There are big differences between primary breast cancer and secondary breast cancer in clinical features, imaging, pathology and immunohistochemistry. This patient started with pericardial effusion and pleural effusion. Breast masses are clues. Adenocarcinoma cells were found through puncture and drainage of pericardial effusion and exfoliated cytology. Combined with immunohistochemistry, tumorous lesions in the lung were further found. At the time of diagnosis, it was at an advanced stage. It is easy to be considered as primary breast cancer at the first diagnosis, or the coexistence of lung cancer and breast cancer. The role of histopathology as the gold standard in the diagnosis of diseases is beyond doubt. However, the morphological identification of small biopsy specimens with atypical morphology is limited, and immunohistochemical testing is indispensable for diagnosis at this time. At present, the commonly used immune markers in lung adenocarcinoma include NapsinA, TTF-1, CK7 and alveolar surface glycoprotein, etc6. Breast cancer mainly expresses ER/PR, GATA-3 and Mamma-globin, etc. The positive rate of GATA-3 is 47%-100%, which is a specific marker of breast cancer7. Immunohistochemistry of the breast tumor in this patient showed positive TTF-1, NapsinA, and CK7, supporting the diagnosis of lung adenocarcinoma. The patient's immunohistochemical results showed TTF-1 positive and ER negative. Although a small number of breast cancers can also express TTF-1, they need to be distinguished from primary breast cancer8,9. Because of the more specific NapsinA positive and GATA-3 negative, the diagnosis of lung adenocarcinoma and breast metastasis is clear.
Primary malignant tumor of breast is one of the most common malignant tumors in adult women, but as the breast is rich in fibrous tissue, poor blood circulation, so secondary metastasis of breast is very rare. Metastatic breast tumors are very rare, accounting for only 0.4–1.3% of breast malignancies, and the most common are leukemia, lymphoma, melanoma, rhabdomyosarcoma, and lung cancer10. The ways of breast metastasis in patients with primary lung cancer are as follows: To the ipsilateral breast through intrathoracic lymphatic metastasis; Tumor cells along with the lymph circulation through the thoracic duct into the vein, through systemic circulation to the contralateral breast; Tumor cells enter the blood circulation and metastasize far away11.
Our patient had metastasis to her right breast, which is the same side affected by the malignant pleural effusion, consistent with the hypothesis by Huang et al12. To this end, they considered a stepwise mechanism involving parietal pleural seeding, followed by invasion into chest wall lymphatic vessels draining to ipsilateral axillary lymph nodes and retrograde lymphatic spreading to the breast. This mechanism of breast metastasis could be supported by findings of enlarged homolateral axillary lymph nodes. Moreover, Barber et al13 demonstrated lymphatic communication between the breast and mediastinal lymphatic channels. These hypotheses could be confirmed by the fact that almost 80% of the cases reported from 2000 to date had ipsilateral lesions. Another potential type of spread could be hematogenous. However, if lung cancer spreads through this route, both breasts should have the same probability of being affected. This is not reflected in the reviewed cases, where only 5.4% of patients had bilateral breast involvement. The last possible explanation could be direct tumor invasion through the chest wall to the breast, but chest CT scans did not reveal this alteration in the reported cases. Therefore, lymphatic spreading might be the most reasonable mechanism of lung cancer dissemination to the breast.
Mirrielees et al. analyzed through a systematic retrospective analysis of 43 cases of lung cancer breast metastasis reported from 1989 to 2013; Among them, 10 cases were small cell lung cancer, 33 cases were non-small cell carcinoma, including 19 cases of adenocarcinoma, 3 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of neuroendocrine carcinoma, 3 cases of undifferentiated carcinoma or others; The report involved 38 female and 5 male patients, with similar incidence in each age group. Among them, the average age of breast metastasis in NSCLC patients was 55 years old, SCLC patients were 58 years old, and patients were between 28 and 83 years old14. The correlation between the incidence of lung cancer and breast metastasis and pathological types remains to be studied with large samples.
In general, patients with solid tumors that have metastasized to the breast already have extensive metastases in other locations, and most patients survive for no more than one year after breast metastasis is found15. In a study of 169 patients with advanced solid tumors of different types of non-breast origin, the median survival time of patients after diagnosis of breast metastasis was 10 months (1 to 192 months)16. At present, there is no clear guideline for patients with breast metastasis, and the management and treatment are mainly based on the pathology, symptoms, stage, and physical condition of the primary malignant tumor15. In general, radical surgery is not recommended in patients with metastatic cancer and may lead to higher complications and mortality15. According to the latest ESMO guidelines, patients with solitary metastasis of lung adenocarcinoma can consider radical treatment of primary and metastatic lesions on the basis of systemic therapy, while patients with multiple metastases of lung adenocarcinoma should be given systemic therapy17.
Our case was advanced lung cancer, genetic testing revealed an EGFR mutation, and Almonertinib was treated. Almonertinibis the second third-generation EGFR-TKI innovative drug in the world. It is mainly used for disease progression during or after treatment with EGFR TKI. The test confirmed the presence of EGFR T790M mutation-positive adult patients with locally advanced or metastatic non-small cell lung cancer. Almonertinibis easier to cross the blood-brain barrier than other EGFR-TKI targeted drugs. We took into account the presence of brain metastases in our patient, so in the case of ineffective immunotherapy, we chose amitinib targeted systemic therapy. As a result, the patient controlled the brain lesions and achieved stable disease control for 2 months. Treatment is currently underway. We will continue to track and record the patient’s disease.