Gene Activity May Explain Deadlier Breast Cancers Among Younger Women

WEDNESDAY July 9, 2008 -- Genetic activity in breast cancer cells from younger patients could explain why tumors tend to more aggressive when they strike at a younger age.

"We haven't had a good reason why younger women do worse than older women," said senior study author Dr. Kimberly Blackwell, director of the clinical trials program in breast cancer at Duke University. "This study offers some insight into why younger women do worse."

"This is a real testament that we're beginning to define, from a molecular basis, why certain patients do so poorly," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "I think this will go a long way to helping define a population that, hopefully, would have more aggressive treatments."

The results are in the July 10 issue of the Journal of Clinical Oncology.

Breast cancer tends to be more aggressive in younger women, responds less well to existing treatments such as radiation, surgery and chemotherapy, and has higher recurrence and lower survival rates.

"You think of breast cancer as sort of like a mosaic pattern with certain patterns that are very bad and certain patterns that are very good," said Dr. Otis Brawley, chief medical officer of the American Cancer Society. "You're talking about 600 different genes in the mosaic patterns, and you end up with certain cancers that are very aggressive and some cancers that are not so aggressive. We tend to see more aggressive cancers in younger women versus older women."

"We've known for 60 or 70 years that cancers tended to be more aggressive in younger women," Brawley said. "Now we're actually looking at the genetics."

For this study, Duke researchers analyzed samples of almost 800 early-stage breast tumors in two groups of women: those aged 45 and under and those aged 65 or older.

More than 350 sets of genes were activated only in the younger women. Tumors in older patients did not share any common gene sets, the authors stated.

The gene sets activated in younger women regulated such things as immune function, breast cancer-related gene mutations such as BRCA1, stem cell biology, cell death and various cancer signaling pathways.

Younger women were less likely to have estrogen-receptor-positive tumors (71 percent versus 80 percent in older women); more likely to have tumors which overexpress the protein HER2neu (52 percent versus 24 percent); more likely to have higher-grade tumors (56 percent versus 26 percent) and larger tumor size; more likely to have positive lymph nodes (38 percent versus 25 percent); and higher recurrence rates.

Women under 40 had even higher recurrence rates than women aged 40 to 45, although there appeared to be no differences in subgroups of women under the age of 40.

Compounds already in development may hold promise for treating younger women, the authors said, although the actual benefit for patients may be some years away.

"This doesn't mean anything for a young woman who has breast cancer [now], like the one that I saw yesterday afternoon," Brawley said. "It does mean that perhaps in five years, perhaps in 10, we will have more drugs like Herceptin. A study like this gives you the target."

Herceptin targets tumors which overexpress the HER2neu protein.

More information

The American Cancer Society has more on breast cancer.

Posted: July 2008


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