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Breast Cancer: a chronic disturbance of the circadien rythme increases the dissemination of cancer cells

24 June 2020

Breast cancer is the most wide-spread cancer in the world and one of the main causes of death in women. A study implicating scientists from the Paris-Saclay University, INSERM and INRAE just established a link between night shift working and an increased risk of cancer, suggesting that disruption of circadian rythms could make tumors more agressive. This study was published in the journal Nature Communications on Wednesday, June 24, 2020.

Breast cancer is the most frequent cancer in women. The cumulated risk that a woman develops breast cancer is approximately 5% in the world, with a risk of death of 1,4%. In 2018, more than 2 million new cases were diagnosed, representing about 25% of cancer cases in the world.

Different epidemiological studies carried forth recently have improved our understanding of the factors that increase the risk of developing breast cancer. We know that less than 10% of these cases are hereditary and have a genetic origin. In most cases, the different risk factors identified are behavioural factors associated with for example poor nutrition or consumption of alcohol; hormonal factors associated with taking a contraceptive pill at a young age or for a long time or hormonal treatments taken during menopause; and finally environmental factors such as air polution or altered light/dark cycles like those encountered by nightshift workers.

It is this effect of chronic light/dark alteration on the development of breast tumors that scientists from the ONCOSTEM (U 935 Inserm/UPSaclay) and the GABI (INRAE/AgroParisTech/UPSaclay, Jouy-en-Josas) laboratories studied.

Scientists used a mouse model that spontaneously develops mammary gland tumors. The animals underwent chronic light/dark differences that experimentally reproduced a rythm of nightshift workers (an alternating day shift and night shift or jet-lag conditions). The scientists then oberved that the circadian disruption[1] had a significant impact on the development of mammary gland tumors. This disruption of the circadian rythm increased the dissemination of cancer cells and the formation of metastases in these animal models.

This study also reveals that chronic disruptions in the circadian rythm makes the immune system more permissive to the dissemination of cancer cells by modifying the tumor's micro-environment. Thus, an increase in the Cxcl5 chemokine in the tumors leads to an increased infiltration of myeloid CXCR2 + cells that favor an immunosuppressing environment. These negative effects may be corrected using a CXCR2/CXCL5 pathway inhibitor, therefore limiting the effects of circadian stress on tumor progression.

These experimental results confirm epidemiological studies showing that premenopaused women exposed through their work to disruption of light/dark cycles over long periods of time are particularly exposed to more agressive breast cancers.

These studies were financed in part by the following associations and fondations: Vaincre le Cancer, ICIG (Institut de Cancérologie et d’Immunogénétique), Fondation de l'Avenir, GEFLUC-IdF Les Entreprises contre le cancer. 


[1]The circadian ryhtm is defined by an alternation of a waking period, which one is awake and sleep, which lasts approximately 24 hours.

See also


Eva Hadadi, William Taylor, Xiaomei Li, Yetki Aslan, Marthe Villote, Julie Rivière, Gaelle Duvallet, Charlotte Auriau, Sandrine Dulong, Isabelle Raymond Letron, Sylvain Provot, Annelise Bennaceur-Griscelliand Hervé Acloque : Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice, Nature Communication 11, 3193 (2020) . DOI : 10.1038/s41467-020-16890-6