As I drove into work on Tuesday, I heard the news that NHS England were announcing a new role for anastrozole in the prevention of breast cancer. It took me by surprise and speaking to colleagues, I wasn’t alone and the NB Medical team WhatsApp was merrily pinging my phone before I even arrived in the car park at my LMC office. My first message there was from a GP wondering what to say to the e-consults that had already arrived!
Of course, the agenda of the day being set by the newspapers and the Today programme is nothing new for us in general practice, and we all recognise the particular anxious interest that cancer stories bring. Sending some background information to us on the why, what, how and when would have been useful ahead of the press release, to give us some idea as to how to field concerns and questions from anxious patients, so we hope that this blog will fill the gap for you!
In actual fact, this indication for the drug is not new. NICE has recommended the off-license use of anastrazole for breast cancer prevention in high risk, post-menopausal patients since as far back as 2017 familial breast cancer guideline CG164, but uptake has been low. This new announcement relates to the re-licensing of the drug to include this new indication and stems from the NHS England’s Medicines Repurposing programme, which NHS England wrote to us about last month. In partnership with the Department of Health and Social Care (DHSC), the Medicines and Healthcare products Regulatory Agency (MHRA), the National Institute for Health and Care Excellence (NICE), and the National Institute for Health and Care Research (NIHR), NHSE has been working looking at new indications for off-patent medication, and facilitating licensing for existing “off-label” prescribing. They used their work on anastrozole as an exemplar for the programme, and it’s the first drug to emerge from it with a new license. The concept of this work is a fascinating one, and it’s feels like an ethical, responsible approach to the stewardship of the medicines we use.
So, why are we looking at this new indication for anastrozole? NHS England assert that if just 25% of the estimated 289 000 eligible women chose to take the drug, then we could see the prevention of around 2000 cases of breast cancer England and the NHS could save around £15m in treatment costs. The key evidence for this comes from the IBIS-II trial (The Lancet, Jan 2020). Anastrozole is an aromatase inhibitor, preventing the production of oestrogen in the peripheral adipose tissue where it is synthesised in post-menopausal women. As such, IBIS-II focussed on post-menopausal women between 40 and 70 and took specific risk criteria into account (such as family history) so the study population encompassed women with a relative risk at least 1.5-2x higher than the population average. They were randomised to anastrazole or placebo for 5 years, with up to 11 years of follow up. Over the trial, taking either 1mg of anastrozole or placebo daily for five years, the authors report a 49% reduction in breast cancer incidence over an average 131-month monitoring period. The NNT for women at high taking anastrazole for 5 years to prevent one case of breast cancer was just 29.
Importantly, the drug was well-tolerated. The major concern would be an increased fracture risk which wasn’t apparent, and no other significant increases in other adverse effects were seen. It’s also worth noting that whilst these post-menopausal women reported the expected side effects of hot flushes, night sweats, vulvovaginal dryness and polyarthralgia, the actual compliance for both the active drug and the placebo were essentially identical. This suggests that the side effect issues were manageable, or at least tolerated given the nature of the trial and hoped-for outcome.
This feels like clear evidence of benefit here, and the MHRA clearly agree hence the announcement of the licensing change on the 7th November. But how do we decide which post-menopausal women are at high risk? We don’t yet have clear information about how we will be working alongside secondary care to risk-profile our patients, but in the meantime it is worth reminding ourselves of the existing tools that we do have for risk assessment. While ultimately the recommendations from NHSE may differ, for primary care clinicians looking for a strategy to discuss breast cancer risk with women NOW, the NICE guideline CG164 from 2013 on familial breast cancer has a useful algorithm to help identify women at increased risk who should be offered referral to secondary care. This is a basic screening tool, quick and easy to use (the specialist clinic does a more detailed assessment) and one that we should re-familiarise ourselves with when patients are asking if they should be offered this drug.
As Amanda Pritchard of NHS England put it, this development "represents the first step to ensuring the risk-reducing option can be accessed by all who could benefit from it,” but GPs will need to see a few more steps before we can confidently discuss referral and support prescribing. It’s also fair to say that it would be helpful for us on the general practice frontline to have communications from NHSE sent in a more measured, prepared manner ahead of the press release. Learning about such changes from the news alongside our patients without the information we need as clinicians to respond to them is difficult for both GPs and patients, and doubly so when it’s on so emotive a topic as breast cancer.
Nevertheless, in our efforts to battle what remains the most common cancer in the UK, it seems that we now have a new ally in a long-established drug – and perhaps something for us to revisit in Hot Topics in 2024!