Breast Cancer In Younger Women Shares Common Genetic Factors
DURHAM, N.C., July 9 (MedPage Today) -- The poorer prognoses of younger women's breast cancers may be the result of a unique set of genomic traits not present in older patients, researchers said.
Tumors of women ages 45 and younger were distinguished by 367 biologically relevant gene sets whereas those of older women had not a single gene set in common, reported Carey K. Anders, M.D., of Duke University here, and colleagues in the July 10 issue of the Journal of Clinical Oncology.
The shared biology among younger women in the large genomic study included genes regulating immune function, BRCA1, and apoptosis, as well as oncogenic signaling pathways including Myc, Ras, AKT, and MapKinase.
Younger age has long been linked to poorer breast cancer prognosis and endocrine therapy response, which have often been blamed on higher circulating estrogen levels and family history of disease, said coauthor Kimberly L. Blackwell, M.D., also of Duke,
However, the findings suggest "breast cancer arising in young women is a unique disease entity driven by complex biologic processes extending beyond hormone receptors and hereditary cancer syndromes," the researchers wrote.
Another implication was that there were common causative factors for breast cancer arising in younger women but "many, many more etiologies for the older women," Dr. Blackwell said.
The exciting part is that many genes overexpressed in younger women can be matched up to drugs targeting these pathways, she said.
The researchers analyzed four publicly available datasets containing clinically annotated samples from 784 early-stage breast tumors. This sample included tumors from 200 premenopausal women ages 45 and younger as well as 211 postmenopausal women ages 65 and older.
Breast cancer was more likely to recur or be fatal in younger women.
Disease-free survival tended to be lower both for ages 45 and younger compared with 65 and older (hazard ratio 1.32, P=0.094) and was significantly lower for ages 40 and younger compared with age 40 to 45 at diagnosis (HR 1.69, P=0.013).
Prognostic factors were also worse in younger women. For ages 45 and younger versus 65 and older, these included:
- Lower occurrence of clinical estrogen-receptor positive tumors (71% versus 80%, P=0.027) and estrogen-receptor alpha and beta gene expression (P<0.0001 and P=0.02, respectively).
- Lower progesterone-receptor gene expression (P<0.0001).
- Higher expression of HER2 histologically (P=0.075) and genetically (P<0.0001).
- Higher-grade tumors (56% grade 3 versus 26%, P<0.0001).
- Larger tumor size (62% larger than 2.0 cm versus 47%, P=0.012).
- Greater incidence of positive lymph nodes (38% versus 25%, P=0.008).
- Higher epidermal growth factor receptor (EGFR) gene expression (P<0.0001).
Predictors of poorer disease-free survival outcomes in multivariate analysis among younger women were younger age at diagnosis (HR 1.96, P=0.004), lower estrogen-receptor beta expression (HR 1.41, P=0.012), and higher EGFR expression (HR 1.24, P=0.026).
Among older women, the predictors were positive lymph node status (HR 1.88, P=0.04) and lower estrogen-receptor beta expression (HR 1.40, P=0.034).
The researchers cautioned that interpretation of long-term outcome was limited as patients received a number of different adjuvant therapies, or even no therapy, across datasets.
The study was funded by the National Institutes of Health through the National Cancer Institute. The researchers reported no conflicts of interest.
Primary source: Journal of Clinical Oncology Source reference: Anders CK, et al "Young Age at Diagnosis Correlates with Worse Prognosis and Defines a Subset of Breast Cancers with Shared Patterns of Gene Expression" J Clin Oncol 2008.
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What breastcancer.org says about this article…
Breast Cancer In Younger Women Shares Common Genetic Factors
Breast cancer diagnosed in younger women tends to be more aggressive, harder to treat, and more likely to come back.
The study reviewed here found that breast cancers from 200 women diagnosed before age 45 all had a large group of genes in common. The group of genes is linked to factors that can promote the development, growth, and spread of cancer cells. In comparison, breast cancers from more than 200 women age 65 and older didn't have any gene groups in common.
Though there's still much to learn, research over the years has led to a better understanding of how cancer happens. This knowledge helped scientists create targeted breast cancer treatments such as Herceptin (chemical name: trastuzumab) and Tykerb (chemical name: lapatinib).
Genetic mistakes of one kind or another usually cause the development and growth of cancer cells. These genetic mistakes allow cells to become cancerous -- to develop, multiply, and spread in uncontrolled, abnormal ways.
Many of the genes that breast cancer cells from younger women had in common already have been linked to cancerous cell behavior. And many of these genes are the targets of targeted therapy medicines already approved to treat breast and other cancers. Researchers hope that a more complete understanding of the genetic profile of breast cancer in younger women will lead to the creation of new targeted therapies in the future.
Stay tuned to Breastcancer.org for the latest news on research that may lead to better ways to prevent, diagnose, and treat breast cancer.