Cytological Examination of Malignant Pleural Effusion in Breast Cancer

The serous pleural cavity is an enclosed space covered by the parietal and visceral layers of serous membranes, which are lined by a monolayer of mesothelial cells supported on fibrous tissue rich in capillaries and lymphatic. Under physiological conditions, these two layers are in juxtaposition and only a small amount of fluid is Present inside these compartments, acting as a lubricant to avoid friction.

Many infectious, benign, and malignant diseases can cause pleural effusion. Approximately one-fourth of all pleural effusions and 30 - 70% of all exudative effusions in hospital settings are secondary to cancer.

Lung cancer is the most common metastatic tumor to the pleura in men, while breast cancer is the most common tumor in women.

Breast cancer is the most commonly diagnosed malignant tumor in women worldwide and the most common cause of malignancy- related deaths. Breast cancer patients constitute approximately 36% of all oncological patients. The incidence of breast cancer is gradually increasing worldwide.

Since breast cancer is a heterogeneous disease that varies from clinical course to molecular subtypes, it includes a wide spectrum of diseases with different presentations and morphological, biological, and clinical phenotypes. Therefore, the behavior and treatment success of breast cancer vary greatly from person to person, and, as a result, it is possible to encounter very different personalized prognosis processes in breast cancer patients.

Malignant pleural effusions are most commonly caused by carcinomas of lung, breast, gastrointestinal tract or ovary, and hematological malignancies. Diagnosis of pleural effusion is done by many maneuvers as simple aspiration for cytological examination, or using more invasive maneuvers as closed pleural biopsy and medical thoracoscopy. Large studies evaluated the sensitivity and specificity of conventional cytology for the detection of malignant cells in effusions, ranging from 40% to 80% and 89% to 98%, respectively.

Molecular classification of breast cancer was developed based on the use of complementary DNA microarrays to represent human genes. Breast cancer was divided into 4 intrinsic molecular subtypes: luminal A, luminal B, v-erb-b2 (ERBB2)/human epithelial growth factor receptor 2 (HER2) gene-overexpressing (HER2), and basal-like.

The presence of MPE in advanced cancer is associated with poor prognosis, and the range of overall survival (OS) time is from 5 to 13 months. MPE is most common in triple-negative breast cancer (TNBC), and TNBC phenotype is an unfavorable characteristic in patients with MPE, worsening the prognosis and reducing life expectancy. For symptomatic patients with MPE, it is recommended to use an indwelling pleural catheter or chemical pleurodesis combined with systemic treatment.

Several factors could be attributed to this great variability, such as different immune-cytochemical staining techniques, dilutions and type of antibody clone used, volume of sample, procedural technique and the experience of the examiner. In addition, lack of uniformity in reporting such specimens could also be a factor for such wide differences in overall values of sensitivity and specificity among studies, with no study yet, to the best of our knowledge, reporting risk of malignancy (ROM) of defined diagnostic categories in pleural fluids.

For the time being, no international recommendations have been made about the rationale of using anti-tumor therapy against standard palliative MPE treatment procedures. The clinical treatment response of MPE is poor in systemic anti-tumor therapy in most malignant conditions. Therefore, there is an urgent need to develop a viable and reliable method to improve therapeutic effects of BC patients with MPE.

Therefore, pleural effusion samples will be sampled, using a diagnostic system and reporting ROM for each defined category, as well as use of immunohistochemistry and overall sensitivity and specificity of cytology when compared to concomitant pleural biopsies.

Inclusion criteria

• Patients will be included if they are presented for thoracentesis with routine cytological examination of pleural effusion before biopsy or thoracoscopy, if the appearance of visceral and parietal pleural was clearly and if malignant diagnosis of breast was confirmed on histological analysis of the biopsy material.

Exclusion criteria

• Age <18 years.
• Patients diagnosed with malignant pleural mesothelioma (MPM)
• Contraindication for pleurocentesis; patient refusing, coagulopathy and active skin infection