Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry

Jiagge, Evelyn; Ulintz, Peter; Wong, Shukmei; McDermott, Sean; Fossi, Sabrina I.; Suhan, Tahra K.; Hoenerhoff, Mark J.; Bensenhaver, Jessica; Salem, Barbara; Dziubinski, Michele; Oppong, Joseph K.; Aitpillah, Francis; Kyei, Ishmael; Osei‐Bonsu, Ernest; Adjei, Ernest; Awuah, Baffour; Aldrich, Jessica; Kurdoglu, Ahmet; Fernando, Kurt; Craig, David W.; Trent, J.M.; Li, Jun; Chitale, Dhananjay; Newman, Lisa A.; Carpten, John D.; Wicha, Max S.; Merajver, Sofía D.

doi:10.1007/s10549-021-06097-8

Cited by 8 publications

(10 citation statements)

References 39 publications

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“…Our reported TNBC proportion of 26.40% though not including equivocal cases is significantly lower than the proportions reported in many earlier publications. With some literature quoting the percentage of TNBC to be up to 80% [ 19 ] but generally around 53.2% in the Ghanaian population it is likely that these rather high reported proportions are partly a result of false negatives due to poor pre-analytics [ 20 ]. Though our TNBC rates are lower than previously reported in the Ghanaian literature, it is still higher when compared to proportions of TNBC in other populations.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana

Akakpo

Imbeah²,

Edusei³

et al. 2023

BMC Women's Health

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Background Breast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among women younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC). Methods A descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Reports of core or incision biopsy, Wide Local Excision or Mastectomy with or without axillary lymph node dissection specimen and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p < 0.05. Results A total of 2418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (< 40 years) and 54.29 (IQR: 16.86) in the LOBC group (≥ 40 years). Invasive carcinoma—No Special Type was the commonest tumour type with grade III tumours being the commonest in both categories of patients. Perineural invasion was the only statistically significant pathologic parameter with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67 > 20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80% vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC. Conclusion EOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger study is recommended to identify the association between relevant pathological features and early onset breast cancer in Ghana. Again, further molecular and genetic studies to understand the molecular genetic drivers of the general poorer pathological features of EOBCs and its relation to patient outcome in our setting is needed.

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Section: Discussionmentioning

confidence: 99%

Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana

Akakpo

Imbeah²,

Edusei³

et al. 2023

BMC Women's Health

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“…Transwell assay. The MDA-MB-231 and Hs578T cells (5x10 4 ) in 100 µl serum-free RPMI-DMEM were seeded into the upper chamber. The bottom chamber was filled with RPMI-DMEM with 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

“…Breast cancer is divided into the following four subtypes according to its molecular phenotypes: i) Luminal A; ii) Luminal B; iii) human epidermal growth factor receptor-2; and iv) triple-negative breast cancer (TNBC) ( 3 ). TNBC accounts for ~15% of all breast cancer cases ( 4 ) and is characterized by an obvious heterogeneity, an early age of onset, a high risk of visceral metastasis, high tumor invasiveness and a high histological grade ( 5 ). Due to the high tumor heterogeneity of TNBC and the lack of a clear therapeutic target, effective treatments are still lacking.…”

Section: Introductionmentioning

confidence: 99%

PD‑L1 mediates triple‑negative breast cancer evolution via the regulation of TAM/M2 polarization

Meng

Zhang

et al. 2022

Int J Oncol

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Tumor-associated macrophages/M2-type (TAM/M2) play a key role in the metastasis and angiogenesis of cancer, and are considered to be critical targets for cancer treatment. However, it remains unclear whether α-programmed death-ligand 1 (αPD-L1; PD-L1 inhibitor) inhibits tumor progression via targeting TAMs. In the present study, it was demonstrated that αPD-L1 significantly inhibited IL-13-induced TAM/M2 polarization in vitro. Moreover, αPD-L1 inhibited the epithelial-mesenchymal transition (EMT) process and the stemness of triple-negative breast cancer (TNBC) cells, which were mediated via the reversal of TAM/M2 polarization. This therefore inhibited the migration and angiogenesis of TNBC cells. Furthermore, αPD-L1 prevented STAT3 phosphorylation and nuclear translocation, which resulted in the arrest of TAM/M2 polarization. In vivo experiments further demonstrated that αPD-L1 reduced the number of lung metastases without affecting tumor growth. Moreover, αPD-L1 reduced the expression levels of TAM/M2, EMT, stemness and vascular markers in tumor tissues. In summary, these data suggest that αPD-L1 plays a vital role in the anti-metastasis and anti-angiogenesis of TNBC in vitro and in vivo via the inhibition of TAM/M2 polarization. These findings may thus provide a novel therapeutic strategy for clinically refractory TNBC.

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“…TNBC is however equally the most frequent molecular subtype in both age groups. Luminal A was also slightly more frequent in EOBC than in the older persons (11.30 With some literature quoting prevalence of TNBC to be up to 80% [19] but generally around 53.2% in the Ghanaian population it is likely that these rather high scores are partly a result of false negatives due to poor pre-analytics. [20] Our TNBC rates are lower than reported in the Ghanaian literature although still higher when compared to TNBC rates in other populations.…”

Section: Years[6]mentioning

confidence: 99%

“…It accounts for 9.2% (42 767) of cancer deaths in Africa [1]. In Ghana, 19.5% (1,147 cases) of all newly diagnosed cancer in 2020 were breast cancers. With a prevalence of 15.2% (1, 938 cases), it is the commonest cancer diagnosed and accounts for 13.6% (440 cases) of all cancer-related death, second only to liver cancer which accounted for 23.2% (752) of cancer deaths among this age group.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic characteristics of early-onset breast cancer: A comparative analysis of cases from across Ghana

Akakpo

Imbeah²,

Edusei³

et al. 2022

Preprint

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Background: Breast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among persons younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC). Methods: A descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Core/incision biopsy, mastectomy and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p<0.05Results: A total of 2,418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1,930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (<40 years) and 54.29 (IQR: 16.86) in the older, LOBC group (>/40 years). Invasive carcinoma - No Special Type (NST) was the commonest tumour type with grade III tumours being the highest recorded tumour grade in both age groups. Perineural invasion was statistically significant with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67>20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80 vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC. Conclusion: EOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger data set is needed to explain the lack of statistical significance of pathological features. Further molecular and genetic studies to understand the molecular genetic drivers of the general poorer outcome of EOBCs in our setting is recommended.

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Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry

Cited by 8 publications

References 39 publications

Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana

Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana

PD‑L1 mediates triple‑negative breast cancer evolution via the regulation of TAM/M2 polarization

Clinicopathologic characteristics of early-onset breast cancer: A comparative analysis of cases from across Ghana

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