Lung cancer with breast metastasis: a case report and review of the literature

Abstract

In this article, we present a rare case of breast metastasis of lung cancer. Chest computed tomography (CT) for a woman in her early 50s indicated right lung malignancy, multiple bone metastases, and an irregular mass in her right breast. Further inquiry into the case history revealed that the patient had been aware of the breast mass for 3 years, without respiratory symptoms. Biopsy of the breast mass suggested estrogen receptor (ER) (+), progesterone receptor (PR) (−), and human epidermal growth factor receptor 2 (HER2) (+ +) breast cancer. The patient was initially diagnosed with breast cancer with lung and bone metastasis. However, comprehensive breast cancer treatment was ineffective, and thyroid transcription factor-1 (TTF-1), napsin A, and cytokeratin 7 (CK7) were evaluated to better understand the origin of the cancer. To the best of our knowledge, this patient had the longest reported disease course from presentation with a breast lump as the first symptom to the final diagnosis of breast metastasis of lung cancer. To provide a better reference for differential diagnosis of ambiguous tumors, we also performed a systematic literature review.

Introduction

Breast cancer has surpassed lung cancer as the most common type of cancer worldwide. ¹ Breast cancer often metastasizes to distant organs, such as bones, lungs, brain, and liver. ² In comparison, the common metastasis sites of lung cancer are the brain, bones, adrenal glands, and lymph nodes. ³ Considering the fact that breast tissue consists of abundant fibrous tissue with a relatively minimal blood supply, lung cancer rarely metastasizes to the breast. ⁴ A previous study showed that only 0.5% to 1.2% and 1.7% to 6.6% of malignant tumors metastasized to the breast, as shown in clinical and autopsy cases, respectively. ⁵ The diagnosis of primary and metastatic tumors is critical when making treatment decisions. In this article, we present a case of breast metastasis from lung cancer and review the existing literature on the subject. The reporting of this study conforms to the CARE guidelines. ⁶

Case report

A woman in her early 50 s noticed a painless mass in her right breast more than 3 years prior to presentation. Physical examination revealed three adjacent palpable masses with diameters of 2.5, 2.0, and 1.5 cm, respectively, located 2 to 2.5 cm from the areolar edge at 10 o’clock in her right breast. The masses were painless and immobile with a firm texture, unclear boundaries, and the masses were unattached to the skin. No enlarged lymph node was identified in either armpit and above or below the clavicle, bilaterally.

Computed tomography (CT) revealed classic signs of a malignant tumor in the upper lobe of the right lung, with metastatic tumors in bilateral ribs, scapula, sternal body, thoracolumbar vertebrae, and the right chest (Figure 1). Mammography revealed an irregular lobulated mass in the right upper quadrant, with rough edges and massive subcutaneous suspensory ligament hyperplasia and thickening (Figure 2). In the upper quadrant of her right breast, two and possibly three, oval hypoechoic masses were identified. The larger mass measured approximately 14 mm × 10 mm, with an aspect ratio of <1 and a clear boundary. However, this mass had irregular internal echogenic signals, and invading blood supply within the mass was identified (Figure 3).

Figure 1.

CT showing a malignant tumor (white arrow) in the upper lobe of the right lung CT, computed tomography.

Figure 2.

Mammogram showing irregular clumps (white arrow) in the upper quadrant of the right breast, with hyperplasia and thickening of a large number of subcutaneous suspensory ligaments

Figure 3.

Ultrasonography showing a hypoechoic mass in the right breast, subsequently staged as IVb

Ultrasound-guided biopsy of the largest mass in the right breast was performed, and the pathology indicated invasive carcinoma with the following results: estrogen receptor (ER): 70%+, human epidermal growth factor receptor 2 (HER2): ++, GATA3: ±, and progesterone receptor (PR) and gross cystic disease fluid protein-15 (GCDFP-15): negative. On the basis of these results, the diagnosis was primary breast cancer with right lung and bone metastasis. The patient then received comprehensive breast cancer treatment (the details of the plan are unknown) at other hospitals, which provided no benefit. To better understand the origin of the breast tumor, immunohistochemical testing was repeated and showed that the tumor strongly expressed lung cancer-related markers, such as thyroid transcription factor-1 (TTF-1) (Figure 4), napsin A (Figure 5), and cytokeratin 7 (CK7) (Figure 6). These results showed that the tumors identified in the breast were actually metastatic tumors of lung cancer. Unfortunately, the patient did not return to our hospital, and her current condition is unknown.

Figure 4.

Immunohistochemistry of the breast lesion; a, b: positive for TTF-1 (×200)

Figure 5.

Immunohistochemistry of the breast lesion; a, b: positive for napsin A (×200)

Figure 6.

Immunohistochemistry of the breast lesion; a, b: positive for CK7 (×200) CK7, cytokeratin 7.

