Friday, February 08, 2008

Oncotype DX Breast Cancer Assay

Many years ago, two of my patients in their early 40's had abnormal mammograms. In both cases, the films showed suspiciously clustered spicules of calcium. The biopsy on one showed invasive ductal carcinoma; her subsequent work-up confirmed no spread of the cancer to lymph nodes or beyond. The other one's biopsy was negative.

Prevailing wisdom at the time was to administer adjunctive chemotherapy to nearly all patients no matter whether their cancer was localized or not. My previously well patient, a professor at a local university, underwent chemo and died from an infection shortly after receiving her first dose. The other lady was found to have the exact same suspicious cluster of calcifications on her mammogram several years later (the first biopsy had missed the area) and underwent another tissue sampling which was positive for cancer. She had a lumpectomy, but no chemotherapy was recommended. Now two-plus decades later, she just retired from her law practice.

Fast forward to two months ago. Another abnormal mammo followed by another biopsy on another lady. This cancer was also localized by all tests, but her tissue was then examined for hormone receptors and genetic content post-lumpectomy. This DNA analysis known as the Oncotype DX Breast Cancer Assay revealed that the chances that her cancer would return without follow-up chemo were "off the charts." No dithering over whether or not chemo is appropriate; in her case it is essential and life-saving.

On average, the outlook for most women with node-negative, estrogen-receptor positive breast cancer treated with estrogen-blockers post-surgery looks good. Overall, these patients have a 15% risk of recurrence in the 10 years after diagnosis. This means that 85% of the women who underwent a course of chemotherapy for this diagnosis in the past could, in fact, have skipped these difficult treatments and still done well. Up until recently, however, we had no good way to counsel these women about which path to pursue.

In 2004, the Oncotype DX test was developed to test for the active expression of tumor-related genes in breast cancer surgical specimens. The results were used to develop a Recurrence Score which predicts the likelihood that the tumor will return in the future. Now women diagnosed with estrogen-receptor positive breast cancer are candidates for more individualized treatment based on these 'biomarkers of recurrence.'

To develop this test, the researchers sorted through 250 candidate genes from a DNA library of genetic material. They then analyzed clinical studies of cancer patients and the genetic nature of their tumors looking for a correlation between the expression of these 250 genes and the likelihood of cancer relapse at a later date. The scientists chose a panel of 21 genes for the final assay based on the strength of association between their expression and risk of recurrence. The Recurrence Score also correlates with the length of time until relapse and overall survival.

The test was lauded at the time by senior investigator JoAnne Zujewski, MD as having "the potential to change medical practice by sparing thousands of women each year from the harmful short- and long-term side effects associated with chemotherapy." Furthermore, those who could benefit most from opting for chemo, like my current patient, can feel more assured that they've made the right decision.

1 comment:

Mauigirl said...

Great news, good to know in case it happens to me or someone I know.