Investigating the Link between Early Life and Breast Anomalies

**Background:** This narrative review investigates the link between exposures during childhood and adolescence and the subsequent development of proliferative benign breast diseases (P-BBD) and breast cancer (BC) in adulthood. The authors note that breast tissue undergoes rapid proliferation between menarche and first full-term pregnancy, making this window particularly vulnerable to carcinogenic influences. Understanding these early-life risk factors could inform prevention strategies and elucidate breast cancer pathophysiology.

**Methods:** The authors conducted an extensive literature search of Medline/Pubmed and Google Scholar databases for clinical studies, reports, and guidelines published in English up to October 2022. The search algorithm included keywords such as breast disorders, adolescence, childhood, and breast cancer. The review covers dietary factors, lifestyle factors (alcohol, physical activity), anthropometric factors (BMI, growth velocity, height), age at menarche, age at thelarche, ionizing radiation, anthracycline exposure, socioeconomic status, smoking, drug abuse, and other factors (antibiotics, vitamin D).

**Key Results:** - **Dietary Factors:** Women in the top quintile of animal fat consumption had a 33% increased risk of P-BBD, while those in the highest quintile of vegetable fat consumption had a 27% reduced risk. Total fruit consumption during adolescence (median 2.9 servings/day) was associated with lower breast cancer risk (HR 0.75). Women in the highest quintile of adolescent fiber intake had a 25% lower risk of P-BBD. Higher red meat consumption was associated with elevated breast cancer risk (RR 1.34; 95% CL 0.94–1.89; p=0.05). Soy intake during childhood showed a protective effect (OR 0.40), weaker during adolescence (OR 0.80) and adulthood (OR 0.75). - **Alcohol:** Heavy alcohol intake (≥30 g/day) was associated with ER+ breast cancer (RR 1.35; 95% CI 1.23–1.48). Among women with a ≥10-year interval between menarche and first pregnancy, each 10 g/day increase in alcohol consumption increased breast cancer risk by 21%. Drinking 6–7 days per week was associated with a more than fivefold risk for BBD. - **Physical Activity:** Women with high levels of activity during both youth (ages 12–22) and adulthood had a 30% reduction in breast cancer risk (RR 0.70; 95% CL 0.53–0.93). - **BMI:** Girls with BMI in the upper two quintiles during adolescence had less than half the risk of BBD (OR 0.46; 95% CL 0.26–0.81). A BMI ≥25 at age 18 was associated with a 33% reduction in BBD risk. - **Growth Velocity:** Height growth from age 8 to 14 years was significantly associated with breast cancer risk (RR 1.17 per 5 cm increase; 95% CI 1.09–1.25). Girls with peak height velocity >8.9 cm/year were nearly twice as likely to develop BBD. - **Age at Menarche:** Each one-year decrease in age at menarche increased breast cancer risk by 5% (meta-analysis of >100 studies). - **Age at Thelarche:** Thelarche prior to 10 years was associated with a 23% greater risk of breast cancer compared with age 12–13 years. Each 1-year delay in thelarche was associated with a 3% decrease in breast cancer risk. - **Ionizing Radiation:** Approximately 40% of girls treated with radiation for Hodgkin lymphoma will develop breast cancer. The cumulative incidence for secondary breast cancer 30 years after Hodgkin disease treatment was 19% (95% CI 12%–29%). The odds ratio for breast cancer at a radiation dose of 10 Gy was 3.9. Female Hodgkin lymphoma survivors had a 25.8-fold increased risk of breast cancer compared to the general population. - **Anthracyclines:** Women who received ≥250 mg/m² of anthracycline had a greater than 13-fold risk for breast cancer. A 2.5- to 6-fold increased risk was reported in women receiving anthracycline chemotherapies. - **Socioeconomic Status:** Girls in the lowest SEP index quantile developed breast budding 7 months earlier than girls in the highest SEP quantile. - **Vitamin D:** Breast cancer risk increased rapidly as serum 25(OH)D concentrations decreased below 12 ng/mL.

**Clinical Implications:** The review identifies childhood and adolescence as critical windows for breast cancer prevention. Lifestyle modifications among high-risk women (e.g., those with positive family history or BRCA mutations) could prevent 25% to 30% of breast cancer cases. The authors recommend that targeted prevention and screening programs be implemented during childhood and adolescence, and that gynecologists and adolescent care specialists be educated to provide appropriate guidance and interventions from early life.