Case 1: Risk Assessment and Treatment Selection in Early-stage HER2+ BC

EP: 1.Case 1: Neoadjuvant Therapy for Early-Stage HER2+ BC

EP: 2.Case 1: Neoadjuvant Treatment Armamentarium for Early-Stage HER2+ BC

EP: 3.Case 1: Selecting Adjuvant Therapy for Early-Stage HER2+ BC

EP: 4.Case 1: Subcutaneous HP FDC Formulation in Early-Stage HER2+ BC

EP: 5.Case 2: Overview of Treatment Strategies for HER2+ Metastatic BC

EP: 6.Case 2: DESTINY-Breast03 and T-DXd in HER2+ Metastatic BC

EP: 7.Case 2: Addressing ILD Associated With HER2-Targeted Therapy in mBC

EP: 8.Case 2: Clinical Experience With Trastuzumab Deruxtecan in HER2+ mBC

EP: 9.Case 3: Selecting Therapy For HER2+ Breast Cancer With Brain Metastases

EP: 10.Case 2: Third-Line Therapy and Beyond in HER2+ Metastatic Breast Cancer

EP: 11.Case 3: HER2+ mBC Treatment After Progression on the HER2CLIMB Regimen

EP: 12.Case 3: CNS Data From Clinical Trials in HER2+ BC

EP: 13.Emerging Treatment Approaches in HER2+ Breast Cancer

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EP: 14.Case 1: Risk Assessment and Treatment Selection in Early-stage HER2+ BC

EP: 15.Case 1: Subcutaneous vs Intravenous Trastuzumab/Pertuzumab

EP: 16.Case 2: Second-line Treatment Selection for Metastatic HER2+ BC

EP: 17.Case 2: Safety Considerations in the Use of T-DXd for HER2+ mBC

Transcript:

Moderator: In clinic today, a 47-year-old woman who has 1 child presented with a palpable mass in the right breast. Mammography and ultrasound showed a right lower outer quadrant 2.3-cm mass. A breast MRI showed a 2.4-cm right outer quadrant plus a 0.5-cm mass at the 12 o’clock position and a large area of nonmass-like enhancement extending between those 2 areas, with a total area of 4 cm by 5 cm; 3 regional lymph nodes appeared enlarged. A biopsy of the 2.4-cm mass showed invasive ductal carcinoma, that is ER [estrogen receptor] and PR [progesterone receptor] negative, HER2 [human epidermal growth factor receptor 2]3+ by IHC [immunohistochemistry], FISH [fluorescence in situ hybridization] amplified with a ratio of 3.7 copy number 6, and Ki-67 of 42%. A biopsy of the axillary region showed metastatic breast cancer in the lymph node, and biopsy of the 12 o’clock area also showed invasive ductal carcinoma with the same immunostains as above. The stage was CT2N1M0 grade 3 and stage IIB.

Chau T. Dang, MD: This is a young patient with high-risk disease based on her burden biology, so the risk of recurrence is based on the tumor burden. She does have a sizable tumor that is a T2, and she has nodal involvement. This is a high-risk biology tumor that is hormone receptor negative and HER2-positive. Certainly, this patient deserves to have systemic neoadjuvant treatment.

She does have clinical stage II HER2+ breast cancer, and we typically give neoadjuvant treatment for patients with clinical stage II/III HER2+ breast cancer. As we all know, the FDA approved the usage of dual-antibody therapy with trastuzumab and pertuzumab in combination with chemotherapy for patients with clinical stage II/III HER2+ breast cancer. This approval was in 2013. This was based on the NeoSphere and TRYPHAENA study, and since that study, trastuzumab-pertuzumab has had its final approval with the data from the APHINITY adjuvant study. This patient should have neoadjuvant trastuzumab-pertuzumab–based treatment with chemotherapy to downstage her breast and axillae. Across several key trials since the publication of NeoSphere and TRYPHAENA, the pathologic complete response [pCR] rate is about 60%, so we expect that she should have a pCR rate of about 60%. This means that at the time of surgery, likely we’ll see pathologic complete response more so than non-pCR. If she does have a pCR, then she’ll complete out her adjuvant therapy with trastuzumab-pertuzumab–based treatment because she has lymph node–positive disease at baseline. If she has non-pCR, we’d typically give her T-DM1 [trastuzumab emtansine] for 14 cycles based on the KATHERINE study.

If she had surgery up front without the opportunity to have neoadjuvant treatment, and she was found to be node positive, then we’d give her a dual-antibody therapy with trastuzumab and pertuzumab with chemotherapy based on the APHINITY study. The APHINITY study randomized almost 5000 patients to chemotherapy with trastuzumab and pertuzumab vs chemotherapy with trastuzumab and showed that dual-antibody therapy led to significant improvement in invasive disease-free survival, especially in patients with node-positive breast cancer. Even if she was to have surgery first and was found to be node positive at the time of surgery, she would still have an opportunity to have the most optimal therapy today, which is dual-antibody trastuzumab-pertuzumab.

This is a young patient, with stage II, node-positive, hormone receptor–negative, HER2+ breast cancer. Many decades ago, it would have been a difficult disease to treat. But with the advent of modern treatments with pertuzumab-trastuzumab and even T-DM1 [trastuzumab emtansine], she should do very well. She’ll have a high pCR rate after neoadjuvant trastuzumab-pertuzumab treatment, but she also has an opportunity to have T-DM1 [trastuzumab emtansine] in the adjuvant setting if she has non-pCR. Her outcomes should be excellent, and she should have the most optimal therapy to improve her outcomes.

Transcript edited for clarity.