Breast cancer in young women: A distinct disease

Breast cancer in young women is a biologically unique disease that requires customized management strategies, researchers report at the 4th IMPAKT Breast Cancer Conference, in Brussels, Belgium.

The reported findings have potentially important implications for treatment, because breast cancer in young women is often aggressive and diagnosed at an advanced stage, meaning the prognosis for these patients is often poor.

Dr. Hatem A. Azim Jr., a medical oncologist from Institut Jules Bordet in Brussels, and colleagues showed that breast cancer in women forty-years or younger is enriched with the aggressive basal-like tumors. Moreover, these patients have a significantly higher risk of relapse independent of stage, histological grade, breast cancer molecular subtypes and treatment received.

A subgroup analysis showed a particularly poor trend in patients with luminal tumors, i.e. estrogen receptor positive. "While some investigators could refer this to poor compliance of young women to hormonal therapies, we performed another analysis in 1,188 women who did not receive any systemic therapy and indeed found significant poor outcome in young women both in luminal-A and luminal-B tumors," Dr Azim said. Luminal-A cancers are ER+ and low-grade, while Luminal-B cancers are ER+ but often high grade.

To elucidate the possible reasons behind the poor outcome in young women, Dr Azim and co-workers went on to study the expression of a variety of genes in women with breast cancer to see if they correlated with age. They adjusted their findings to take into account the size of the tumor at diagnosis, whether the disease had spread to lymph nodes and breast cancer molecular subtype, in addition to other variables.

The researchers performed their analysis on two independent datasets, including 1,188 and 2,334 patients, and found the same results in both cases.

"What we found was that even after adjustment for these parameters, there are several genes and gene signatures that are significantly associated with age in breast cancer patients," Dr Azim explained. "Some were highly expressed in young women -including stem cells, luminal progenitors, RANK-ligand (RANKL) and c-kit- while others were down-regulated, such as genes related to programmed cell death, or apoptosis."

The findings show that breast cancer arising at a young age seems to be associated with age-related biological processes, which appear to be independent of other prognostic factors that are commonly used by oncologists.

The genomic analysis also identified a number of signaling pathways in the breast cancers of young women that could be potential targets for treatment, Dr Azim's group reports.

For example, a gene signature of the phosphoinositide 3-kinase molecular pathway was highly associated with young age. "PI3k is an important targetable signaling pathway in breast cancer and perhaps these results could encourage investigating its role in breast cancer arising in young women," Dr Azim said.