BCRF-Supported Study Shows Many Women with Early Stage Breast Cancer Can Avoid Chemotherapy

The groundbreaking TAILORx Study is the largest trial of its kind with over 10,000 patients enrolled in 6 countries.

BCRF investigator Dr. Joseph Sparano reported results from the TAILORx clinical trial showing no added benefit of chemotherapy for women with early stage, ER-positive breast cancer with an intermediate Oncotype Dx^® Recurrence score. The study results were reported during the 2018 annual meeting of the American Society of Clinical Oncology (ASCO).

Study results are game changing for the majority of breast cancer patients

“Half of all breast cancers are hormone receptor-positive, HER2-negative, and axillary node-negative,” Dr. Sparano explained in the ASCO press release. “Our study shows that chemotherapy may be avoided in about 70 percent of these women when its use is guided by the [Oncotype Dx^®] test, thus limiting chemotherapy to the 30 percent who we can predict will benefit from it.”

Chemotherapy plus endocrine (anti-estrogen) therapy has been the standard of care for early-stage, hormone-positive breast cancer since it was shown to reduce recurrence 30 years ago. However, not all women need this agressive therapy and it can have both short– and long–term side effects. Side effects during chemotherapy include nausea, vomiting, hair loss, fatigue, and infection, and, in younger women, early menopause or infertility. Neuropathy, with symptoms including numbness, tingling, or severe pain in the hands and feet, can persist for many years after treatment ends.

Stratifying risk to personalize treatment

Oncotype Dx^® is a widely used prognostic assay that measures the level of 21 genes in the tumor biopsy to determine the risk of recurrence in newly diagnosed patients with early stage, hormone receptor (ER-positive) breast cancer. The test provides a score from 1-100 (called the Recurrence Score- RS) which indicates a patient’s risk that her breast cancer may come back. The information is used to guide treatment in early stage disease, particularly to determine whether chemotherapy should be added to reduce the risk of recurrence. 

Earlier studies showed that women with a very low Recurrence Score (1-10) did just as well on anti-hormone therapy (such as tamoxifen or aromatase inhibitors) as did those who received added chemotherapy. Conversely, patients with a RS greater than 26 had a higher risk of recurrence and thus had better outcomes with the addition of chemotherapy.

“Before TAILORx, there was uncertainty about the best treatment for women with a mid-range [Recurrence] score of 11-25,” Dr. Sparano said. “[TAILORx] was designed to address this question, and provides a very definitive answer.”

Shedding new light on the gray zone in risk prediction

The National Cancer Institute trial, supported in part by BCRF, is the largest of its kind and the first ever precision-based clinical trial. More than 10,000 women were enrolled who had early stage, ER-positive, HER2-negative, node negative breast cancer across 1,182 sites in the United States, Australia, Canada, Ireland, New Zealand, and Peru from April 2006 to October 2010.

Based on results from earlier studies, women in the low-risk group (RS 1-10) were treated with hormone therapy alone; Women in the high-risk group (RS greater 26) were given hormone therapy and chemotherapy.

Women in the intermediate group (RS 11-25), approximately 70 percent of the study participants, were randomized to receive hormone therapy alone or hormone therapy plus chemotherapy after surgery and radiation therapy. The goal was to determine whether the addition of chemotherapy improved disease-free survival in the intermediate risk group.

After a median of seven and a half years of follow up, the trial demonstrated that hormone treatment alone was just as effective as the hormone therapy plus chemotherapy in the intermediate risk group. Disease-free survival, distant recurrence and overall survival rates were similar between both treatment groups.

Unanswered questions remain

In a subset analysis, the researchers found that women under age 50 with a RS between 21-25 may receive additional benefit from chemotherapy. The reasons for this are unclear but may be due to poor adherence to hormonal therapy in younger women or to an ovarian suppression effect of chemotherapy that can reduce estrogen levels. Dr. Sparano stressed that doctors should discuss the benefits and risks of chemotherapy with patients in this category as part of a shared decision-making process.

In addition, the study authors noted that 13 percent of patients in the RS 26-100 group had a recurrence despite the addition of chemotherapy, stressing the need for better therapies for this group of patients.

The co-primary objective of the study was to create a biorepository of tissue and blood so that researchers can learn more about the patients in the low-risk groups who had a recurrence and in the high-risk groups who recurred despite added chemotherapy.

In a conversation with BCRF, Dr. Sparano noted that without BCRF support, researchers could not have established a biorepository of tissue and blood from the more than 10,000 participants on the trial.

“These samples are a valuable resource that will allow us to uncover the factors that are driving those recurrences,” he said.

Though TAILORx did not include patients whose cancer has spread to the lymph nodes, an ongoing study, RxPONDER, conducted by the SWOG clinical trial group and also supported in part by BCRF, is designed to answer similar questions in women with stage II/III ER-positive breast cancer.