Study: Gene test validates NCCN guidelines on chemo for breast cancer

Some early stage patients can skip chemo

chemo for breast cancer
mCancerPartner interviewed Dan Hayes, M.D., clinical director of the Cancer Center’s breast oncology program. In late September 2015, investigators – including Dr. Hayes – showed that many women with early stage breast cancer can skip chemotherapy with good results, based on a gene test assessing which tumors were more likely to respond to chemotherapy. This study validates clinical recommendations in place since 2007 made by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Dr. Hayes served on both recommendation task forces and provided the following remarks on the origin of these recommendations.

mCancerPartner: How has the standard of care for women with the most common type of breast cancer (early stage, hormone positive, HER2 negative, not spread to lymph nodes) evolved over the years?

Dr. Hayes: From the late 1980s to the mid-2000s, just about everyone with early stage breast cancer got chemotherapy after surgery, called adjuvant chemotherapy. Why? Because of the fear of under treatment, because we knew by then that chemo offered the greatest benefit to women with a poor prognosis. There was a lot of research-backed discussion among breast cancer specialists about the long-term effects of chemotherapy for women who have an extremely low risk of recurrence, and whether it was worth the risk to an early stage patient to forego chemo. Roughly 1%-2% of patients experience toxicity from chemotherapy through their lifetime. But what defines choice and risk, whether it’s risk of toxicity or risk of recurrence, and choosing between the two? There just wasn’t agreement among doctors in those days about the risks versus benefits of skipping chemo for this group of women.

mCancerPartner: What changed so that you and your colleagues felt it was the right treatment recommendation for these women to skip chemo?

Dr. Hayes: In 2005, something called the Oncotype DX®test was validated and adopted. This test measures the expression of 21-different genes within the cancer tissue and generates what is called a “recurrence score.” A patient may have a high, intermediate, or low recurrence score. For women with node negative, ER positive breast cancer who have a low recurrence score, the odds of having their breast cancer recur if they only took anti-estrogen therapy, like Tamoxifen, for at least five years, was less than 10% at 10 years. Since chemotherapy only reduces the chances of recurrence by approximately 1/3, only 2-3 women out of 100 treated would benefit, which is almost the same as the number who have really bad toxicities. So for these women, we no longer recommended chemo. We highly recommend adjuvant chemotherapy for those with a high recurrence score, and we are waiting for the results of a large trial in which half the women with intermediate score received chemotherapy and half did not.

The current paper published in the New England Journal of Medicine presented findings from that same prospective trial, but it is from a registry of early stage patients who are node negative, ER positive and had a low recurrence score. These patients were treated after surgery with anti-estrogen therapy only. At the five-year follow up, thee patients are doing remarkably well, reassuring us that we have been doing the right thing (recommending that this group of patients skip chemo) for the last 10 years. As I noted, this same study is looking at the benefit of chemotherapy for patients with intermediate risk, but results won’t be ready to report for several more years.

mCancerPartner: Is there any other research on chemotherapy and breast cancer that may affect clinical guidelines in the future?

Dr. Hayes: Yes, we have a prospective randomized trial that has just completed enrollment that is looking at women low to intermediate Oncotype DX® recurrence scores but who have ER positive, node POSITIVE diseasetest. In this case, we expect their prognosis to be sufficiently poor to justify the use of chemotherapy, since they have node positive breast cancer, but our hypothesis is that cancers with low recurrence score may not respond to chemotherapy the way that cancers that have high recurrence scores do. The study is measuring the number of patients who benefit – or don’t benefit – from taking adjuvant chemotherapy. But results won’t be out for a few years. In the meantime, ASCO and NCCN continue to recommend adjuvant chemotherapy for node positive patients, especially if they have multiple positive nodes.

Take the next step:

  • Read more about clinical practice guidelines for breast cancer from ASCO and NCCN.
  • Learn more about the medical terms used in this article from the National Cancer Institute.

Daniel F. Hayes, MD

Daniel F. Hayes, MD

The U-M Comprehensive Cancer Center’s Breast Care Center provides people diagnosed with breast cancer a team-based approach to treatment. During the initial visit, patients may talk with surgical oncologists, medical oncologists, radiation oncologists, plastic surgeons, gynecologists, social workers and nurses. In addition, they will have their mammograms and pathology slides read all in one day. For people who need treatment for breast cancer, we offer the most comprehensive, effective and least invasive treatment methods. Our philosophy is breast preservation, through lumpectomy and radiation therapy, when possible. We also offer immediate reconstruction using the patient’s own tissues.


Cancer-center-informal-vertical-sig-150x150The University of Michigan Comprehensive Cancer Center’s 1,000 doctors, nurses, care givers and researchers are united by one thought: to deliver the highest quality, compassionate care while working to conquer cancer through innovation and collaboration. The center is among the top-ranked national cancer programs, and #1 in Michigan according to U.S. News & World Report. Our multidisciplinary clinics offer one-stop access to teams of specialists for personalized treatment plans, part of the ideal patient care experience. Patients also benefit through access to promising new cancer therapies.