Most Early-Stage Breast Cancer Patients with Intermediate Risk of Recurrence can Safely Avoid Chemotherapy

Major Research, Co-Authored by University of Maryland School of Medicine Physician-Scientist, Published in NEJM

The majority of women with early-stage estrogen receptor (ER)-positive breast cancer, considered at intermediate risk of having their cancer recur based on a 21-gene test, can safely forgo treatment with chemotherapy, according to a large multicenter clinical study published in the New England Journal of Medicine.

“The findings of this landmark clinical trial will have immediate clinical impact for thousands of women with early-stage ER-positive, HER2-negative breast cancer who have a mid-range Oncotype DX^® recurrence score, sparing them from unnecessary chemotherapy with its negative side effects,” says study co-author John A. Olson, Jr., MD, PhD, the Campbell & Jeanette Plugge Professor and vice chairman of the Department of Surgery at the University of Maryland School of Medicine (UMSOM), who helped to design the study.

“Chemotherapy provided no improvement in invasive disease-free survival rates compared to endocrine therapy alone, showing that the biologically-based biomarker guides therapy more effectively than standard pathologic variables,” says Dr. Olson, who is also chief of general and oncologic surgery at the University of Maryland Medical Center and associate director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. “This work adds to refinements in the surgical treatment of breast cancer that seeks to “right-size” treatment for patients.”

The results of The Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, were also reported June 3 at a plenary session at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

Previously, TAILORx investigators reported that low-risk patients with recurrence scores less than 11 could safely skip chemotherapy in favor of hormone therapy alone. In light of the latest findings, a combined 70 percent of women with this common type of breast cancer can now safety avoid adjuvant chemotherapy, researchers say.

More than 100,000 women in the United States are diagnosed each year with early-stage ER-positive breast cancer that is node-negative, meaning it has not been detected in nearby lymph nodes. Patients are typically treated with surgery, followed by hormone therapy, such as an aromatase inhibitor to limit the production of estrogen, and adjuvant chemotherapy.

TAILORx is the largest adjuvant breast cancer treatment clinical trial ever conducted, enrolling 10,273 women with early-stage breast cancer at approximately 1,200 sites in the United States and five countries. It was conducted by the ECOG-ACRIN Cancer Research Group with support from Genomic Health, Inc., under the sponsorship of the National Cancer Institute, part of the National Institutes of Health. Joseph A. Sparano, MD, professor of medicine & and obstetrics, gynecology and women’s health at the Albert Einstein College of Medicine in New York, is the lead author.

Participants in the clinical trial received treatment based on their scores on the Oncotype DX test – a 21-gene assay that provides a score based on the genetics of a woman’s tumor to gauge her risk of recurrence and predicts the potential benefit of chemotherapy.

In 2015, TAILORx investigators reported that low-risk patients with recurrence scores of less than 11 could safely skip chemotherapy. They found that less than 1 percent of the 1,626 women who took estrogen-limiting drugs and skipped chemotherapy based on their Oncotype DX test results experienced a recurrence of their cancer five years later. That rate rose to 3 percent after nine years, investigators reported in NEJM. Patients considered high-risk, with scores of 26 to 100, were found to benefit from both chemotherapy and hormone therapy, although the recurrence rate was 13 percent.

The primary study group consisted of more than 6,711 women, or 69 percent of the patients in the trial, who had Oncotype DX recurrence scores of 11 to 25, which is deemed to be intermediate risk. They were randomly selected to receive hormone therapy (also called endocrine therapy), such as anti-estrogen drugs called aromatase inhibitors, with or without chemotherapy. Researchers followed them for about nine years.

Investigators found that hormone therapy alone was “not inferior” to chemotherapy and hormone therapy, with similar rates of invasive disease-free survival, recurrence in a distant site or any site in the body, and overall survival between the two groups of patients.

But the researchers also said that some women age 50 or younger whose recurrence scores were at the high end of the intermediate range (16 to 25) may benefit from chemotherapy, although the reasons for this are not clear.

“This groundbreaking clinical trial will help patients and their physicians make more informed decisions about treating early-stage, ER-positive breast cancer using sophisticated genetic testing. It offers clear evidence that chemotherapy offers no additional benefit to anti-estrogen therapy alone,” says E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs at UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and UMSOM Dean.

“The findings also underscore the effectiveness of hormone therapy in treating ER-positive breast cancer,” Dr. Reece says, noting that the late UMSOM breast cancer researcher Angela H. Brodie, PhD, played a pivotal role in developing aromatase inhibitors, a hormone therapy widely used to treat postmenopausal women with breast cancer.

About the University of Maryland School of Medicine

Commemorating its 210^th Anniversary, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research.  With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically-based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and nearly $450 million in extramural funding, with more than half of its academic departments ranked in the top 20 among all public medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has a total budget of $5 billion and an economic impact of nearly $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8^th-highest public medical school in research productivity, is an innovator in translational medicine with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu/

About the University of Marlene and Stewart Greenebaum Comprehensive Cancer Center

The University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center in Baltimore. The center is a joint entity of the University of Maryland Medical Center and University of Maryland School of Medicine. It offers a multidisciplinary approach to treating all types of cancer and has an active cancer research program. It is ranked among the top cancer programs in the nation by U.S. News & World Report. www.umgccc.org.