Hazel B. Nichols

Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality

Background: Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined postdiagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods: We analyzed data from a cohort of 3,993 women with ages 20 to 79 years living in New Hampshire, Massachusetts, or Wisconsin with invasive nonmetastatic breast cancers diagnosed in 1988 to 1999 identified through state registries. Participants completed a structured telephone interview 1 to 2 years after diagnosis and returned a mailed follow-up questionnaire in 1998 to 2001 that addressed postdiagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models and adjusted for prediagnosis weight, age, stage, smoking, physical activity, and other important covariates. Results: During an average 6.3 years of follow-up from the postdiagnosis questionnaire, we identified 421 total deaths, including 121 deaths from breast cancer and 95 deaths from cardiovascular disease. Increasing postdiagnosis weight gain and weight loss were each associated with greater all-cause mortality. Among women who gained weight after breast cancer diagnosis, each 5-kg gain was associated with a 12% increase in all-cause mortality (P = 0.004), a 13% increase in breast cancer–specific mortality (P = 0.01), and a 19% increase in cardiovascular disease mortality (P = 0.04). Associations with breast cancer mortality were not modified by prediagnosis menopausal status, cigarette smoking, or body mass index. Conclusion: These findings suggest that efforts to minimize weight gain after a breast cancer diagnosis may improve survival. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1403–9)

Declining Incidence of Contralateral Breast Cancer in the United States From 1975 to 2006

PURPOSE Contralateral breast cancer (CBC) is the most frequent new malignancy among women diagnosed with a first breast cancer. Although temporal trends for first breast cancers have been well studied, trends for CBC are not so well established. PATIENTS AND METHODS We examined temporal trends in CBC incidence using US Surveillance, Epidemiology, and End Results database (1975 to 2006). Data were stratified by estrogen receptor (ER) status of the first breast cancer for the available time period (1990+). We estimated the annual percent change (EAPC) in CBC rates using Poisson regression models adjusted for the age at and time since first breast cancer diagnosis. RESULTS Before 1985, CBC incidence rates were stable (EAPC, 0.27% per year; 95% CI, -0.4 to 0.9), after which they declined with an EAPC of -3.07% per year (95% CI, -3.5 to -2.7). From 1990 forward, the declines were restricted to CBC after an ER-positive cancer (EAPC, -3.18%; 95% CI, -4.2 to -2.2) with no clear decreases after an ER-negative cancer. Estimated current age-specific CBC rates (per 100/year) after an ER-positive first cancer were: 0.45 for first cancers diagnosed before age 30 years and 0.25 to 0.37 for age 30 years or older. Rates after an ER-negative cancer were higher: 1.26 before age 30 years, 0.85 for age 30 to 35 years, and 0.45 to 0.65 for age 40 or older. CONCLUSION Results show a favorable decrease of 3% per year for CBC incidence in the United States since 1985. This overall trend was driven by declining CBC rates after an ER-positive cancer, possibly because of the widespread usage of adjuvant hormone therapies, after the results of the Nolvadex Adjuvant Trial Organisation were published in 1983, and/or other adjuvant treatments.

Oral Contraceptive Use, Reproductive Factors, and Colorectal Cancer Risk: Findings from Wisconsin

We investigated the association of oral contraceptive (OC) use and reproductive factors with colorectal cancer risk in a large population-based case-control study. Cases were women ages 20 to 74 years, living in Wisconsin, with a new diagnosis of colon (n = 1,122) or rectal (n = 366) cancer. Control participants were randomly selected from population lists of similarly aged female Wisconsin residents (n = 4,297). Risk factor information was collected through structured telephone interviews. Compared with never users, OC users had an odds ratio (OR) of 0.89 [95% confidence interval (95% CI), 0.75-1.06] for colorectal cancer. OC use associations did not differ significantly between colon and rectal cancer sites; however, when compared with never users, recent OC users (<14 years) seemed at reduced risk of rectal cancer (OR, 0.53; 95% CI, 0.28-1.00). Women with age at first birth older than the median (23 years) had 0.83 times the risk of colon cancer compared with women with age at first birth below the median (95% CI, 0.70-0.98). We observed an inverse trend between increasing parity and rectal cancer risk (P = 0.05). Compared with nulliparous women, women with five or more births had 0.66 times the risk of rectal cancer (95% CI, 0.43-1.02). Compared with postmenopausal women, premenopausal women were at reduced risk (OR, 0.67; 95% CI, 0.47-0.97) of colorectal cancer. No significant associations were observed between colorectal cancer risk and age at menarche or age at menopause. These findings suggest differential roles of reproductive factors in colon and rectal cancer etiology.

Childhood abuse and risk of smoking onset

Study objective: To determine the association between childhood abuse and becoming a smoker. Design: Retrospective cohort study. Setting: Boston, Massachusetts. Participants: 722 women aged 36–45 years who completed the baseline questionnaire for the Harvard study of moods and cycles and the survey of interpersonal relationships. Main results: Women who experienced either physical or sexual abuse as a child were 40% more likely to begin smoking compared with women with no history of abuse (95% CI 1.0 to 2.0). Virtually all of this association was confined to sexual abuse (OR = 2.2, 95% CI 1.1 to 4.3) as compared with physical abuse (OR = 0.7, 95% CI 0.7 to 1.6). However, the joint effect of experiencing both physical and sexual abuse as a child led to a 3.5-fold increase in the likelihood of becoming a smoker (95% CI 1.3 to 9.4) compared with women who did not experience any childhood abuse after adjustment for religion, social class, and poverty. Conclusions: Women who experience childhood abuse, even in the absence of depression, are at increased risk of becoming cigarette smokers.

