By Deborah Grainger
Since 1985, October has been designated Breast Cancer Awareness Month (BCAM) in the USA, which is now observed by many countries the world over. Originating from an initiative to promote mammography as the most effective way to beat breast cancer, BCAM has since evolved to a really big deal (and perhaps too big a deal?)
So as the swathes of pink wash over us, I thought the Proteintech Blog could do its bit by bringing you some often forgotten and lesser-known facts about the disease. Read on to find out how Pomegranates may help prevent breast cancer, (and how plasticware may cause it...)
Most of our readers are involved in scientific research in some form, so it’s not so earth‑shattering to reveal that breast cancer is not just one disease: it’s several grouped together. Typing and classifying tumors by their histopathology, grade, stage and even hormone receptor status, is routine in most healthcare settings. It’s well known that different tumor types have different progression rates and prognoses, for example: cancers positive for the estrogen receptor, the progesterone receptor or another receptor molecule called HER2, have more favorable clinical outcomes than those that lack all of these – so called triple negative breast cancers. It’s obvious that tumors falling into distinct categories require different treatment approaches; so why raise this point at all?
Well, we know that the classification and typing criteria we have at present is not the entire picture. Analyzing the genomes of a large cohort of breast cancers tells us that there could be at least 10 distinct subtypes of breast cancer, each with their own unique set of genetic drivers. Moreover, a lesson from the field of blood cancers has taught us that comparing the phenotypic similarities of tumor cells and normal cells can improve cancer classification. Santagata and colleagues set out to repeat this example in breast cancer, and found that there are 11 differentiation states of normal tissue – Until recently, only two cell types have been morphologically described in the human breast: the inner luminal cells and the outer myoepithelial cells. The paper goes on to suggest that the presence of vitamin D and androgen receptors be considered in the classification and treatment of breast cancers.
Several studies have reported that breast cancer is more common in the left breast than the right. Yet despite this intriguing correlation being first documented over sixty-five years ago, oncologists and scientists are still in the dark as to why this might be. One hypothesis puts it down to body asymmetry: the left breast is, on average, larger than the right and so more breast tissue simply leads to a greater risk. The same phenomenon has also been seen in patterns of male breast cancer.
Perhaps even more bizarre is the claim that handedness may play a role in breast cancer risk.
As women in developed countries are, on average, having children later in life, with an increasing number remaining childless, studies have linked nulliparity with an increased risk of developing breast cancer. Altered breastfeeding habits are also thought to contribute. The correlation between nulliparity and breast cancer wasn't lost on our medieval counterparts either: during the 14th century breast cancer was known as the nuns' disease because of its high frequency among this particular group of women. It’s an observation reinforced by a 1968 study, which found that nuns were more likely to die from breast, ovarian and uterine cancers than the general population. A group of medical researchers from Melbourne, Australia have gone on record to recommend that nuns take oral contraceptives to reduce their risk of reproductive cancers (though, unfortunately, there are no benefits associated with contraceptive use and the reduction of breast cancer risk – but there is now thought to be no elevated risk either.)
The vast majority of breast cancer patients are post-menopausal women, but the disease is not exclusive to individuals of this age group or gender: for instance, it widely known that men can develop breast cancer – around 2,000 a year in the US. A form of the disease can also affect children – one of the youngest breast cancer survivors on record underwent a radical modified mastectomy operation at just three years old in 2011 after being diagnosed with juvenile breast carcinoma at just two years of age. Juvenile breast carcinoma is extremely rare and is actually the same disease as secretory breast carcinoma that is also documented in adults. Secretory breast carcinoma is a distinct form of breast cancer that affects both sexes, and despite being described as a triple-negative cancer, it has generally favorable outcomes.
Eating the daily recommended intake of fruit and vegetables has many associated health benefits, but what if this food group could also inspire a generation of drugs designed to prevent cancer developing? Pomegranates, for instance, are touted to contain compounds that may prevent the growth of breast cancer cells. These antioxidant compounds – in particular one named urolithin B – dampen the activity of an enzyme called aromatase. Aromatase can drive the growth of estrogen receptor-positive cancers as it plays a key role in estrogen hormone synthesis. But before you go reaching for the toothpick and tucking into a fruit that requires the patience of a saint to consume one of these seeded treats, it’s worth remembering that our bodies are poorly equipped to absorb the levels of urolithin B used in the initial, in vitro study.
Aromatase inhibition and antioxidant activity, however, don’t seem to be the full story: when “pomegranate extract” was added to MCF-7 cells, a breast cancer cell line, genes associated with mitosis, chromosome organization, RNA processing, DNA replication and DNA repair were downregulated, and genes involved in the regulation of apoptosis and cell proliferation were boosted. This observation purports greater universal effects of pomegranate active ingredients. As these studies look at the effects of pomegranate derivatives on cancer cell lines it’s a big leap to say at this stage whether they will have the same effects in the human body. To varying degrees, there are similar stories to be found with blueberries, grapes and citrus fruits including oranges. Whatever the prospects of chemopreventative drugs developed from fruit-derived compounds, in the meantime eating more fruit and veg is one of the recommendations for lowering your overall risk of developing all cancers.
Taking vitamin and antioxidant supplements on the other hand has become a point of contention in cancer research of late, but it seems women (who are non-smokers at least) have no need to ditch the supplements just yet.
Bisphenol A, often referred to as BPA, is a carbon-based synthetic compound found at low levels in a significant amount of plasticware and canned items. BPA is interesting – and also worrying –because of its origins, uses, and effects on the body. First synthesized in the earlier half of the 20th century, it was originally used to enhance the growth of cattle and poultry. Terrifying Fascinating then, that upon the discovery it could mimic estrogen it was briefly used as a means of hormone replacement in women in the 1930's. As it binds weakly to both isoforms of the estrogen receptor, ESR1 and ESR2, it is now classed as a hormone disruptor. So how did it end up in plastic? Well in the 1950's the chemical industry figured out BPA could harden plasticware (go figure) and this delightful chemical has been in a lot of product packaging ever since. It hasn't set off major alarm bells because it is present in low levels, but there is mounting evidence that even at low levels chronic BPA exposure can increase the risk of breast and other cancers. Another way women can reduce their risk of developing breast cancer is to avoid or reduce their risk of BPA exposure. Steps like using glassware for food storage and avoiding certain types of plastic packaging can help. Breast Cancer UK provide more advice on how to reduce BPA exposure and how to advocate for the ban of BPA.
There were an estimated 40,000 breast cancer deaths in the US in 2013: an equivalent of one every 15 minutes. Only lung cancer accounts for more US cancer-related deaths in women. But the good news is that breast cancer death rates have decreased by at least 34% since 1990. This drop in breast cancer mortality has been attributed to both improvements in breast cancer treatment and early detection. To continue this trend, earlier detection methods using an enhanced cohort of reliable biomarkers and stratified treatment options are tipped to be the way forward.