As a practicing medical oncologist with a specialty in breast cancer for the past 22 years, I have been fortunate to see substantial advances in treatment. A majority of women are now diagnosed with early stage disease, and five-year survivals without recurrence for women with estrogen receptor positive stage I and II breast cancer now exceed 85-90%. The question I now deal with is not: “Will I survive this,” but rather, “What will it take to get me there?”

 When I started 22 years ago, many women with early stage breast cancer received chemotherapy in addition to anti-hormonal therapies, such as tamoxifen or anastrozole. We would make an educated guess as to the need for chemotherapy based on the size of the cancer, presence and number of involved axillary lymph nodes, and how aggressive the tumor looked under the microscope. Chemotherapy can be very toxic, and around 15-20 years ago some of us were curious as to whether we could come up with a test to determine whether we could identify those women with early stage breast cancer who could avoid chemotherapy altogether, take an anti-hormonal therapy alone, and still have an excellent long-term outcome.

 Genomic tests were developed in the early 2000s to address this problem. These tests looked at the expression of various genes in the cancer itself which not only could tell us whether a woman with early stage estrogen receptor positive breast cancer would recur in 10 years, but also which women would benefit from chemotherapy. The biology of the disease could therefore individualize treatment, leading to excellent outcomes with less toxicity for the 50-60% of women who would now not need chemotherapy. Currently there are 4 to 5 of these tests available, with Oncotype Dx (21 genes) and Mammaprint (70 genes) being the most popular.

 The TAILOR-Rx trial, recently published in the New England Journal of Medicine, is one of the first trials prospectively demonstrating that a genomic test (Oncotype Dx) in early stage estrogen receptor positive breast cancer can be used to avoid chemotherapy with outcomes identical to women receiving chemotherapy. Pittsburgh oncologists were central contributors to this trial.

 In TAILOR-Rx, over 11,000 women with estrogen receptor positive, node negative early stage breast cancer had an Oncotype Dx test of their breast cancer. Thosewith a low score (less than 11, about 20% of women) received hormonal therapy alone, and had an excellent 9-year distant recurrence free survival (over 97%). Those with a high score (greater than 25, about 14% of women) received chemotherapy and hormonal therapy, and also had an excellent 9-year distant recurrence free survival of about 87%. Women with an intermediate score (11-25, about 65% of women) all received hormonal therapy, but half received chemotherapy. These women had no benefit to chemotherapy, and both arms of this intermediate group had a 9-year distant recurrence free survival in excess of 95%. The trial could not rule out some chemotherapy benefit in women under 50 years of age with recurrence scores of 15-25, but this benefit was likely small (perhaps 2% fewer distant recurrences at 9 years).

 With genomic tests such as Oncotype Dx or Mammaprint, close to 60-70% of women with node negative, estrogen receptor positive breast cancer can now avoid the toxicity of chemotherapy with excellent outcomes. This represents a major advance, as many women with early stage breast cancer can now to get to the ultimate goal of living a life free from breast cancer recurrence without the side effects of chemotherapy.

 From the National Surgical Adjuvant Breast and Bowel Project (NSABP) trials in the 1980s (spearheaded by Dr. Bernie Fisher) demonstrating that lumpectomy and radiation is equivalent to mastectomy in terms of outcome, to the trials of today demonstrating that more than 60-70% of women diagnosed with node negative breast cancer can now avoid chemotherapy, Pittsburgh has been at the center of innovation in breast cancer. We are fortunate in Allegheny County to be frontline observers and contributors to this revolution in personalized therapy.

 

Author profile
Adam Brufsky, MD, PhD

Adam Brufsky, MD, PhD, is Professor of Medicine at the University of Pittsburgh.