PMC7900143_01
Therapeutic course timeline followed in the patient. (A) Doxorubicin+Cyclophosphamide+Docetaxel (AC-T), (B) Tamoxifen, (C) Anastrozole, (D) Fulvestrant, (E) Fulvestrant+Palbociclib, (F) Albumin paclitaxel+radiotherapy, (G) Camrelizumab+Vinorelbine. bTMB, blood TMB; CR, complete response; PR, partial response; PD, progressive disease; DFS, disease-free survival; PFS, progression-free survival; AF, allelic frequency; CN, copy number.
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The patient management is described in  Figure 1 . TP53, which were all presented in tumor tissue samples from surgery and supraclavicular lymph node biopsy assessed by the same NGS panel ( Figure 1 ,  Supplementary Table 1 ). The blood TMB (bTMB) from the plasma was 7.9 mutations/megabase [mut/Mb], tissue TMB (tTMB) detected from surgery and supraclavicular lymph node biopsy were at modest levels of 5.98 mut/Mb and 4.99 mut/Mb respectively.
MR Image scans revealed the clinical response to the treatment of PD-1 antibody camrelizumab combined with vinorelbine.
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After two cycles of treatment, MRI displayed that the intrahepatic lesions had markedly shrunken in size and maintained after four treatment cycles ( Figure 2 ), also carbohydrate antigen (CA) level in the blood decreased rapidly during the first 4-cycle treatment ( Figure 3 ), yielding the best response of partial response (PR).
Fluctuation of CA level during immunotherapy in the blood including CA125, CA153, CA199. CA, carbohydrate antigen.
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After two cycles of treatment, MRI displayed that the intrahepatic lesions had markedly shrunken in size and maintained after four treatment cycles ( Figure 2 ), also carbohydrate antigen (CA) level in the blood decreased rapidly during the first 4-cycle treatment ( Figure 3 ), yielding the best response of partial response (PR).
Progression of cfDNA mutation burden during camrelizumab treatment, analyzed by variant allele frequencies. Frequencies of variants in Cluster 1 and 2 fluctuated along with treatment effectiveness, while those in Cluster 5 remained steadily; Mutations in cluster 3 acquired as disease progression and those in cluster 4 vanished before PR achieved. Broken vertical white lines correspond to plasma sample before immunotherapy, PR, and relapse subsequent to treatment.
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NGS of plasma cfDNA performed after two cycles of treatment showed a decrease in bTMB level from 149.2 to 40.88 mut/Mb, also other plasma cfDNA mutations were divided into 5 clusters according to their frequency referred to the computational method SciClone and frequencies fluctuated accordingly during immunotherapy ( Figure 4 ), suggesting that treatment had been effective from the molecular aspect.