Continuing treatment with aromatase inhibitors (a type of hormone therapy) for another five years further reduces the risk of developing secondary breast cancer by over a quarter for certain women. These results from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), based at Oxford Population Health, are published in The Lancet.
About three quarters of postmenopausal women with operable breast cancer have hormone-sensitive disease. For these women, five years of endocrine (hormone) treatment after surgery, either with tamoxifen or aromatase inhibitor tablets, reduces the risk of dying from breast cancer by about a third, with benefits continuing well beyond the end of treatment. However, despite this, there remains a substantial and constant risk of late breast cancer recurrence and death.
Addressing variation in clinical practice
Current clinical practice varies, with some women recommended five years of treatment in total, some seven years, and some longer. Individual trials where endocrine treatments have been continued for two to five years after an initial five years of treatment have shown promising but inconclusive results on the benefits of continuing treatment for longer.
Researchers from the EBCTCG, which is funded by Cancer Research UK and the Breast Cancer Research Foundation (BCRF), gathered data from over 22,000 women in all 12 randomised clinical trials that compared further endocrine therapy using an aromatase inhibitor with no further treatment to assess the benefits and risks of additional treatment.
Key results:
- Allocation to five more years of aromatase inhibitor therapy (AIT) reduces the risk of secondary breast cancer by over one-quarter (27%) compared to stopping therapy in postmenopausal women with oestrogen receptor positive (hormone-sensitive) early breast cancer who have completed five years of hormone treatment that included AIT;
- This proportional benefit was consistent among all women, but absolute benefits were greater in women who were at higher risk of secondary breast cancer, particularly those whose initial cancer had spread to their lymph nodes;
- Over one-third of women stopped taking their treatment, so the benefits may be even larger in women who are able to adhere to treatment;
- The follow-up period in the trials was too short to determine whether this improvement would translate into reducing death from breast cancer;
- There was no evidence of an increased risk of death from other non-breast cancer causes, including heart disease. However, women allocated to longer treatment experienced a small increase in bone fracture incidence of 1.2%.
Robert Hills, Professor of Medical Statistics at Oxford Population Health, head of the EBCTCG Secretariat, and an author of the study said ‘Endocrine therapy is the most commonly prescribed treatment for breast cancer worldwide, so these findings are of relevance to a huge number of women, and have the potential to prevent many thousands of recurrences.’
Co-author, Dr Jeremy Braybrooke, Senior Clinical Research Fellow at Oxford Population Health and a consultant medical oncologist in Bristol, added ‘It is only by combining all the available evidence in an analysis like this that we can give the most reliable information to women with breast cancer to help them, and their clinicians, to make informed decisions about the benefit of prolonged treatment, and reassure them about possible side-effects.’
As someone who has gone through breast cancer treatment, I know how vital clear, evidence-based information is when making difficult decisions about ongoing therapy. These findings offer much-needed clarity and hope for (postmenopausal) women and their clinicians.
- Tanja Spanic, a patient representative who supported this study
Dr Dorraya El-Ashry, Chief Scientific Officer at the BCRF, said ‘These findings speak to the value of the work of the EBCTCG. Nowhere else are these kinds of analyses being conducted and their impact on informing standards of care cannot be overstated. BCRF’s support of this work is integral to its mission to end breast cancer by advancing the most promising research.’
Vanda Taylor, specialist information nurse at Cancer Research UK, added ‘These important findings strengthen the evidence that extended hormone therapy can help reduce the risk of cancer coming back for some patients. But we know that hormone therapy isn’t without side effects. More research is needed to understand the long-term impacts of extended therapy, especially for women at lower risk of their cancer returning. We encourage women to speak with their doctor or specialist nurse about the potential benefits and risks, so they can make the decision that’s right for them.’
Supporting women taking AIT
Many women discontinued treatment in the placebo-controlled trials included in the study, but almost as many did so with placebo as with AIT. The researchers suggest that strategies to support women taking long-term AIT and to help manage any symptoms reported (many of which may not actually be due to the AIT) might substantially improve adherence, and breast cancer outcomes.
Women who have been taking aromatase inhibitor therapy will know their individual experience of symptomatic side-effects, and that decisions about further treatment should balance absolute benefits and risks. Nevertheless, for women who have already had about five years of endocrine therapy, the finding that five more years of aromatase inhibitor treatment further reduces any remaining risk of developing secondary breast cancer by about one-quarter can usefully inform current and future decisions about treatment.