Estrogen and colorectal cancer incidence and mortality.

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. RESULTS: Colorectal 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.

Hormone Use, Reproductive History, and Risk of Lung Cancer: The Women's Health Initiative Studies.

INTRODUCTION: Results from the Women's Health Initiative clinical trials demonstrated no increase in the risk of lung cancer in postmenopausal women treated with hormone therapy (HT). We conducted a joint analysis of the Women's Health Initiative observational study data and clinical trials data to further explore the association between estrogen and estrogen-related reproductive factors and lung cancer risk. METHODS: Reproductive history, oral contraceptive use, and postmenopausal HT were evaluated in 160,855 women with known HT exposures. Follow-up for lung cancer was through September 17, 2012; 2467 incident lung cancer cases were ascertained, with median follow-up of 14 years. RESULTS: For all lung cancers, women with previous use of estrogen plus progestin of less than 5 years (hazard ratio = 0.84; 95% confidence interval = 0.71-0.99) were at reduced risk. A limited number of reproductive factors demonstrated associations with risk. There was a trend toward decreased risk with increasing age at menopause (ptrend = 0.04) and a trend toward increased risk with increasing number of live births (ptrend = 0.03). Reduced risk of non-small-cell lung cancer was associated with age 20-29 years at first live birth. Risk estimates varied with smoking history, years of HT use and previous bilateral oophorectomy. CONCLUSIONS: Indirect measures of estrogen exposure to lung tissue, as used in this study, provide only weak evidence for an association between reproductive history or HT use and risk of lung cancer. More detailed mechanistic studies and evaluation of risk factors in conjunction with estrogen receptor expression in the lung should continue as a role for estrogen cannot be ruled out and may hold potential for prevention and treatment strategies.

Mammography interval and breast cancer mortality in women over the age of 75.

The purpose of this study is to evaluate the relationship between mammography interval and breast cancer mortality among older women with breast cancer. The study population included 1,914 women diagnosed with invasive breast cancer at age 75 or later during their participation in the Women's health initiative, with an average follow-up of 4.4 years (3.1 SD). Cause of death was based on medical record review. Mammography interval was defined as the time between the last self-reported mammogram 7 or more months prior to diagnosis, and the date of diagnosis. Multivariable adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) for breast cancer mortality and all-cause mortality were computed from Cox proportional hazards analyses. Prior mammograms were reported by 73.0 % of women from 7 months to ≤2 year of diagnosis (referent group), 19.4 % (>2 to <5 years), and 7.5 % (≥5 years or no prior mammogram). Women with the longest versus shortest intervals had more poorly differentiated (28.5 % vs. 22.7 %), advanced stage (25.7 % vs. 22.9 %), and estrogen receptor negative tumors (20.9 % vs. 13.1 %). Compared to the referent group, women with intervals of >2 to <5 years or ≥5 years had an increased risk of breast cancer mortality (HR 1.62, 95 % CI 1.03-2.54) and (HR 2.80, 95 % CI 1.57-5.00), respectively, p trend = 0.0002. There was no significant relationship between mammography interval and other causes of death. These results suggest a continued role for screening mammography among women 75 years of age and older.

Racial/ethnic differences in use and duration of adjuvant hormonal therapy for breast cancer in the women's health initiative.

BACKGROUND: Five-year breast cancer survival rates are lower among Hispanic and African-American women than among Non-Hispanic White women. Differences in breast cancer treatment likely play a role. Adjuvant hormonal therapies increase overall survival among women with hormone receptor-positive breast cancer. METHODS: We examined racial/ethnic differences in use and duration of adjuvant hormonal therapy among 3,588 postmenopausal women enrolled in the Women's Health Initiative (WHI) Extension Study. Women diagnosed with hormone receptor-positive localized or regional stage breast cancer after study enrollment were surveyed between September 2009 and August 2010 and asked to recall prior use and duration of adjuvant hormonal breast cancer therapy. ORs comparing self-reported use and duration with race/ethnicity (Hispanic, African-American, Asian/Pacific Islander vs. Non-Hispanic White) were estimated using multivariable-adjusted logistic regression. RESULTS: Of the 3,588 women diagnosed from 1994 to 2009; 3,039 (85%) reported any use of adjuvant hormonal therapy, and 67% of women reporting ever-use who were diagnosed before 2005 reported using adjuvant hormonal therapy for the optimal duration of 5 years or more. In adjusted analysis, no statistically significant differences in use or duration by race/ethnicity were observed. CONCLUSIONS: This study did not find significant differences in use or duration of use of adjuvant hormonal therapy by race/ethnicity. IMPACT: Findings should be confirmed in other population-based samples, and potential reasons for discontinuation of therapy across all racial/ethnic groups should be explored. Cancer Epidemiol Biomarkers Prev; 22(3); 365-73. ©2012 AACR.

