PMC8201609_01
Timeline of antitumor regimens and outcomes. Line graph illustrating disease progression, antitumor lines, regimens, and outcomes from July 2018 to November 2020. ALND, axillary lymph node dissection; AC-T, doxorubicin, cyclophosphamide followed by paclitaxel; PD, progressive disease; NP, vinorelbine plus carboplatin; RFA, radiofrequency ablation; DFS, disease-free survival; PFS, progression-free survival.
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She was recognized as having stage III triple-negative breast cancer (TNBC) according to the American Joint Committee on Cancer Staging Manual, 7th edition. She received 8 cycles of adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) with tolerable adverse effects but refused to receive radiotherapy ( Figure 1 ).
Immunohistochemical analysis of PD-L1 expression and next-generation sequencing of pretreatment tumors. (A) Hematoxylin-eosin staining. (B) Immunohistochemical analysis of PD-L1 expression was conducted with an anti-PD-L1 antibody (Dako PD-L1 22C3 PharmDx assay). PD-L1 was not expressed in tumor cells (black arrow), whereas positive staining for PD-L1 in peritumoral lymphocytes was observed (white arrow). Immunohistochemical detection of CD3+ (C), CD4+ (D) and CD8+ cells (E). (F) Next-generation sequencing results based on the FoundationOne CDx assay. The test analyzes 324 genes as well as genomic signatures, including microsatellite instability and tumor mutation burden.
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She underwent liver fine-needle aspiration, and the pathology was confirmed as metastatic TNBC ( Figure 2A ). A magnetic resonance imaging (MRI) scan showed that her disease had further worsened, as extensive and large lesions were observed in the liver, but there was no tumor spread to the brain, lungs, and bone ( Figure 2A ). Her tumor did not harbor BRCA1/2 mutations, other homologous recombination deficiencies, or potential mutations associated with HPD ( Figure 2F ). At that time, IHC using the PD-L1 IHC 22C3 pharmDx assay showed a tumor cell PD-L1 expression percentage of 0% and immune cell PD-L1 expression of 5% (Dako, Inc.) ( Figure 2B ). CD4+ and CD8+ cells were absent ( Figures 2C-E ). Considering that the IMpassion130 trial revealed that atezolizumab plus nab-paclitaxel is superior to placebo plus nab-paclitaxel in unresectable locally advanced or metastatic TNBC and that atezolizumab was available in China at that time, a fourth-line treatment with nab-paclitaxel plus the PD-L1 inhibitor atezolizumab (200 mg every 3 weeks) was started in March 2020.
Radiological evaluation and altered levels of circulating tumor markers before and after HPD. (A) After receiving immunotherapy with pembrolizumab, this patient developed HPD. An MRI scan showing more extensive and large metastatic lesions in the liver, which responded well to rechallenge with atezolizumab in May 2020, and necrotic areas. (B) Dynamics of the levels of circulating tumor markers (CEA, CA125, and CA153) before and after HPD.
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Following 2 cycles of treatments, the previous lesions in the liver rapidly progressed, new lesions occurred and the levels of CEA and CA153 were increased ( Figure 3B ). At the time of the first radiological tumor reassessment, the lesions in her liver had responded well to this regimen, with a significant objective partial response ( Figure 3A ). Unexpectedly, the treatment reduced alanine transaminase, aspartate transaminase, alkaline phosphatase, creatinine, CEA, and CA125 levels to normal levels ( Figure 3B ). She continued to receive atezolizumab until November 2020, when the lesions in her liver progressed again ( Figure 3A ).
Evaluation of HPD by the RECIST1.1 criteria and tumor growth kinetics after starting immunotherapy with pembrolizumab. (A) Evaluation of HPD by measuring the variation in the SLD of target lesions according to RECIST1.1 criteria. (B) Evaluation of HPD by measuring the TGKR. SLD, sum of the longest diameters; TGKR, tumor growth kinetics ratio; HPD, hyperprogressive disease; RECIST, response evaluation criteria in solid tumors.
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HPD was confirmed through MRI scanning according to a previously reported definition of HPD in terms of tumor burden ( Figure 4A ) and the tumor growth kinetics ratio (TGKR) ( Figure 4B ).
Positron emission tomography/computed tomography (PET/CT). PET/CT scan confirmed slightly high fluorodeoxyglucose (18F-FDG) uptake with an SUVmax of 5.9 for limited metastatic liver lesions (white arrow).
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A positron emission tomography/computed tomography (PET/CT) scan confirmed slightly high fluorodeoxyglucose (18F-FDG) uptake with an SUVmax of 5.9 for limited metastatic liver lesions ( Figure 5 ).