Breast cancer (BC) is the most common cancer in women worldwide. In 2012, breast cancer was reported to cause the death of more than 522,000 women by the International Agency for Research on Cancer. Siegel et al. found that BC accounts for 29% of all new cancers in women in 2015 [1] . Estrogens stimulate the proliferation and the differentiation of breast epithelial cells through the activation of downstream mitogenic signaling pathways, namely via the estrogen receptors ERα and ERβ. These receptors function as ligand-dependent transcription factors [2] - [4] , acting either through the transcriptional regulation of genes (genomic pathway) or through membrane and cytoplasmic signaling cascades (non-genomic pathway). Current BC treatment options exclusively target the genomic signaling pathway. Even though ERα is expressed at low levels in normal mammary cells [5] , 70% of BC express high levels of ERα and are either treated by agents that suppress the function of the receptor (anti-estrogen) or the estrogen synthesis (aromatase inhibitors) [6] .

Despite the fact that ERα is a standard predictive marker used to prescribe endocrine therapy, about 40% of these patients initially display or eventually become resistant to treatment [7] [8] . This represents a burden on public healthcare and a serious issue to be considered when designing the treatment plan of the patients, highlighting an urgent need to identify new predictive markers of therapeutic response, to ensure a better survival rate for the patients. Therefore, the identification of new actors of estrogen signaling pathways should improve treatment specificity and thus overcome cancer drug resistance. For instance, it has been extensively shown that the PI3K/Akt/mTOR pathway is frequently activated in BC, leading to the use of the mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, in clinical trials [9] [10] . Although the latter has become a standard treatment in hormone-resistant BC, its use is accompanied with many side effects (stomatitis, rash, diarrhea, arthralgia/myalgia and anemia) and only 50% of patients respond to the treatment. LKB1 is a known regulator of both mTOR [11] [12] and estrogen signaling pathways [13] [14] , and given its role in BC tumorigenesis [15] , it may emerge as an attractive novel cancer biomarker.

Breast cancers can be classified into several subtypes based on their epidemiological risk factors, molecular markers and response to systemic and local therapies. Norum et al. presented an overview of the intrinsic molecular subtypes of breast cancer, as well as their prognostic and therapeutic implications [16] summarized in the Table 1. The most common breast cancer subtype is the luminal A, with the best prognosis, a low grade and an increased survival rate compared to other subtypes. Luminal A tumors are characterized by an estrogen receptor-positive (ERα+), a progesterone receptor-positive (PR+) and a human epidermal growth factor receptor 2-negative (HER2−) profile. The luminal B cancer subtype shares some similarities with the luminal A subtype. It is also ERα- and/or PR-positive, HER2-negative and has a high level of Ki67 expression, reflecting a high number of proliferating cancer cells. Endocrine therapy is usually the recommended treatment for these subtypes. It entails either targeting the estrogen signaling pathway, using ERα-blocking drugs in premonopausal women, primarily the selective estrogen receptor modulator tamoxifen, or inhibiting estrogen synthesis, using aromatase inhibitors in postmenopausal women, such as exemestane and anastrozole,