Three studies, BIG 1-97/MA.17, BIG 2-97/IES and BIG 1-98, together recruiting a total of 17,958 patients, contributed to the body of evidence that aromatase inhibitors could be used as a safe alternative to tamoxifen, a drug used to treat oestrogen receptor (ER) positive breast cancer that is associated with dangerous side effects for some women.

Not only did these trials prove the effectiveness of the new drugs, but they also answered important additional questions about whether the drugs should be given in combination or in sequence with others, the likelihood of side effects with long-term use, and patients’ overall quality of life.

These trials gave women with ER-positive early breast cancer more treatment options than tamoxifen alone, and hence contribute to improving the quality of life for countless women around the globe, an important step forward towards personalised treatments for women with ER-positive disease.

These trials were all run under the BIG umbrella with BIG 1-97/MA.17 being coordinated by the National Cancer Institute of Canada Clinical Trials Group, BIG 2-97 IES by the International Collaborative Cancer Group, and BIG 1-98 by the International Breast Cancer Study Group.

Main Publications

• A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer - Goss PE, et al., New England Journal of Medicine, 9 October 2003
• Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer - BIG 1-98 Collaborative Group, Mouridsen H, et al., New England Journal of Medicine, 20 August 2009
• Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrineresponsive early breast cancer: update of study BIG 1-98 - Coates AS, et al., Journal of Clinical Oncology, 10 February 2007
• A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer - Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B et al., New England Journal of Medicine, 29 December 2005
• Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial - Coombes RC et al., The Lancet Oncology, 17 February 2007
• Disease-related outcomes with long-term follow-up: an updated analysis of the intergroup exemestane study - Bliss J et al., Journal of Clinical Oncology, 1 March 2012