Estrogen plus progestin and colorectal cancer incidence and mortality.

PURPOSE: During the intervention phase in the Women's Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up. PATIENTS AND METHODS: The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed. RESULTS: After a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P = .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320). CONCLUSION: The findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer.

Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.

BACKGROUND: By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort. METHODS: Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50-79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611. FINDINGS: After a median follow-up of 11·8 years (IQR 9·1-12·9), the use of oestrogen for a median of 5·9 years (2·5-7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62-0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61-1·02) and post-intervention phase effects (0·75, 0·51-1·09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13-0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39-0·97; p=0·04). INTERPRETATION: Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer. FUNDING: US National Heart, Lung, and Blood Institute; Wyeth.

Evaluating breast cancer risk projections for Hispanic women.

For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model") combines 1990-1996 breast cancer incidence for Hispanic women with relative risks for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk projections have never been comprehensively evaluated for Hispanic women. We compared the relative risks and calibration of BCRAT risk projections for 6,353 Hispanic to 128,976 NHW postmenopausal participants aged 50 and older in the Women's Health Initiative (WHI). Calibration was assessed by the ratio of the number of breast cancers observed with that expected by the BCRAT (O/E). We re-evaluated calibration for an updated BCRAT that combined BCRAT relative risks with 1993-2007 breast cancer incidence that is contemporaneous with the WHI. Cox regression was used to estimate relative risks. Discriminatory accuracy was assessed using the concordance statistic (AUC). In the WHI Main Study, the BCRAT underestimated the number of breast cancers by 18% in both Hispanics (O/E = 1.18, P = 0.06) and NHWs (O/E = 1.18, P < 0.001). Updating the BCRAT improved calibration for Hispanic women (O/E = 1.08, P = 0.4) and NHW women (O/E = 0.98, P = 0.2). For Hispanic women, relative risks for number of breast biopsies (1.71 vs. 1.27, P = 0.03) and age at first birth (0.97 vs. 1.24, P = 0.02) differed between the WHI and BCRAT. The AUC was higher for Hispanic women than NHW women (0.63 vs. 0.58, P = 0.03). Updating the BCRAT with contemporaneous breast cancer incidence rates improved calibration in the WHI. The modest discriminatory accuracy of the BCRAT for Hispanic women might improve by using risk factor relative risks specific to Hispanic women.

Racial differences in colorectal cancer incidence and mortality in the Women's Health Initiative.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates are higher in African-Americans as compared with other racial/ethnic groups. The women's health initiative (WHI) study sample was used to determine whether differences in CRC risk factors explain racial/ethnic differences in incidence and mortality. METHODS: The WHI is a longitudinal study of postmenopausal women recruited from 40 centers. Baseline questionnaires were used to collect sociodemographic and health status information. All CRC diagnoses were centrally adjudicated. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by race/ethnicity. RESULTS: The study sample included 131,481 (83.7%) White, 14,323 (9.1%) African-American, 6,362 (4.1%) Hispanic, 694 (0.4%) Native American and 4,148 (2.6%) Asian/Pacific Islanders. After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was the highest in African-Americans (annualized rate = 0.14%), followed by Whites and Native Americans (0.12% each), Asian/Pacific Islanders (0.10%), and Hispanics (0.08%). After adjustment for age and trial assignment, Hispanics had a lower risk compared with Whites, HR 0.73 (95% CI: 0.54-0.97) (P = 0.03), and African-Americans had a marginally greater risk, HR 1.16 (95% CI: 0.99-1.34), P = 0.06. Multivariable adjustment attenuated the difference in incidence between African-Americans and Whites (HR 0.99, 95% CI: 0.82-1.20), while strengthening the lower HR for Hispanics (HR 0.68, 95% CI: 0.48-0.97). CONCLUSIONS: African-American/White differences in CRC risk are likely due to sociodemographic/cultural factors other than race. IMPACT: A number of modifiable exposures could be a focus for reducing CRC risk in African-Americans.

Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers.

BACKGROUND: Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear. METHODS: In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided. RESULT: The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors. CONCLUSION: Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.

25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women.

INTRODUCTION: Low 25-hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms. STUDY DESIGN: Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial. MAIN OUTCOME MEASURES: 25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling. RESULTS: The 25(OH) D levels were commonly low with 53% having deficient (<50 nmol/L) and only 17% having sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R=0.29, p<0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P=0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile. CONCLUSIONS: Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials.

Lung cancer among postmenopausal women treated with estrogen alone in the women's health initiative randomized trial.

