Daily anastrozole therapy given to postmenopausal women who are at high risk of breast cancer, with the intention of preventing breast cancer occurrence, does not cause impairment of cognitive performance after 24 months of treatment, concludes a substudy of the International Breast Intervention Study (IBIS II), published early Online, and in the October edition of The Lancet Oncology.
Adjuvant trials have demonstrated that anastrozole is superior to tamoxifen in preventing breast cancer recurrence, and contralateral breast cancer in postmenopausal women. However, cross-sectional studies have suggested that women receiving endocrine therapies show significantly poorer performance on verbal memory and processing tasks compared with an age-matched control group. Since breast-cancer prevention needs to be achieved with minimal iatrogenic harm, further assessment of potential cognitive effects in a randomised setting is needed.
The IBIS II trial was specifically designed to investigate the clinical benefit of anastrozole, given daily for 5 years, as a primary chemopreventive treatment, compared with placebo. In a double-blind substudy, Dr Valerie Jenkins (Cancer Research UK Psychosocial Oncology Group, Brighton and Sussex Medical School, University of Sussex, Brighton, UK) assessed 227 women for psychological morbidity, endocrine symptoms and self-reported cognitive complaints. Standardised cognitive assessments and interviews were conducted by experienced psychologists and included auditory verbal tasks, logical memory tasks, spatial span tests, and assessment of verbal fluency. The first assessment was made at baseline and subsequently at 6 and 24 months after the start of treatment.
No significant differences between the anastrozole group and the placebo group were noted in changes in attention or memory, or in the proportions of women experiencing psychological distress. Few women in either group showed a reliable decline in three or more cognitive tasks at 6 months or 24 months. The only difference observed between the groups at the 24-month time point was in endocrine symptoms: significantly more women in the anastrozole group reported hot flushes.
This substudy of the IBIS II trial provides no clear evidence that anastrozole produced cognitive impairments over a 24-month period, but the authors point out that the longer-term effects of anastrozole alone, or following chemotherapy, is unknown. It is also unclear how endocrine side effects, such as hot flushes, affect the frequency of patient-initiated 'drug holidays'. However, Dr Jenkins says, "These findings should be reassuring in the short term for postmenopausal women being treated with anastrozole, their clinicians and carers."
Dr Valerie Jenkins, Cancer Research UK Psychosocial Oncology Group, Brighton & Sussex Medical School, University of Sussex, Brighton, UK T) +44 (0)1273 873016/9
email: val@sussex.ac.uk
Notes for editors
- The International Breast Intervention Study (IBIS II) is a large randomised double-blind placebo-controlled trial of anastrozole in postmenopausal women at high risk of developing breast cancer.
- One of the strengths of the substudy reported is that its double-blind design provides a better assessment of putative cognitive impairment than cross-sectional or observational studies.
- One of the weaknesses is the relatively small study sample, but this sample is much larger than those in other published neuropsychological studies involving women with breast cancer.
- Cognitive research in this field is limited by methodological challenges and the lack of standardisation in neuropsychological studies: an international task force has been proposed to provide guidelines for future research to address these issues.
Full paper: http://press.thelancet.com/TLOjenkinsfinal.pdf
Journal
The Lancet Oncology