Sunday, 4 October 2015

Prophylactic mastectomy

Prophylactic mastectomy reduces the risk of getting breast cancer (here), but does it reduce your overall risk of dying? And what are the other risks?

Firstly, there are two different treatments that need to be considered separately: CPM and BPM. CPM is contralateral prophylactic mastectomy and it means removing the opposite breast in someone who has breast cancer in one breast. BPM is bilateral prophylactic mastectomy and this is where both breasts are removed in someone who does not have breast cancer. I will cover BPM briefly, but CPM is the main topic.

BPM is only done for people with very high risk of getting breast cancer, usually those with certain genetic factors (BRCA1 or BRCA 2 mutations). Less than 1% of women carry either of these mutations, and they are only responsible for about 5% of breast cancers. If you have one of these mutations, your lifetime risk of breast cancer is high (around 90%) and this can be reduced to less than 30% with BPM. The effect on overall survival is much less (around 12% better with BPM) and there is also evidence that regular screening might work just as well (here). Unfortunately, women with some increased risk (but without the genetic mutations) think that they will also benefit from BPM, but there is very little evidence of an effect on overall mortality either way for those patients, mainly because it is not a common procedure and we don’t have sufficient research on this topic yet.

CPM, however, is commonly performed and there is much more information on its effectiveness. The benefit of CPM is that you are less likely to get breast cancer in the opposite breast, and therefore less likely to die of breast cancer from a new tumour in the opposite breast. Essentially this is removing one possible cause of death. But unless the risk of dying from a new cancer in the opposite breast is high (in which case we have a similar argument as for BPM), the woman might be making a big commitment for a small gain: what the Americans call a long run for a short slide.

We know that the uptake of CPM has been increasing for some time now, with as many as half of all women with breast cancer now opting for this. One reason for this is that women perceive the risk of cancer in the other breast to be high, and therefore the benefit from CPM to be high. However, studies have shown that women greatly overestimate both the risk of breast cancer on the opposite breast, and the benefit of CPM (here, here, here and here).

Women may also be underestimating the risks of CPM, such as physical impairments and psychological distress, which affect quality of life. Even though breast reconstruction is commonly used to improve quality of life, complication rates are 15-20% and there is a risk of reoperation in about 1/3 to ½.

A Cochrane systematic review (here) concluded that there was insufficient evidence to show that CPM improves disease-specific survival. Other studies have either shown a small overall survival benefit from CPM, but most studies found no difference in survival (here).
A recent publication (here) reported the results of a decision analysis tool to weigh up the risks and benefits of CPM for women with breast cancer. They looked at the effect of CPM on overall survival (life expectancy) and on quality adjusted life expectancy. “Quality adjusted” means that they took into account the reduction in quality of life associated with having CPM. For quality-adjusted life expectancy, a simple example is that if somebody lived for an extra 10 years from a treatment, but the treatment reduced their quality of life by 10%, this would be the equivalent of 9 quality adjusted life years.

The researchers chose women aged 45 because that is around the age that people have CPM, and because the benefit of CPM diminishes as you get older due to competition from all the other things that can cause death.

The study found that depending onto the type of tumour, the increase in life expectancy from having CPM ranged between 3 and 28 weeks. Women with higher grade (worse) tumours benefited the least, mainly because the risk of dying from the first cancer swamped the reduction in risk of dying from a new cancer in the other breast. For example, women with a higher grade of cancer had a 77% risk of dying from their index cancer over 20 years, and a 0.5% chance of dying from a tumour from the other breast over the same period. And that’s without CPM. There was no gain in life expectancy from CPM once women hit 67 years of age.

When factoring in the reduction in quality of life from CPM, even using a very small reduction in quality of life (5%, around the same as having a course of mild chemotherapy) they found that regardless of the tumour type or age, CPM resulted in a decrease in the quality adjusted life expectancy (QALE), ranging from 18 to 33 weeks.

The bottom line

I am not calling for a ban on CPM, I just want the decision to be made on realistic probabilities of the likely gain and the likely harms, not on the outside chances. The decision should be based on what CPM can achieve, not what we wish it to achieve. Based on the information above, CPM decreases the chance of getting breast cancer on the opposite side,  but it only has a marginal effect (if any) on overall survival and it has a downside due to complications and psychological impact.

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