Which medications in the drug class Monoclonal Antibodies are used in the treatment of Breast Cancer?

Updated: Dec 27, 2019
  • Author: Pavani Chalasani, MD, MPH; Chief Editor: John V Kiluk, MD, FACS  more...
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Answer

Monoclonal Antibodies

Monoclonal antibodies have been engineered to react against specific antigens on cancer cells, which can help to enhance the patient’s immune response and prevent cancer cell growth. The combination of both HER2 receptor antibodies (pertuzumab plus trastuzumab) is superior to either agent alone.

ado-trastuzumab emtansine (Kadcyla)

Ado-trastuzumab emtansine is an HER2-targeted antibody (trastuzumab) covalently linked to a microtubule inhibitor (DM1, a maytansine derivative). It is indicated for the treatment of HER2-positive metastatic breast cancer after prior trastuzumab and taxane therapy. It is also indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane- and trastuzumab-based treatment.

Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death

Denosumab (Prolia, Xgeva)

Denosumab is a monoclonal antibody that specifically targets RANK ligand, an essential regulator of osteoclasts. This agent is indicated to prevent skeletal-related events (ie, bone fractures, spinal cord compression, or hypercalcemia) in patients with bone metastases from solid tumors whose expected survival exceeds 3 months.

Osteonecrosis of the jaw in patients receiving denosumab has often been associated with dental procedures. Consequently, patients should undergo a dental examination before the initiation of denosumab therapy to determine whether they might benefit from preventive dentistry procedures.

Trastuzumab (Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera, trastuzumab-dkst, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-qyyp)

Trastuzumab is a monoclonal antibody that binds to extracellular HER2. It mediates antibody-dependent cellular cytotoxicity against cells that overproduce HER2.

It is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) breast cancer, as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel, as part of a treatment regimen with docetaxel and carboplatin, or as a single agent following multimodality anthracycline based therapy. This agent is also used for HER2-overexpressing metastatic breast cancer as first-line treatment in combination with paclitaxel OR as a single agent for patients who have received 1 or more chemotherapy regimens for metastatic disease.

The combination of trastuzumab and an anthracycline is associated with significant cardiac toxicity.

Pertuzumab (Perjeta)

Pertuzumab is a monoclonal antibody that binds to the extracellular domain of the HER2 receptor. It is indicated for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. It is also the first drug approved for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer . Pertuzumab was also indicated the adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence.

Trastuzumab/hyaluronidase (Herceptin Hylecta)

Trastuzumab is a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2). It mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells which overexpress HER-2 protein. It is indicated in combination with chemotherapy in patients with HER2-positive early breast cancer, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen. Administered SC over 2-5 minutes.

Trastuzumab deruxtecan (Enhertu, fam-trastuzumab deruxtecan-nxki)

HER2-targeted antibody-drug conjugate (ADC) which contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the topoisomerase I inhibitor, deruxtecan. It is indicated for unresectable or metastatic HER2-positive breast cancer in adults who have received 2 or more prior anti-HER2-based regimens in the metastatic setting.


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