Background: Breast density is a well-established early marker of breast cancer risk, and adolescence represents a critical window for breast tissue development. In recent years, the consumption of non-nutritive sweeteners has increased substantially, particularly in Chile. In 2023, the International Agency for Research on Cancer (IARC) classified aspartame as possibly carcinogenic to humans, while the Joint FAO/WHO Expert Committee on Food Additives (JECFA) reaffirmed an acceptable daily intake of 40 mg/kg body weight. Aspartame intake from all dietary sources has been associated with increased breast cancer risk in adults. To our knowledge, no studies have evaluated aspartame consumption during adolescence—a critical period for breast carcinogenesis—in relation to breast density (early marker of breast cancer risk). The Growth and Obesity Cohort Study (GOCS) provides a unique opportunity to examine this question, given its repeated dietary assessments using 24-hour recalls since puberty and breast density measurements at key developmental stages.

Objective: To evaluate the association between aspartame consumption during adolescence and breast composition—absolute fibroglandular volume (AFGV) and percent fibroglandular volume (%FGV)—among female participants of the GOCS at 18 years of age.

Methods: We included 310 girls from middle- to low-socioeconomic neighborhoods of southeastern Santiago. Diet was assessed using at least two 24-hour dietary recalls collected between the ages of 12 and 16. We estimated average daily aspartame intake and categorized participants as: non-consumers (0 mg/day), low consumers (<P50, <32.51mg/day), and high consumers (≥P50). Breast density at age 18 (2021) was measured via dual-energy X-ray absorptiometry (DXA), a validated method for quantifying fibroglandular tissue, and considered both as a continuous and a dichotomous variable (≥P75). Crude and adjusted linear and logistic regression models were used to examine associations between aspartame intake and breast composition. Models were adjusted for maternal education, age at menarche, energy intake, total sugar intake, body mass index, oral contraceptive use, smoking, alcohol consumption, physical activity, number of dietary recalls, and intake of other non-nutritive sweeteners (saccharin, sucralose, stevia, and cyclamate).

Results: Overall, 95.8% consumed at least one non-nutritive sweetener in at least one dietary recall during the period, and 77.1% consumed aspartame; among them, 38.4% were high consumers (≥P50). Mean aspartame intake was 38.5 ± 47.3 mg/day. Average aspartame intake, as well as aspartame consumption (yes/no) and high aspartame intake, were associated with higher odds of having %FGV above the 75th percentile at age 18 (OR 1.5, 95% CI: 1.1–2.1; OR 3.1, 95% CI: 1.2–8.2; and OR 3.3, 95% CI: 1.2–9.5, respectively), after adjustment for covariates including other non-nutritive sweeteners. No association was observed for AFGV.

Conclusions: Higher aspartame intake during adolescence—including any consumption and higher-level consumption—was positively associated with %FGV in nulliparous Chilean females at 18 years of age. These findings suggest that aspartame exposure during a sensitive developmental window may influence breast tissue composition, warranting further investigation.