Tailored Treatment: All About the TAILORx Trial

Ever buy one of these Breast Cancer Research postage stamps? ​​

Because, if you did, you helped partially fund a clinical trial that will affect how we treat early stage breast cancer. Thank you!

The trial, published this week in the New England Journal of Medicine, and making the rounds in every major newspaper today, is called the TAILORx trial. It is thought to be the largest breast cancer treatment trial ever performed.

Before we discuss how the results from this trial will change how we treat breast cancer, we need a little background.

Every breast cancer tumor expresses certain cancer related genes in the tumor itself, therefore, every tumor's so-called genomics can be profiled and compared against many other tumors. The most commonly used genomic profile test (called OncotypeDx) looks at 21 specific cancer-related genes in the tumor and gives us a "Recurrence Score." This is a precise way of classifying a tumor based on how likely it is to grow, spread, and benefit from chemotherapy.

(The way I usually explain this conceptually is to think of the genomic profile as a sort of fingerprint, which allows us to look thru a large database of other genomic profiles for very similar fingerprints, and then make inferences about the behavior of tumor in question based on the patterns we see in the database. Certain fingerprint patterns mean that the tumor is rather indolent and not likely to spread and therefore not likely to be thwarted by chemotherapy. Other fingerprints tell us the opposite: the tumor is a bad actor, likely to metastasize, very responsive to chemotherapy, etc.) The caveat is that OncotypeDx and the TAILORx trial focus only on hormone receptor positive, HER-2 negative, and axillary node negative early stage breast cancers, which is only half of the breast cancers diagnosed. But, for these women, the OncotypeDx score can influence therapy recommendations greatly.

Prior to the TAILORx trial results, hormonally sensitive, HER-2 negative early stage breast cancers found in women less than 75 years old, would have the OncotypeDx test performed on the tumor after surgery. Those with "low" recurrence scores (0-18) would be counseled that they could safely avoid chemotherapy if they completed endocrine therapy (like Tamoxifen or Arimidex for 5-10 years). Those with "high" recurrence scores (above 30) would be counseled that they should strongly consider chemotherapy in addition to endocrine therapy. But those women whose tumors scored "intermediate"? Well, we didn't have a great answer. ​​Endocrine therapy was a given, but was chemotherapy? Yes or no? Its not like chemotherapy is a walk in the park, and if it is not going to help prevent death from breast cancer, its hardly worth it. If only ​there was a randomized controlled trial to evaluate this group of women with intermediate scoring tumors...

TAILORx did just that. The study enrolled 10,273 women with hormonally sensitive, HER-2 negative early stage breast cancers found in women less than 75 years old. Of these women, 6,711 had intermediate recurrence scores on their OncotypeDx test and these women were randomly assigned to endocrine therapy alone versus chemotherapy and endocrine therapy. The "endpoint" (or the question we are trying to answer) was disease-free survival (no further breast cancer). After a median follow up time of 7.5 years, it was clear that avoiding chemotherapy was not less effective in treating the breast cancer. Looking back 9 years, the overall survival between the two groups, those with and without chemotherapy, were essentially the same, almost 94% (meaning almost 94% of women lived at least 9 years after their diagnosis.) There was no measurable benefit from getting chemotherapy for this type of breast cancer. Except...

Except in women less that 50 years of age. I think this is actually one of the most powerful findings in the study. Looking at the data amassed from the 6,711 women randomized and diving deeper into the various subgroups, women less than 50 had better outcomes with chemotherapy when their recurrence score was considered intermediate. We've known for quite a while that breast cancer in older women behaves differently from breast cancer in younger women: its nice to have some data to help guide treatment decisions in this population.

So, in summary, chemotherapy may be safely spared in all women older than 50 years with hormone receptor positive, HER2 negative, node-negative, early stage breast cancer and a Recurrence Score of 0 to 25 (about 85% of women with breast cancer in this age group) and all women 50 years or younger with hormone receptor positive, HER2 negative, node-negative early stage breast cancer and a Recurrence Score of 0 to 15 (about 40% of women with breast cancer in this age group).

As you can see, a lot of women will benefit from the knowledge gathered by this trial.

So, thanks again for buying those stamps!