Patient outcomes and clinician perspectives following one year of ad hoc implementation of neoadjuvant endocrine therapy in early breast cancer.

Abstract

Background: Neoadjuvant endocrine therapy (NAET) can induce a reduction of Ki-67 in hormone receptor-positive breast cancer, predicting response to adjuvant endocrine therapy and potentially allowing patients to forego chemotherapy without increasing recurrence risk. However, Ki-67 interpretation is highly variable. Implementation requires careful multidisciplinary planning to mitigate the effects of Ki-67 variability on treatment eligibility. Feasibility and short-term oncological outcomes of implementation of short-course NAET were studied during a "window of opportunity" where it was adopted by several unit surgeons without formal pathway development. A concurrent qualitative study identified barriers to NAET from surgeons' perspectives and gained insight from pathologists about Ki-67's suitability as a response marker. This identified potential issues with implementing this treatment based on existing protocols, which rely heavily on Ki-67 interpretation. The aims of this study were to investigate the feasibility of implementing short course NAET on the basis of Ki-67 values on an ad hoc basis and to use our experience to make recommendations for optimal translation of this treatment from research to clinical practice.

Methods: Eligible patients were identified from multidisciplinary meeting (MDM) agendas from May 2023 to May 2024. These patients were post-menopausal women with hormone receptor-positive, HER2-negative breast cancer who were eligible for surgery and who had a Ki-67 of greater than 10% on core biopsy. Patients were split into a group of patients who received the treatment and a group who did not. Outcomes were recorded including treating surgeon, Ki-67 index changes, NAET duration, and choice of adjuvant therapy. Surgeons and pathologists were interviewed and a qualitative analysis was done identifying key themes and limitations of the treatment and existing protocols.

Results: During the study, 44 eligible patients were discussed at the MDM. Fifty-five percent received NAET. Of these, 72% exhibited a reduction in Ki-67 compared to 40% in the non-NAET group. A substantial reduction (from >10% to <10%) was observed in 44% of NAET patients. Forty-four percent of patient values reduced across a threshold value of 10% (quoted in the POETIC study as indicating response to NAET). Where a substantial reduction occurred, no patients were recommended for adjuvant chemotherapy. In the qualitative arm, there was no overlap in key themes between surgeons and pathologists, demonstrating that surgeons may underestimate the limitations of Ki-67 interpretation. Pathologists raised concerns around limitations of Ki-67 interpretation, reproducibility and lack of common protocols in different units. Surgeons noted some barriers to prescribing and uncertainty that the treatment confers a benefit in a short time period.

Conclusions: This study demonstrates the feasibility of implementing NAET ad hoc and underscores the importance of thorough multidisciplinary planning for standardization of Ki-67 interpretation if this marker will determine eligibility. While the sample size is small, more than half of eligible patients received the treatment and reductions in Ki-67 were considered by the MDM. The study highlights the role of surgeons in initiating this treatment. The qualitative findings give valuable insights into barriers to implementing NAET based on Ki-67 values from a surgeon and pathologist perspective. Our experience provides valuable insights for other units considering implementing this treatment.