Interviews

Neoadjuvant Endocrine Therapy Less Toxic Than Chemo in Advanced, ER-Positive Breast Cancer

abMiami, Florida—At the 37th Annual Miami Breast Cancer Conference, Aditya Bardia, MD, MPH, Director, Precision Medicine, Center for Breast Cancer, and Attending Physician, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, will discuss the use of neoadjuvant endocrine therapy versus chemotherapy for the treatment of patients with locally advanced, estrogen receptor (ER)-positive breast cancer.

In an interview with Oncology Learning Network, Dr Bardia spoke about how therapy for locally advanced, ER-positive breast cancer has advanced in recent years, the challenges associated with management of this disease, and a study comparing neoadjuvant endocrine therapy with chemotherapy in this patient population.

How has the treatment landscape for locally advanced, ER-positive breast cancer evolved in recent years?

Over the past few years, there has been a spurt in clinical trials investigating endocrine therapy–based regimens in the neoadjuvant setting.

For example, the LORELEI trial evaluated letrozole with or without the PI3K inhibitor taselisib, the NEO-ORB trial evaluated letrozole with or without the PI3K inhibitor alpelisib, the neoMONARCH trial evaluated anastrozole with or without the CDK 4/6 inhibitor abemaciclib, the PALLET trial evaluated letrozole with or without the CDK 4/6 inhibitor palbociclib, and the CORALEEN trial evaluated letrozole plus the CDK 4/6 inhibitor ribociclib versus chemotherapy—all in the setting of locally advanced, ER-positive breast cancer.

What challenges do clinicians face with the management of ER-positive breast cancer?

ER-positive tumors are generally highly responsive to endocrine treatment. While endocrine therapy is the mainstay of treatment for ER-positive breast cancer, including localized breast cancer, the use of neoadjuvant endocrine therapy is very low despite the various advantages of the neoadjuvant approach.

This is partly due to concerns of delayed time to response compared to cytotoxic chemotherapy, lack of large trials comparing neoadjuvant endocrine therapy with chemotherapy, lack of validated biomarkers to guide choice of neoadjuvant endocrine therapy versus chemotherapy, and debate on the optimal endocrine-based backbone.

Please briefly discuss the use of neoadjuvant endocrine therapy versus chemotherapy for locally advanced, ER-positive breast cancer.

In a comprehensive systematic review and meta-analysis conducted by our group, we evaluated the efficacy of various neoadjuvant endocrine therapies, including combination strategies, for ER-positive breast cancer, and identified that neoadjuvant endocrine therapy, even as monotherapy, is associated with similar response rates as neoadjuvant combination chemotherapy, but with significantly lower toxicity.

Given the low toxicity associated with neoadjuvant endocrine therapy, and the recent development of better targeted therapies, it would be important to reconsider it as a treatment option in the neoadjuvant setting for the “correct” patient population. However, determining the “correct” patient population for neoadjuvant endocrine-based therapy remains an unanswered question, and will be best addressed by additional biomarker-based neoadjuvant studies.

While there have been prospective biomarker-guided studies in the adjuvant setting, like the TailoRx trial, we need well-powered studies in the neoadjuvant setting to help guide the appropriate choice of neoadjuvant endocrine-based versus chemotherapy-based treatment for patients with advanced, ER-positive breast cancer.

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