Most breast cancer patients could avoid chemo with use of genetic testing

Dr Joseph Sparano - Albert Einstein Cancer Center, New York, USA

Today I presented the results of the TAILORx trial. This trial was launched in 2006 and integrated one of the newest tests that was available, a gene expression test, into the treatment algorithm for women with early stage breast cancer, specifically hormone receptor positive, HER2 negative, node negative breast cancer, a subtype and stage of breast cancer that accounts for about half of all breast cancers in the US and about 8-9% of all cancers in the US.
So what we did was we integrated the test into the treatment paradigm and leveraged the information that we had at the time. So, for the one-third of patients who had a score that was either very low or very high we assigned them to treatment with either endocrine therapy alone if their score was low, standard endocrine therapy, or standard chemo-endocrine therapy if their score was high. For the majority of patients, the two-thirds of patients who had a score in the mid-range who still had a substantial risk of distant recurrence but where the benefit of chemo was unknown we randomised those patients to chemotherapy plus endocrine therapy, which we regarded as a standard arm because those patients met established criteria for recommending or considering chemotherapy, or endocrine therapy alone, which we considered the experimental arm.

What we found was that adding chemotherapy was of no benefit. The trial met its primary endpoint of establishing unequivocally non-inferiority for women who were randomly assigned to endocrine therapy. We also found that women who had a recurrence score of 0-10 had a nine year risk of distant recurrence of about 3%, indicating that they would have a low likelihood of benefitting from chemotherapy. We found that for the women who had the high scores, 26-100, who were assigned to chemotherapy and endocrine therapy, that 13% of those women relapsed despite it.
Finally, in order to make sure that there was no subgroup of patients in the mid-range, 11-25, who were deriving some benefit from chemotherapy, even if small, we performed an exploratory analysis and we found statistically significant interactions between age 50 or under, recurrence score and chemotherapy treatment such that if a woman was 50 or under and had a recurrence score of 21-25 she had about a 6-7% reduction in the rate of distant recurrence which is a rate of reduction that is comparable to the use of chemotherapy in an unselected population. The reduction in the risk of distant recurrence was about 2% for women who had a recurrence score of 16-20.

So at the end of the day doctors are still going to need to be doctors but they do have an important new piece of information, the highest level of evidence, supporting a precision approach to therapy with the information clear for women who are over the age of 50 and with physicians and patients needing to enter into a shared decision-making process for that relatively small subgroup who had the upper range of the mid-range score.