Risk-Benefit Profiles of Women Using Tamoxifen for Chemoprevention

BACKGROUND Tamoxifen has been US Food and Drug Administration-approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer. METHODS This research was conducted within The Sister Study, a cohort of 50884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009. Eligible women were breast cancer-free at enrollment and had a sister who had been diagnosed with breast cancer. Participants reported tamoxifen use, ages started and stopped taking tamoxifen, and total duration of use at enrollment. We identified 788 tamoxifen users and 3131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer). Characteristics associated with tamoxifen initiation were evaluated with multivariable conditional logistic regression. All statistical tests were two-sided. RESULTS Based on published risk-benefit indices, 20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects. After 4.5 years, 46% of women had discontinued tamoxifen. CONCLUSIONS While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.

No Difference Between Red Wine or White Wine Consumption and Breast Cancer Risk

Epidemiologic studies have reported an increased risk of breast cancer among women who drink alcohol, including wine ([1][1], [2][2]) Two meta-analyses estimated a ∼10% [95% confidence interval (CI), 5-15%] increased risk of breast cancer with each additional 10 grams (∼1 drink) of alcohol/day

Effects of birth order and maternal age on breast cancer risk: modification by whether women had been breast-fed

Background: Early life risk factors for breast cancer have been investigated in relation to hormonal, nutritional, infectious, and genetic hypotheses. Recent studies have also considered potential health effects associated with exposure to environmental contaminants in breastmilk. Methods: We analyzed data from a population-based case-control study of women living in Wisconsin. Cases (n = 2016) had an incident diagnosis of invasive breast cancer in 2002–2006 reported to the statewide tumor registry. Controls (n = 1960) of similar ages were randomly selected from driver’s license lists. Risk-factor information was collected during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariable logistic regression. Results: In multivariable models, maternal age and birth order were not associated with breast cancer risk in the full study population. The odds ratio for breast cancer risk associated with having been breast-fed in infancy was 0.83 (95% CI = 0.72–0.96). In analyses restricted to breast-fed women, maternal age associations with breast cancer were null (P = 0.2). Increasing maternal age was negatively associated with breast cancer risk among women who were not breast-fed; the odds ratio for breast cancer associated with each 5-year increase in maternal age was 0.90 (0.82–1.00). Higher birth order was inversely associated with breast cancer risk among breast-fed women (for women with 3 or more older siblings compared with first-born women, OR = 0.58 [CI = 0.39–0.86]) but not among nonbreast-fed women (1.13 [0.81–1.57]). Conclusion: These findings suggest that early life risk factor associations for breast cancer may differ according to breast-feeding status in infancy.

Cigarette smoking and risk of breast carcinoma in situ

Background: Although the associations with cigarette smoking have been explored extensively for invasive breast cancer, the relation to in situ cancer has not previously been examined in depth. Methods: We analyzed data from a population-based case-control study of women living in Wisconsin, Massachusetts, and New Hampshire. Eligible cases of incident breast carcinoma in situ were reported to statewide registries in 1997–2001 (n = 1878); similarly aged controls (n = 8041) were randomly selected from population lists. Smoking history and other risk factor information were collected through structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated from logistic regression models adjusting for potential confounders. Results: In multivariate models, the OR for breast carcinoma in situ among current smokers was 0.8, compared with never-smokers (95% CI = 0.7−1.0). Risk estimates increased towards the null with greater time since smoking cessation. Odds ratios were also less than 1.0 among women who initiated smoking in adolescence (OR = 0.8) or after a full-term birth (OR = 0.7), relative to women who never smoked. The reduced odds ratios associated with current smoking were strongest among women with annual screening mammograms (OR = 0.7; 95% CI = 0.6−0.9). Odds ratios were not less than 1.0 among current smokers without a recent screening mammogram (1.3; 0.9−2.0). Conclusions: Our findings suggest an inverse association between current smoking and risk of breast carcinoma in situ among women undergoing breast cancer screening.

Oral Contraceptive Use and Risk of Breast Carcinoma In situ

There is some indication that oral contraceptive use may be associated with a small increase in risk of invasive breast cancer; however, oral contraceptive use in relation to breast carcinoma in situ (BCIS) has rarely been studied. We investigated oral contraceptive use in relation to risk of BCIS in a large population-based case-control study. Female residents of Wisconsin, Massachusetts, and New Hampshire aged 20 to 74 years with a new diagnosis of BCIS (n = 1,878) were identified from statewide tumor registries in 1997 to 2001. Age-matched female controls (n = 8,041) were randomly selected from population lists. Information on oral contraceptive use and other risk factors was collected during structured telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. In multivariate models, ever use of oral contraceptives was associated with a small and marginally significant increase in BCIS overall (OR, 1.11; 95% CI, 0.99-1.25) and for ductal carcinoma in situ (OR, 1.15; 95% CI, 1.01-1.31). No strong associations were detected according to age started, duration, time since first or last use, or oral contraceptive use relative to the first full-term pregnancy. The slightly increased risk of BCIS seemed limited to former users (OR, 1.13; 95% CI, 1.00-1.27) and women without a family history of breast cancer (OR, 1.16; 95% CI, 1.01-1.32 for ever versus never use). Consistent with invasive breast cancer, these results suggest that oral contraceptive use is at most a minor contributor to BCIS risk. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2262–9)

Childhood and Adolescent Pesticide Exposure and Breast Cancer Risk.

Background: To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype-specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype. Methods: During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression. Results: HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0–18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval: 0.92, 1.7). Conclusion: These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women.