YEARS AGO, THERE was no standard guidance for the treatment of breast cancer. Since the early nineties, however, doctors have based their treatment recommendations on scientific evidence from research studies that have looked at the outcomes of hundreds of thousands of women with breast cancer taking different treatments, often over a 10- to 20-year period. These studies are usually randomised controlled trials (RCTs) in which cancer patients are randomly allocated (e.g. using a random number generator on a computer) to an intervention group (who receive a new treatment) or a control group (who receive the standard treatment, or no treatment at all). All of this is done in a carefully controlled setting and the results are accurately recorded. Randomisation is important, since non-random allocation (e.g. giving the new treatment to people with more advanced cancer) would mean you couldn’t prove anything reliable about the benefits of the treatment.
Breast cancer is now one of the most researched conditions in any branch of medicine. Hundreds of RCTs have been done looking at many different treatment options. To help doctors make their decisions, they look at the combined results from lots of RCTs using a statistical technique called meta-analysis, which can increase the confidence with which they can say that treatment A is better than treatment B.
The results of breast cancer RCTs and meta-analyses are used by leading experts to write national and international guidelines advising doctors how to treat patients with primary and secondary breast cancer. In the UK, evidence-based guidelines produced by the National Institute for Health and Care Excellence (NICE) summarise all the relevant high-quality evidence. Every doctor treating you should follow these guidelines (whether on the NHS or privately), although it’s important to bear in mind that these are only guidelines and every patient is considered on an individual basis. In America, the guidelines are produced by the American Society of Clinical Oncology (ASCO). We have drawn mainly on NICE guidelines when writing this book.
We have not listed all the major research trials and meta-analyses because there are so many of them, but they can all be found in the relevant NICE guidelines which are free to download. Where we do mention a trial, you should be able to find it by searching online for key words (e.g. the author’s name, the drug or other intervention, and ‘breast cancer’).
Most cancer research trials are designed to measure whether a certain treatment gives patients a better outcome. There are different ways of describing this, and they are often recorded as a percentage. ‘Overall survival’ means how many people are alive at the end of the trial. ‘Disease-free survival’ means how many patients are alive and haven’t developed a recurrence. ‘Quality of life’ measures give an indication of whether the side effects of treatments are so bad that they outweigh any survival benefits.
Careful consideration is needed when a trial (or a story in the press) claims that it improves these outcomes. Results can be expressed in absolute terms or relative terms (absolute is better). A trial could claim that ‘eating X doubles your risk’ of getting breast cancer. This sounds scary! However, it is a relative benefit. The actual, absolute benefit is that ‘eating X increases your risk of getting breast cancer from 1 in 1,000 to 2 in 1,000’. Both statements are true, but the absolute benefit is less misleading – even if you eat X, you still have 998 chances in 1,000 of not getting breast cancer!
Cancer trials take a long time to get results, especially if they set out to study long-term survival over many years. A 10-year study of people who developed breast cancer in 2006, for example, is unlikely to be published until 2020. Since treatments are improving all the time, this means that your chances of survival are at least as good as the odds reported in published trials – and very often considerably better, because new treatments are always being developed.
NICE guidelines mean that if a patient is seen by any breast surgeon, anywhere in the UK, they should be offered the same treatment plan. However, every case is discussed by a team of doctors in a multidisciplinary team (see here), before the plan is then discussed with you, the patient. You can then ask about alternative options, and fit the treatment plan around your own priorities and lifestyle choices. Your doctor can help you weigh up the balance between potential benefits, the potential risks or side effects, and what might be called the ‘hassle value’ (how many visits to hospital, how many blood tests, how much time needed off work, and so on). Sometimes there may be two equally effective treatment options, and the decision will be yours to make.
You may not want to get involved in this decision-making process, preferring to simply go ahead with whatever your doctor recommends, based on the evidence and guidelines. Your doctor should talk to you about the pros and cons of surgery, chemotherapy and radiotherapy as part of the consent process. If you do want to get more involved with ‘shared decision-making’, here are five key questions to consider asking about any test or treatment:
1. What are my options?
2. What are the absolute benefits of each option?
3. What are the absolute risks (side effects) of each option?
4. What is the evidence for this treatment?
5. What happens if I don’t have the test or treatment?
We understand that having cancer can be scary as it is a serious and potentially fatal condition. You may feel a strong temptation to ‘clutch at straws’ and sign up to anything that promises a cure (common ones are extreme diets, mega-vitamins, homeopathy and spiritual therapies), maybe as an attempt at regaining control over your body and your life, and we discuss these so-called miracle cures in more detail in Chapter 18. While we understand this pressure, we want to warn you of the dangers of taking treatments that are not evidence-based. If you do decide to take such treatments, please consider taking them alongside traditional medical treatments. We know that breast cancer can still come back despite everything medicine has to offer, but if you don’t follow the advice of your medical team, the risk of recurrence could be far, far higher.
