Proposed hypothesis and rationale for association between mastitis and breast cancer

Breast cancer is amongst the most common forms of cancer, is predominantly a woman’s illness, and is the most frequently reported invasive cancer in women worldwide (Bray et al., 2018). Varying risk factors have been identified, including genetics, family history, lifestyle, age and the use of hormone replacement therapy. Mastitis, also predominantly a woman’s illness, is an inflammatory condition of the breast that, despite being an inflammation-related condition, is not currently considered a risk factor for breast cancer. This appears counterintuitive as epidemiological studies have identified chronic inflammation as a contributor to cancer risk, for example in gastric, oesophageal and colon cancers (Lin et al., 2016; Qadri et al., 2014; Principe et al., 2017). Previous reports have focused on women hospitalised for mastitis, and most commonly on puerperal mastitis, perhaps underestimating the relationship between breast cancer and non-lactational mastitis. Our hypothesis, based on systematic review, suggests that a longitudinal study of this disease, affecting women predominantly, is warrante

Expression of annexin A2 promotes cancer progression in estrogen receptor negative breast cancers

When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype