A synchronous occurrence of breast cancer and pleural mesothelioma: a case report

Abstract

Background

Malignant mesotheliomas are aggressive forms of tumors arising from mesothelial cells. The most common type is malignant pleural mesothelioma, which progresses rapidly and leads to pleural effusion. It typically affects older men and is strongly associated with asbestos exposure. However, a few studies have reported cases of malignant pleural mesothelioma resulting from non-asbestos factors, including radiotherapy for breast cancer, viruses, chronic inflammation, and BRCA1-associated protein-1-associated genetic mutations. Breast cancer is the most common sporadic cancer among women, and a small percentage of cases are related to genetic factors, such as BRCA1/2 and BRCA1-associated protein-1 mutations. While breast cancer can be linked with other primary malignancies through germline mutations, the synchronous occurrence of breast cancer with pleural mesothelioma is extremely rare.

Case presentation

We present the case of a 40-year-old Pashtun woman diagnosed with primary breast cancer. She underwent surgery followed by chemotherapy (paclitaxel). During chemotherapy, she developed right-sided chest pain and dyspnea. A computed tomography scan revealed pleural thickening, and a pleural biopsy confirmed the diagnosis of malignant pleural mesothelioma, with positive results for the diagnostic markers WT1 and D240.

Conclusion

This case represents a rare occurrence of synchronous breast cancer and pleural mesothelioma in a 40-year-old female, and is the first case reported in Khyber Pakhtunkhwa, Pakistan. These findings demonstrate the importance of comprehensive diagnostic testing and the potential role of genetic mutations in concurrent cancers. The challenge of simultaneously treating these cancers highlights the need for further research and the importance of multidisciplinary approaches.

Background

Malignant mesotheliomas are aggressive forms of tumors arising from mesothelial cells. These tumors line the pleura, peritoneum, tunica vaginalis testis, and pericardium. The most common type is malignant pleural mesothelioma (MPM), which rapidly progresses and extensively disseminates within the pleural cavity. It is accompanied by pleural effusion [1]. Pleural mesothelioma accounts for 65–70% of all cases [2]. The incidence of this disease increases with age, and it is more common in men. Female patients have a better prognosis, with survival rates of 17.3 months for females compared with 11.8 months for males [2].

Asbestos exposure remains the primary cause of malignant mesothelioma, often developing after a latency period of 40 years [3]. However, recent studies have reported rare cases of MPM resulting from non-asbestos (idiopathic) factors, including radiotherapy for breast cancer, exposure to minerals and mineral fibers, organic chemicals, viruses, chronic inflammation, and BRCA1-associated protein-1 (BAP1)-associated mutations [4, 5].

In contrast, breast cancer is the most common type of cancer among women worldwide. Most cases are sporadic. Approximately 5–10% of breast cancer cases are related to hereditary syndromes, which involve BRCA1/2 and BAP1 mutations [6].

The synchronous occurrence of breast cancer and pleural mesothelioma is extremely rare despite the known risk factors of both malignancies. Our case also highlights the potential non-asbestos-related causes of mesothelioma. To the best of our knowledge, this is the first documented case of synchronous breast cancer and pleural mesothelioma in a patient from Khyber Pakhtunkhwa, Pakistan.

Case presentation

We present the case of a 40-year-old Pashtun woman diagnosed with left-sided breast carcinoma (invasive breast cancer, grade 3) in March 2024, for which she underwent modified radical mastectomy followed by chemotherapy (paclitaxel). There was no regrowth on follow-up imaging.

However, at the end of July 2024, she complained of right-sided chest pain persisting for the past month. The pain had a gradual onset and was dull in character. It was associated with dyspnea, scoring 2 on the Medical Research Council (MRC) dyspnea scale (moderate breathlessness affecting daily activities, such as hurrying on level ground or walking up a slight hill). She was a non-smoker and had no history of asbestos exposure. Her medical history included hypertension, which was managed with angiotensin-converting enzyme (ACE) inhibitors. The family history was not significant for major pathologies. She experienced significant weight loss of 10 kg over 2 months, along with loss of appetite and fatigue.

Chest examination revealed stony dull percussion notes with decreased breath sounds on the right side, from mid-scapula downward. A chest X-ray revealed homogeneous opacification in the right middle and lower zones with blunting of the costophrenic and cardiophrenic angles (Fig. 1). Chest computed tomography (CT) revealed nodular pleural thickening on the right side with pleural effusion (Fig. 2).

Fig. 1

Chest X-ray (July 2024) showing hypodensity in the right middle and lower zones as indicated by arrows

Fig. 2

Computed tomography scan (August 2024) of the patient with malignant pleural mesothelioma. Part A showing pleural thickening. Parts B and C highlight the areas of thickening with arrows

Thoracoscopic pleural biopsy confirmed mesothelioma (WT1, D240, CD45 positive and TTF-1, CEA negative). WT1 and D240 positivity suggests pleural mesothelioma, particularly the epithelioid subtype. However, CD45 positivity in mesothelioma cells is a relatively rare condition requiring further investigation. TTF-1 and CEA negativity help differentiate pleural mesothelioma from lung and gastrointestinal adenocarcinomas. A chest drain was inserted to manage the pleural effusion.

