Vol 19, No 6 (2023)
Case report
Published online: 2023-08-07

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Metachronous breast cancer in a BRCA1 mutation carrier

Karolina Pięta1, Izabela Rudy1, Maksymilian Kruczała2
Oncol Clin Pract 2023;19(6):445-447.

Abstract

Breast cancer is the most common neoplasm among women in Poland and worldwide. Approximately 8000 women die from breast cancer in Poland each year. It is the second leading cause of cancer-related deaths among Polish women, following lung cancer. This cancer is highly heterogeneous in terms of morphology as well as molecular characteristics, and it requires different therapeutic approaches. Several risk factors for breast cancer have been identified, including genetic, environmental, and individual factors. Mutations in the BRCA1 and BRCA2 genes are the best-known genetic factors responsible for approximately 5–10% of breast cancer cases worldwide. The risk of developing bilateral breast cancer in patients with BRCA1 mutation is significantly higher than in the general population. Furthermore, attention is drawn to the increased risk of metachronous tumors in patients with a BRCA1 gene mutation who have previously had breast cancer. This article presents a case report on a patient with metachronous breast cancer who has developed bone and liver metastases. Based on the genetic test result showing a BRCA1 mutation, the patient was qualified for talazoparib treatment.

CASE REPORT

Oncology in Clinical Practice

DOI: 10.5603/OCP.2023.0039

Copyright © 2023 Via Medica

ISSN 2450–1654

e-ISSN 2450–6478

Metachronous breast cancer in a BRCA1 mutation carrier

Karolina Pięta1Izabela Rudy1Maksymilian Kruczała2
1Student Research Oncology Club at the Department of Oncology, Radiotherapy and Translational Medicine, Institute of Medical Sciences, College of Medical Sciences of the University of Rzeszów, Poland
2Department of Oncology, Radiotherapy and Translational Medicine, College of Medical Sciences of the University of Rzeszów, Poland

Address for correspondence:

Karolina Pięta

Institute of Medical Sciences, College of

Medical Sciences of the University

of Rzeszów

ul. Rejtana 16C, 35–310 Rzeszów, Poland

e-mail: karolinapietax@gmail.com

Received: 14.06.2023 Accepted: 26.06.2023 Early publication date: 07.08.2023

ABSTRACT

Breast cancer is the most common neoplasm among women in Poland and worldwide. Approximately 8000 women die from breast cancer in Poland each year. It is the second leading cause of cancer-related deaths among Polish women, following lung cancer. This cancer is highly heterogeneous in terms of morphology as well as molecular characteristics, and it requires different therapeutic approaches. Several risk factors for breast cancer have been identified, including genetic, environmental, and individual factors. Mutations in the BRCA1 and BRCA2 genes are the best-known genetic factors responsible for approximately 5–10% of breast cancer cases worldwide. The risk of developing bilateral breast cancer in patients with BRCA1 mutation is significantly higher than in the general population. Furthermore, attention is drawn to the increased risk of metachronous tumors in patients with a BRCA1 gene mutation who have previously had breast cancer. This article presents a case report on a patient with metachronous breast cancer who has developed bone and liver metastases. Based on the genetic test result showing a BRCA1 mutation, the patient was qualified for talazoparib treatment.

Keywords: breast cancer, metachronous tumors, BRCA1 mutation

Oncol Clin Pract 2023; 19, 6: 445447

Introduction

Breast cancer is the most common malignant tumor among women, and one of the three most prevalent cancers worldwide alongside lung cancer and colorectal cancer [1]. It is estimated that approximately 1.6 million new cases of breast cancer occur worldwide each year, and its incidence continues to increase [2]. In 2020, about 17500 new cases of breast cancer were diagnosed in Poland, and nearly 8 000 patients died of this disease. The highest incidence is observed among women aged 55–65, and the highest number of deaths was recorded in the sixth and seventh decades of life [3]. Mortality from breast cancer may decrease due to early diagnosis, disease detection, and the development of new treatment methods. However, breast cancer remains the leading cause of cancer-related deaths among women in developing countries and the second most common cause of death — after lung cancer — in developed countries [1]. Most breast cancers are invasive tumors that spread to surrounding tissues and lymph nodes. Currently, there are 21 histologically different types of breast cancer and 4 different molecular subtypes [4]. The vast majority of breast cancers are sporadic tumors (approximately 90%), that develop due to somatic mutations in an individual’s lifetime [2]. Many known factors may contribute to the development of breast cancer including genetic, hormonal, environmental, dietary, and reproductive factors as well as exposure to ionizing radiation [4]. About 5–10% of breast cancer cases occur in individuals with a known hereditary germline mutation. Among these genetic factors, mutations in the BRCA1 and BRCA2 genes, responsible for DNA repair, have been best characterized. The risk of developing breast cancer in carriers of mutated genes is significantly higher than in the general population and ranges from 69% to 72%. There is also a significantly higher risk of developing bilateral breast cancer in this population [5]. Additionally, these individuals are at an increased risk of developing ovarian, pancreatic, and prostate cancer [2]. Metachronous tumors occurring in BRCA1 mutation carriers who have previously had breast cancer are more common than in non-carriers, with second breast cancer being most frequently observed [5].

