New data on breast cancer and chemotherapy: more women with early stage disease do not need chemotherapy

More than 300,000 women were diagnosed in the US with breast cancer in 2017. Of those, approximately 63,000 were diagnosed with ductal carcinoma in situ, DCIS, or non-invasive breast caner. The remaining 250,000 had breast cancer that was invasive. Of those, 60,000 were diagnosed with early stage breast cancer that had intermediate Oncotype DX score, and the decision about whether to recommend chemotherapy was unclear.

The Oncotype DX test analyzes the activity of a group of genes that describes the behavior of cancer and its response to treatment, and whether it is likely to grow and spread. This test is used in patients who have been diagnosed with Stage 1 or 2 breast cancer that is estrogen-receptor positive and lymph node negative for cancer cells. The test is used to determine if chemotherapy would be useful to prevent recurrence. It is also used to determine if  DCIS is likely to be recurrent or progress to invasive cancer, and whether radiation would be helpful.

It is typical that tamoxifen or aromatase inhibitors (endocrine therapy) are used after surgical removal of the tumor to prevent recurrences, but some women are more at risk of having recurrences, and the Oncotype DX is used to determine who would benefit from chemotherapy.

The results of the Oncotype DX will provide a recurrence score, between 0 and 100. If the recurrence score is less that 18, the cancer’s risk of recurrence is low and the benefits of chemotherapy may not outweigh the risks of the treatment. If the score is 18-30, the risk of recurrence is considered intermediate, and it was not clear whether the benefits of chemotherapy  would outweigh the risks. If the score is 31 or greater, it is felt that the benefits outweigh the risks, and chemo is offered to the patient.

Prior to the most recent data, patients who found themselves in the intermediate category found themselves in a conundrum. The decision on whether to offer chemotherapy was a shared decision between doctor and patient, taking into account many factors including age, other medical problems, and the patient’s wishes.  Data were needed to further clarify the benefits in this group of patients.

The TailorRx was a prospective clinical trial that enrolled 10,000 women between 2010 and 2016. These women had estrogen-receptor positive, HER2 negative, lymph node negative breast cancer. If the recurrence score was less than 11, the women received only endocrine therapy. If the score was greater than 26, the women received chemotherapy and endocrine therapy. If the score was between 11 and 25, the women were randomized to receive either endocrine therapy only, or endocrine therapy plus chemo. These women were followed on average 8-9 years. The results were published last week in the New England Journal of Medicine.

There were 6711 women who were in the mid-range, and who were randomized. In that group, there were 836 events, which included recurrence, a new primary, or death. The study demonstrated that the women who had undergone chemotherapy and endocrine therapy did no better than those who had endocrine therapy alone. The exception to this were women who were diagnosed with breast cancer at age 50 or younger. If the recurrence score in this group was 16 or greater, they received substantial benefit from chemotherapy. This could be accounted for by the fact that chemotherapy induced early menopause.

In women with a score of 10 or less, the risk of recurrence at 9 years was 3%. In the intermediate score group (11-25) the nine year risk of recurrence was 5% for those who did and did not have chemotherapy.

There are other gene assays besides the Oncotype DX that can be used, and it is expected the further research will identify and analyze additional genes that will be useful.

All medical decisions, including those that regarding the treatment of cancer, must take into account an individual’s specific disease and medical situation. Medical oncologists should be consulted to get an accurate assessment of risks and benefits.

Marilyn C. Jerome, MD
Foxhall Ob-Gyn Associates

References:

The Washington Post: Health and Science,  June 3, 2018
Most women with a common type of early-stage breast cancer can skip chemo, a new report finds, by Laurie McGinley

The New England Journal of Medicine. June 3, 2018
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer, Sparano, et al.

Breast cancer.org. Oncotype DX