Gene expression improves definition of hormone-sensitive breast cancer subtype

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The definition of hormone-sensitive breast tumors known as luminals has been changed by a recent study. The study compared gene expression data on tumors with histopathological data, and has proposed a new definition that improves the current classification of these tumors in routine clinical practice.

In any breast cancer case, establishing the molecular subtype is important. Gene expression has identified two major groups of hormone-sensitive tumors in recent year, luminal A and luminal B. Treatment is based on this classification, and therefore it needs to be extremely precise.

“Luminal A tumors have a good prognosis with hormone treatment, while luminal B tumors have a less optimistic prognosis and in most cases require chemotherapy. The problem lies in the fact that the current method for defining these groups by histopathological data is not perfect, and we therefore need an additional parameter to help us yet further fine-tune the histopathological diagnosis of luminal A and B tumors," explained Aleix Prat, MD, of Vall d'Hebron Institute of Oncology in Barcelona, Spain, and leader of the study.

Currently, luminal, or hormone-sensitive, tumors are identified as testing positive to hormone receptors and negative to HER2 expression. Luminal A and B tumors are differentiated by the amount of Ki-67 protein detected by the pathologist in the tumor cells. Tumors in which less than 14% of cells are positive for Ki-67 are defined as luminal A. The problem with this definition is that 30% of these tumors are actually luminal B by gene expression, which have an unfavorable prognosis with hormone treatment alone.

This study checked thousands of tumors from three independent groups from Spain, Canada, and the United States to compare whether histopathological data matched the profiles of gene expression, and detected some major discrepancies. The research team then sought a new parameter that could be measured in the laboratory to fine-tune the definition.

“The genomic study we conducted has shown that the amount of progesterone receptor is important in distinguishing the two biological entities. We can use this new variable as a marker to improve the current histopathological definition of luminal A tumors,” explained Prat. The higher the number of progesterone-receptor positive tumor cells, the more likely the tumor will be defined as a luminal A tumour.

The new histopathological definition of luminal A tumors proposed by this study is “hormone receptor positive, negative HER2 expression, Ki-67-positive lower than 14% and progesterone-receptor positive higher than 20%,” specified Prat.

These findings were published in the Journal of Clinical Oncology (2013; doi:10.1200/JCO.2012.43.4134).

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