Colleagues said Professor Lester was a 'great leader, colleague and friend' who would be sorely missed.
The Society for Academic Primary Care (SAPC), which Professor Lester had chaired, has set up a book of condolence for GPs and colleagues to pay their respects.
In a statement, the SAPC said Professor Lester had been 'committed' to improving primary care. 'Helen continued to lead both academic primary care and SAPC despite her illness. Her passion and energy were an inspiration to all who worked with her. She will be sorely missed.
'We are shattered by the news. Yet it is also a great tribute to Helen that even as she leaves us we feel both inspired and determined to continue her work.'
Professor Lester qualified as a GP at the University of Wales College of Medicine in 1985 and entered general practice in Birmingham in 1990, where she led a homelessness service and undergraduate medical student teaching.
She embarked on a respected academic primary care career at the universities of Birmingham and Manchester, and became an academic lead on the QOF in 2005, playing a leading part in the development of new indicators. Professor Lester continued to contribute heavily to the development of QOF working with NICE's primary care QOF indicator advisory committee.
Professor Lester was secretary to the SAPC from 2004-10, and chair from 2010-13. She was also an elected member of the RCGP council, and in 2005 she was awarded the prestigious John Fry medal from the college for her services to research.
In November 2012, she gave the James Mackenzie Lecture at the RCGP annual general meeting, where she made an impassioned plea for GPs to improve care for patients with mental illnesses.
Professor Amanda Howe, RCGP honorary secretary, said: 'This is a devastating loss for the college and for primary care. Helen was the most amazing person - an inspirational and energising leader.
'She was absolutely committed to change for the better - whether for patients, practice, vulnerable communities such as those with mental ill health and the homeless, the academic primary care community, or for the RCGP. She was a brilliant, inspirational woman who will be sorely missed by all those who knew her and worked with her.
'Our thoughts and thanks go to her family, without whose support Helen would not have given so much to the rest of us.'
Dr Gillian Leng, deputy chief executive and health and social care director for NICE said: 'Helen was a great support to NICE in establishing our work on indicator development for the QOF. Her wide-ranging knowledge of the issues surrounding data collection in primary care were invaluable, and her passionate support for improving the quality of services in primary care will be greatly missed.'