Discussion

Breast cancer is one of the most common malignant tumors in women; however, metastasis of extramammary malignant tumors to the breast is rare. ⁴ Currently, only a small number of reports have described metastasis of malignant tumors, such as melanoma, lymphoma, and rectal cancer, to the breast. ⁷ Patients with breast metastasis usually have widespread disease and a poor prognosis. ⁴ Breast lump(s), pain, and nipple discharge are typical symptoms of primary breast cancer. ⁸ Metastatic breast tumors typically manifest as a palpable, rapidly growing, hard, painless, well-defined isolated mass.^9–11 It is important to note that skin changes and nipple discharge are extremely rare with metastatic breast tumors.^12,13

Unlike primary breast cancer, with mammography, metastatic breast tumors are characterized as dense, round, and microlobulated masses that may have smooth boundaries. ¹³ In contrast, primary breast cancer is characterized by disrupted structure, spiculated boundaries, and calcification.^13,14 Ultrasonography of metastatic breast tumors of lung cancer often shows a round or oval mass with homogeneous or heterogeneous hypoechogenicity, indistinct margins, and no calcification.^13–15 Most metastatic lesions have low signal intensity on T1-weighted sequences and medium signal intensity on T2-weighted sequences with magnetic resonance imaging. ¹⁴ Instant and homogeneous enhancement can be observed with contrast agents.^13,14 CT and positron emission tomography (PET)-CT can be used to locate primary and metastatic tumors. These lesions are typically seen on CT as round or oval masses with enhanced contrast. ¹⁴ Although it can detect rare/asymptomatic metastases, PET-CT cannot differentiate between metastatic lesions and primary cancer.^14,16 It is difficult to distinguish between primary and metastatic breast lesions by imaging without consulting the case history. Therefore, the differential diagnosis of primary and metastatic tumors typically relies on immunohistochemistry. ¹⁵

TTF-1 is expressed in 70% to 80% of all small cell carcinomas and adenocarcinomas but not in other types of lung cancer.^15,17 TTF-1 has been used as a marker to determine the origin of metastatic masses in lung cancer.^15,17 Napsin A expression can be identified in 80% to 90% of lung adenocarcinomas but is usually negative in breast cancer, making it a good alternative biomarker for lung adenocarcinoma diagnosis. ¹⁵ CK7 expression can be identified in lung metastatic cancers and thyroid cancer, and can be used to identify the origin of metastatic lesions.^12,18 ER is expressed in 80% and PR in 60% of breast cancers, ¹⁹ whereas GCDFP-15 is expressed in 45% to 53% of breast cancers. ¹⁴ GATA3 is positive in most lung and urinary tract carcinoma metastases of breast cancer. ¹⁷ Unfortunately, no single marker can provide 100% specificity or sensitivity in identifying the origin of a metastatic tumor; therefore, the diagnosis must be confirmed by comprehensive analysis using several markers. TTF-1, napsin A, and CK7 are considered useful markers of lung adenocarcinoma. ¹⁸ In contrast, ER, PR, HER2, and GATA3 are commonly used to identify breast cancer. ¹⁵

Our patient had a long disease course, and the presence of a breast mass was first noticed 3 years prior to presentation. The patient had minimal symptoms during the 3-year period, and the mass changed very little after it was first noticed. Consequently, this condition was largely neglected by the patient. In this case, the breast mass was the first sign of a tumor, and the patient did not present with respiratory symptoms. Therefore, the first immunohistochemical study was limited to breast cancer-related markers; no markers were measured to evaluate a differential diagnosis. However, we reconsidered a different diagnosis after the patient’s poor response to comprehensive breast cancer treatment, and the metastatic nature of the breast tumor was finally confirmed by additional immunohistochemistry.

Conclusion

Breast cancer and lung cancer are both common malignant tumors. Breast cancer is prone to metastases to lung and bone, while lung cancer metastasis to the breast is relatively rare. On the basis of our experience, when diagnosing breast tumors, the possibility of lung cancer metastasis should be considered, particularly in patients with simultaneous lung involvement. In addition to advanced imaging, pathological immunohistochemistry should be used to differentiate primary or metastatic breast lesions. Our experience suggests that it is important to correctly diagnose primary or metastatic breast tumors when patients have multiple lesions in different body sites so that proper treatment can be selected.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605231188287 - Supplemental material for Lung cancer with breast metastasis: a case report and review of the literature

Supplemental material, sj-pdf-1-imr-10.1177_03000605231188287 for Lung cancer with breast metastasis: a case report and review of the literature by Xuan Cao, Peiqing Chen, Enock Adjei Agyekum, Qing Zhang, Xiaoqin Qian, Ting Wu, Kevoyne Hakeem Chambers and Liang Yin in Journal of International Medical Research

Supplemental Material

sj-pdf-2-imr-10.1177_03000605231188287 - Supplemental material for Lung cancer with breast metastasis: a case report and review of the literature

Supplemental material, sj-pdf-2-imr-10.1177_03000605231188287 for Lung cancer with breast metastasis: a case report and review of the literature by Xuan Cao, Peiqing Chen, Enock Adjei Agyekum, Qing Zhang, Xiaoqin Qian, Ting Wu, Kevoyne Hakeem Chambers and Liang Yin in Journal of International Medical Research

Supplemental Material

sj-pdf-3-imr-10.1177_03000605231188287 - Supplemental material for Lung cancer with breast metastasis: a case report and review of the literature

Supplemental material, sj-pdf-3-imr-10.1177_03000605231188287 for Lung cancer with breast metastasis: a case report and review of the literature by Xuan Cao, Peiqing Chen, Enock Adjei Agyekum, Qing Zhang, Xiaoqin Qian, Ting Wu, Kevoyne Hakeem Chambers and Liang Yin in Journal of International Medical Research