Case report
We showed that a 52-year-old HER2-positive breast cancer patient underwent left breast modified radical mastectomy, and was diagnosed in December 2014 with left pT1N2M0, which immunological histological chemistry (IHC) confirmed ER-negative, PR-negative, HER2-positive 3+ (FISH+), Ki67 50%. She was then treated with 8-cycles of doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab (AC-TH) and radiotherapy (DT) (Figure 1A). However, the PET-CT scan revealed lung metastases in January 2015. Subsequently, the patient received 4-cycles of gemcitabine/capecitabine /trastuzumab (G+X+H) and approximately ten months of lapatinib/capecitabine (L+Cap) (Figure 1A), but both options achieved progressive disease (PD) as assessed by computed tomography (CT) scans using the RECIST criteria (1.1) 7. In December 2016, metastases appeared in many organs of the body, including liver, lung and brain. To ease the neurological symptoms, the patient received the whole brain radiation therapy (WBRT) and 2-cycles of trastuzumab/navelbine (H+NVB) for metastatic disease. Disappointingly, the patient continuously progressed (Figure 1A ).
Looking forward to identify other therapeutic options, the archived primary breast tumor tissue and the peripheral blood samples were collected for 425 cancer-related genes sequencing (Geneseeq, Nanjing, China) (Figure 1B ), which showed ERBB2 magnification consistent with the result of HER2-positive FISH. Intriguingly, the PIK3R1 p.EY451delinsD (c.1352_1354delAAT) and TP53 p.V173M (c.G517A) mutations were also detected at the high allele frequency (Figure 1B ). Due to the identification of the PIK3R1 mutation and considering the increased PI3K pathway activity, we thought that the combination treatment of trastuzumab and everolimus (mTOR inhibitor) was worth applying. Therefore, the patient began the fourth-line treatment, everolimus was given combining with trastuzumab and carboplatin (H+EVER+CBP) for eight cycles (Figure 1A). After eight cycles of everolimus containing regimen, CT and MRI scans revealed the decreased lung metastasis and the stable liver lesions (Figure 1A). A peripheral blood sample collected again after eight cycles was profiled using the Geneseeq ctDNA assay, which revealed the same PIK3R1 p.EY451delinsD mutation along with the persistent brain metastasis growth (Figure 1). Unfortunately, the H+EVER+CBP therapy could not block the intracranial tumor growth and the patient died shortly thereafter.