American Association for Cancer Research

Studies Reveal More Clues on How Full-Term Pregnancy Protects Against Breast Cancer

At the AACR 2014 Annual Meeting in San Diego, Fox Chase scientists presented findings from three studies that examined how pregnancy reduces women’s risk of developing breast cancer.

Julia Santucci-Pereira, PhD

Julia Santucci-Pereira, PhD

In the first study, Julia Santucci-Pereira, PhD, a research associate in the Breast Cancer Research Laboratory led by Jose Russo, MD, FACP, and colleagues used gene expression microarrays to compare the breast genomic profiles of cancer-free breast tissue samples from more than 100 premenopausal women — 79 parous, 30 nulliparous. They found that immune response genes are activated for a few years after pregnancy, whereas genes related to both cell differentiation and to the development of breast anatomy are permanently activated independently of the time of last pregnancy — findings that confirm pregnancy’s protective effect, as more differentiated cells are less prone to carcinogenesis.

In another study, they looked at 10 postmenopausal women using sophisticated DNA sequencing technology, and found that mothers and non-mothers displayed differences in the methylation patterns of their genes. Most of these differences occur in genes that control development — again implying differences in processes associated with the development of breast anatomy.

Jose Russo,  MD, FACP

Jose Russo,
MD, FACP

Finally, in a third study, Santucci-Pereira and other scientists looked deeply at differences in long non-coding RNAs in eight mothers and eight non-mothers through RNA sequencing and identified 42 non-coding RNAs with differences in expression. The researchers believe it is possible that these non-coding regions work with the genes identified in the other two studies to induce changes in the differentiation and development processes, thereby protecting women who have given birth.

The ultimate goal is to understand how these protective effects occur in order to find ways to mimic them in non-mothers — perhaps by administering compounds that target these molecular mechanisms — so that they experience the same protection against breast cancer.

Santucci-Pereira and Russo’s co-authors on the gene expression research include Eric A. Ross, PhD, Michael Slifker, MS, Suraj Peri, PhD, Ricardo López de Cicco, PhD, Yubo Zhai, BS, Irma H. Russo, MD, Theresa Nguyen, BS, and Fathima Sheriff, MD from Fox Chase, as well as researchers from New York University and Sweden’s Sunderby Hospital and Umeå University. For the other studies, they were joined by Colleen O’Malley, intern from Drexel University; Maria Barton, MSc, of Fox Chase; and researchers at the University of Texas Health Science Center.