Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

Authors: Sparano, J.A. et. al.
Source: NEJM doi:10.1056/NEJMoa1804710
www.nejm.org/doi/pdf/10.1056/NEJMoa1804710

Chemotherapy reduces the risk of breast cancer recurrence and improves disease-specific survival. However, it has been understood for several years that many women who receive chemotherapy do not benefit from it. The 21-gene recurrence-score (or Oncotype DX) assay provides a score for each patient with estrogen receptor positive, Her2neu negative, node negative breast cancer. This score corresponds to the likelihood of disease recurrence over 10 years. Women with low (0-10) recurrence scores have a very low risk of disease recurrence and are offered endocrine therapy alone; chemotherapy is not expected to improve their prognoses. Women with high (31-100) recurrence scores have elevated risks of recurrence and are expected to benefit from chemotherapy in addition to endocrine therapy. The majority of women tested have recurrence scores in the intermediate range (11-30). It is unclear if chemotherapy actually benefits them.

This trial evaluated outcomes among women with recurrence scores between 11 and 25 (the cutoff for high recurrence risk was made 26 instead of 30 to avoid undertreating women with higher scores). The goal of the investigators was to determine if women with intermediate scores had reduced recurrence and improved survival if they were given chemotherapy in addition to endocrine therapy.

Women aged 18-75 years of age were enrolled in the study. Participants with recurrence scores between 11 and 25 were randomized to receive chemotherapy and endocrine therapy or endocrine therapy alone. Over 6,000 women were observed during an approximately 9 year period.

Regarding disease-free survival, women who received chemotherapy and endocrine therapy fared no better than women who received endocrine therapy alone. There was also no difference between the groups regarding cancer recurrence or overall survival.

One subgroup had different results: women aged 50 and younger with recurrence scores 16-25. These women had improved disease-free survival when they were given chemotherapy in addition to endocrine therapy.

The investigators predict that this study may result in as many as 85% of women with early stage breast cancer being spared chemotherapy.

Based on this study, the American Society of Breast Surgeons released the following recommendations:

• Women of any age with a recurrence score of <10 should routinely omit chemotherapy.
• Women aged >50 years with recurrences scores of 11-25 should routinely omit chemotherapy.
• Women <50 years with a recurrence score of 11-15 should routinely omit chemotherapy.