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Fig. 1 | Genome Medicine

Fig. 1

From: Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy

Fig. 1

a Dose-Dense trial design. All patients (n = 109) received sequential epirubicin and docetaxel monotherapy*. Biopsies were collected before treatment, after epirubicin, and after docetaxel. Whole exome sequencing (WES) was performed for 51 patients in pretreatment tumor biopsies and matched blood samples. Among these 51 patients, repeated tumor biopsies after epirubicin (n = 48) and after docetaxel (n = 43) were subjected to WES (all 43 patients with biopsies after docetaxel were among the 48 with biopsies after epirubicin). Out of the remaining 58 patients in the trial, pretreatment tumor biopsies from 45 underwent amplicon-based targeted sequencing of a six-gene panel. b Diagram depicting the number of tumor biopsies used for DNA sequencing pretreatment (green), after epirubicin (red), and after docetaxel (blue). Out of 96 pretreatment biopsies, WES was performed on 51 (dark gray) and amplicon-based sequencing on the remaining 45 samples (light gray), whereas subsequent analyses after epirubicin (n = 48) and docetaxel treatment (n = 43) were performed by WES only. The distribution of breast cancer subgroups (hormone receptor positive, HER2 normal (HR+HER2−), HER2 positive (HER2+), and triple-negative breast cancers (TNBC)) are indicated by light green, purple, and pink bars, respectively, in the lower panel. c Mutation status pretreatment. Oncoplot showing mutations of six genes in pretreatment samples from all patients in the study with available tumor DNA (n = 96). The mutation list is sorted by the subgroups; HR+/HER2−, HER2+, and TNBC. Mutations are colored according to mutation type. Percentages and bars on the right indicate the prevalence of mutations in each of the genes, among the 96 tumor samples analyzed. Each column represents one tumor/patient. Colors in the lower panel show the individual clinical responses to sequential epirubicin and docetaxel* neoadjuvant chemotherapy, and the molecular analysis used for each tumor sample (whole exome sequencing (WES) or amplicon-based sequencing). Responses listed: CR (complete response), PR (partial response), SD (stable disease), according to RECIST, and PD (progressive disease), according to UICC criteria. *HER2-positive breast cancers received concomitant docetaxel and trastuzumab

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