Case Report

Case Report on Complete Response to Treatment of Metastatic Metaplastic Breast Cancer with Sacituzumab Govitecan

by Angélica Nogueira-Rodrigues1,2,3,4,5*, Daniela Jessica Pereira2, Martina Parenza Arenhardt6, Giovanna Vieira Giannecchini2

1Professor and Researcher, Federal University MG, Brazil

2Oncoclínicas, Brazil

3Brazilian Group of Gynecologic Oncology (EVA)

4LACOG (Latin American Cooperative Oncology Group)

5DOM Oncologia, Brazil

6Medical Oncology Resident, Hospital de Clínicas, Porto Alegre, Brazil

*Corresponding author: Angélica Nogueira Rodrigues, Professor and Researcher, Brazilian Group of Gynecologic Oncology (EVA), Federal University MG, Brazil.

Received Date: 28 December 2023

Accepted Date: 02 January 2024

Published Date: 05 January 2024

Citation: Rodrigues AN, Pereira DJ, Arenhardt MP, Giannecchini GV (2024) Case Report on Complete Response to Treatment of Metastatic Metaplastic Breast Cancer with Sacituzumab Govitecan. Ann Case Report 9: 1579. https://doi.org/10.29011/2574-7754.101579

Abstract

Metaplastic breast cancer (MBC) is rare, has a worse prognosis than invasive ductal breast carcinoma, and most cases are triple-negative phenotype. Due to its low incidence, clinical studies of the disease are rare, and relatively poor outcomes are observed in clinical practice despite treatment. The present case report focuses on a patient with triple-negative MBC, clinical stage IIIB at diagnosis, and with local disease progression during standard neoadjuvant treatment. The patient was referred for surgical treatment but developed a distant recurrence of the disease shortly after. She was then treated with sacituzumab govitecan, an antibody-drug conjugate (ADC), and responded very well to treatment. Because this aggressive disease has a low response rate to chemotherapy, a better understanding of its molecular biology and therapeutic possibilities using new agents such as ADCs is crucial to advancing treatment.

Keywords: Metaplastic Breast Cancer; Antibody-Drug Conjugate; Sacituzumab Govitecan; Case Report

Introduction

Breast cancer is a global health problem and became the most common neoplasm in 2020 with approximately 2.3 million new cases and 685.000 deaths worldwide [1]. Metaplastic carcinoma is rare and accounts for 0.2% to 5% of breast cancers [2]. It is histologically defined by the presence of one or more cell populations that have undergone metaplastic differentiation and have been converted from glandular cells to a non-glandular morphology [3], commonly with epithelial and mesenchymal components [4].

Approximately 90% of metaplastic breast cancers (MBCs) present with triple-negative phenotype, which is characterized by the lack of expression of hormone receptors (HRs) and human epidermal growth factor receptor type 2 (HER2). Compared with non-metaplastic triple-negative tumors, MBCs are associated with worse prognoses, are twice as likely to recur, and have lower disease-free survival rates and worse overall survival outcomes [3].

The most common clinical presentation of this disease is a large, rapidly growing mass in the breast in women usually after the age of 50. Nodal involvement is less common than in other breast cancers, and in most cases, MBC presents a high histological grade and high expression of Ki67 [2]. Around 90% of patients present with localized disease at diagnosis, and 50% of these metastasize [5].

The characteristics related to worse 5-year overall survival are tumor size greater than 5 cm, lymph node involvement, and high Ki67 [5].

Due to the low incidence of MBCs, their inclusion in randomized clinical trials is very sparse and there is no standard treatment regimen. Therefore, treatments used end up being similar to those for invasive ductal carcinomas, however, metaplastic tumors are less responsive to chemotherapy [2]. Chen et al. evaluated the response rates of 46 cases of metaplastic tumors in patients who received neoadjuvant chemotherapy or chemotherapy as the first-line treatment for metastatic disease, with results of 18% and 8%, respectively [6]. None of the patients responded to anthracycline, cyclophosphamide, or vinorelbine, and a small cohort of patients showed a partial response to taxane.

In the metastatic setting, the median overall survival (OS) of metaplastic carcinoma is poor. As reported by Takala et al. the median OS is around 3.4 months [7].

Because this is an aggressive disease with a low response rate to chemotherapy and no known biomarkers to drive treatment so far, a better understanding of its molecular biology and new therapeutic options is crucial.

Clinical oncology has entered the era of personalized and precision medicine with the approval of new drugs that have changed the course of treatment and resulted in significant improvements in patient outcomes. These include target therapy, immunotherapy, and antibody-drug conjugates (ADCs). Among the ADCs currently approved for breast cancer is sacituzumab govitecan, which was approved for use in triple-negative and hormone receptor-positive/ HER2-negative metastatic disease based on the ASCENT [8] and TROPiCS-02 [9] studies, respectively.

The present case is about a patient with metastatic metaplastic breast carcinoma who achieved a complete metabolic response while being treated with sacituzumab govitecan.

Case Report

A 60-year-old female patient, post-menopausal, noticed a rapidly growing nodule in her left breast. She underwent a biopsy of this lesion and received the diagnosis of metaplastic carcinoma grade 2 in June 2022. Immunohistochemistry indicated a triple negative tumor with a Ki67 of 90%, and systemic staging tests revealed no evidence of metastasis. In the patient´s first oncological consultation, physical examination revealed an inflammatory mass occupying the entire left breast, with clinical staging cT4dcN0M0.

Neoadjuvant protocol was initiated in accordance with the Keynote 522 study [10]. In the first phase, four cycles of doxorubicin and cyclophosphamide were administered concomitantly with the immunotherapy pembrolizumab every 21 days. At the end of this phase, there was no objective clinical response, and ulceration of the breast lesion was present (Figure 1). The second phase then began with proposed 12 weekly cycles of carboplatin/paclitaxel associated with pembrolizumab every 21 days. However, in the second cycle, clinical evaluation revealed that the patient’s disease had progressed (Figure 2).

 

Figure 1: Breast lesion after 4 cycles of doxorrubicin, cyclophosphamide and pembrolizumab.