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However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log (OR)) of responding to each drug given knowledge of (intrinsic\/prior) response to all other agents. This OR matrix assumes (1) response is based on intrinsic rather than acquired characteristics, and (2) intrinsic sensitivity remains unchanged at the time of the next decision point. Fisher\u2019s exact test is used to identify predictive pairs and groups of agents (BH\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Recommendation systems are used to make further drug recommendations based on past \u2018history\u2019 of response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 90 compounds, 57 have sensitivity profiles significantly associated with those of at least one other agent, mostly targeted drugs. Nearly all associations are positive, with (intrinsic\/prior) sensitivity to one agent predicting sensitivity to others in the same or a related class (OR\u2009&gt;\u20091). In vitro\n                      <jats:italic>conditional<\/jats:italic>\n                      response patterns clustered compounds into five predictive classes: (1) DNA damaging agents, (2) Aurora A kinase and cell cycle checkpoint inhibitors; (3) microtubule poisons; (4) HER2\/EGFR inhibitors; and (5) PIK3C catalytic subunit inhibitors. The apriori algorithm implementation made further predictions including a directional association between resistance to HER2 inhibition and sensitivity to proteasome inhibitors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Investigating drug sensitivity conditioned on observed sensitivity or resistance to prior drugs may be pivotal in informing clinicians deciding on the next line of breast cancer treatments for patients who have progressed on their current treatment. This study supports a strategy of treating patients with different agents in the same class where an associated sensitivity was observed, likely after one or more intervening treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-021-07912-7","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T15:02:58Z","timestamp":1614610978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Toward developing a metastatic breast cancer treatment strategy that incorporates history of response to previous treatments"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-8306","authenticated-orcid":false,"given":"Aleksandra K.","family":"Olow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura van \u2019t","family":"Veer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"7912_CR1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.5306\/wjco.v5.i2.125","volume":"5","author":"BS Yadav","year":"2014","unstructured":"Yadav BS, Sharma SC, Chanana P, Jhamb S. 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Merck, Sharpe and Dohme Corp. has not been involved in funding of the presented research, nor play any role in the study design, collection, analysis, and interpretation of data, nor in writing of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"212"}}