Bioinformatics methods for analyzing anti-hormonal treatment resistance in breast cancer

One in eight women are affected by breast cancer. Most of them receive hormonal therapy. Neoadjuvant hormonal therapy is a form of hormonal therapy given before surgery. Treatment for 6 months causes tumours to shrink, after which residual tumour is removed by surgery. Unfortunately, in some cases, the tumour cells are resistant to hormonal therapy and the patients relapse. This can be caused by intra-tumour heterogeneity: hormonal therapy eliminates drug-sensitive clones, leaving behind resistant clones. Understanding why some clones are resistant and what their characteristics are may lead to the development of alternative therapies. We compare DNA copy number profiles before and after treatment in the case of ER+ breast cancers. Very low depth sequencing was performed (Illumina GAIIx technology) on biopsies from breast tumours, before and after treatment. Reads were aligned to the human genome hg19 (bwa). CNAnorm was used to partition reference genome in intervals G = (i 1 , ...,i n) of non-overlapping sliding windows. Number of reads was converted to a count vector C = (c 1 , ...,c n) and then to a ratio vector with respect to a pool of normal female DNA.