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Study on early puberty advances breast cancer research

By Eddy Ball
September 2010

Frank  Biro, M.D.
Biro was one of three physicians involved in training clinical staff to evaluate breast and pubic hair development in the subjects. (Photo courtesy of the University of Cincinnati)

A new study led by NIEHS-funded investigators adds to widespread concern among parents, physicians, and researchers that girls are increasingly entering puberty at an earlier age. The study was co-funded by the National Cancer Institute (NCI) and led by two NIEHS grantees - University of Cincinnati (UC) pediatrician Frank Biro, M.D.(http://www.cincinnatichildrens.org/svc/find-professional/b/frank-biro.htm) Exit NIEHS, first author, and Mount Sinai School of Medicine preventive medicine and oncological sciences specialist Mary Wolff, Ph.D.(http://www.mssm.edu/profiles/mary-snow-wolff) Exit NIEHS, principal investigator.

The findings also support a protocol for use in large-scale studies by the NIEHS/NCI Breast Cancer and the Environment Research Centers (BCERC)(http://www.niehs.nih.gov/research/supported/dert/programs/breast-cancer/) that examine environmental factors involved in the development of breast cancer. While the study set out to report the maturation status of a cohort of 1,239 girls at ages 7 and 8 years - and their findings are dramatic (see text box) - a significant outcome was a pubertal assessment protocol that could add reliability and standardization across multiple sites for longitudinal studies of larger, nationally representative cohorts.

"What causes earlier onset of puberty isn't entirely clear at this time, but we are looking closely at several different potential factors, including genes and environmental exposures, as well as how those two may interact with each other," said Biro in a UC HealthNews report. Biro is the director of adolescent medicine at Cincinnati Children's Hospital Medical Center and a professor of pediatrics at the UC College of Medicine.

According to the researchers, a number of epidemiological studies have found a significant association between early onset of pubertal maturation and increased risk of developing breast cancer - possibly due to greater lifetime exposure to female hormones and the susceptibility of rapidly developing breast tissue to environmental exposures. Past studies, however, have used different criteria to evaluate sexual maturation in girls.

Determining onset of puberty

The new study successfully implemented a clinical assessment method for using measurement of breast and pubic hair development in determining the onset of puberty. Teams of physicians, nurse practitioners, and research staff examined girls in East Harlem, the Cincinnati metropolitan area, and the San Francisco Bay area, after training in a standardized protocol and scoring criteria.

Investigators and study coordinators used what is known as the Marshall and Tanner criteria to measure breast maturation and pubic hair stages in the subjects. Clinical staff underwent a training program with the three physicians involved in the study, including the review of photographs of anonymous girls at various stages of development, and then performed dual examinations of a group of peripubertal girls. At each of the sites, one of the three physicians also performed inter-rater assessments for quality assurance to maintain comparability among the centers.

By minimizing measurement error between sites and examiners, the researchers sought to better account for differences among sites that may be influenced by environmental exposures and dietary patterns.

Looking ahead

The researchers were candid about the weaknesses of their study, which include a small cohort, possible recruitment bias, and baseline differences in maturation by site. However, the consistency of assessment across the three BCERC sites was a major accomplishment, overcoming some of the methodological limitations in earlier studies.

"The ability to capture with reasonable accuracy the timing and tempo of pubertal breast maturation in this prospective study," they concluded, "should allow us to pool data for detecting associations between specific factors, including diet and environmental chemicals with variations in patterns of pubertal maturation."

Citation: Biro FM, Galvez MP, Greenspan LC, Succop PA, Vangeepuram N, Pinney SM, et al.(http://www.ncbi.nlm.nih.gov/pubmed/20696727) Exit NIEHS. 2010. Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls. Pediatrics. [Epub ahead of print]

A disturbing trend for the next generation of young women

Anecdotal accounts from parents and physicians, as well as associations found in epidemiological studies, point to progressively earlier maturation among young girls today than among young girls studied 10 to 30 years earlier. According to the study led by Biro and Wolff, girls in their cohort showed high rates of breast stage 2 development at age 7 and 8:

  • At age 7, 23.4 percent of black non-Hispanic girls, 14.9 percent of Hispanic, and 10.4 percent of white girls had reached stage 2
  • At age 8, the rates had as much as doubled, with 42.9 percent of black non-Hispanic, 30.9 percent of Hispanic, and 18.3 percent of white girls measured at stage 2.

The study reports that higher BMI, older age, black race, and being from the Harlem or Cincinnati site were also associated with breast stage 2 or greater development. The proportion of white girls with stage 2 development at age 7 was more than twice that reported in a 1997 study of the Pediatric Research in Office Settings Network.

The authors note that earlier maturation in girls is associated with breast and endometrial cancer, hyperinsulinemia, and elevated blood pressure. It is also associated with potentially harmful psychological effects, such as low self-esteem, eating disorders, suicide, and engagement in risky behavior.



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