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Background: There is strong evidence that breast cancer risk is influenced by environmental factors. Blood lipid and lipoprotein levels are also influenced by environmental factors and are associated with some breast cancer risk factors. We examined whether serial measures of serum lipids and lipoproteins were associated with breast cancer risk., Methods: We carried out a nested case-control study within a randomized long-term dietary intervention trial with 4690 women with extensive mammographic density followed for an average of 10 years for breast cancer incidence. We measured lipids in an average of 4.2 blood samples for 279 invasive breast cancer case subjects and 558 matched control subjects. We calculated subaverages of lipids for each subject based on menopausal status and use of hormone replacement therapy (HRT) at blood collection and analyzed their association with breast cancer using generalized estimating equations. All statistical tests were two-sided., Results: High-density lipoprotein-cholesterol (HDL-C) (P = .05) and apoA1 (P = .02) levels were positively associated with breast cancer risk (75(th) vs 25(th) percentile: HDL-C, 23% higher; apoA1, 28% higher) and non-HDL-C (P = .03) and apoB (P = .01) levels were negatively associated (75(th) vs 25(th) percentile: non-HDL-C, 19% lower; apoB, 22% lower). These associations were observed only when lipids were measured when HRT was not used. Total cholesterol and triglyceride levels were not statistically significantly associated with breast cancer risk., Conclusions: These results demonstrate that serum lipids are associated with breast cancer risk in women with extensive mammographic density. The possibility that interventions for heart disease prevention, which aim to reduce non-HDL-C or raise HDL-C, may have effects on breast cancer risk merits examination., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We have previously shown that a low-fat dietary intervention for 2 years in women with extensive mammographic density decreased mammographic density to a greater extent than in the control group. Post-hoc analysis indicated that this effect was strongest in women who became postmenopausal during the follow-up period. The purpose of the present study was to determine if this potentially important finding could be confirmed in a new and larger group of subjects with a longer follow-up time. Participants in a low-fat dietary intervention trial who were premenopausal at entry and became postmenopausal during follow-up were examined. Total breast, dense, and non-dense area and percent density were measured in baseline and postmenopause mammograms using a computer-assisted method. Total breast and non dense area increased more in the control group compared to the intervention group (for breast area 2.6 and 0.2 cm(2), respectively; P=0.05, and for non-dense area 10.9 and 8.1 cm(2), respectively; P=0.06). Dense area decreased to a similar degree in both groups (-8.2 and -8.0 cm(2), respectively; P=0.84). Percent density decreased to a slightly greater degree in the control compared to intervention group (-9.4 and -7.8%, respectively, P=0.11). There were no significant differences between study groups after adjustment for weight change. Menopause reduced density to a similar extent in the low-fat diet and control groups. If a low-fat diet reduces breast cancer risk, the effect is unlikely to be through changes in mammographic density at menopause.

Background: Later age at menopause is associated with a greater risk of breast cancer. Dietary factors may at least partially influence breast cancer risk through an effect on the age at menopause., Objective: We studied the effect of a low-fat, high-carbohydrate (LFHC) dietary intervention on the timing of menopause in women with greater risk of breast cancer., Design: The study population included participants from an LFHC dietary intervention trial for the prevention of breast cancer in women with extensive mammographic density, a strong risk factor for breast cancer. Women who were premenopausal at baseline (n = 2611) were followed for an average of 7 y for menopause. Survival analysis was used to compare the time to menopause between the LFHC and control groups and to assess other factors associated with age at menopause., Results: The LFHC intervention did not affect the time to natural menopause overall (P = 0.72 for log-rank test comparing study groups; n = 699 events). An observed interaction between study group and baseline body mass index (BMI; P = 0.01) indicated that the intervention group experienced earlier menopause than did the control group when BMI was low and that a higher BMI was associated with later menopause in the intervention group only. Greater parity, weight, and education were associated with later menopause, and greater age at first birth and baseline smoking were associated with earlier menopause., Conclusions: Overall, the LFHC dietary intervention did not influence the timing of menopause. Factors associated with age at menopause in this population were consistent with those reported in other populations.

To examine the effects of dietary fat intake on breast cancer risk, we are conducting a randomized trial of dietary intervention in women with extensive areas of radiologically dense breast tissue on mammography, a risk factor for breast cancer. Early results show that after 2 years on a low-fat, high-carbohydrate diet there is a significant reduction in area of density, particularly in women going through menopause. In women who went through menopause during the 2-year follow-up, the mean decreases in area of density and percentage of density in the intervention group were 11.0 cm2 and 11.0%, respectively, whereas the control group decreased 4.5 cm2 and 5.2%. The purpose of this analysis was to determine whether changes in intake of specific macronutrients could account for the observed reduction in breast density in these women. Differences between 2-year and baseline values of macronutrients (averaged over 3 nonconsecutive days of food intake) were calculated. We examined the effect of dietary variables, adjusted for changes in total calorie intake and weight and for family history of breast cancer, on changes in area of density and percentage of density using linear regression. Reduction in total or saturated fat intake or cholesterol intake was significantly associated with decreased dense area (p < or = .004). The most significant dietary variable associated with reduction in percentage of density was reduction in dietary cholesterol intake (P = 0.001), although reducing saturated fat intake was of borderline significance (P = 0.05). The effect of the membership in the intervention and control groups on change in area of density or percentage of density was reduced by models that included changes in intake of any fat, or cholesterol, or carbohydrates. The observation of an effect of diet at menopause on breast density, a marker of increased risk of breast cancer, may be an indication that exposures at this time have an enhanced effect on subsequent risk.

Objectives: While decreased intake of dietary fat may have significant positive effects on women's health by reducing the risk of cancer and other diseases, little research has been carried out to determine the potential adverse effects of dietary fat reduction. This study compares the self-reported physical and emotional health of 402 low fat intervention and control group participants in the Canadian Diet and Breast Cancer Prevention Trial., Methods: Subjects who had been participating in the dietary intervention trial for at least 2 years completed 3 mailed questionnaires: two designed to assess physical and emotional health (MOS 36-Item Short-Form Health Survey (SF-36) and the Women's Health Questionnaire (WHQ)) and a Health Practices Survey., Results: There were no significant differences between the study groups on total scores or any of the subscales/health domains for the SF-36 or the WHQ. In premenopausal women only, intervention group subjects scored significantly lower on the vasomotor symptoms scale, indicating less symptom experience. Frequency of visits to physicians and alternative health practitioners were not significantly different between the study groups., Conclusions: The results of this study suggest that participation in a low-fat, high-carbohydrate dietary intervention did not have any detrimental effects on participants' self-reported physical health or emotional well-being.

Little research has been undertaken to determine why healthy people agree to enroll in randomized controlled trials of cancer prevention. This study describes the beliefs of Canadian women participating in a trial designed to determine the effect of reducing dietary fat on the development of breast cancer. Healthier eating, nutritional counseling, contributing to science, and helping others were the most frequently cited advantages of participation. Weight control and general better health were specifically associated with the dietary regimens. Attending appointments and difficulties when eating out were the main disadvantages of participation. Suggestions that would promote adherence to the trial protocol also were elicited. Responses cited most often included opportunities to meet other participants, more nutritional counseling (particularly psychological tips), updates about the trial, and more recipes. Attention should be paid to these suggestions as they characterize some of the major determinants of adherence behavior.