Case Report: Molecular Profiling Assists in the Diagnosis and Treatment of Cancer of Unknown Primary

Bo Yu; Qifeng Wang; Xin Liu; Silong Hu; Liangping Zhou; Qinghua Xu; Yifeng Sun; Xichun Hu; Zhiguo Luo; Xiaowei Zhang

doi:10.3389/fonc.2022.723140

Case Report: Molecular Profiling Assists in the Diagnosis and Treatment of Cancer of Unknown Primary

Front Oncol. 2022 Mar 30:12:723140. doi: 10.3389/fonc.2022.723140. eCollection 2022.

Authors

Bo Yu^{1

2}, Qifeng Wang^{2

3}, Xin Liu^{1

2}, Silong Hu^{2

4}, Liangping Zhou^{2

5}, Qinghua Xu^{6

7}, Yifeng Sun⁶, Xichun Hu^{1

2}, Zhiguo Luo^{1

2}, Xiaowei Zhang^{1

2}

Affiliations

¹ Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.
⁵ Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁶ Canhelp Genomics Research Center, Canhelp Genomics, Hangzhou, China.
⁷ Institute of Machine Learning and Systems Biology, College of Electronics and Information Engineering, Tongji University, Shanghai, China.

Abstract

Background: For cancer of unknown primary (CUP), non-selective empiric chemotherapy is usually used. However, patients suffering from CUP are generally assumed to have a dismal prognosis with median overall survival of less than 1 year. Therefore, clinicians eagerly await the establishment of effective strategies for diagnosis and treatment. In recent years, the remarkable advances in next-generation sequencing (NGS) technology have enabled the wide usage of DNA/RNA sequencing to comprehensively analyze the molecular information of individual tumors and identify potential targets for patients' diagnosis and treatment. Here, we describe a patient of CUP who was successfully diagnosed and treated with targeted therapy directed by comprehensive molecular profiling.

Case presentation: A 61-year-old Asian woman with a painless, slow-growing mass lesion in the mesosternum underwent fluorodeoxyglucose-positron emission tomography/computed tomography and was found to have malignant metastatic tumors in the mesosternum. Conventional pathological examination of metastatic lesions could not conclude the primary origin of the tumors. The patient was diagnosed with CUP at first. Then, comprehensive molecular profiling was employed to identify the tumor origin and genetic alterations. A gene expression-based tissue origin assay was performed using a tissue biopsy sample. The test result suggested that the lesion tumors might be breast cancer metastasis. Furthermore, liquid biopsy-based circulating tumor DNA profiling detected an ERBB2 copy number amplification. Subsequent surgery and additional postoperative pathology analysis confirmed that the primary tumor site was indeed located in the right outer upper quadrant of the breast. After local surgical resection, the patient received 8 cycles of Docetaxel + Carboplatin + Trastuzumab + Pertuzumab (TCbHP) chemotherapy with subsequent human epidermal growth factor receptor 2 (HER2)-targeted maintenance therapy. Currently, the patient is on regular follow-up and has achieved disease control for up to 6 months.

Conclusion: Our findings suggest that molecular identification of the tumor origin and the detection of actionable molecular alterations may offer promise for improved diagnostic accuracy and important therapeutic implications for patients with the CUP syndrome.

Keywords: HER2 amplification; cancer of unknown primary; gene expression profiling; next-generation sequencing; tumor of origin.

Publication types

Case Reports