Case report

The patient, aged 35, was diagnosed with left breast cancer (triple-negative subtype, clinical stage pT1cN1) in 2010. The patient underwent breast-conserving surgery and received 6 cycles of adjuvant chemotherapy with doxorubicin and cyclophosphamide as well as adjuvant radiotherapy. In 2021, suspicion of metachronous right breast cancer was raised. Biopsy showed invasive ductal carcinoma grade 3 and luminal B subtype. Immunohistochemical analysis of the tumor cells showed estrogen receptor expression (10%), progesterone receptor expression (5%), negative HER2 status, and a Ki-67 index of 70%. The patient underwent surgery and postoperative examination showed stage pT1cN0. Despite being informed about the risks associated with her decision, the patient declined adjuvant chemotherapy as well as hormonal therapy in the form of goserelin and zoledronic acid. The patient was still menstruating, which is why zoledronic acid was suggested only on the condition of obtaining her consent to goserelin therapy to pharmacologically induce menopause. Treatment with tamoxifen was initiated (as the only form of systemic therapy acceptable for the patient) along with adjuvant radiotherapy.

In May 2022 abdominal computed tomography (CT) raised suspicion of a secondary lesion in the liver. Metastatic disease was confirmed in June on positron emission tomography (PET), which showed skeletal and liver secondary deposits. After a multidisciplinary consultation, a liver biopsy was performed to determine metastasis phenotype. Zoledronic acid therapy was initiated and — after an oncological consultation on radiation – the patient underwent palliative radiotherapy for the Th3–Th5 segment of the spine as well as the left iliac crest and sacrum. The pathology result of the liver biopsy was inconclusive, as only benign tissue was obtained.

Due to the patient’s rapidly deteriorating general condition, low expression of steroid receptors in the primary tumor, and impending visceral crisis, palliative chemotherapy with paclitaxel (80 mg/m2 every week) was initiated, which was completed in October.

In September 2022, remission of liver lesions was observed. A liver biopsy was repeated, and it indicated metastasis of adenocarcinoma. Immunohistochemical analysis of the tumor cells demonstrated the absence of estrogen receptors (ER–), progesterone receptors (PR–) and HER2(–). In January 2023 disease progression was observed, confirming the metastasis of “triple-negative” breast cancer with disease progression after the first-line palliative chemotherapy (paclitaxel). Genetic testing identified the presence of a BRCA1 mutation (5382 ins. C). Based on this, the patient received talazoparib. After three months of therapy, partial remission (PR) was found according to RECIST 1.1 criteria. The patient continues the treatment.

Discussion

The risk of breast cancer is higher in women with a history of breast cancer and ranges from 10–15% for a 55-year-old woman with a previous breast cancer compared to 2.5% for a healthy 55-year-old woman during a 15-year observation period. From the initial diagnosis, the risk of developing metachronous breast cancer significantly increases over time [5]. The prevalence of BRCA1 gene mutations in the Polish population is approximately 6% in breast cancer patients diagnosed before the age of 50 [6]. Breast cancers associated with BRCA1 mutation occur at an early age (42–45 years) and are bilateral in 18–32% of cases [6–9]. The presence of a BRCA1 mutation increases the risk of developing breast cancer to 50–80% and ovarian cancer to approximately 40%, depending on the type of mutation [10, 11]. In a study by Kruczała et al. [5], the development of metachronous malignancy was observed in 50% of patients with BRCA1 mutation, with 38% of cases being second breast cancer compared to only 4.8% with metachronous ovarian cancer (possibly because 40% of patients in the studied population underwent prophylactic hysterectomy with bilateral adnexectomy). Due to the high incidence of breast cancer and a significant number of patients undergoing radical treatment as well as the increasingly common and accessible diagnostics for BRCA1 gene mutations, it is expected that the number of cancer patients with identified mutations will increase in daily clinical practice. With this in mind, it is necessary to raise awareness of the scale of metachronous tumors in patients with BRCA1 mutations in the medical community, intensify surveillance of BRCA1 mutation carriers after breast cancer treatment to detect the occurrence of subsequent tumors and consider prophylactic bilateral adnexectomy and mastectomy for BRCA1 mutation carriers previously treated for breast cancer [5].

A significant prognostic factor in breast cancer patients is the presence of expression of ER and PR as well as HER2 on tumor cells. This is particularly important in the case of tumor metastases, as their presence is one of the most common causes of treatment failure in oncology. The expression status of ER, PR, and HER2 on metastatic tumor cancer cells is crucial for selecting a therapeutic strategy. However, it should be noted that there is often a significant discordance in the expression of ER and PR receptors between metastatic tumors and the primary tumor focus, while the expression status of HER2 remains relatively stable [12]. In the case of the described patient, the biopsy of liver metastases revealed a discrepancy in the expression of ER and PR receptors compared to the metachronous cancer that occurred later. This suggests the presence of “triple-negative” breast cancer metastases which occurred in the patient in 2010.

Article Information and Declarations

Ethics statement

The patient's consent was obtained for the presentation of a clinical case.

Author contributions

K.P.: responsible for conception, design, execution, writing the paper; I.R.: responsible for conception, design, execution, writing the paper; M.K.: responsible for conception, design, execution, writing the paper.

All authors have read and agreed to the published version of the manuscript.

Acknowledgments

None.

Conflict of interest

The authors declare no conflict of interest.

Funding

This research received no external funding.

Supplementary material

None.

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