Update: On December 9, 2020, initial findings from a study related to TAILORx, known as RxPONDER, were reported at the virtual San Antonio Breast Cancer Symposium.
The RxPONDER trial presented the first evidence that some postmenopausal women with hormone receptor-positive, HER2-negative breast cancer that has spread to no more than three lymph nodes can safely skip chemotherapy. The findings apply only to women whose OncotypeDX® score is 25 or less. The randomized, controlled phase III trial also confirmed that chemotherapy benefits premenopausal women whose disease has the same characteristics.
The study, which included data from more than 5,000 patients who were assigned to receive either hormone therapy alone or hormone therapy combined with chemotherapy, is likely to change the way many people with breast cancer are treated.
“RxPONDER and the previous TAILORx study show the value of large, simple trials based on solid science to inform clinical practice,” says Dr. Norton. “They also raise important questions that will drive more science. For the small number of women whose cancer did come back, not having to give chemotherapy for many cases of primary breast cancer in postmenopausal women will open the door for trials of other types of drugs that could improve the prognosis.”
In the past several decades, many advances have been made to develop safer and more precise treatments for breast cancer. Chemotherapy remains a cornerstone of care and has extended survival for countless women. For those with a certain type of breast cancer, the standard treatment has been chemotherapy combined with endocrine therapy (also called hormone therapy).
New results from a clinical trial that began in 2006, called TAILORx, show that women with intermediate-risk breast cancer may not need chemotherapy. Joseph Sparano of Montefiore Medical Center presented the data at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO).
Medical oncologist Diana Lake, the principal investigator for this trial at Memorial Sloan Kettering, says the results support a growing body of research showing no chemotherapy benefit for older women. They also provide guidance for treating younger women with the disease.
The trial evaluated more than 10,000 women whose breast cancer was hormone receptor positive and HER2 negative and whose disease had not spread to lymph nodes in the armpit. After surgery to remove the tumor, patients were randomly assigned to receive either chemotherapy and endocrine therapy or endocrine therapy alone. The study found that chemotherapy did not add to the efficacy of endocrine therapy in intermediate-risk patients, especially those older than 50.
We spoke with breast cancer expert Larry Norton, Senior Vice President at MSK and Medical Director of the Evelyn H. Lauder Breast Center, to learn more about the impact of these results and what’s next for research in this area.
The women in this group are considered to be at intermediate risk. Can you explain what that means and how that determination is made?
Intermediate risk refers to the likelihood that a breast cancer will come back — recur — or spread after surgery. In the United States, recurrence risk is most commonly determined with a genetic test called Oncotype DX®. It looks at 21 genes within a tumor sample, and the score falls on a scale from zero to 100.
We have known that women who have a recurrence score of ten or lower should not receive chemotherapy because they have an excellent prognosis with endocrine therapy alone. It’s also understood that those with a score greater than 25 should be treated with chemotherapy along with endocrine therapy because it can significantly reduce the risk of the cancer coming back.
But it has been a big mystery as to how people should be treated when their Oncotype DX score is in the range of 11 to 25. This study sheds light on that question.
What does this study tell us? What do women with breast cancer need to know?
These study results showed us that patients with an Oncotype DX score of 11 to 25 who were treated with endocrine therapy alone had a very good prognosis. This group doesn’t need to undergo chemotherapy.
Over the years, we have made major advances in reducing the side effects of chemotherapy. We used to have a range of symptoms, including nausea, vomiting, and low blood counts. But today, chemotherapy is not anywhere as tough as it used to be. Nevertheless, it is a treatment that involves some side effects, cost, and time, so it is a huge achievement to learn that we can eliminate it for some people.
It cannot be overlooked that the prognosis is very good for women treated with endocrine therapy alone. Though these results apply to a particular subset of people with breast cancer, it’s still a large group — maybe 100,000 people in the United States alone. This is a very large clinical trial, and it was well conducted and well designed, so I expect it to have an immediate impact on patient care.
What are the next steps for this research?
First, I think we need to go back over the tissue samples from patients and try to understand the situation even more. It is being reported that chemotherapy might benefit women who are younger than 50 and have scores higher than 15, for example. Are there biological differences in younger women at intermediate risk compared with women over 50 who are at intermediate risk?
Further, since chemotherapy provides no additional benefit, what else could we add to endocrine therapy to achieve an even better prognosis for intermediate-risk patients? Could we target specific gene mutations associated with breast cancer, like PI3K? Can we teach the immune system to get rid of cancer cells? These are all research projects that we are involved with here at MSK since our goal is 100% eradication of breast cancer.