MRC Institute of Genetics & Molecular Medicine
MRC Institute of Genetics & Molecular Medicine

Distinguishing acquired resistance from dormant tumours in neoadjuvant treatment of breast cancer

A study led by researchers from the Cancer Research UK Edinburgh Centre sheds new light on differences between dormant and treatment resistant tumours: January 2019

Breast cancer diagram

Neoadjuvant therapy refers to medicines that are administered before surgery for the treatment of breast cancer. The aim of such treatment is to reduce the size of breast tumour, for example if it is too big to be removed in an operation. If successful, this approach kills many cancer cells and results in a shrunken tumour and less invasive surgery, however some cancer cells often attain a state of dormancy – suspended or slowed down activity. Unfortunately, with time, some dormant tumour cells acquire resistance to therapy and resume aggressive growth. Therefore it is important to understand the mechanisms involved in breast cancer dormancy and acquired resistance.

Recent work published in the journal “Breast Cancer Research” led by Doctor Andy Sims and Professor Mike Dixon at the Cancer Research UK Edinburgh Centre describes molecular changes during extended neoadjuvant treatment of breast cancer with the drug letrozole to distinguish acquired resistance from dormant tumours. Growth of around 70% of breast cancers is stimulated by the hormone oestrogen and letrozole (a drug known as aromatase inhibitor) lowers the levels of oestrogen in the body stopping or slowing tumour growth.

The work represents the first patient-matched gene expression study investigating long-term aromatase inhibitor-induced dormancy and acquired resistance in breast cancer. It suggests that molecular differences between dormant and resistant tumours are initially subtle, becoming more obvious only after extended treatment. It also highlights that alternations in DNA methylation in the first months of treatment may predict which patients will eventually develop acquired resistance.

The research was funded by a European Research Council Marie Curie Fellowship to Cigdem Selli (lead author), Breast Cancer Now and Wellcome Trust (Institutional Strategic Support Fund).

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