influence the incidence of colorectal cancer or deaths from or after colorectal cancer. A possibly higher risk of colorectal cancer in women with prior colon polyp removal who use estrogen alone requires confirmation. Cancer 2015. © 2015 American Cancer Society.
    No preview · Article · May 2015 · Cancer

Publication Stats

23k Citations
3,995.93 Total Impact Points

Institutions

  • 2003-2015
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, Washington, United States
    • George Washington University
      Washington, Washington, D.C., United States
  • 1987-2015
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
    • Emory University
      Atlanta, Georgia, United States
  • 1980-2015
    • Harbor-UCLA Medical Center
      • Department of Pediatrics
      Torrance, California, United States
    • University of California, Los Angeles
      • • Division of Hematology and Medical Oncology
      • • Department of Medicine
      Los Ángeles, California, United States
  • 2012-2014
    • Torrance Memorial Medical Center
      Torrance, California, United States
  • 2013
    • University of Balamand
      • Faculty of Health Sciences
      Amiun, Liban-Nord, Lebanon
  • 2003-2010
    • Stanford University
      • Department of Medicine
      Palo Alto, California, United States
  • 2008
    • Maine Medical Center
      Portland, Maine, United States
  • 2007
    • University of Alabama at Birmingham
      • Division of Preventive Medicine
      Birmingham, Alabama, United States
  • 2006
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
  • 2005
    • University of Hamburg
      Hamburg, Hamburg, Germany
    • University of Oxford
      Oxford, England, United Kingdom
  • 2002
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1999
    • American Society of Clinical Oncology
      Alexandria, Virginia, United States
  • 1996
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1990
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 1980-1982
    • University of Southern California
      • Department of Medicine
      Los Angeles, California, United States