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Exploring breast cancer histologic types

Researchers have extended The Cancer Genome Atlas Breast Cancer dataset to define transcriptomic and genomic profiles of six rare, special histological types.

Breast cancer is a heterogeneous disease that is comprised of multiple entities. Breast cancers can be classified into biologically and clinically meaningful subgroups according to histological grade and type. Histological grade represents the aggression of the cancer and is determined by the degree of a tumour’s differentiation and proliferative activity. Histological type refers to the growth pattern of a tumour.

Expanding on breast cancer histologic types

Breast cancer is known to have at least 21 different histologic types, classified using a combination of architectural and cytological features. But many of the rarer types have limited characterisation. Recently, researchers at the UNC Lineberger Comprehensive Cancer Center extended The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset to define transcriptomic and genomic profiles of six rare, special histological types (cribriform, micropapillary, mucinous, papillary, metaplastic, and invasive carcinoma with medullary pattern).

The team added histologic type annotations in a total of 1,063 breast cancers. They then showed the broader applicability of their constructed special histologic type gene signatures in the TCGA Pan-Cancer Atlas dataset. This was done using a predictive model that detected mucinous histologic type across cancers of other organ systems. Additionally, the group used a normal mammary cell differentiation score analysis to order the histologic types into a continuum, from stem cell-like, to luminal progenitor-like, to mature luminal-like. They were then able to classify TCGA-BRCA into 12 consensus groups based on integrated genomic and histological features. 

Enabling the study of a range of breast cancers

This study presents a rich, openly accessible resource of genomic, molecular, and histologic characterisation of TCGA-BRCA. In the future, it will enable studies across the range of rare breast cancers and aid the faster translation of molecular findings into clinical use.

Charles Perou, corresponding author of the research, said:

“We’ve known for a long time that breast cancer is not one disease, and now through years of molecular research, added to decades of pathology knowledge, we have begun to integrate the two into one language. This should greatly aid future research efforts and enable faster translation of molecular findings into the pathology lab for clinical use.”

Next, the researchers are interested in investigating why some of the 12 biological groups show evidence of immune cells capable of infiltrating tumour cells, when others do not. This would have exciting therapeutic implications, particularly for breast cancer immunotherapies.

Aatish Thennavan, first author of the paper, explained:

“Our effort finishes all planned analyses on TCGA, which has been a major undertaking. In our study, we validated our findings with other datasets that also had rarer subtypes. We would urge future studies to incorporate rarer subtypes so we can build on this foundational analysis.”

Image credit: Medical News Today