Grant: Travel Awards - Institute Community Support

Breast cancer is the most frequently diagnosed type of cancer among women in Canada with more than 21 000 new cases every year. Because of its high incidence and severity around the world, an extensive amount of research is being done to better understand and treat this disease. Despite all invested efforts, resistance to current therapies remains a big issue. Recently, the Basik lab found that levels of the SPEN protein in breast cancers could predict patients' response to therapy. In fact, patients with high SPEN protein levels tend to respond very well to Tamoxifen, the standard of care for breast cancer patients. Consistently, patients with low SPEN protein levels tend to have a poor response to treatment and a significantly lower survival. We thus hypothesized that SPEN favors patients' response to Tamoxifen and that its loss is associated with resistance to therapy. To address this hypothesis, we performed in vitro experiments with two breast cancer cell lines. As anticipated, cells with high SPEN protein levels were highly sensitive to Tamoxifen and died very quickly. Cells in which SPEN protein levels are very low, on the other hand, were much less sensitive to the drug and resisted to death, highlighting a potential role for SPEN in Tamoxifen resistance. To directly measure the effect of SPEN on response to treatment, SPEN was either removed from cells with high SPEN protein levels or re-introduced in cells with low SPEN protein levels. Unpublished data show that loss of SPEN correlates with decreased sensitivity to treatment and re-introduction of SPEN is associated with increased sensitivity to Tamoxifen. Hence, because SPEN protein levels follow sensitivity of breast cancer cells to Tamoxifen, our results strongly suggest that loss of SPEN contributes to resistance of breast cancers to that drug. Together, our in vitro and clinical data highlight a role for SPEN in drug resistance and in predicting breast cancer patients' response to Tamoxifen.