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. 2023 Aug 29;220(11):e20211743. doi: 10.1084/jem.20211743

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© 2023 Bhin et al.

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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Figure 9. — MYC status is a poor prognostic factor for everolimus-based therapy. (A) MYC CN status of tumors from the HMF cohort (n = 40) prior to mTORi treatment. MYC CN status was normalized to sample ploidy (SP), and samples with MYC CN > 2*SP were defined as MYC-amplified tumors (Priestley et al., 2019). Bar plots show MYC CN status of samples with clinical response to mTORi treatment. PD, progressive disease. Red dotted line denotes MYC amplification cutoff. The gray dotted line denotes normal MYC CN status (CN ratio = 1). BC, breast cancer; PC, pancreatic cancer; UC, uterine cancer; SC, skin cancer; HNC, head and neck cancer; LC, lung cancer; NET, neuroendocrine tumor; NCPSC, nasal cavity and paranasal sinus cancer; CUP, cancer of unknown primary; n/d, not determined. (B) Comparisons of MYC CN status of responders (PR + SD) vs. non-responders (PD) in all tumor types (total, n = 40; PR + SD, n = 16; PD, n = 24) and in ER+ breast cancer (total, n = 31; PR + SD, n = 9; PD, n = 22), specifically. Data are represented as median ± IQR (box) and quartiles ± 1.5 × IQR (whiskers) and Wilcoxon rank-sum test was performed to compute P values (*P < 0.05; n.s, not significant; all tumor types, P = 0.04; ER+ breast cancer, P = 0.13). (C) Percentages of tumors with MYC amplifications in the pre and post mTORi-treated HMF cohorts (all tumor types, n = 121; untreated, n = 54; treated, n = 67; ER+ breast cancer, n = 104; untreated, n = 43; treated, n = 61). Proportion test was performed to compare the percentages between groups (n.s, not significant; all tumor types, P = 0.19; ER+ breast cancer, 0.31). (D and E) Kaplan–Meier curves showing everolimus treatment duration for patients with MYC WT or MYC-amplified cancers (D; n = 40) or specifically ER+ breast cancers (E; n = 31) using data from the HMF cohort. P values were calculated with log-rank (Mantel–Cox) test. (F) Univariate cox regression analysis to evaluate the association between individual therapeutics used in ER+/HER2− breast cancer and treatment duration from HMF cohort. Data are represented as estimated hazard ratio (HR) ± 95% confidence interval (CI). (G) Kaplan–Meier curve showing progression-free survival (PFS) of ER+/HER2− breast cancer patients (n = 101) from the everolimus biomarker study (EudraCT number 2013-004120-11) during everolimus/exemestane treatment stratified for MYC positivity using IHC. P values were calculated with log rank (Mantel–Cox) test. (H) Multivariate Cox regression analysis on breast cancer specimens from G using indicated clinicopathological variables. For each variable, data are represented as estimated hazard ratio ± 95% CI. ECOG, Eastern Cooperative Oncology Group performance status; PR, progesterone receptor status of the primary tumor of study participants.