Kathryn Williams

Focal Adhesion Kinase and Wnt Signaling Regulate human ductal carcinoma in situ stem cell activity and response to radiotherapy

Cancer stem cells (CSCs) can avoid or efficiently repair DNA damage from radio and chemotherapy, which suggests they play a role in disease recurrence. Twenty percentage of patients treated with surgery and radiotherapy for ductal carcinoma in situ (DCIS) of the breast recur and our previous data show that high grade DCIS have increased numbers of CSCs. Here, we investigate the role of focal adhesion kinase (FAK) and Wnt pathways in DCIS stem cells and their capacity to survive irradiation. Using DCIS cell lines and patient samples, we demonstrate that CSC‐enriched populations are relatively radioresistant and possess high FAK activity. Immunohistochemical studies of active FAK in DCIS tissue show high expression was associated with a shorter median time to recurrence. Treatment with a FAK inhibitor or FAK siRNA in nonadherent and three‐dimensional matrigel culture reduced mammosphere formation, and potentiated the effect of 2 Gy irradiation. Moreover, inhibition of FAK in vitro and in vivo decreased self‐renewal capacity, levels of Wnt3a and B‐Catenin revealing a novel FAK‐Wnt axis regulating DCIS stem cell activity. Overall, these data establish that the FAK‐Wnt axis is a promising target to eradicate self‐renewal capacity and progression of human breast cancers. Stem Cells 2015;33:327–341

The TeaM (Therapeutic Mammaplasty) study: Protocol for a prospective multi-centre cohort study to evaluate the practice and outcomes of therapeutic mammaplasty

Highlights • Multicentre prospective study involving breast and plastic surgical units across the UK.• Will produce valuable data regarding the practice and outcomes of therapeutic mammaplasty.• Will inform decision-making and lead to future definitive study.• Will strengthen the collaborative network to facilitate the delivery of future projects.• Will increase awareness of the techniques among trainees such that participation is educational.

Acute painful breast in a non-lactating woman

#### What you need to know A 50 year old woman describes a three day history of a painful right breast. Non-lactating women may present with a painful red breast because of periductal inflammation, which can evolve into a breast abscess. This condition must be differentiated from inflammatory breast cancer, a rare type of breast cancer that mimics the signs and symptoms of mastitis (table 1⇓). View this table: Table 1 Differentiation of inflammatory breast cancer from mastitis or breast abscess Smoking is the main predisposing factor for periductal mastitis due to ductal damage (relative risk from 6.2 to 26.4 for heavy smokers).1 2 3 There is usually an infective element; commonly Staphylococcus aureus , enterococci, or Bacteroides . Poor hygiene and lower socioeconomic status are associated with breast abscess.4 ### History Pain of mastitis typically starts over hours to days—typical symptoms are …