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While she was initially considered to play the lead role of Cady Heron, played by Lindsay Lohan, the producers of the film decided that Seyfried should play Karen Smith, Regina's dim-witted "Plastic" friend and sidekick.Seyfried's performance in the film earned her, along with Lohan, Lacey Chabert, and Mc Adams, an MTV Movie Award in the category of "Best On-Screen Team".She starred in the dramas Fathers and Daughters (2016) and First Reformed (2017), the crime comedy Gringo (2018), and the comedy-drama The Art of Racing in the Rain (2019).
She also played the lead role of Sylvia Weis in Andrew Niccol's In Time, which reunited her with her Alpha Dog co-star, Justin Timberlake, released in October 2011 to mixed reviews but grossed more than US2 million worldwide.
(2008) and reprised her role in the sequel, Mamma Mia! Seyfried had lead roles in the black comedy horror Jennifer's Body (2009), the erotic thriller Chloe (2009), the romantic war drama Dear John (2010), and the romantic drama Letters to Juliet (2010).
She starred in the dark fantasy historical romance Red Riding Hood (2011), the dystopian science fiction thriller In Time (2011), the thriller Gone (2012), the musical drama Les Misérables (2012), the biographical drama Lovelace (2013), and in the Seth Mac Farlane comedies A Million Ways to Die in the West (2014) and Ted 2 (2015).
In 2005, Seyfried played the lead character, Samantha, a role written by director Rodrigo García specifically for her, in one of the nine parts of the film Nine Lives, composed of nine short films with different themes and an ensemble cast.
For her performance, Seyfried, along with the film's other female leads, won an award from the Locarno International Film Festival, for Best Actress.