A novel oral endocrine therapy, giredestrant, has demonstrated a significant improvement in invasive disease–free survival (iDFS) for patients with estrogen receptor–positive (ER+), HER2-negative early breast cancer. Results from the global, randomized Phase III lidERA Breast Cancer trial, presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), indicate that giredestrant significantly reduced the risk of invasive recurrence or death by 30% compared to standard-of-care endocrine therapy. This translates to a 3-year iDFS rate of 92.4% with giredestrant versus 89.6% with standard therapy, marking an absolute benefit of approximately 3%. Giredestrant, developed by Genentech (a member of the Roche Group), is a next-generation oral selective estrogen receptor degrader (SERD) and full antagonist, designed to induce full estrogen receptor antagonism and degradation. This mechanism aims to provide deep and sustained inhibition of estrogen receptor signaling, potentially overcoming resistance mechanisms seen with older therapies. The study also reported a favorable safety profile for giredestrant, with a notably lower rate of treatment discontinuation due to adverse events compared to standard endocrine therapy. While common adverse events included arthralgias and mostly asymptomatic grade 1 bradycardia, the overall safety was consistent with its known profile. Experts suggest these findings could position giredestrant as a new standard of care, representing the first significant advance in adjuvant endocrine therapy for this patient population in over two decades. Given that ER-positive, HER2-negative breast cancer is the most common subtype and accounts for a significant proportion of cases in India, this development holds substantial relevance for the Indian audience, offering new hope for improved outcomes.