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CDK4 6 Inhibitors for Breast Cancer

CE / CME

Expert Insights and FAQs on CDK4/6 Inhibitors in the Care of Today’s Patients With HR-Positive/HER2-Negative Breast Cancer

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™

ABIM MOC: maximum of 0.75 Medical Knowledge MOC point

Released: February 20, 2025

Expiration: August 19, 2025

Jame Abraham
Jame Abraham, MD, FACP
William J. Gradishar
William J. Gradishar, MD, FACP, FASCO
Laura Spring
Laura Spring, MD
CME/CE Information

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1.

A 58-year-old woman who is postmenopausal presents with a 5-cm right breast mass with 1 suspicious node. Initial breast biopsy reveals invasive lobular carcinoma (ILC), grade 2, with the following biomarkers: estrogen receptor (ER) positive, 80%; progesterone receptor (PgR) positive, 30%; HER2 negative by immunohistochemistry (IHC). Fine-needle aspiration of a palpable right axillary lymph node reveals adenocarcinoma of the breast. BRCA testing is negative; PIK3CA mutation is identified as part of a clinical trial. She receives 6 cycles of neoadjuvant docetaxel and cyclophosphamide (TC) and then undergoes bilateral mastectomy. The right mastectomy specimen reveals a 3-cm ILC with minimal chemotherapy effect and 4/15 positive nodes. She returns to the clinic now to discuss adjuvant treatment options.

Which of the following would you select as adjuvant therapy for this patient?

2.

A 42-year-old premenopausal woman presents with a right-breast, 3.2-cm, grade-2 invasive ductal carcinoma (IDC) status post (s/p) lumpectomy and sentinel lymph node biopsy (SLNB) with the following biomarkers: ER positive, 95%; PgR positive, 50%; HER2, 1+ by IHC; HER2 negative by fluorescence in situ hybridization (FISH); Ki-67, 35%. One of 3 nodes is positive for isolated tumor cells (pT2pN0i+). BRCA testing is negative. She receives doxorubicin, cyclophosphamide, and paclitaxel (ACT) for 6 cycles and radiation and is ready to start endocrine therapy.

Which therapy would you recommend?

3.

A 62-year-old woman with a history of stage IIA, ER-positive/HER2-negative breast cancer that was diagnosed 7 years ago presented recently with persistent back pain for which she has been taking ibuprofen. Previously, she had surgery followed by adjuvant chemotherapy (4 cycles of TC) and 5 years of adjuvant letrozole therapy, which was completed 2 years ago. Now, imaging shows widespread bone lesions consistent with MBC and supraclavicular lymphadenopathy. Laboratory test results are normal aside from elevated alkaline phosphatase. A node biopsy confirms ER-positive/HER2 1+ MBC. Evaluation of circulating tumor DNA (ctDNA) was notable for lack of ESR1 or PIK3CA mutations. 

Which first-line systemic therapy would you recommend?

4.

A 55-year-old woman was recently diagnosed with metastatic ER-positive/HER2-negative breast cancer 2 years after completing adjuvant endocrine therapy with asymptomatic bone-only disease. Four weeks ago, she began receiving first-line letrozole and ribociclib (600 mg daily, 3 weeks on/1 week off). Laboratory monitoring at cycle 2, Day 1 shows that liver enzyme levels are now 5 times the upper limit of normal (grade 3 hepatotoxicity); she is otherwise asymptomatic; ECGs are stable.

Which of the following is optimal management for this patient’s grade 3 hepatotoxicity?

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