This excerpt is from a blog published in the Huffington Post (17 April 2017) from Dr Lawence Saez (a cancer survivor himself) entitled ‘Cancer and the Snake Oil Industry’:
Vitamin B17, frankincense, apricot seeds, blue scorpion tail extract, moringa, turmeric, essiac tea. These are among the hundreds of alleged cancer-killing cures that will be unfamiliar to most people, but not for those of us who are cancer patients. Information about these products typically emerges from online discussion boards or closed Facebook chatrooms. Sometimes concerned friends inundate you with information about such miracle cancer cures. For cancer patients, who are overwhelmed with the traditional treatments for cancer, these alternative cures can offer a sign of hope. However appealing, we must be aware about the dangerous implications of natural cancer cures.
Every cancer patient is likely to have come across a number of videos relating to non-traditional medicine cancer cures. The general premise of these videos is that oncologists are puppets of the pharmaceutical industry. According to this narrative, traditional medicine cancer treatments are, at best, ineffective or, in the worst of cases, they actually cause the spread of cancer.
Oftentimes, a natural health cure ‘doctor’ will claim that everything that a cancer patient has been told about cancer by their oncologist is wrong. These ‘doctors’ will then offer some sort of miraculous cancer cure, typically a juice cocktail or some vitamin protocol. These snake oil salesmen offer no concrete scientific evidence for their extraordinary claims. Normally, the only evidence offered by these ‘doctors’ are testimonials, allegedly from cancer patients who claim to have been cured by these non-traditional treatments. Individually, these ‘cures’ are unlikely to harm a cancer patient. The real damage comes when these snake oil doctors then encourage cancer patients to forego traditional medicine treatment for these purported cures.
This is wise advice. We have both seen friends and patients refuse scientifically-proven, free (in the UK) medical treatments and instead use ‘alternative cures’ at great expense. Some of these ‘cures’ cost hundreds of thousands of pounds, and involve flying monthly to countries like Mexico and Japan.
A major study published in 2018 in the Journal of the National Cancer Institute by a team led by Dr Skyler Johnson showed that women with breast cancer were more than five times as likely to die if they took alternative medicines only, compared with women who had traditional breast cancer treatment. Dr Johnson has an excellent blog where he introduces what he calls the ‘Cancer Claims CRAP Test’, which he has kindly given us permission to reproduce on the next page. In short, if a cancer claim is a) too good to be true, b) made by someone who is after your money, c) based on nothing more than anecdote, and d) hard to verify in the published literature, it fails the CRAP test and you should be very cautious about it.
Evaluating Cancer Claims: Are they CRAP?
Use the questions below to help you evaluate cancer claims from people, websites, social media or videos. Place a 1 next to each section if you answer yes. Add up the nal score to decide whether the cancer claim is crap.
Here are some rules of thumb for interpreting scientific claims that are pitched at the general public, instead of doctors and scientists. They may be particularly useful when assessing alternative therapies.
Real scientists do not set up a research study in order to confirm a preconceived idea. They do it to test a hypothesis from the neutral position which assumes that the results could go either one way or the other. An honest scientist is cautious and critical of their own work and that of others and will always underplay rather than overplay the significance of their work.
Just because something cures cancer in mice doesn’t mean it’s going to cure the same cancer in humans. Arguably animal studies have a place in science (we acknowledge those who disagree with this) but even when the findings of such studies are promising, they are still preliminary. To draw conclusions about humans, they have to be repeated, and the results reproduced, in human trials.
Cancer treatments have to be tested, and shown to work, on cancer patients. Drugs are often given to healthy volunteers first, to make sure that the side effects are not too terrible, but this doesn’t mean that the drug is going to work effectively against your cancer.
It is not necessarily true that a big study is better than a small one. But, all others things being equal, the larger the study, the more likely it is to approximate to the truth. Most large breast cancer trials recruit thousands of patients, whereas some ‘alternative cures’ are marketed on the basis of tiny studies looking only at a handful of patients. Before they change their clinical practice, doctors want to know that the results can be reproduced in lots and lots of patients, to make sure that the small trial isn’t a one-off. A meta-analysis (see here) can be done to combine the findings from several smaller studies to give a clearer picture of how effective (or not) the drug is.
One commonly used scientific approach in the study of cancer causation is to measure a lot of different things (known as ‘variables’) in a large number of people and then follow these people over a few years to see who gets cancer. This is known as a ‘cohort study’. Variables typically measured include smoking status, alcohol intake, different aspects of diet, exercise levels, and so on. But the best such a study can ever produce is an estimate of association (meaning: two things occurring together); it can almost never prove causation (that one of the variables actually caused the cancer).
