Chest Irradiation Increases Girls' Risk of Breast Cancer

Pre-pubertal and teen-aged girls with cancer who are treated with chest irradiation are at higher risk of developing breast cancer at an early age than previously thought, according to researchers presenting new data at the AACR meeting.

"We found that this increased risk was elevated regardless of the girls' age when they received radiation treatment," said Joseph Neglia, M.D., associate professor of pediatrics at the University of Minnesota in Minneapolis and principal investigator for the study. Dr. Neglia explained that previous studies found an elevated risk of breast cancer only among girls who had already reached puberty when treated for childhood cancer.

Dr. Neglia cautioned, however, that these new findings should not cause undue alarm among women who have survived childhood cancer, since this study also shows that the vast majority of survivors of childhood cancer do not develop second cancers.

This is one of the largest retrospective ("look-back") studies to focus on the risk of second cancers in individuals successfully treated for cancer as children. The research team studied 13,581 people diagnosed with cancer before age 21 who had survived for at least five years. The average age of those studied was 23, with an age range of 8 to 47. A total of 282 people developed one second cancer that was not a relapse of their original disease; 16 people were diagnosed with two new cancers. Breast cancer was the most common second cancer (60 cases), followed by thyroid cancer (43 cases), and brain tumors (36 cases). The researchers found that the risk of a second cancer varied depending on what the original diagnosis was and how it was treated.

"The message to survivors of childhood cancer is to find out what type of treatment you received, and talk with a knowledgeable physician about what your risks are and what you should do as far as screening and monitoring," said Dr. Neglia. For instance, he suggests that women treated with irradiation in childhood should consider getting a baseline mammogram in their 20s.

From the medical side, doctors who treat cancer in children need to intensify efforts to modify treatment regimens to reduce patients' risk for second cancers later on, said Dr. Neglia. He further explained that many pediatric oncology centers are already reducing the use of certain chemotherapeutic drugs known to increase the risk of secondary cancers, and that there are new methodologies for reducing radiation.

Dr. Neglia and his colleagues plan to continue their study to learn more about childhood-cancer survivors' risks for second cancers, as well as heart disease and other health problems, as
they age.

Genetic Findings Offer Hope of New Treatment for Common Childhood Brain Cancer

Compelling new research findings suggest that medulloblastoma - the most common malignant brain tumor in children - is in fact two diseases with distinctly different genetic characteristics.

"These findings are significant because they could lead to a new therapy for one type of medulloblastoma that would directly target the genetic mechanisms of the disease," said Torsten Pietsch, M.D., professor of neuropathology at the University of Bonn, Germany.

Scientists had previously identified two types of medulloblastoma - classic and desmoplastic, or nodular - with different tumor characteristics. Dr. Pietsch and his colleagues identified several genetic mutations in a series of 63 desmoplastic medulloblastomas, some of which were recently removed from patients while others came from stored samples. About a quarter of all medulloblastoma cases are of this type. The same mutations were not found in patients with classic medulloblastoma. The researchers also found genetic evidence that the two types of medulloblastoma develop from different "parent" cells. An estimated 400-500 children are diagnosed with medulloblastomas each year in the United States.

The mutations associated with desmoplastic medulloblastoma were found in two genes, PTCH and SMOH, which help regulate normal development of the brain and other organs as components of a developmental control signaling pathway. Mutations in either gene result in over-activation of this developmental pathway, which can lead to uncontrolled growth of cancerous cells, explained Dr. Pietsch.

Dr. Pietsch noted that other researchers at Johns Hopkins University School of Medicine in Baltimore, Maryland, and Stanford University School of Medicine in Stanford, California concurrently identified substances that, in laboratory experiments, blocked the uncontrolled cell growth resulting from these genetic mutations. Further animal and human studies are needed to validate the findings from both research groups. If both sets of findings are confirmed, said Pietsch, patients with desmoplastic medulloblastoma could benefit from a new treatment targeting the genetic flaw at the root of their disease.

Founded in 1907, the American Association for Cancer Research (AACR) is a professional organization of more than 17,000 laboratory and clinical scientists engaged in cancer research in the United States, Canada, and more than 60 other countries. Working to prevent and cure cancer, AACR's principal activities include scientific communication; education and training of early career scientists; public education; scientific meetings for the presentation and discussion of discoveries in the cancer field; international programs; and the publication of four major peer-reviewed scientific journals (Cancer Research, Clinical Cancer Research, Cell Growth & Differentiation, Cancer Epidemiology, Biomarkers & Prevention, and Molecular Cancer Therapeutics).