Gene Activity May Explain Deadlier Breast Cancers Among Younger ...

Tag : Pattern Mosaic

"We haven't had a good reason why younger women do worse than olderwomen," said senior study author Dr. Kimberly Blackwell, directorof 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 amolecular basis, why certain patients do so poorly," said Dr. JayBrooks, chairman of hematology/oncology at Ochsner Health System inBaton Rouge, La. "I think this will go a long way to helping definea population that, hopefully, would have more aggressivetreatments."
The results are in the July 10 issue of theJournal of ClinicalOncology.
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 lowersurvival rates.
"You think of breast cancer as sort of like a mosaic pattern withcertain patterns that are very bad and certain patterns that arevery good," said Dr. Otis Brawley, chief medical officer of theAmerican Cancer Society. "You're talking about 600 different genesin the mosaic patterns, and you end up with certain cancers thatare very aggressive and some cancers that are not so aggressive. Wetend to see more aggressive cancers in younger women versus olderwomen."
"We've known for 60 or 70 years that cancers tended to be moreaggressive in younger women," Brawley said. "Now we're actuallylooking at the genetics."
For this study, Duke researchers analyzed samples of almost 800early-stage breast tumors in two groups of women: those aged 45 andunder and those aged 65 or older.
More than 350 sets of genes were activated only in the youngerwomen. Tumors in older patients did not share any common gene sets,the authors stated.
The gene sets activated in younger women regulated such things asimmune function, breast cancer-related gene mutations such asBRCA1, stem cell biology, cell death and various cancer signalingpathways.
Younger women were less likely to have estrogen-receptor-positivetumors (71 percent versus 80 percent in older women); more likelyto have tumors which overexpress the protein HER2neu (52 percentversus 24 percent); more likely to have higher-grade tumors (56percent versus 26 percent) and larger tumor size; more likely tohave positive lymph nodes (38 percent versus 25 percent); andhigher recurrence rates.
Women under 40 had even higher recurrence rates than women aged 40to 45, although there appeared to be no differences in subgroups ofwomen under the age of 40.
Compounds already in development may hold promise for treatingyounger women, the authors said, although the actual benefit forpatients 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 willhave more drugs like Herceptin. A study like this gives you thetarget."
Herceptin targets tumors which overexpress the HER2neu protein.
More information
The American Cancer Society has more on breast cancer.
SOURCES: Kimberly Blackwell, M.D., director, clinical trialsprogram in breast cancer, Duke University, Durham, N.C.; OtisBrawley, M.D., chief medical officer, American Cancer Society,Atlanta; Jay Brooks, M.D., chairman, hematology/oncology, OchsnerHealth System, Baton Rouge, La.; July 10, 2008,Journal of ClinicalOncology