Very rarely, a really good cohort study can demonstrate causation. For example, the original research linking smoking and lung cancer was done using a cohort study. In that study, the association was very strong (over 90 per cent of the lung cancers occurred in the smokers); there was a ‘dose response’ effect (the more you smoked, the more likely you were to get lung cancer); and as people were followed up for several decades, it became clear that giving up smoking was (after a few years) associated with a reduction in the risk of lung cancer. All these things helped to show that in this case, the association between smoking and lung cancer was causal. But most associations – for example between drinking coffee and getting cancer, or taking a particular vitamin and preventing cancer – are much, much weaker overall; the dose-response effect is weak or non-existent; and change in behaviour has not been shown to change risk. Whatever you may read in the press, the biggest risks for getting breast cancer are still being a woman and getting older, neither of which you can change.
We talked about RCTs (or randomised control trials) earlier (here). When evaluating cancer treatments, you should generally ignore any claim that is not based on a RCT. If the person claiming that their miracle treatment cures cancer can’t back it up with at least one RCT, think twice before signing up for it.
Apologies for the jargon in this title, but these terms are important. Clinical trials have definitive endpoints that can be accurately measured – such as overall survival and disease-free survival (see here). If a treatment is scientifically proven to improve cancer survival, your doctors will recommend it to you. A surrogate endpoint is something that’s usually easy to measure (for example, your cancer appears to shrink on a scan) but which isn’t always a true indicator of whether a treatment is working, i.e. whether you will live longer because of your treatment. If the only evidence in favour of a particular treatment is a change in a surrogate endpoint, this is relatively weak evidence.
If you’d like to get more deeply into how to assess scientific papers, Trish has written a book called How to Read a Paper: the Basics of Evidence-based Medicine (Wiley-Blackwell, 2014). Liz actually used this book herself when she sat her surgical exams.
We both know how important scientific research is when it comes to improving survival from breast cancer, because we’ve done research ourselves and because the treatments we received as patients were based on research trials. One goal of the UK Association of Breast Surgery is that every patient should be offered the opportunity to be involved in a research trial.
Most breast units in the UK will be running several different research trials at any one time. Your doctor will talk to you about any suitable trials and ask you if you would like some more information. This information is normally given to you by a specialist research nurse. If you’re not keen, say so. You don’t have to be part of a trial and your clinical care will not be compromised if you say no (you will simply be treated according to the current standard guidelines, as discussed above).
Taking part in a research study means you are contributing to the development of new treatments for breast cancer, and hopefully, one day, a cure. Even if you don’t gain personally, future generations of patients will. There are different kinds of trials, which include:
● new ways of analysing breast cancer and genetic testing
● surgical operations, chemotherapy and radiotherapy regimens
● the effects of a particular treatment on your quality of life
● the effects of counselling, diet, and exercise on your survival from breast cancer
There are some downsides to agreeing to take part in a research trial. It may be too much information to take in when you are still coping with a cancer diagnosis and the trial could mean extra hospital visits, blood tests or scans. You may also be allocated to the standard treatment and not get the new trial drug, but you won’t know until the trial has finished. Trials of drug treatments can go on for several years or more, so it can be a long-term commitment.
On the upside, being part of a research study means that you will be very carefully monitored and followed up, usually with more frequent appointments than someone who is not in a trial.
Most hospitals in the UK are involved in several breast cancer trials at any time. Your doctor should tell you about all the trials in your hospital that are suitable for you. If you have heard of a different trial, either online or from other patients, you can ask your doctor about this. You may have to be treated in a different hospital, which could be far away from you, if you want to take part. There are relatively few trials for patients with secondary breast cancer, and most of these are run at the larger cancer centres, which may mean travelling to take part. The Cancer Research UK website has a list of all the current breast cancer trials: www.cancerresearchuk.org/about-cancer/find-a-clinical-trial
QUESTIONS TO ASK YOUR DOCTOR ABOUT RESEARCH TRIALS
If you’re unsure whether you want to be involved in a particular trial or not, ask your doctor or the research nurse these questions adapted from the Breast Cancer Care website:
● What does the trial involve?
● Will I know if I’m getting the new treatment or not?
● How long will I be in it for?
● Can I change my mind during the trial?
● Will I need to have extra blood tests or scans? How often?
● Will I need to have extra hospital visits? If so, will the trial pay for the extra travel?
● What will you do with the data collected about me?
● Who can I contact if the research nurse is not available?
● Will there be a questionnaire or diary to fill in?
● What are the side effects of the treatment?
● What treatment will I get if I don’t enter the trial?
● Will I get to know the results?
● Will I be treated at the same hospital or will I have to attend a different unit?
If you want more information on what a clinical research trial is and what goes on in them, try the Clinical Trials Explained website: http://clinicaltrialsexplained.com
Now that we’ve talked about the science of breast cancer treatment and the rigorous research involved, we hope you have a better understanding of why your doctor recommends certain treatments to you. We also hope you’re feeling a little more confident in assessing the pros and cons of alternative cancer treatments. Let’s now go through, in detail, what each breast cancer treatment involves, and give you our tips and tricks to cope with each in turn.