BACKGROUND: In the Women's Health Initiative (WHI) randomized controlled trial, use of estrogen plus progestin increased lung cancer mortality. We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer. METHODS: The WHI study is a randomized, double-blind, placebo-controlled trial conducted in 40 centers in the United States. A total of 10 739 postmenopausal women aged 50-79 years who had a previous hysterectomy were randomly assigned to receive a once-daily 0.625-mg tablet of conjugated equine estrogen (n = 5310) or matching placebo (n = 5429). Incidence and mortality rates for all lung cancers, small cell lung cancers, and non-small cell lung cancers in the two randomization groups were compared by use of hazard ratios (HRs) and 95% confidence intervals (CIs) that were estimated from Cox proportional hazards regression analyses. Analyses were by intention to treat, and all statistical tests were two-sided. RESULTS: After a mean of 7.9 years (standard deviation = 1.8 years) of follow-up, 61 women in the hormone therapy group were diagnosed with lung cancer compared with 54 in the placebo group (incidence of lung cancer per year = 0.15% vs 0.13%, respectively; HR of incidence = 1.17, 95% CI = 0.81 to 1.69, P = .39). Non-small cell lung cancers were of comparable number, stage, and grade in both groups. Deaths from lung cancer did not differ between the two groups (34 vs 33 deaths in estrogen and placebo groups, respectively; HR of death = 1.07, 95% CI = 0.66 to 1.72, P = .79). CONCLUSION: Unlike use of estrogen plus progestin, which increased deaths from lung cancer, use of conjugated equine estrogen alone did not increase incidence or death from lung cancer.

Estrogen alone in postmenopausal women and breast cancer detection by means of mammography and breast biopsy.

PURPOSE: As the influence of estrogen alone on breast cancer detection is not established, we examined this issue in the Women's Health Initiative trial, which randomly assigned 10,739 postmenopausal women with prior hysterectomy to conjugated equine estrogen (CEE; 0.625 mg/d) or placebo. METHODS: Screening mammography and breast exams were performed at baseline and annually. Breast biopsies were based on clinical findings. Effects of CEE alone on breast cancer detection were determined by using receiver operating characteristic (ROC) analyses of mammogram performance. RESULTS: After a 7.1-year mean follow-up, fewer invasive breast cancers were diagnosed in the CEE than in the placebo group, but the difference was not statistically significant. Use of CEE alone increased mammograms with short-interval follow-up recommendations (cumulative, 39.2% v 29.6.3%; P < .001) but not abnormal mammograms (ie, those suggestive of or highly suggestive of malignancy; cumulative, 7.3% v 7.0%; P = .41). Breast biopsies were more frequent in the CEE group (cumulative, 12.5% v 10.7%; P = .004) and less commonly diagnosed as cancer (8.9% v 15.8%, respectively, with positive biopsies; P = .04). Mammographic breast cancer detection in the CEE group was significantly compromised only in the early years of use. CONCLUSION: CEE alone use for 5 years results in approximately one in 11 and one in 50 women having otherwise avoidable mammograms with short-interval follow-up recommendations or breast biopsies, respectively. Although the breast biopsies on CEE were less commonly diagnosed as cancer, breast cancer detection was not substantially compromised. These findings differ from estrogen-plus-progestin use, for which significantly increased abnormal mammograms and a compromise in breast cancer detection are seen.

Social Support for Chamorro Breast Cancer Survivors on Guam.

PURPOSE: The purpose of this study was to assess the types of social support used by Chamorro (indigenous) breast cancer survivors on Guam. METHODS: We assessed social support use among 25 self-reported Chamorro women with a diagnosis of breast cancer through interviews and construction of genograms and ecomaps -pictorial displays of the women's family relationships, medical history, and their social networks. RESULTS: The mean age of the participants was 54.5 years. The average number of years since the diagnosis of breast cancer was 7.8 years. Respondents indicated that the nuclear family was the most important form of social support (34.2%). Indeed, nuclear family and other types of informal systems were the most common type of social support used by the women (60.2%). Formal support services, clubs, and organizations were reported by 17.9% of participants while spiritual and/or religious resources were reported by 21.9% of them. CONCLUSION: These Chamorro breast cancer survivors depended largely on family for social support. Support from family, although informal, should be recognized as a pivotal factor in recovery and survivorship. Future directions could incorporate formal and informal mechanisms to utilize this natural support resource.

Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial.

BACKGROUND: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period. METHODS: The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611. FINDINGS: After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups. INTERPRETATION: Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer. FUNDING: National Heart, Lung and Blood Institute, National Institutes of Health.

Vasomotor symptoms, adoption of a low-fat dietary pattern, and risk of invasive breast cancer: a secondary analysis of the Women's Health Initiative randomized controlled dietary modification trial.

