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Background: Younger women are often diagnosed with advanced breast cancer. Beliefs about risk are instrumental in motivating many health protective behaviours, but there may be confusion around which behaviour is appropriate to detect breast cancer earlier. Breast awareness, defined as an understanding of how the breasts look and feel so changes can be identified early, is widely recommended. In contrast, breast self-examination involves palpation using a specified method. We aimed to investigate young women's beliefs about their risk and experiences of breast awareness. Methods: Thirty-seven women aged 30–39 years residing in a North West region of England with no family or personal history of breast cancer participated in seven focus groups (n = 29) and eight individual interviews. Data were analysed using reflexive thematic analysis. Results: Three themes were generated. "Future me's problem" describes why women perceive breast cancer as an older woman's disease. Uncertainty regarding checking behaviours highlights how confusion about self-checking behaviour advice has resulted in women infrequently performing breast checks. Campaigns as a missed opportunity highlights the potential negative effects of current breast cancer fundraising campaigns and the perceived absence of educational campaigning about breast cancer for this demographic. Conclusions: Young women expressed low perceived susceptibility to developing breast cancer in the near future. Women did not know what breast self-checking behaviours they should be performing and expressed a lack of confidence in how to perform a breast check appropriately due to limited knowledge about what to look and feel for. Consequently, women reported disengagement with breast awareness. Defining and clearly communicating the best strategy for breast awareness and establishing whether it is beneficial or not are essential next steps. [ABSTRACT FROM AUTHOR]

Introduction: Although oestrogen is essential for the development of the normal breast, adult mammary stem cells are known to be oestrogen receptor alpha (ER) negative and rely on paracrine signals in the mammary epithelium for mediation of developmental cues. However, little is known about how systemic oestrogen regulates breast cancer stem cell (CSC) activity. Methods: Here, we tested the effects of oestrogen on CSC activity in vitro and in vivo and investigated which paracrine signalling pathways locally mediate oestrogen effects. Results: CSC-enriched populations (ESA+CD44+CD24low) sorted from ER positive patient derived and established cell lines have low or absent ER expression. However, oestrogen stimulated CSC activity demonstrated by increased mammosphere and holoclone formation in vitro and tumour formation in vivo. This effect was abrogated by the anti-oestrogen tamoxifen or ER siRNA. These data suggest that the oestrogen response is mediated through paracrine signalling from non-CSCs to CSCs. We have, therefore, investigated both epidermal growth factor (EGF) and Notch receptor signals downstream of oestrogen. We demonstrate that gefitinib (epidermal growth factor receptor (EGFR) inhibitor) and gamma secretase inhibitors (Notch inhibitor) block oestrogen-induced CSC activity in vitro and in vivo but GSIs more efficiently reduce CSC frequency. Conclusions: These data establish that EGF and Notch receptor signalling pathways operate downstream of oestrogen in the regulation of ER negative CSCs. [ABSTRACT FROM AUTHOR]

Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival. [ABSTRACT FROM AUTHOR]