Comparative study between neoadjuvant hormone therapy plus CDK-4/6 inhibitors versus neoadjuvant chemotherapy for hormone receptor–positive breast cancer patients.

e12667 Background: Neoadjuvant Chemotherapy (NACT) has traditionally been employed in patients with operable and locally advanced breast cancer to downstage the primary tumour and to facilitate breast conservation and to provide in vivo assessment of treatment response. However, in HR+/HER2- breast cancer NACT response rates remains low with substantial chemotherapy related side effects. Given the evolving emphasis on treatment de-escalation, personalisation of therapy and avoidance of unnecessary chemotherapy in HR+/HER2- breast cancer there is a growing need to evaluate NAHT combined with CDK4/6 inhibitors can offer comparable surgical outcomes and treatment response in appropriately selected patients. Methods: This prospective, single-centre study included patients with non-metastatic HR+/HER2- breast cancer treated between January 2023 - November 2025. Eligible patients had operable or locally advanced disease and were planned for neoadjuvant systemic therapy following multidisciplinary discussion. Treatment plan was individualised with patients receiving either standard neoadjuvant chemotherapy (NACT) or neoadjuvant endocrine therapy combined with CDK-4,6 inhibitors (NAHT + CDK-4,6) for a duration of 4-6 months. Treatment response was assessed, followed by definitive breast and axillary surgery. Breast conservation (BCS) rates, changes in KI67, nodal down staging rates were analysed and compared between both treatment cohorts using appropriate statistical methods. Results: A total of 52 patients were included (NACT, n = 26; NAHT+CDK4,6, N = 26) with similar baseline clinicopathological characteristics. Breast conserving surgery (BCS) rates were identical in both groups (65.39%). In the NAHT + CDK-4,6 inhibitor cohort demonstrated higher response rates (19.23% vs 3.84%) and lower stable disease rates (19.23 vs 38.4%). Toxicity profiles differed between both groups: NAHT + CDK 4,6 inhibitors was predominantly associated with low grade, manageable side effects most commonly being diarrhoea and fatigue. No grade 4 toxicities were observed. In contrast, NACT was associated with fewer but more prominent side effects including grade III peripheral neuropathy. Conclusions: NAHT plus CDK-4,6 inhibitors achieved comparable breast conservation rates to NACT while demonstrating higher complete response rates and a more favourable toxicity profile in HR+HER2- breast cancer. These findings support NAHT + CDK-4,6 inhibitors as a feasible and effective chemotherapy sparing strategy in appropriately selected patients. Comparative response rates & BCS rates: NAHT+CDK-4,6 v/s NACT. SURGICAL OUTCOMES NAHT + CDK-4,6 NACT BCS (%) 65.39 65.39 MASTECTOMY (%) 34.61 34.61 RESPONSE RATES NAHT +CDK-4,6 NACT CR (%) 19.23 3.84 PR (%) 51.5 57.69 SD (%) 19.233 38.4