PURPOSE: To assess whether the effect of a low-fat dietary pattern on breast cancer incidence varied by report of baseline vasomotor symptoms. METHODS: Postmenopausal women age 50 to 79 years enrolled onto the Women's Health Initiative (WHI) Dietary Modification trial from 1993 to 1998 were randomly assigned to a low-fat dietary intervention (n = 19,541) or comparison (n = 29,294). Presence of vasomotor symptoms at baseline was ascertained from a 34-item self-report symptom inventory. Women were queried semi-annually for a new diagnosis of breast cancer. Each case report was verified by medical record and pathology report review by centrally trained WHI physician adjudicators. RESULTS: Among participants who reported hot flashes (HFs) at baseline (n = 3,375), those assigned to the low-fat diet had a breast cancer rate of 0.27 compared with their counterparts in the control group who had a rate of 0.41 (hazard ratio [HR] = 0.65; 95% CI, 0.42 to 1.01). Among women reporting no HFs (n = 45,160), the breast cancer rate was 0.42 in those assigned to the low-fat diet compared with 0.46 in the control group (HR = 0.93; 95% CI, 0.84 to 1.03; P for interaction = .12 by HF status). Furthermore, the dietary benefits observed seemed to be specific to estrogen receptor (ER) -positive/progesterone receptor (PR) -positive tumors (ER positive/PR positive v other, P for risk = .03). Although women with and without HFs differed with regard to breast cancer risk factors, the effect of the diet intervention on breast cancer incidence by HF status was consistent across risk factor strata. CONCLUSION: The results of this trial, which are hypothesis generating, suggest that HFs may identify a subgroup of postmenopausal women whose risk of invasive breast cancer might be reduced with the adoption of a low-fat eating pattern.

Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women's Health Initiative clinical trial and observational study.

BACKGROUND: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. PARTICIPANTS AND METHODS: Postmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. RESULTS: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. CONCLUSION: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up.

Calcium plus vitamin D supplementation and the risk of breast cancer.

BACKGROUND: Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships. METHODS: Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided. RESULTS: Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20). CONCLUSIONS: Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

Self-sampling for human papillomavirus in a community setting: feasibility in Hispanic women.

BACKGROUND: The aim of the study was (a) to assess sensitivity and specificity of self-sampling in a community setting for identifying high-risk human papillomavirus (HPV) infection and abnormal Papanicolaou (Pap) smears and (b) to assess satisfaction with this collection method among Hispanic women. METHODS: Lay health workers distributed self-collection kits to Hispanic women in the community. Participants collected an unsupervised vaginal sample at home or in the place and time of their preference. RESULTS: A total of 1,213 Hispanics were included and provided a self-sample for HPV testing and were invited for a Pap smear; 662 (55%) of them had a Pap smear and the first 386 of these also had a physician-collected sample for HPV retesting. Using physician collection as the gold standard, unsupervised self-collection had a sensitivity of 90% and specificity of 88% for identifying high-risk HPV. Compared with physician sampling, self-sampling in a community setting had comparable sensitivity for identifying a low-grade lesions or greater in the Pap smear (50% versus 55%; P = 0.45) but lower specificity (94% versus 79%). Overall experience with self-sampling was reported as excellent or very good by 64% and only 2.6% reported a poor or fair experience. CONCLUSIONS: Unsupervised self-collection of vaginal samples for HPV testing in a community setting has a high sensitivity for identifying high-risk HPV and a high satisfaction among Hispanics. This approach may benefit populations with limited access to health care or with cultural barriers to cervical cancer screening.

Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study.

The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

Cancer-related knowledge, attitudes, and behaviors among Chamorros on Guam.

BACKGROUND: Cancer is the second leading cause of death among Chamorros, the indigenous population of Guam. This study assessed cancer-related knowledge, attitudes, and preventive behaviors (KAB) among Chamorros on the island. METHODS: We conducted a self-administered English language survey regarding cancer-related KAB using a non-probability purposive sample design in 266 self-identified Chamorros (149 women and 117 men) over the age of 50 years. The survey included demographics; health status; access to medical care; and KAB about breast, cervical, prostate, colorectal, lung, and nasopharyngeal cancer. Descriptive statistics and bivariate analysis were used to assess the data. RESULTS: Overall, 83.3% of women reported having a mammogram and 62.8% reported having a Pap smear within the past 2 years. Only 20.3% of men reported having a prostate specific antigen (PSA) test within the past year. Of concern, only 43.1% had heard of PSA. Only 38.3% of participants reported ever having fecal occult blood testing, 15.5% ever having sigmoidoscopy, and 33.1% ever having colonoscopy. Respondents who had a regular source of care were more likely to receive up to date mammography screening (p<0.01). Likewise, those who had visited their doctor within the past year were more likely to be screened for breast (p<0.01), cervical (p<0.05), prostate (p<0.01), and colorectal cancer (p<0.05). In addition, residents living in the south were less likely to report screening for breast (p<0.05), prostate (p<0.05), and colorectal (p<0.01) cancer. CONCLUSION: These results provide important data about Chamorro's KAB that can help to guide a comprehensive cancer control program on Guam.