Analysis of tumor heterogeneity at the molecular level: a case report of efficacy separation in metastatic breast cancer

Although breast cancer frequently metastasizes to the lungs, rarely breast cancer patients develop separation of the efficacy of different lesions in pulmonary metastases. Differentiation at genetic level between drug-resistant lesion and sensitive lesion may be very challenging but is essential for prognostic and therapeutic considerations. In the present case study of a 51-year-old patient who had recurrent disease with pulmonary metastases after a left modified radical mastectomy three years later. Her two lesions of left pulmonary metastatic disease had a separation of therapeutic effects by treatment with albumin paclitaxel in imaging. Histological and immunohistochemical finds suggested that these two lesions were not inconsistent. A total of 230 cancer predisposition genes were analyzed by next generation sequencing and 25 gene mutations were detected, including MUTYH, ALK, MSH6, PIK3CA, TP53, AR, BRAF, EGFR, EPHX1, NRAS, RET, STK11, FBXW7, CD274 and MET were identified. The unique gene mutations of drug-resistant lesion were: CD274, MET, EPHX1, FBXW7 and TP53. The mutation genes specific to sensitive lesions were: KDR, FGFR4, CDH1, FGFR2, PTEN and SLC22A4. Which indicated that there was a difference between the two lesions at the genetic level. Even if there are efficacy separation in different metastatic lesions of the same organ in the same patient, the underlying cause may be genetic differences. Moreover, gene sequencing is also a supplement to traditional pathology. In summary, our results support the usage of next generation sequencing as a supplementary tool, assisting in revealing genetic heterogeneity. This is the first case report, to our knowledge, of difference between lesions in lung metastases, suggesting the existence of a patient with distant metastases who would be different for therapy as a result of carrying heterogeneity.