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Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor

Author

Listed:
  • Valentina Scabia

    (Ecole Polytechnique Fédérale de Lausanne)

  • Ayyakkannu Ayyanan

    (Ecole Polytechnique Fédérale de Lausanne)

  • Fabio Martino

    (Ecole Polytechnique Fédérale de Lausanne)

  • Andrea Agnoletto

    (Ecole Polytechnique Fédérale de Lausanne)

  • Laura Battista

    (Ecole Polytechnique Fédérale de Lausanne)

  • Csaba Laszlo

    (Ecole Polytechnique Fédérale de Lausanne
    Philip Morris Products S.A.)

  • Assia Treboux

    (Breast center, Lausanne University Hospital (CHUV))

  • Khalil Zaman

    (Breast center, Lausanne University Hospital (CHUV))

  • Athina Stravodimou

    (Breast center, Lausanne University Hospital (CHUV))

  • Didier Jallut

    (Réseau Lausannois du Sein)

  • Maryse Fiche

    (International Cancer Prevention Institute)

  • Philip Bucher

    (Ecole Polytechnique Fédérale de Lausanne)

  • Giovanna Ambrosini

    (Ecole Polytechnique Fédérale de Lausanne
    Bioinformatics Competence Center (BICC))

  • George Sflomos

    (Ecole Polytechnique Fédérale de Lausanne)

  • Cathrin Brisken

    (Ecole Polytechnique Fédérale de Lausanne
    Institute of Cancer Research)

Abstract

Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-β-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option.

Suggested Citation

  • Valentina Scabia & Ayyakkannu Ayyanan & Fabio Martino & Andrea Agnoletto & Laura Battista & Csaba Laszlo & Assia Treboux & Khalil Zaman & Athina Stravodimou & Didier Jallut & Maryse Fiche & Philip Buc, 2022. "Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30898-0
    DOI: 10.1038/s41467-022-30898-0
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    References listed on IDEAS

    as
    1. Hisham Mohammed & I. Alasdair Russell & Rory Stark & Oscar M. Rueda & Theresa E. Hickey & Gerard A. Tarulli & Aurelien A. Serandour & Stephen N. Birrell & Alejandra Bruna & Amel Saadi & Suraj Menon & , 2015. "Progesterone receptor modulates ERα action in breast cancer," Nature, Nature, vol. 523(7560), pages 313-317, July.
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