Sarah Nechuta

Lifetime Reproductive and Anthropometric Risk Factors for Breast Cancer in Postmenopausal Women

Hormonally-linked adult reproductive and anthropometric risk factors have been well established in the etiology of postmenopausal breast cancer, though early life exposures have been evaluated only more recently. Here, we examine the evidence for associations between lifetime reproductive and anthropometric risk factors for postmenopausal breast cancer. The review finds some evidence for the hypothesis that breast cancer risk is determined by the number of susceptible stem cells, modified by the hormonal environment. The in utero experience of an infant may be associated with postmenopausal breast cancer; preeclampsia may decrease and greater birthweight increase risk, but more evidence is needed. Earlier and more rapid childhood growth appears to increase postmenopausal breast cancer risk and childhood obesity to decrease risk, but very few studies have yet examined these associations. Increased final height and earlier age at menarche are consistently associated with increased risk for postmenopausal breast cancer. Later age at first birth, decreased parity, later menopausal age, use of hormone replacement therapy (especially progestin containing), and increased postmenopausal adiposity are well-established risk factors for postmenopausal breast cancer. The effect of a womans own pregnancy conditions and lactation are not established. Further investigation is needed to identify whether events occurring early in life modify later events or accumulate over the life course. Many aspects of this research can be conducted by examining the influence of early life events on intermediary events without the need for longitudinal data.

Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women

BACKGROUND Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. OBJECTIVE We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. DESIGN The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. RESULTS After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). CONCLUSION In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.

Vitamin supplement use during breast cancer treatment and survival: a prospective cohort study

Background: Antioxidants may protect normal cells from the oxidative damage that occurs during radiotherapy and certain chemotherapy regimens; however, the same mechanism could protect tumor cells and potentially reduce effectiveness of cancer treatments. We evaluated the association of vitamin supplement use in the first 6 months after breast cancer diagnosis and during cancer treatment with total mortality and recurrence. Methods: We conducted a population-based prospective cohort study of 4,877 women aged 20 to 75 years diagnosed with invasive breast cancer in Shanghai, China, between March 2002 and April 2006. Women were interviewed approximately 6 months after diagnosis and followed up by in-person interviews and record linkage with the vital statistics registry. Results: During a mean follow-up of 4.1 years, 444 deaths and 532 recurrences occurred. Vitamin use shortly after breast cancer diagnosis was associated with reduced mortality and recurrence risk, adjusted for multiple lifestyle factors, sociodemographics, and known clinical prognostic factors. Women who used antioxidants (vitamin E, vitamin C, multivitamins) had 18% reduced mortality risk (HR = 0.82, 95% CI: 0.65–1.02) and 22% reduced recurrence risk (HR = 0.78, 95% CI: 0.63–0.95). The inverse association was found regardless of whether vitamin use was concurrent or nonconcurrent with chemotherapy, but was present only among patients who did not receive radiotherapy. Conclusions: Vitamin supplement use in the first 6 months after breast cancer diagnosis may be associated with reduced risk of mortality and recurrence. Impact: Our results do not support the current recommendation that breast cancer patients should avoid use of vitamin supplements. Cancer Epidemiol Biomarkers Prev; 20(2); 262–71. ©2010 AACR.

Combined impact of lifestyle-related factors on total and cause-specific mortality among chinese women: Prospective cohort study

Findings from the Shanghai Womens Health Study confirm those derived from other, principally Western, cohorts regarding the combined impact of lifestyle-related factors on mortality.

Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project

Background: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI). Methods: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I–III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%–<10% and ≥10% loss and gain] with mortality were estimated using Cox proportional hazards models. Results: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14–1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a nonsignificant increased risk of death. Conclusions: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Impact: Weight control strategies for breast cancer survivors should be personalized to the individuals medical history. Cancer Epidemiol Biomarkers Prev; 21(8); 1260–71. ©2012 AACR.

Pregnancy characteristics and maternal breast cancer risk: a review of the epidemiologic literature.

