Clinical Scenario - HR-Positive Breast Cancer

The panel reviews a 58-year-old patient with HR-positive, HER2-negative metastatic breast cancer progressing after endocrine therapy plus CDK4/6 inhibitor treatment. The patient has hepatic and bone metastases with radiographic and symptomatic progression, ECOG performance status 1, controlled hypertension, and mild dry eye syndrome. She prioritizes maintaining professional activity and independence.

Dr. Nunnery emphasizes maximizing endocrine therapy lines before transitioning to cytotoxic treatments, noting that hepatic metastases should not preclude additional endocrine approaches. The duration of first-line CDK4/6 inhibitor therapy serves as a surrogate for continued endocrine sensitivity.

Treatment selection considers HER2-low/ultra-low status for T-DXd eligibility as first-line cytotoxic therapy after endocrine progression. For non-HER2-low patients, oral capecitabine represents an appealing option maintaining oral administration convenience without alopecia concerns.

The patient's dry eye history raises questions about Dato-DXd candidacy. Dr. Sunshine provides reassurance that well-controlled mild dry eye doesn't represent a contraindication to treatment, emphasizing the importance of baseline ophthalmologic optimization including preservative-free artificial tears at least 4 times daily and addressing any underlying conditions like meibomian gland disease.

Severe dry eye with scarring, corneal infection, or other significant complications might preclude Dato-DXd use, but baseline examinations rarely identify absolute contraindications. Baseline evaluation helps establish vision expectations and identify other ocular conditions affecting vision to prevent unrealistic treatment goals.

Ms. Davidson addresses the emotional challenges of transitioning from endocrine to cytotoxic therapy, emphasizing psychological support, social work referrals, and comprehensive multidisciplinary care during this difficult transition period when patients feel everything is falling apart with disease progression.