The case was discussed with the thoracic tumor multidisciplinary team. It was determined that local resection or chemoradiation was not suitable because of the invasive and diffuse nature of the MPM. Subsequently, it was decided that management would include the use of paclitaxel. The patient continued paclitaxel at a dose of 175 mg/m². On the basis of a body surface area of 1.5 m², the resulting total dose was 262.5 mg. The patient tolerated the regimen well. The therapeutic options were limited. The patient was counseled about potential adverse effects, and no serious unanticipated events occurred. An indwelling pleural catheter was planned for the future if the patient developed recurrent pleural effusion. The patient’s prognosis was discussed. Regular follow-up was recommended. On follow-up at the end of August 2024, the patient’s symptoms (dyspnea and chest pain) had improved. The patient was satisfied with the treatment received.

Discussion

Malignant mesotheliomas are rare neoplasms that occur on the peritoneal, pericardial, and pleural mesothelial surfaces. Malignant pleural mesothelioma (MPM) is the most prevalent type of mesothelioma, accounting for 65–70% of cases. It is followed by peritoneal (30%) and pericardial (1–2%) types. There are three histological subtypes of pleural mesothelioma: sarcomatoid, biphasic, and epithelial. Mesothelioma has an extremely poor prognosis, with a median lifespan of only 9–12 months from the time of manifestation [3].

Sometimes, malignant mesotheliomas may present synchronously with other cancers, such as Hodgkin’s lymphoma, Wilms’ tumor, cervical tumors, testicular carcinoma, and breast carcinoma, as observed in this study [7].

MPM is strongly associated with asbestos exposure [8], along with non-asbestos (idiopathic) causes that contribute to its occurrence, including minerals, mineral fibers, radiation, chronic inflammation, viruses, and genetic factors, including BAP1 (BRCA1-associated protein–1)-associated mutations [5]. Minerals, including beryllium, and mineral fiber types, such as erionite, fluoroedenite, and possibly balangeroite, have the potential to cause mesothelioma in specific geographical areas. Exposure to therapeutic radiation can increase the relative risk by up to 30-fold. Chronic pleural inflammation, such as that observed in empyema and pulmonary tuberculosis, may be a factor in mesothelioma; however, data on this are limited. Similarly, the role of viruses in MPM development remains unclear. Germline mutations or deletions of BAP1 account for a small percentage of mesotheliomas (less than 1%). There is a complex relationship between malignant mesothelioma and its etiological factors [5].

Furthermore, BAP1 acts as a risk factor for malignant mesothelioma and other malignancies [5, 9]. BAP1 germline mutations are inherited as autosomal dominant traits and a high risk of mesothelioma among affected individuals and families [5]. BAP1 is suspected of contributing to the development of breast cancer [10]. This highlights the potential role of these genetic factors in developing rare concurrent malignancies.

Our case involved a patient who presented with breast cancer, followed by mastectomy and chemotherapy, and then developed MPM. Several factors can increase the risk of multiple primary malignancies, including genetics (Lynch syndrome, Li-Fraumeni syndrome, and BRCA gene mutation), radiation, chemotherapy, viruses [human papillomavirus (HPV), Epstein–Barr virus (EBV), Hepatitis B virus (HBV), Hepatitis c virus (HCV), and human herpesvirus 8 (HHV8)], other associated cancers, and environmental factors (smoking, alcohol, chemical exposures, diet, ionizing radiation, and contamination) [11]. Additionally, a significant body of literature has demonstrated the development of MPM after radiotherapy for breast cancer [4, 7, 12].

Among the tools used for diagnosing MPM, immunohistochemistry is a crucial technique. The main markers that are positive in MPM include calretinin, WT1, CK 5/6, and HBME-1, whereas GCDFP-15 and mammaglobin are used to detect breast cancer [13]. In our case, the tumor cells tested positive for WT1, D240, and CD45.

Further research is needed to develop a single standard chemotherapeutic drug for the treatment of MPM. Most guidelines recommend the use of platinum compounds in combination with pemetrexed [14]. Docetaxel is mildly effective in the treatment of MPM [15]. Exemestane has been proposed to be effective either alone or in combination therapy [11]. Local delivery of paclitaxel via expansile nanoparticles has shown promising outcomes in patients with limited disease and can be combined with cytoreductive surgery in patients with advanced disease [16]. Notably, our study involved the administration of paclitaxel as a chemotherapeutic agent for the treatment of breast cancer. The patient continued paclitaxel for MPM owing to limited therapeutic options.

This case highlights a causal relationship between the synchronous occurrence of breast cancer and MPM. These findings underscore the significance of both genetic and diagnostic testing and highlight the necessity for further research to understand the genetic pathways implicated in the development of MPM in patients suffering from primary breast cancer.

Conclusion

Our 40-year-old female patient had breast cancer and pleural mesothelioma, highlighting the synchronous presentation of two cancers. This is the first documented case of its kind from Khyber Pakhtunkhwa, Pakistan. This case report emphasizes the importance of comprehensive diagnostic testing in early identification. Genetic testing is recommended because of the potential role of genetic mutations in the development of concomitant malignancies. Treating cancers concurrently can lead to complications. Further research is needed to develop effective treatment guidelines for patients with coexisting malignancies. This finding contributes to limited literature on concurrent malignancies. It also illustrates the need for a multidisciplinary approach in the treatment of multiple cancers.