Trastuzumab emtansine associated nodular regenerative hyperplasia: A case report and review of literature

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Abstract

Background

Trastuzumab emtansine (T-DM1), a novel drug-antibody conjugate, has shown promising activity in HER2-positive breast cancer and is the recommended agent of choice for second line therapy for advanced HER 2-positive breast cancer. Elevations in transaminase levels have been reported in up to 40% of patients treated with T-DM1 on phase I-III clinical studies. More serious hepatotoxicity can also result from this drug-antibody conjugate, but has been infrequently described in the literature.

Case Presentation

Here we report a 73 year old female with previously untreated metastatic HER 2-positive breast cancer who developed nodular regenerative hyperplasia and noncirrhotic portal hypertension while on treatment with single agent T-DM1. Liver biopsy demonstrated nodular regenerative hyperplasia, bile duct injury, and portal fibrosis.

Conclusion

A high index of suspicion for liver injury and NRH must be maintained for patients who develop liver test abnormalities and/or signs of portal hypertension during treatment with T-DM1. Abdominal imaging, liver biopsy, and prompt discontinuation of T-DM1 is recommended for patients with signs or symptoms of liver injury.

Section snippets

Background

Trastuzumab emtansine (T-DM1) is a drug-antibody conjugate linking trastuzumab to emtansine by non-reducible thioester linker, 4-[N-maleimidomethyl] cyclohexane-1 carboxylate (MCC) [1]. Trastuzumab is a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2) and emtansine (DM-1), a maytansine derivative, and is a cytotoxic agent that acts by microtubule inhibition. The drug-antibody conjugate binds the HER2 receptor and becomes internalized whereby DM-1 can then

Case presentation

A 73-year-old female was diagnosed with locally advanced estrogen receptor (ER) positive, progesterone receptor (PR) negative, HER 2-positive (HER 2 FISH 4.2), stage IIIA (T3N2) left breast CA in January 2010. She received 6 cycles of neoadjuvant Docetaxel, Carboplatin, Herceptin (TCH) and underwent modified radical mastectomy. Following surgery, she completed 52 weeks of adjuvant Herceptin and was placed on adjuvant endocrine therapy with anastrazole. She was found to have new mediastinal and

Discussion

T-DM1 is a drug-antibody conjugate consisting of trastuzumab, emtansine, and a thioester linker that has shown very promising activity in advanced HER 2-positive breast cancer. T-DM1 is an appealing treatment option for metastatic HER 2-positive breast cancer as it is devoid of toxicities associated with conventional cytotoxic agents.

Transaminase elevations and thrombocytopenia with T-DM1 are well known with grade 3 and 4 events in acceptable ranges for treatment of advanced breast cancer. Mild

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Competing interests

The authors declare that they have no competing financial interests.

Authors' contributions

LHP, ID, RMA, JCO, QJK, PS obtained the data

LHP, ID, RMA, JCO, QJK, PS documented the case and

LHP, ID, RMA, JCO, QJK, PS performed the literature search

LHP, ID, RMA, JCO, QJK, PS contributed to the writing process

LHP, ID, RMA, JCO, QJK, PS critically reviewed the data

LHP, ID, RMA, JCO, QJK, PS contributed to the writing process

All authors read and approved the final manuscript.

Acknowledgments

None.

References (20)

  • J.M. Baron et al.

    Ado-trastuzumab emtansine (T-DM1): a novel antibody-drug conjugate for the treatment of HER2-positive metastatic breast cancer

    J. Oncol. Pharm. Pract.

    (2015)
  • S. Girish et al.

    Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody-drug conjugate in development for the treatment of HER2-positive cancer

    Cancer Chemother. Pharmacol.

    (2012)
  • I.E. Krop et al.

    Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer

    J. Clin. Oncol.

    (2010)
  • I.E. Krop et al.

    A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine

    J. Clin. Oncol.

    (2012)
  • S.A. Hurvitz et al.

    Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

    J. Clin. Oncol.

    (2013)
  • S. Verma et al.

    Trastuzumab emtansine for HER2-positive advanced breast cancer

    N. Engl. J. Med.

    (2012)
  • K.D. Miller et al.

    Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer

    J. Clin. Oncol.

    (2014)
  • S.H. Giordano et al.

    Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline

    J. Clin. Oncol.

    (2014)
  • V. Dieras et al.

    Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis

    J. Clin. Oncol.

    (2014)
  • J. Force et al.

    Nodular regenerative hyperplasia after treatment with trastuzumab emtansine

    J. Clin. Oncol.

    (2014)
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