Other highlights in the April 19 JNCI

Number of Pregnancies Associated With Decreased Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

BRCA1 and BRCA2 genetic mutation carriers older than 40 years display a similar reduction in breast cancer risk with increasing number of pregnancies carried to full-term, a risk parallel to that in the general population, according to a new study.

BRCA1 and BRCA2 mutations are known to increase a women's risk of breast cancer. In women without the mutations, reproductive factors such as giving birth, young age at first childbirth, and history of breast-feeding are associated with a reduced risk of breast cancer, but few have studied those factors in women with these mutations. Nadine Andrieu, Ph.D., of INSERM (Institute National de la Sante et de la Recherche Medical) at the Curie Institute in Paris, and colleagues retrospectively examined 1601 women in the International BRCA1/2 Carrier Cohort Study (IBCCS) who had been asked about childbirth history, age at time of pregnancy, and breast-feeding habits. Of those women, 853 women had been diagnosed with breast cancer.

The authors found that there was no difference in risk of breast cancer between mutation-carrying women who had a full-term pregnancy and those who did not. Among women who had given birth, the risk of breast cancer for BRCA1 and BRCA2 mutation carriers decreased by 14% with each additional birth for women ages 40 and older. This decrease is similar to that found in the general population. The researchers also observed that first childbirth at age 20 years or older was associated with increased risk of breast cancer in BRCA2 mutation carriers. In BRCA1 mutation carriers, first childbirth at age 30 years or older was associated with decreased risk of breast cancer.

Contact: Severine Ciancia, Service de Presse de la Inserm, 33-1-44-23-60-86, [email protected]

Evalation of PSA Changes to Indicate Outcomes in Prostate Cancer

A new study suggests that certain changes in PSA levels may be a marker for prostate cancer survival. Researchers looking to speed up the process of clinical trials have suggested that such biomarkers could be used to measure true outcomes of interest, such as survival.

Daniel P. Petrylak, M.D., of Columbia University in New York, and colleagues retrospectively analyzed results from 551 men with prostate cancer treated in the Southwest Oncology Group Protocol 99-16, looking at several different changes in prostate-specific antigen (PSA) levels as possible surrogate endpoints for survival of men the clinical trial.

The authors observed that the risk of death in men whose serum PSA levels declined by of at least 30% in the first three months of treatment was reduced more than 50%. However, they point out that this and other candidate surrogate endpoints must be validated in independent clinical trials of men with prostate cancer.

In an accompanying editorial, Stuart G. Baker, Sc.D., of the National Cancer Institute, suggests that analysis of data from a single trial limits the conclusions that can be drawn from Petrylak and colleagues' analysis and suggests that data from multiple trials with the same surrogate and true endpoints should be pooled for analysis. He writes, "Only with [validation using a meta-analysis] will it be possible to determine if surrogate endpoints are closer to wishful thinking or reality."

Article: Elizabeth Streich, Columbia University, 212-305-6535, [email protected], and Tracy Hinkenbottom, New York Presbyterian Hospital, 212-305-5587, [email protected]
Editorial: NCI Press Officers, 301-496-6641, [email protected]

Molecular Target Identified For Novel Anticancer Agent

PI3K, an enzyme involved in cancer cell proliferation, is a molecular target for a novel antitumor agent ZSTK474, a new study has found. In research led by Takao Yamori, Ph.D., of the Japanese Foundation for Cancer Research in Tokyo, and colleagues, ZSTK474 displayed strong antitumor activity against human cancer tissue in mice. Additionally, treatment with ZSTK474 was not noticeably toxic to vital organs after 14 days of treatment. The authors suggest ZSTK474 should be investigated further as an anticancer drug.

Contact: Takao Yamori, Japanese Foundation for Cancer Research, [email protected]


Also in the April 19 JNCI:

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

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