The impact of biological age on breast cancer

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Published: 20 Dec 2013
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Dr Alistair Ring - Brighton and Sussex Medical School, UK

Dr Ring talks to ecancertv at SABCS 2013. The prognosis of a woman with early breast cancer is dependent on both tumour and patient characteristics. Tumour-related prognostic factors, such as stage, grade, and biomarker expression are well-described in the breast cancer literature and remain the focus of considerable ongoing research efforts. However patient-related factors which may influence risks of death from competing causes of mortality or tolerance of adjuvant therapies receive less attention. Risks of death from other causes and likely tolerance of treatment are particularly important considerations in the management of the increasing number of older women who are now presenting with early breast cancer. Chronological age itself may be a useful predictor of these outcomes. However older patients represent a heterogeneous population in terms of co-morbidities, fitness, life expectancy, social situation, cognitive function as well as desire for treatment. Therefore an objective definition of 'biological age' might be a more accurate predictor.

Ongoing studies are evaluating whether more extensive assessments, incorporating more domains of a CGA, such as functional status, cognitive function and nutrition add to the predictive model. Any incorporation of such measures into routine clinical practice will require further validation and confirmation of clinical utility. Nonetheless such tools assessing biological age do offer the promise to improve further on the advances made in personalising adjuvant therapies that pathological and molecular tumour characterisation have already achieved. As such it seems likely that assessment of these factors in order to more objectively take into account the risks of death from competing causes of mortality and likely tolerance of treatment will become core components to informed adjuvant treatment decisions in the future.

I have an interest in breast cancer in the elderly and the challenge here is we live in an aging population. The number of people over the age of 65 globally is going to double over the next 30-40 years to half a billion to a billion individuals so we’re seeing huge potential increases in the size of the older population. Pretty much all cancers but in particular breast cancer are a disease of aging. Already over a third of the women whom we see diagnosed with breast cancer are aged 70 or older the time of diagnosis. When one looks at some of the data from across the UK and Europe, survival rates for older women with breast cancer have not improved at the same rates as they have for younger women. There is therefore, I would argue, an unmet need in this area and particularly the issue is our poor enrolment of older patients, older women with breast cancer, to clinical trials. Whereas a third of those women diagnosed with breast cancer are over the age of 70, it is very much single figure per cents of women over the age of 70 who go into our large randomised trials looking at new treatments. Even when older women do go into breast cancer trials, they’re not truly representative of those women, of the women we see in a day to day clinic, they tend to be the fitter, selected populations.

How are the elderly assessed?

There are a number of issues surrounding the treatment of older women with breast cancer, surgery and, in particular, the use of adjuvant therapies. We recently published a paper at the beginning of this year, 2013; we published the AChEW study which looked at patterns of care in over 800 women in the UK diagnosed with early breast cancer. These were all women over the age of 70 at the time of diagnosis and we found that only 14% of those women were offered adjuvant chemotherapy. Even when we looked specifically at those women with the very highest risk disease, only 30%, one in three of those women, were offered adjuvant chemotherapy. Now the challenge here is to work out whether the lower rates of use of adjuvant chemotherapy in this population are responsible for some of the worst survival rates seen. But there is, of course, a problem here because the benefits of adjuvant chemotherapy will be limited if the woman you have in front of you is at high risk of death from another cause, a competing cause of mortality, which is a particularly salient issue in older women. In addition, adjuvant chemotherapy, for example, may be ill advised if that woman is at high risk of the toxicities of treatment. One of the areas of my, and many other people’s, research is whether more formal assessments of older women with breast cancer, and indeed other cancers, may help inform decision making because it may be that more formal assessments of health may enable us to identify those women who are at high risk of death from competing causes of mortality or less likely to tolerate their treatment. So there are a number of ways that we may be able to assess general health and predict those outcomes, they include clinical assessments, the so-called comprehensive geriatric assessment, or looking in blood biomarkers which may help also to predict biological age.

Firstly, a comprehensive geriatric assessment involves an assessment in a number of domains such as functional status, comorbidities, nutrition and social status. It involves asking patients largely a number of questionnaires and simple measurements about their general health and what they can do. They’re not simple assessments to conduct, they may take 1-2 hours to complete and for that reason sometimes screening tests are used to try and tease out those women who need a more complete assessment. There is also a challenge in looking at the literature in this area because different units and different centres and different trials use different forms of the comprehensive geriatric assessment. As a result it would be very difficult to compare between studies. The final issue with conducting one of these assessments is the purpose is not simply to assess and identify those who are vulnerable and frail and those who are fit and then proceed with treatment or not, it is also to identify areas in which someone’s health may be potentially improved so areas where their current healthcare may be optimised or new interventions may improve their general health status and make them potentially fitter to tolerate the proposed treatment. So there are clear challenges in implementing such comprehensive health assessments, nonetheless they do provide the promise of more objective assessments of health above and beyond simple measurements of chronological age or subjective assessments of health that we conduct at the moment.

The second area is an area of looking at blood-borne biomarkers of aging and this involves looking at markers such as telomeres. Telomeres are caps on the end of chromosomes, repetitive sequences that shorten with every cell division. They also shorten with physiological and psychological stress and other extrinsic factors such as obesity and smoking. So telomere length may actually be a good predictor of not just chronological but also biological age and it’s relatively straightforward to measure telomere length on the whole blood DNA using a PCR assay.  We’ve known that other blood-borne biomarkers may also be associated with age, such as markers of chronic inflammation IL-6 and TNFα increase with age and with increasing expression of inflammatory markers we see decreased mortality and cognitive impairment. We also see deterioration in the immunological system as patients get older which may make them more susceptible to infections, perhaps those infections associated with chemotherapy. We see changes in DNA methylation and there are various single nucleotide polymorphisms of genes involved in lipid metabolism and other pathways that are associated with longevity. So there’s a panel, if you like, of potential blood-borne biomarkers of aging that might also help measure biological age and inform treatment decisions by telling us about a patient’s risk of death from competing causes of mortality or fitness for treatment.