Treating breast cancer as effectively as possible: which drugs, when?

By Jane Lewis
Two meta-analyses, both by the Early Breast Cancer Trialists’ Collaborative Group and published in The Lancet, have examined the use of aromatase inhibitors (AIs) and bisphosphonates to treat postmenopausal women with breast cancer, finding that both therapies can significantly improve survival.

Commenting on the studies, Professor John Boyages, Director of Breast Oncology at Macquarie University Faculty of Medicine and Health Sciences and author of Breast Cancer: Taking Control, said while each treatment had its merits, ‘the reality is that there is no single solution,’ and several factors need to be considered for each patient, such as family history, pathology and the features of the cancer itself.

The AI meta-analysis – involving 31,920 postmenopausal women with oestrogen-receptor-positive early breast cancer – found that, compared with five years of tamoxifen alone, AI-based therapy reduced the 10-year breast cancer mortality rate from 14.2% to 12.1%. In the first five years, there was no difference in survival, and less than 1% difference in recurrence rates, in women treated with up-front AI therapy, compared with those treated with tamoxifen followed by an AI, a finding Professor Boyages described as ‘reassuring.’

‘These results show that for selected patients undergoing hormonal treatment alone or after chemotherapy, there is a small advantage in including aromatase inhibitors in the treatment equation,’ he said. However, he cautioned that AIs were not suitable for women who had not yet reached menopause, and can be ‘potentially problematic’ in women in their late 40s or early 50s who have just finished chemotherapy.

An invited comment published with the study pointed out that women on antioestrogen treatments often endure substantial side effects, and suggested that ultimately the best choice for adjuvant endocrine therapy ‘is a treatment the patient is willing to take.’

The second meta-analysis, which included data from 18,766 women included in randomised adjuvant bisphosphonate trials over the past 20 years, reported that bisphosphonates improved survival and reduced recurrence rates, but there was ‘definite benefit only in women who were postmenopausal when treatment began.’ In this patient group, the addition of bisphosphonates resulted in highly significant reductions at 10 years, both for bone recurrence (6.6% with bisphosphonates, vs 8.8% without) and breast cancer mortality (14.7% vs 18.0%). The number of bone fractures was also reduced, while there was no change in the risk of contralateral breast cancer, or metastasis at other locations.

‘When you look at the details of this study, it becomes clear that the benefits are mainly in patients with node-positive disease, and those with grade 2 or 3 breast cancer,’ said Professor Boyages. It was also important to note that two years’ treatment with bisphosphonate ‘was just as useful as longer treatments,’ he added.

An invited commentary on this study described it as a ‘landmark report’ and said it ‘should lead to widespread adoption of bisphosphonates as a standard of care for the adjuvant therapy of early-stage breast cancer in postmenopausal women.’

Lancet 2015; http://dx.doi.org/10.1016/S0140-6736(15)60908-4.
Lancet 2015; http://dx.doi.org/10.1016/S0140-6736(15)61163-1.
Lancet 2015; http://dx.doi.org/10.1016/S0140-6736(15)61074-1.
Lancet 2015; http://dx.doi.org/10.1016/S0140-6736(15)61206-5.

Picture credit: © SPL. Breast cancer cell in culture (SEM).