Gene expression profiling tests to guide adjuvant chemotherapy decisions in lymph node-positive early breast cancer: a systematic review

Purpose

To systematically review the effectiveness of gene expression profiling tests to inform adjuvant chemotherapy decisions in people with hormone receptor-positive (HR+), lymph node-positive (LN+) breast cancer.

Methods

This systematic review assessed the effectiveness of Oncotype DX, Prosigna, EndoPredict and MammaPrint for guiding adjuvant chemotherapy decisions in HR+ early breast cancer with 1–3 positive nodes, in terms of prognostic ability, prediction of chemotherapy benefit, impact on chemotherapy decisions, quality of life and anxiety. Searches covered MEDLINE, EMBASE and Cochrane databases in April 2023.

Results

Fifty-five articles were included. All four tests were prognostic for distant recurrence in LN+ patients. The RxPONDER trial reported no chemotherapy benefit in post-menopausal LN+ patients with low Oncotype DX (RS 0–25), whilst pre-menopausal patients had statistically significant chemotherapy benefit. An RCT reanalysis of Oncotype DX (SWOG-8814) suggested greater chemotherapy benefit with higher RS in post-menopausal LN+ patients. The MINDACT trial reported that LN+ patients with high clinical risk and low MammaPrint risk had a non-statistically significant chemotherapy benefit, but was not designed assess differential chemotherapy benefit per risk group. Decisions to undergo chemotherapy reduced by 12–75% following Oncotype DX testing in LN+ patients in the UK and Europe. No studies in LN+ populations were identified for prediction of chemotherapy benefit by Prosigna or EndoPredict; or for chemotherapy decisions for Prosigna, EndoPredict or MammaPrint; or for anxiety or quality of life impact for any test.

Conclusions

All four tests have prognostic ability in LN+ patients. Evidence on predictive benefit is weaker, with equivocal evidence that Oncotype DX may predict chemotherapy benefit in LN+ post-menopausal patients. Use of Oncotype DX leads to fewer patients being recommended chemotherapy.