By: Elaine Schattner
Last week’s San Antonio Breast Cancer Symposium featured new evidence* for a tool that might inform treatment decisions in women with low-grade breast tumors. Since the 1980s, diagnoses of DCIS (ductal carcinoma in situ) have risen dramatically due to enhanced screening. Questions about this condition – whether it’s likely to cause harm, and how to manage it – are central to debate about mammography, the concept of overdiagnosis, and overtreatment.
The investigators presented new results for Oncotype Dx (Genomic Health GHDX +2.03%) a molecular pathology test, for evaluating DCIS. The multi-gene DCIS assay yields a prognostic score for the likelihood that DCIS will recur or lead to invasive breast cancer.
A key finding is that a low Oncotype DX DCIS Score™ conferred a low chance of recurrent disease in the affected breast – around 12.7 percent – after lumpectomy alone, with a median follow-up of 9.4 years. This clear result has huge implications for women with DCIS. It suggests that many – and possibly most – women with this condition can safely forgo radiation after lumpectomy.
More generally, it suggests that risks and costs attributed to breast cancer screening might be substantially reduced by widespread application of risk-assessing pathology tools including Oncotype Dx.
“Many women get radiation, because we can’t predict who will recur or go on to develop invasive disease,” said Dr. Eileen Rackovitch of the University of Toronto. She presented results of a prospective, population-based trial at a plenary session at the Symposium.
The Oncotype test has the power to change the usual DCIS treatment strategy, she said. “It provides women the opportunity to make informed treatment decisions based on individualized assessment of risk.”
Rackovitch and her colleagues identified DCIS cases between 1994 and 2003 in Ontario Province, Canada. They retrieved 718 samples from women who had breast-conserving surgery (lumpectomy) without radiation. Central pathologists, expert in breast pathology, reviewed the specimens to confirm the diagnosis of DCIS. The surgical margins were deemed clear in 571 of those cases. All the samples were evaluated, separately, by Oncotype Dx.
Over 10 years, among women with intermediate or high-risk DCIS scores, the chances of developing either recurrent DCIS or an invasive breast cancer in the affected breast were similar, approximately 30 percent. But among those with low Oncotype DCIS scores, only 12.7 percent developed either recurrent DCIS or an invasive tumor. These differences were statistically significant.
This Sunnybrook study is the largest, population-based combined molecular and clinical analysis of DCIS to date. Most of the women included were over 50 years old. Some did take Tamoxifen; the effects of that medication could not be assessed. Another limitation is the lack of data on disease that might recur outside of the breast, but that sort of outcome would unlikely be affected by radiation.
Dr. Michael Alvarado is a surgeon at University of California, San Francisco, who works with Genomic Health. “If a woman is found with DCIS in 2014, chances are probably 90 percent that she’ll be offered a lumpectomy followed by radiation, or a mastectomy,” he said. “Those would be the book answers, standard across the country.” But there’s essentially no mortality from DCIS, he considered.
As things stand, very few women with DCIS are offered the option of lumpectomy alone, without additional treatment. “Those few tend to have very, very, very small cases of DCIS, or they’re women over the age of 70,” he said.
“With this test, women may be more comfortable accepting less treatment,” Alvarado said. It affords many with DCIS the convenience of not having to go through radiation. “Radiation has possible effects on the heart and lungs. In some cases it may compromise the cosmetic outcome,” he added.
The study was funded by the Canadian Cancer Society Research Institute and Genomic Health. The new findings validate and extend an earlier, smaller analysis of the same tool, Oncotype DX DCIS, published in 2013.
Genomic Health markets two related assays. Oncotype Dx for estrogen-receptor positive invasive breast cancer has been commercially available for almost a decade. Results from this test have persuaded many women with low-risk scores to opt out of chemotherapy after surgery. Not surprisingly, most insurance companies cover payment for this evaluation, as it has the potential to reduce direct costs of chemotherapy and complications of those harsh drugs. A similar test is available for colon cancer.
The assay for DCIS costs approximately $4,000. The costs of an Oncotype Dx DCIS evaluation have been covered by Medicare since 2013 but as of this date are not covered by most private insurers.
Some of the harder questions about Oncotype Dx are comparative in nature: How do the Genomic Health assays stack up against similar kinds of tumor RNA assays, such as Agendia‘s MammaPrint which is FDA-approved, evaluates a greater number of genes, and has the capacity to evaluate a wider swath of breast cancer subtypes? There is no directly comparing these tests, supplied by different companies, in their predictive accuracy. It’s likely that several of these will be useful and that, over time, some will prove better than others for evaluating particular cancer forms.
Finally, it’s worth considering how these RNA assays fit in with all-the-rage DNA-sequencing, mutation-finding tests, in terms of information they might provide about individual tumors. It could be that measures of gene expression, including Oncotype Dx, MammaPrint and others, will prove useful as a supplement, in terms of how cancers behave, to current and forthcoming DNA analyses.
*San Antonio Breast Cancer Symposium, plenary December 12, 2014, Abstract S5-04
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.