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Background: The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. Objectives: This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. Methods: The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. Results: Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (beta(T3vsT1) = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (beta(T3vsT1) = 3.12; 95% CI: 0.99, 5.25) and gondoic (beta(T3vsT1) = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (beta(T3vsT1) = 5.22; 95% CI: 3.15, 7.29) and elaidic (beta(T3vsT1) = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (omega-6) linoleic (beta(T3vsT1) = -5.49; 95% CI; -7.62, -3.35) and arachidonic (beta(T3vsT1) = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo. gamma-linolenic acids were associated with higher MD. Conclusions: Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.

Objectives: Mammographic density (MD) is a strong risk factor for breast cancer. The present study evaluates the association between relative caloric intake and MD in Spanish women. Study design: We conducted a cross-sectional study in which 3517 women were recruited from seven breast cancer screening centers. MD was measured by an experienced radiologist using craniocaudal mammography and Boyd's semi-quantitative scale. Information was collected through an epidemiological survey. Predicted calories were calculated using linear regression models, including the basal metabolic rate and physical activity as explanatory variables. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using center-specific mixed ordinal logistic regression models, adjusted for age, menopausal status, body mass index, parity, tobacco use, family history of breast cancer, previous biopsies, age at menarche and adherence to a Western diet. Main outcome measure: Mammographic density. Results: Those women with an excessive caloric intake ( > 40% above predicted) presented higher MD (OR = 1.41, 95%CI = 0.97-2.03; p = 0.070). For every 20% increase in relative caloric consumption the probability of having higher MD increased by 5% (OR = 1.05, 95%CI = 0.98-1.14; p = 0.178), not observing differences between the categories of explanatory variables. Caloric restriction was not associated with MD in our study. Conclusions: This is the first study exploring the association between MD and the effect of caloric deficit or excessive caloric consumption according to the energy requirements of each woman. Although caloric restriction does not seem to affect breast density, a caloric intake above predicted levels seems to increase this phenotype.