The short- and long-term effects of pregnancy on breast cancer risk are well documented. Insight into potential biological mechanisms for these associations may be gained by studying breast cancer risk and pregnancy characteristics (e.g., preeclampsia, twining), which may reflect hormone levels during pregnancy. To date, no review has synthesized the published literature for pregnancy characteristics and maternal breast cancer using systematic search methods. We conducted a systematic search to identify all published studies. Using PUBMED (to 31 July 2009), 42 relevant articles were identified. Several studies suggest that multiple births may be associated with a lowered breast cancer risk of about 10–30%, but results were inconsistent across 18 studies. The majority of 13 studies suggest about a 20–30% reduction in risk with preeclampsia and/or gestational hypertension. Six of seven studies reported no association for infant sex and breast cancer risk. Data are sparse and conflicting for other pregnancy characteristics such as gestational age, fetal growth, pregnancy weight gain, gestational diabetes, and placental abnormalities. The most consistent findings in a generally sparse literature are that multiple births and preeclampsia may modestly reduce breast cancer risk. Additional research is needed to elucidate associations between pregnancy characteristics, related hormonal profiles, and breast cancer risk.

Lifetime Cigarette Smoking and Breast Cancer Prognosis in the After Breast Cancer Pooling Project

BACKGROUND There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked. METHODS Data were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803). RESULTS Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54). CONCLUSIONS Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality.

Factors associated with women's perceptions of physical activity safety during pregnancy.

UNLABELLED Health benefits of physical activity (PA) during pregnancy have been noted, but womens perceptions of PA safety have been little studied. OBJECTIVES To examine associations among PA participation, safety perceptions, and demographic characteristics. METHODS Pregnant women were recruited from nine clinics in Grand Rapids, MI (USA) from April to October, 2006. Demographics, participation in moderate and vigorous PA, and perceived safety of both intensities (5-pt Likert scales) were reported. Logistic regression analyses were used to estimate associations. RESULTS Of 342 eligible women, 296 provided complete PA information. Most (88%) participated in some PA and felt moderate PA was safe (89%), but only 36% felt vigorous PA was safe. Feeling unsafe/unsure about moderate PA was associated with non-White race/ethnicity, low education, low income, not participating in moderate PA, and/or not intending to be active during pregnancy. Hispanic ethnicity, low education, nulliparity, and not participating in moderate or vigorous PA were associated with feeling unsafe/unsure about vigorous PA. CONCLUSIONS Pregnant women generally feel that moderate PA is safe, but are less certain about vigorous PA. More work is needed to inform pregnant women about the benefits of moderate PA, especially among non-White and low education/income populations.

Postdiagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project

Background: Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear. Methods: We conducted an investigation of postdiagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors from three prospective US cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire. HR and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors. Results: After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (≥0.36 g/day of alcohol, ≥0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with nondrinking, regular alcohol intake (≥6.0 g/day) was not associated with risk of recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86–1.24; HR for 12 to less than 24 g/day, 1.12; 95% CI, 0.93–1.34; HR for ≥24 g/day, 1.04; 95% CI, 0.84–1.31). However, risk varied significantly by menopausal status (P for interaction < 0.05). Postmenopausal women who regularly consumed alcohol (≥6.0 g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01–1.40). Alcohol intake was not associated with mortality. Conclusions: Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women. Impact: The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev; 22(1); 32–41. ©2012 AACR.

Prospective cohort study of tea consumption and risk of digestive system cancers: results from the Shanghai Women's Health Study

BACKGROUND Data from in vitro and animal studies support a protective role for tea in the etiology of digestive system cancers; however, results from prospective cohort studies have been inconsistent. In addition, to our knowledge, no study has investigated the association of tea consumption with the incidence of all digestive system cancers in Chinese women. OBJECTIVE We investigated the association of regular tea intake (≥3 times/wk for >6 mo) with risk of digestive system cancers. DESIGN We used the Shanghai Womens Health Study, a population-based prospective cohort study of middle-aged and older Chinese women who were recruited in 1996-2000. Adjusted HRs and associated 95% CIs were derived from Cox regression models. RESULTS After a mean follow-up of 11 y, 1255 digestive system cancers occurred (stomach, esophagus, colorectal, liver, pancreas, and gallbladder/bile duct cancers) in 69,310 nonsmoking and non-alcohol-drinking women. In comparison with women who never drank tea, regular tea intake (mostly green tea) was associated with reduced risk of all digestive system cancers combined (HR: 0.86; 95% CI: 0.74, 0.98), and the reduction in risk increased as the amount and years of tea consumption increased (P-trend = 0.01 and P-trend < 0.01, respectively). For example, women who consumed ≥150 g tea/mo (∼2-3 cups/d) had a 21% reduced risk of digestive system cancers combined (HR: 0.79; 95% CI: 0.63, 0.99). The inverse association was found primarily for colorectal and stomach/esophageal cancers. CONCLUSION In this large prospective cohort study, tea consumption was associated with reduced risk of colorectal and stomach/esophageal cancers in Chinese women.