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.