Breast cancer in patients with Li-Fraumeni syndrome - a case-series study and review of literature

Abstract

Background: Li-Fraumeni Syndrome (LFS) is a rare disease with autosomal dominant inheritance linked to germline mutations of tumor suppressor gene TP53. These patients are predisposed to malignancies such as sarcoma, breast cancer, leukemia, and other malignancies. Breast cancer, the most common malignancy in adult patients with LFS, has an early-onset presentation and is usually treated as per the guidelines for the general population due to the limited literature about breast cancer in LFS. We aimed to describe our institutional experience treating patients with breast cancer and LFS to contribute to literature about this entity.

Design: Retrospective single-institution case-series study. We searched for cases with LFS and breast cancer from 01/01/2000 to 12/31/2015 with treatment received at our institution.

Results: We identified 4 cases (2 African Americans, 1 Indian, and 1 Hispanic) in 4 different families, who were diagnosed with LFS after presenting with breast cancer. Three cases were triple-negative disease and 1 case was ER+, HER2 positive disease. They were treated with mastectomy and a third-generation breast chemotherapy regimen and/or trastuzumab-containing regimen. Radiation therapy was used in 2 patients. Breast cancer recurrence was seen in 1 patient, while three other malignancies were identified after breast cancer treatment (1 breast sarcoma, 1 leiomyosarcoma, and 1 myelodysplastic syndrome). A patient, who underwent surveillance with a positron emission tomography-computed tomography scan, was found to have a stage I leiomyosarcoma and was treated with surgical resection, but then developed metastatic disease requiring cytotoxic chemotherapy.

Conclusion: Breast cancer among patients with LFS needs a multidisciplinary treatment approach. Surgical management follows the guidelines for the general population. Risk-benefit assessment of chemotherapy and radiotherapy needs to be performed carefully in a case-by-case approach. Patients should undergo multimodality cancer surveillance, preferably in the context of a clinical trial.

Keywords: Li–Fraumeni syndrome; TP53; breast cancer; hereditary breast cancer.

Figure 1

Pre-neoadjuvant chemotherapy PET-CT (C, D) and post-neoadjuvant chemotherapy PET-CT (A, B) in case 3 revealing right large mass with progression after neoadjuvant chemotherapy. Abbreviation: PET-CT, positron emission tomography/computed tomography.

Figure 2

Surveillance PET-CT revealing uterine uptake, which led to diagnosis of stage I uterine leiomyosarcoma. Abbreviation: PET-CT, positron emission tomography-computed tomography.