Resistance to therapy in estrogen receptor positive and human epidermal growth factor 2 positive breast cancers: progress with latest therapeutic strategies.
LOUSBERG, Laurence; COLLIGNON, Joëlle; Jerusalem, Guy
2016 • In Therapeutic Advances in Medical Oncology, 8 (6), p. 429-449
breast cancer; endocrine therapy; human epidermal growth factor 2; resistance; therapy; trastuzumab
Abstract :
[en] In this article, we focus on the subtype of estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-positive breast cancer (BC). Preclinical and clinical data indicate a complex molecular bidirectional crosstalk between the ER and HER2 pathways. This crosstalk probably constitutes one of the key mechanisms of drug resistance in this subclass of BC. Delaying or even reversing drug resistance seems possible by targeting pathways implicated in this crosstalk. High-risk patients currently receive anti-HER2 therapy, chemotherapy and endocrine therapy in the adjuvant setting. In metastatic cases, most patients receive a combination of anti-HER2 therapy and chemotherapy. Only selected patients presenting more indolent disease are candidates for combinations of anti-HER2 therapy and endocrine therapy. However, relative improvements in progression-free survival by chemotherapy-based regimens are usually lower in ER-positive patients than the ER-negative and HER2-positive subgroup. Consequently, new approaches aiming to overcome endocrine therapy resistance by adding targeted therapies to endocrine therapy based regimens are currently explored. In addition, dual blockade of HER2 or the combination of trastuzumab and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOP) inhibitors targeting the downstream pathway are strategies to overcome resistance to trastuzumab. This may lead in the near future to the less frequent use of chemotherapy-based treatment options in ER-positive, HER2-positive BC.
Disciplines :
Oncology
Author, co-author :
LOUSBERG, Laurence ; Centre Hospitalier Universitaire de Liège - CHU > Service d'oncologie médicale
COLLIGNON, Joëlle ; Centre Hospitalier Universitaire de Liège - CHU > Service d'oncologie médicale
Jerusalem, Guy ; Université de Liège > Département des sciences cliniques > Oncologie
Language :
English
Title :
Resistance to therapy in estrogen receptor positive and human epidermal growth factor 2 positive breast cancers: progress with latest therapeutic strategies.
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