Test coming that could help customize cancer treatment

Up until just recently, treating cancer was a lot like filling a teacup with a fire hose: Hit the cancer with the big, poisonous guns (chemotherapy) and hope that the cancer cells die and not too many of the body’s normal cells die with them. We’re all familiar with the ravages of chemotherapy: nausea, vomiting, loss of appetite (the cells in the gut are dying) hair loss (the hair-making cells are dying), extreme fatigue and overall, feeling lousy.

We know from data collected by the National Surgical Adjuvant Breast and Bowel Project that patients with a particular type of breast cancer, the most common type, in fact, have about a 15 percent chance of recurrence in the ten years following initial surgical treatment and added treatment with tamoxifen, a drug which counteracts the effects of estrogen. These tumors are “estrogen receptor positive,” meaning that the cancers respond to estrogen as a kind of growth hormone, and the cancer has not spread to the lymph nodes. That 15 percent can be further reduced by adding chemotherapy. But how does an oncologist decide who should get the chemotherapy, when apparently 85 percent of patients don’t need it?

Until now, researchers have looked at factors like tumor size and the patient’s age (post-menopausal is better). But looking at these factors has not been that helpful in predicting just who will get a recurrence of their breast cancer.

Researchers have been poking around, looking for genes in breast cancer tumor cells that might help them identify which cancers are the most likely to come back. Now, according to an article in the New England Journal of Medicine, the search has zeroed in on some likely candidates. Researchers first looked at 250 gene candidates and narrowed the number down to 16, along with five reference genes.

Until a company called Genomic Health stepped in, fresh tissue was required to identify these genes. Cancer cells needed to be examined at the time of surgery or shortly thereafter, and the techniques were cumbersome and expensive.

The usual process at the time of surgery is to embed the removed tumor in paraffin blocks. Thin slices are shaved off the block and examined under the microscope for diagnosis. These blocks can be saved indefinitely, and are available for research if needed. Scientists at Genomic Health developed a test, using the 21 genes identified, that could be run on the processed cells. This was great news, because patients enrolled in the NSABP had their tumor blocks saved, and some of these patients have been followed for as long as 20 years.

Looking at tumor blocks from 668 patients, all of whom received tamoxifen post surgery (but not the more drastic chemotherapy), they were able to profile 675 of them. Using the assay, they assigned low-, intermediate- and high-risk scores.

Were patients with low risk scores more likely to be disease free in ten years? They were. Only 6.8 percent in the low risk group had distant recurrences. Was the recurrence score better at predicting recurrences than the standard measures of the patient’s age and the tumor size? It was. The higher the score, the greater the chance of distant recurrence, up to 30 percent in the high-risk group.

They found that about 50 percent of the patients were in the low-risk category. Presumably, these patients don’t require chemotherapy, since the survival advantage would be offset by a similar risk of life-threatening toxic events from the chemotherapy itself.

The test, called Oncotype DX ™ is almost ready for prime-time. If other studies confirm the test’s ability to predict just who will benefit from chemotherapy after surgery, radiation and tamoxifen, then we will be at the threshold of individualizing treatment for patients based on their risk of cancer recurrence. And it looks like fully 50 percent of patients with node-negative, estrogen receptor positive cancer, a diagnosis that accounts or 50 percent of newly diagnosed breast cancer each year, can forego the debilitating effects of chemotherapy and face just as good a prognosis.