The statistics have become familiar enough to most of us: Breast cancer accounts for almost 200,000 new cases and 40,000 deaths every year. The National Cancer Institute estimates that 12.7 percent of women alive today will be diagnosed with some form of breast cancer during their lifetime. This makes breast cancer by far the leading cancer in women, accounting for almost 40% of all cancers diagnosed in women.
These statistics have become very fear-inspiring to many women. Breast cancer charities and research foundations want to stress the impact of the disease on society. This means that they can increase their funding but it has also made breast cancer seem inevitable to many women.
It is not, of course. That same estimate of lifetime risk means almost 9 out of every 10 women will never personally experience breast cancer. There are certain things, however, that increase the risk of breast cancer, some greatly.
What are these risk factors? The three most common risks are age, gender and family history. Being female is the greatest risk, although men are not immune and in fact almost 2,000 men are diagnosed every year with breast cancer. Breast cancer risk also increases with age. The vast majority, 95% of newly-diagnosed cancers and 97% of cancer deaths, occur in women over 40. Last year, there were 1.4 cases for every 100,000 women age 20-24, rising to 442 cases for every 100,000 age 75-79. Having a close family member (mother, sister, etc.) that had breast cancer also increases risk. If one family member had cancer, the risk is approximately double. If two family members had cancer, the risk is approximately four times as high.
Other risk factors include previous breast cancer, benign breast disease, early first menstrual period, late menopause, late first full-term pregnancy, obesity, low physical activity, use of synthetic postmenopausal hormone replacement therapy, use of oral contraceptives, and exposure to ionizing radiation.
Recent scientific advances have identified specific genetic mutations that also are linked to a higher risk of developing breast cancer. These genes, BRCA1 and BRCA2 help suppress tumor development by repairing DNA strands that get damaged through aging or other factors. Mutations to these genes allow chromosomes to degrade more easily, allowing aging cells to develop into cancer cells. The lifetime risk of women who have these mutations developing cancer may increase to approximately 50-60%.
This sounds especially scary, and fear is causing some people to take steps that are not supported by good data. Some organizations recommend women with the BRCA mutations have annual MRIs plus mammograms to catch possible cancer as early as possible. This is despite research showing the mammograms have no added benefit over the already-costly MRI alone, but do increase exposure to ionizing radiation (which is also a risk factor). There are women that have gone even farther, to removing the breasts before there is any sign of cancer (prophylactic mastectomy) plus removing the ovaries.
Think about that for a minute. Based on a genetic test that’s little better than flipping a coin, some women are choosing to undergo major surgery, with all the risks that entails, plus ripping out one of the key endocrine glands. Even in a woman nearing menopause this is a difficult decision, but what about a young teenager that tests positive for these mutations. Are her parents supposed to approve such a drastic solution to a problem she might never face? Needless to say, this is a preposterous remedy.
The problem with any discussion of risk factors is that they only tell half the statistical story. For example, BRCA mutations increase the risk by a factor of 5 at the outside (12% to 60%), which sounds incredibly dangerous. At the same time, only a very, very small number of breast cancer cases diagnosed are in women with this mutation, on the order of about 5%. The seeming discrepancy is, in part, because these relative risk factors were established in large families with many breast cancer cases among particular ethnic subgroups. Generalizing to the population at large is still inexact.
Some risk factors are controllable, but many are not. How can you change your family history? Clearly that’s impossible. And, the most important risk factor for breast or any cancer is aging, which is inevitable. The inability to control these factors pushes fear to even greater heights.
All this talk of risk factors and genetic mutations and cancer genes is missing a very vital piece of the story about aging on a cellular and DNA level. That is that DNA has a built-in aging protection mechanism related to something called telomeres. “Teleo-“ means the end or last and “mer” means piece, and telomeres are sequences of repeating DNA at the end of each chromosome.
When DNA replicates during the life of a cell, enzymes open each chromosome in the nucleus like a zipper. Each half of a chromosome is the template to build the other half, resulting in 2 new DNA strands. As the new chromosome is built from the old, enzymes work along the DNA strand, attaching new DNA “letters” one at a time. When they get to the end of the chromosome, the way that this process has to work means that the last few letters get left off, and are not copied for the new chromosome. Effectively, each time a cell divides, the chromosomes shorten.
Telomeres evolved as DNA that is expendable on the end of the chromosome. It doesn’t encode for any function or protein or anything else. Until recently, it was thought to be a sort of “junk” DNA. Each time the chromosome is replicated it is the telomere that shortens, preserving and protecting all of the functional DNA.
Telomeres have a function besides just withering away, though. Imagine that each time a chromosome replicates a section is lost that was, say, 10% of the original length of the whole telomere. That means the telomere can only protect the rest of the DNA 10 times. What would happen on the eleventh time the DNA replicated? Off comes something that might be functional. After replication, the new cell would be missing the instructions to create certain enzymes or some structure, and would be a mutant cell.
As the cell ages and the telomeres get shorter, then, there is a mechanism that has to ensure they don’t get too short. In fact, there is just such a thing in your cells, and when the telomere gets too short, a series of processes are started that cause the death of the cell. In 1965 a geneticist named Leonard Hayflick determined that each cell divides about 80 times before reaching this limit. It has come to be known as the “Hayflick limit”.
Something goes wrong with this process in cancer cells, however. Instead of dying when they should, cancer cells evade this cellular cop and go on reproducing without controls. When a cell divides and grows without control, it becomes cancer.
