Tumour Heterogeneity of Breast Cancer: From Morphology to Personalised Medicine

Aleskandarany, Mohammed A.; Vandenberghe, Michel; Marchiò, Caterina; Ellis, Ian O.; Sapino, Anna; Rakha, Emad A.

doi:10.1159/000477851

Cited by 80 publications

(66 citation statements)

References 99 publications

(117 reference statements)

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“…To outline this heterogeneity may aid in the design of more nuanced and personalized treatment regimens. [26] Therefore, with the expression-based clusters as a structured framework to operate within, we aimed to assess both intra-and interpatient heterogeneity in our data.…”

Section: Exploring Intra-and Interpatient Heterogeneitymentioning

confidence: 99%

Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships

Andersson

Larsson

Stenbeck

et al. 2020

Preprint

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In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra-and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. We integrate and spatially map tumor-associated types from single cell data to find: segregated epithelial cells, interactions between B and T-cells and myeloid cells, co-localization of macrophage and T-cell subsets. A model is constructed to infer presence of tertiary lymphoid structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define novel interactions between tumor-infiltrating cells in breast cancer and provide tools generalizing across tissues and diseases.

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Section: Exploring Intra-and Interpatient Heterogeneitymentioning

confidence: 99%

Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships

Andersson

Larsson

Stenbeck

et al. 2020

Preprint

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“…Inclusion of multigene assay results will necessitate regular updating and reformatting of modified PS as evidence of their clinical validity emerges [44, 46]. Improved understanding of BC heterogeneity at morphological and molecular level with implications for the efficacy of targeted therapy [47] will also need to be considered. …”

Section: Discussionmentioning

confidence: 99%

The American Joint Commission Cancer 8th Edition Prognostic Stage Including Oncotype DX® Recurrence Score: Impact on Staging of Early Breast Cancer

et al. 2018

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Background: The American Joint Commission Cancer (AJCC) Cancer Staging Manual 8th edition introduced a breast cancer (BC) Prognostic Stage (PS) that combines tumour grade, oestrogen (ER), progesterone (PgR), and human epidermal growth factor-2 (HER2) receptor status with Anatomic TNM Stage (AS). In a further modification, patients with early BC and an Oncotype DX® Recurrence Score (RS) < 11 are assigned to PS 1A irrespective of grade and size up to 5 cm. This study profiles the impact of these changes on staging in patients with early BC and RS < 11. Methods: A total of 127 patients, with primary BC and RS < 11, were identified from a consecutive series of 729 patients with ER-positive, HER2-negative, lymph node-negative, primary BC whose tumours were tested using the Oncotype DX® 21 multigene assay. Each patient was assigned AS, PS, and RS-modified PS, and staging categories were compared. Results: Applying AS, 100 patients were stage IA and 27 IIA. Applying PS, 89 were stage IA, 33 IB, 4 IIA, and 1 IIB. All patients were IA according to RS-modified PS. Comparing PS to AS, 26.7% of patients (n = 34) changed stage, 9.4% (n = 12) to a higher and 17.3% (n = 22) to a lower stage. RS-modified PS versus AS resulted in downstaging in 21.3% (n = 27). Comparing PS modified by RS to PS alone, 29.9% (n = 38) were downstaged. Conclusion: Application of PS and RS-modified PS results in tumour downstaging in approximately 20% of patients with early BC. Upstaging was observed in 9% of patients when staged according to PS and was primarily due to the impact of high histological grade.

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“…Breast Cancer (BC) is the most common malignant tumour in women accounting for onequarter of all cancers in females worldwide. Breast Cancer is characterized by a remarkable degree of morphological and molecular heterogeneity, not only between tumours (inter tumoral heterogeneity) but also among the same tumours (intra tumoral heterogeneity) [1]. Intra tumour heterogeneity which denotes the co existence of subpopulations of cancer cells that differ in their genetic, phenotypic or behavioural characteristics can be attributed to genetic, epigenetic factors and to non hereditary mechanisms [2].…”

Section: Introductionmentioning

confidence: 99%

Institutional Spectrum of Rare Histological Types of Breast Carcinoma

P¹,

S²,

Chaitanya³

2019

SJPM

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Background: Invasive breast cancer is a heterogeneous disease in its presentation, pathological classification and clinical course. Most tumors are derived from mammary ductal epithelium, principally the terminal duct-lobular unit. However, there are more than a dozen histological variants which are less common but still very well defined by the World Health Organization (WHO) classification. The prime objective of the current study is to document our institutional experience of such rare histological entities with review of literature of the same. Methods: The clinicopathological records of resected breast lesions submitted to histopathology department over the period of three years from Jan 2016 to December 2018 were reviewed retrospectively. It was observational, retrospective and descriptive analysis of 4 unusual histological types of breast carcinoma. The most common lesions like infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma in malignant category and benign lesions were excluded from the study. Results: Among 528 breast malignancies reported in the institute, 48 unusual histological types were recognized, of which 4 are very rare histological types with less than 1% incidence. Conclusions: Here in we highlighted the rare varieties of cribriform, squamous, apocrine and signet ring cell carcinoma of breast with relevance to clinical, histopathological and immunohistochemical features. It is with significance to the fact that histological diversity of breast carcinoma has relevant prognostic implications.

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Tumour Heterogeneity of Breast Cancer: From Morphology to Personalised Medicine

Cited by 80 publications

References 99 publications

Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships

Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships

The American Joint Commission Cancer 8th Edition Prognostic Stage Including Oncotype DX® Recurrence Score: Impact on Staging of Early Breast Cancer

Institutional Spectrum of Rare Histological Types of Breast Carcinoma

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