Often, women with BRCA mutations watch anxiously as their mothers, sisters, aunts and cousins battle cancer. And in the back of their minds, a troubling question must linger: Am I next?
BRCA1 and BRCA2 genes have gained notoriety for their role in inherited breast and ovarian cancers. Women who carry harmful mutations in these genes account for 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers.
 Researchers are looking beyond BRCA gene mutations to other molecular risk factors affecting breast and ovarian cancers. |
But City of Hope scientists are finding that there is more to inherited breast and ovarian cancer risk than BRCA1 and BRCA2 genes alone. So they’re turning to the human genetic map, searching for other factors behind how these two women’s cancers develop.
This work could advance efforts to realize personalized medicine — care guided by characteristics unique to each patient.
“The hope is that you can better define which women are at the highest risk and then target them for prevention or for better therapies,” said Susan L. Neuhausen, Ph.D., Morris & Horowitz Families Professor in Cancer Etiology and Outcomes Research.
Tests that detect BRCA mutations have enabled women to better understand their risk and act accordingly. But the tests don’t tell the whole story. Women who carry the mutation know that they are at increased risk for cancer — but not by exactly how much.
Neuhausen and her colleagues believe that other genes also influence risk in women affected by BRCA mutations, and they want to empower these women to make more informed decisions. Their choices can range from more frequent screenings to surgery removing their breasts or ovaries.
“They need to know: ‘What is my true risk? Are there preventive things I should be doing?’” Neuhausen said.
The researchers have turned their attention to a protein called IGF and the processes within cells that are linked to it.
So far, she and colleagues like Jeffrey N. Weitzel, M.D., chief of the Division of Clinical Cancer Genetics, have identified variations in several genes related to IGF that seem to affect breast cancer risk for women with BRCA mutations.
Neuhausen said the results are preliminary. She is working with a worldwide group of scientists to look at some of these genes in larger studies. If their studies confirm the early results, new genetic tests using these and other genes that have been found could more accurately predict women’s true risk.
