Frank Biro, MD
Dr. Biro has been working in the fields of STIs and puberty; currently he is PI on projects funded through two U01 grants. The working model is that prepubertal obesity, driven by environmental, psychosocial, and genetic factors, leads to a pathway of pubertal development in which estrogen and insulin-like growth factor stimulate breast development as the initial manifestation of puberty, and that girls with a family history of breast cancer are more likely to develop through this pathway. This pathway leads to earlier menarche, as well as other physiological states such as central adiposity, that increases the susceptibility of the mammary gland to carcinogenic insults.
To examine these aims, we recruited 379 girls, ages 6 and 7, between August 2004 and July 2007. They are seen every six months at their school or in the GCRC. As of November 1, 2008, there were 2078 clinical assessments that were generated from the original group of 379 participants. During the clinical visits, girls receive several evaluations: blood pressure, height, weight, skin folds, waist and hip circumference, bioelectrical impedance, and pubertal maturation. Blood is drawn every visit, and once a year, urine and blood is obtained for selected biomarkers. Blood is obtained for DNA and RNA (microarray analysis). Parents are called every 3 months for a 24 hour diet recall. Adherence to the protocol has been very high, with >90% retention. Blood has been obtained at over 89% of visits, urine over 95% of scheduled visits, and study questionnaires over 97%.
Average age at intake into the study was 7.1 years of age. At age 8, 29% of white, 48% of black, and 33% of Hispanic girls were breast stage 2 or greater; these proportions are significantly greater than those published by Herman-Giddens et al (1997).
Of the 379 recruited into the study, 237 are currently breast stage 2 or greater. A “pathway” (breast or pubic hair development, without any maturation of the other characteristic) could be defined in 201/237 (85%) of participants. Among those with a defined “pathway” 143/201 had initial breast development (“gonadarche”) and 58/201 had initial pubic hair (“pubarche”). Those with gonadarche, or those with undefined pathway, had great BMI than those with pubarche (p < .0001). The ratios of estradiol to estrone, as well as estradiol to testosterone, were greater in longitudinal analyses across the 18 months prior to onset of puberty, with the ratio greater in those with the gonadarche pathway. Of note, an earlier study showed that girls with breast development first had younger age of menarche and greater bone mineral density, factors associated in epidemiologic studies with breast cancer. The hormone ratios (estradiol to estrone or to testosterone) are consistent with greater activity of aromatase and 17-dehydrogenase, the activity of both which are increased in those who have greater adipose tissue.
