*Article* **Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response**

**Viktor Hlaváˇc 1,2 , Radka Václavíková 1,2 , Veronika Brynychová 1,2 , Renata Koževnikovová 3 , Katerina Kopeˇcková 4 , David Vrána 5 , Jiˇrí Gat ˇek <sup>6</sup> and Pavel Souˇcek 1,2, \***


Received: 19 November 2020; Accepted: 11 December 2020; Published: 15 December 2020

**Abstract:** Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (*n* = 105). A total of 43 prioritized variants associating with response or survival in the above testing phase were then analyzed by allelic discrimination in the large validation set (*n* = 802). Variants in *ABCA4, ABCA9, ABCA12, ABCB5, ABCC5, ABCC8, ABCC11,* and *ABCD4* associated with response and variants in *ABCA7, ABCA13, ABCC4*, and *ABCG8* with survival of the patients. No association passed a false discovery rate test, however, the rs17822931 (Gly180Arg) in *ABCC11,* associating with response, and the synonymous rs17548783 in *ABCA13* (survival) have a strong support in the literature and are, thus, interesting for further research. Although replicated associations have not reached robust statistical significance, the role of ABC transporters in breast cancer should not be ruled out. Future research and careful validation of findings will be essential for assessment of genetic variation which was not in the focus of this study, e.g., non-coding sequences, copy numbers, and structural variations together with somatic mutations.

**Keywords:** ABC transporter; therapy response; disease-free survival; breast cancer; next-generation sequencing; competitive allele-specific PCR
