Endocrine therapy response provides information on need of adjuvant chemotherapy

Endocrine therapy response and standard gene expression testing should be considered when deciding whether to use chemotherapy or not in patients with HR-positive/HER2-negative, N0–1, early breast cancer, according to findings from the multicentre ADAPTcycle trial.

Previously, findings from the prospective WSG-ADAPT HR+/HER2- trial (NCT01779206) showed that the 5-year distant disease-free survival (DDFS) rate associated with adjuvant endocrine therapy alone was 97% among patients who were pre-menopausal (or ≤50 years), had HR-positive/HER2-negative, N0–1, early breast cancer, had an Oncotype DX risk score ≤25, and who had achieved a response to short pre-operative endocrine therapy [1]. In contrast, other prospective trials (TAILORx, RxPONDER, MINDACT) suggest that, in pre-menopausal patients, adjuvant chemo/endocrine therapy has benefits over adjuvant endocrine therapy alone, even in case of a favourable gene expression profile [2–4]. To investigate possible explanations for the difference between these trial results, subgroup analyses were performed on patients enrolled in the phase 3 ADAPTcycle trial (NCT04055493). Prof. Oleg Gluz (Breast Center Niederrhein, Germany) presented the results [5].

Data was available from 4,334 patients (1,368 pre-menopausal, 2,966 post-menopausal) with clinical intermediate- to high-risk HR-positive/HER2-negative early breast cancer. Response to endocrine therapy (i.e. Ki67^pos ≤10% after 2–4 weeks of pre-operative endocrine therapy) was observed in 48.2% of pre-menopausal patients and in 72.7% of post-menopausal patients. The data showed that adding ovarian function suppression to treatment with tamoxifen or aromatase inhibitors significantly increased the likelihood of (pre-operative) response to endocrine therapy in pre-menopausal patients: 34.7% with tamoxifen alone, 55.7% with tamoxifen plus ovarian function suppression, and 76.4% with aromatase inhibition plus ovarian function suppression. The latter was similar to the response seen in post-menopausal patients previously treated with an aromatase inhibitor. This association between type of (pre-operative) endocrine therapy and endocrine response was observed both in patients with Oncotype DX risk score ≤25 or >25, and was independent of menopausal status.

Based on these results, Prof. Gluz concluded that “with optimal endocrine therapy, no difference in endocrine therapy-sensitivity is observed between pre- and post-menopausal patients. Therefore, endocrine response should be considered in addition to gene expression testing for routine decision-making regarding chemotherapy use in HR-positive/HER2-negative, N0–1, early breast cancer, to maximise the number of patients in whom chemotherapy can be spared.”

1. Nitz U, et al. J Clin Oncol. 2022;40:2557-2567.
2. Sparano JA, et al. N Engl J Med. 2019;380:2395-2405.
3. Kalinsky K, et al. N Engl J Med. 2021;385:2336-2347.
4. Piccart M, et al. Lancet Oncol. 2021;22:476-488.
5. Gluz O, et al. Impact of age and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Results from the multicenter ADAPTcycle trial (n=4,334). Abstract LBO1-05, SABCS 2023, 5–9 December, San Antonio, TX, USA.

 

Copyright ©2024 Medicom Medical Publishers



Posted on 11 January, 2024