Cancer genes like the BRCA mutations would be logical culprits for this change. But when researchers have looked at cancer cells, the presence of a single mutation is not the only thing that turns a normal cell into a cancer cell. That is to say, it is not just the presence of a mutated cancer gene like BRCA that determines if a cell becomes cancerous.
It turns out that the length of the telomeres is closely linked to developing cancer. Telomeres provide stability to the genetic material preventing the types of mutations that can lead to cancer. This can be seen by looking at the statistics for all cancers by age group, which steadily rises after early childhood. In the cells of children and young adults with long telomeres, cancer has a hard time getting started. In the cells of elderly people with little stub telomeres, a cancer gene mutation is much more likely to cause runaway growth. Similarly, other lifestyle-related factors, such as obesity, stress and physical inactivity are associated with both shortened telomeres and an increased breast cancer risk. Of course, there’s also a lifetime of environmental exposures to consider, but long telomeres are definitely a factor. In fact, several studies have directly linked telomere length to cancer risk – the longer the telomeres are, lower the risk of cancer.
The bottom line is that there are so many cellular-level processes operating that there are no absolutes. There is no way, even with the most sophisticated genetic testing, to accurately predict who will develop breast cancer. If we can’t accurately predict breast cancer in an individual, we can’t meaningfully say that it can be or can’t be prevented.
So when we consider the question of preventing breast cancer, we need to think instead about relative risks. Some factors that raise risks of breast cancer are absolutely controllable. These include things like diet, obesity, alcohol consumption, physical inactivity, and sleep disruption. It is not incorrect to say that, generally, healthy living lowers breast cancer risk and improves telomere maintenance. Whether these lifestyle changes affect cancer risk by altering the telomeres directly or through other mechanisms is still being debated, but their efficacy is clear.
There are other exciting new developments about ways to reduce breast cancer risk. We’ve known for quite some time that many phytochemicals in food such as fruits, nuts, and vegetables have properties that reduce cancer risk or help slow cancers that get established. Although there have been some misleading reports in the popular press saying antioxidants and other plant compounds are ineffective at modifying cancer risk, a healthy, plant-based diet is still a good way to lower risk, and is a good idea anyway.
Even more exciting is the possibility of directly affecting telomere length. Telomere length can be restored by an enzyme in our cells. Telomerase is a naturally-occurring enzyme that is inactive in most adult human cells, except immune cells and stem cells. Telomerase is attached to a short piece of RNA. RNA is a molecule that can encode genetic information, like DNA. The major difference is that RNA is single-sided instead of double-sided. One way to think of it is to picture DNA as a ladder that has been twisted. If some person came and cut each rung in half while leaving the rails alone, then that would be a molecule of RNA. The enzyme uses this short piece of RNA to form the letters of the telomere.
A recent study found a startling association between short telomeres and both a significantly increased incidence of and risk of dying from breast cancer. Another study using the same population in which the BRCA genes were isolated found that those members of the group that live the longest had not only long telomeres, but also a version of telomerase that is activated. This is exciting because the implication is if we can transiently stimulate the telomerase enzyme, we would be able to lengthen telomeres. This is not a cancer treatment, but it would be a way of directly reducing cancer risk at the cellular level.
As much as we’d like to be able to, we can’t directly give people such hyperactive telomerase. Instead, researchers are looking into substances that can stimulate the activity of the telomerase we already have. One such compound has been isolated from a Chinese herb, Astragalus, and is in testing phases right now.
There have been some scientists that worry active telomerase in cells might itself be a cancer risk. This has not been shown to be the case so far, however. Although tumor cells also have active telomerase enzymes, those same cells have critically shortened telomeres that make genetic mutations possible. Short-term activation of telomerase does not appear to turn normal cells into cancer cells.
Using exciting cutting-edge science and good nutrition and lifestyle choices, women can take back some measure of control over their risk of developing breast cancer. Instead of living in fear of the possibility, women can make a positive change in their lives.
- American Cancer Society. Breast cancer facts & figures 2009-2010. Atlanta: American Cancer Society, Inc. 2009
- Anisimov VN, Khavinsov VKh, Alimova IN, et al. Epithalon inhibits tumor growth and expression of HER-2/neu oncogene in breast tumors in transgenic mice characterized by accelerated aging. Bull Exp Biol Med. 2002 Feb;133(2):167-70.
- Cherkas LF, Hunkin JL, Kato BS, et al. The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008 Jan 28;168(2):154-8.
- Gradishar WJ. Magnetic resonance imaging screening without mammography: A new standard? Journal Watch Oncology and Hematology March 23, 2010
- Harley CB. Telomerase is not an oncogene. Oncogene. 2002 Jan 21;21(4):494-502.
- Jiang H, Ju Z, Rudolph KL. Telomere shortening and ageing. Z Gerontol Geriatr. 2007 Oct;40(5):314-24
Life Extension. Health concerns; Breast cancer [Internet monograph]. Fort Lauderdale, FL. Life Extension Foundation. 2010. accessed 07-30-2010. available from http://www.lef.org/protocols/prtcl-022.shtml
- National Institutes of Health National Institute on Aging. Exploring the Role of Cancer Centers for Integrating Aging and Cancer Research [Internet report]. Washington, DC. National Institutes of Health. August 6, 1009.accessed 07-30-2010. available from http://www.nia.nih.gov/ResearchInformation/ConferencesAndMeetings/WorkshopReport
- Ornish D, Lin J, Daubenmier J, et at. Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol. 2008 Nov;9(11):1048-57.
- Willeit P, Willeit J, Mayr A, et al. Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010 Jul 7;304(1):69-75.
- Wong JM, Collins K. Telomere maintenance and disease. Lancet. 2003 Sep 20;362(9388):983-8.