RxPONDER trial finds some women with hormone receptor-positive cancer in lymph nodes do not need chemotherapy

Postmenopausal women with early-stage, hormone receptor-positive, HER2-negative breast cancer in one to three lymph nodes who get an Oncotype DX score of 25 or lower can be treated with hormonal therapy alone after breast surgery, according to the RxPONDER trial.

These results, presented Thursday during the San Antonio Breast Cancer Symposium, increase the number of women with hormone receptor-positive breast cancer who can safely forego chemotherapy to include those who have cancer in up to three lymph nodes.

The RxPONDER trial found that there was no difference in the risk of cancer returning 5 years after surgery for this group whether they were given chemotherapy or not. In line with previous findings, women who have not gone through menopause should still be recommended for chemotherapy, which lowered their risk of cancer returning.

Background

Oncotype DX is a genomic assay, or test, for hormone receptor-positive, HER2-negative breast cancers. A genomic assay looks at features in the DNA of a tumor and predicts how likely the cancer is to come back after treatment. After being removed, a piece of the tumor is tested in the lab, and assigned a Recurrence Score ranging from 1 to 100.

Past studies, most recently the TAILORx trial, have found that the Oncotype DX Recurrence Score can predict whether adding chemotherapy to treatment will lower the chance of cancer returning.

TAILORx found that whether you have gone through menopause — when menstrual periods stop occurring and the ovaries stop producing estrogen and other hormones — affects how you should interpret an Oncotype DX score. That trial found that chemotherapy would not lower the risk of cancer retuning for postmenopausal women with Recurrence Scores of 25 or less. But women who had not been through menopause and had scores between 16 and 25 should consider chemotherapy, depending on other clinical features of their diagnosis.

TAILORx and other past studies only looked at breast cancers that had not spread to the lymph nodes. The RxPONDER trial looked at whether Oncotype DX scores could guide treatment decisions for women with cancer cells found in up to three lymph nodes.

RxPONDER trial

Women included in the RxPONDER trial had early-stage, hormone receptor-positive, HER2-negative breast cancer and cancer cells present in one to three lymph nodes. All participants had Oncotype DX scores of 25 or less and were randomly assigned to one of two treatment groups:

• Chemotherapy followed by hormonal therapy
• Hormonal therapy alone

Anyone with an Oncotype DX score above 25 was recommended chemotherapy and not included in this trial.

The primary aim of the study was to see if there was a relationship between Oncotype DX scores and the effect of chemotherapy on the risk of breast cancer returning, called invasive disease-free survival. When researchers found that Oncotype DX scores and the effect of chemotherapy on recurrence risk were not related in the overall study population, they moved on to analyze certain participant groups within the trial that they had identified in the trial design.

Researchers separated participant data based on whether they had gone through menopause or not. They found that women who had not been through menopause had a lower risk of cancer returning if they were given chemotherapy. The invasive disease-free survival rate for premenopausal women after 5 years was

• 89.0 percent if given just hormonal therapy
• 94.2 percent if given chemotherapy then hormonal therapy

Women who had already been through menopause, on the other hand, showed no difference in the risk of cancer returning whether they were given chemotherapy or not. The 5-year invasive disease-free survival rate for postmenopausal women was

• 91.9 percent if given just hormonal therapy
• 91.6 percent if given chemotherapy then hormonal therapy

When researchers looked more closely at these results they found no subgroup of postmenopausal women lowered their risk of recurrence by adding chemotherapy to treatment.

What this means for you

These findings expand the use of the Oncotype DX Recurrence Score to help women with cancer cells found in some lymph nodes make informed treatment decisions. Finding breast cancer in the lymph nodes is one of many important features used in making treatment decisions and usually it means that you will need more treatment. Adding Oncotype DX to the conversation for women with cancer in just a few lymph nodes should be a relief for those who will be able to safely remove chemotherapy from their treatment plan.

For premenopausal women with similar Recurrence Scores, it can be frustrating to learn that these findings don’t change your need for chemotherapy. More research is needed to learn why premenopausal women react differently to chemotherapy and if there are options besides chemotherapy to get the same effect. But these results also reinforce that chemotherapy is working to reduce the chance of cancer returning and that you are getting the best treatment based on the research.