PREDICTING WHICH WOMEN WITH DCIS WILL DEVELOP INVASIVE CANCER

April 29 2010 — New research suggests that it might be possible to identify which women with ductal carcinoma in situ (DCIS) are likely to go on to develop invasive breast cancer and which women are at very low risk.

The finding, published online April 28 in the Journal of the National Cancer Institute, could prevent overtreatment of DCIS, say the researchers.

"As much as 44% of patients with DCIS may not require any further treatment, and can rely instead on surveillance," said lead author Karla Kerlikowske, MD, professor of medicine, epidemiology and biostatistics at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.

There is a growing concern in the breast cancer community that, currently, DCIS is being overtreated, as previously reported by Medscape Oncology.

However, until now, there has been no way to predict which women with DCIS are at risk of developing invasive breast cancer. They are all "lumped together into one risk group," Dr. Kerlikowske said in a statement.

The new study shows that this risk can be quantified using 2 factors — detection of a breast lump by palpation and the high expression of 43 biomarkers.

This is an exciting and powerful beginning, to be able to predict which precancers will lie dormant and which will lead to invasive cancers,'' said colleague and coauthor Thea Tlsty, PhD, professor of pathology at the Helen Diller Family Comprehensive Cancer Center. "For the first time, we've identified the group of patients at the lowest risk and the group at highest risk of developing invasive cancer. It's a big step forward.''

"Thought-Provoking" Study

Describing the study as "thought-provoking" in an accompanying editorial, Craig Allred, MD, from Washington University School of Medicine in St. Louis, Missouri, said that these new results — if validated in other studies — could lead to optimization of current therapy in certain settings.

The current standard of care for most patients with DCIS is lumpectomy followed by radiation, but these new results suggest that adjuvant radiation could be withheld from patients with low-risk DCIS as defined by the study, he noted.

However, as the researchers themselves acknowledge, Dr. Allred concludes that "there is still much to learn before translating these results to routine clinical practice."

This study was statistically underpowered, and some of the results with biomarkers were "somewhat mystifying." Dr. Allred notes.

In addition, the women with DCIS in this study were treated with a lumpectomy only, but this is rarely the case today, because most women also have adjuvant radiation, and those with estrogen-positive disease are also prescribed tamoxifen for 5 years, he points out.

So, in addition to independent validation, "it will be critical to determine whether the results of this study are influenced by adjuvant radiation and hormonal therapy," he adds.

Two Factors Were Predictive

In the study, Dr. Kerlikowske and colleagues followed the medical histories of 1162 women, 40 years and older, who were diagnosed with DCIS and treated with lumpectomy only. They found that 2 factors predicted invasive cancer developing within 8 years of the DCIS diagnosis — the method by which it was detected and the expression of several biomarkers.

The team found that a breast lump that was diagnosed as DCIS was more predictive of a high risk of subsequent invasive cancer than DCIS diagnosed by mammography.

In addition, women with DCIS lesions that express high levels of 3 biomarkers — p16, cyclooxygenase (COX)-2, and Ki67 — were more likely to develop invasive cancer after their initial DCIS diagnosis, the team reported.

The team found that women with initial DCIS lesions that had both of these factors (i.e., were detected by palpation and had high expression of p16, COX-2, and Ki67) were at high risk of developing subsequent invasive cancer (but not subsequent DCIS). Just over a quarter of the women in their study (27.6%) fell into this category.

But many women (44.1%) did not demonstrate either of these 2 factors, and were categorized as having a low risk of developing subsequent invasive cancer.

Using both of these factors could be useful in stratifying a woman's risk of subsequent invasive cancer and help her decide whether she should undergo adjuvant therapies, the researchers conclude.

"Women choose their treatment based on their level of concern of developing invasive cancer,'' Dr. Kerlikowske explained. "DCIS is noninvasive, so women do not die of it. Their real concern arises if they develop invasive cancer and the cancer spreads.''

The researchers have disclosed no relevant financial relationships.

J Natl Cancer Inst. 2010;102:585-587, 627-637.