Breast cancer awareness is very relevant (not only in this month of October). This disease is a big health problem, particularly in industrialised western countries.

It is one of the most common cancers, the number-one cause of cancer deaths in all women, and the commonest cause of death in relatively young women aged between 40 and 55 years. Its incidence in Malta (about 200 new cases annually) is not among the highest in Europe, as is often claimed in the media - the highest incidences are in northern Europe. However, our incidence is apparently higher than in neighbouring Mediterranean countries. I say "apparently" because our cancer incidence and mortality figures are as accurately collected and analysed as those in Scandinavian countries, but those of other Mediterranean countries are "estimates".

I will briefly discuss the nature of cancer in general and then move on to the specific problem of breast cancer. Different cancers are different diseases, but they have some things in common. They are all now thought to be a disease of stem cells. There are two broad types of stem cells - the germ cells (eggs and sperm) responsible for the creation of new individuals, and those found in all our adult organs, lying dormant until they are "instructed" to "wake up" and start dividing to replace worn out cells or cells damaged by trauma, infections, chemical toxins or other assaults on their viability. The remarkable difference between the stem cells of the very early foetus and those in our adult organs is that each one of the early foetal ones can produce a whole new individual, but the ones in our adult tissues can only make new ones similar to themselves.

After early foetal life therefore, stem cells lose the potential of making different tissues and whole new different organs - their initial pluri-potentiality is later suppressed and they are unable, for example, to regenerate an amputated limb. Understanding how this toti-potentiality of early foetal stem cells is later suppressed is one of the greatest and most interesting challenges of biology and medicine - if we learn how to unlock the suppressed pluri-potentiality of adult tissue stem cells, we would be able to make new cells and new organs damaged or destroyed by disease processes. It would also help in the endeavours to conquer cancer.

Cancer is caused when the mechanisms controlling our adult stem cells are damaged by the wear and tear of aging (hence most cancers occur after middle-age), harmful chemicals (e.g., smoking, environmental toxins), excessive or abnormal hormones, ionising radiation, longstanding stem cell overstimulation (as in chronically-inflamed organs) and viruses. Some damage to the stem cells' controlling mechanisms results in pre-cancerous changes; further acquired defects in these mechanisms then induce stem cells to go completely out of control to produce an invasive cancer. Depending on how big the acquired defects are in the growth controlling mechanisms of the cancer's cells, will depend on how slow-growing or how aggressively the cancer will behave. Aggressive cancers have the ability of spreading to other parts of the body, the most aggressive via the blood stream, and that is why some of them are more dangerous and life-threatening than others.

Early detection of cancer is vital because once it escapes to other parts of the body, a fatal outcome can usually only be delayed rather than prevented. Cancer screening means having apparently normal individuals undergo a test for early cancer detection, ideally when the disease is still in a precancerous stage without the potential to spread. Controversy raged a few decades ago about whether or not early detection of breast cancer was in fact useful - did it actually reduce mortality? Landmark Swedish mammographic breast screening research, initiated more than 30 years ago, eventually showed that detecting and removing breast cancers of less than one centimetre diameter greatly improved the chances of long-term survival, suggesting that cancers may not have spread while still small.

There is no doubt that mammography can detect small cancers which cannot be felt by self-examination or a doctor's hand. There is, of course, no harm in promoting self-examination, but not to the exclusion of mammographic screening.

There is no proof that self-examination alone reduces breast cancer mortality. Mammography is far from foolproof, because some breast cancers cannot be seen on a mammogram. Apart from this proviso, mammography (combined with ultrasound) currently remains the most practical means of early breast cancer detection. Breast MRI (magnetic resonance imaging) is now claimed by some specialist centres to be superior to mammography for picking up precancerous changes. However, there are currently few radiologists around the world experienced in breast MRI interpretation, and MRI is far more expensive than x-ray mammography.

Should therefore the introduction of a Maltese national mammographic breast screening programme be a public health responsibility? In theory, the answer should be "yes", particularly when our welfare state still claims to provide comprehensive medical services, including radiology and laboratory investigations, free to all citizenry irrespective of means. The answer should be "yes", in spite of two past health ministry expert reports casting doubt on the usefulness of mammographic screening on a national scale. I write "in theory yes" because there is no way the present set-up of the health division's mammographic service could cope with the workload and administrative complexity of a national breast screening programme, like the highly organised ones in the UK and Scandinavia. However, if human and other resources within our national health service (NHS) are insufficient for such a national programme, I believe it is our NHS's responsibility to at least provide mammographic screening to women who are 40 years and over and who demand it. Our NHS has provided free Pap smears for cervical cancer screening for 30 years, and it's about time it did the same for mammographic breast screening.

Earlier detection also enhances the chances of breast preservation, removing only part of the breast containing the tumour. This was a landmark advance in breast surgery because, with small cancers, the extent of local surgery has no significant effect on long-term survival. The next big advance was the introduction of chemotherapy immediately after surgery, improving long-term survival by killing cancer cells that were already spreading to other parts of the body. Researchers then stumbled across another landmark advance in anti-breast cancer drug therapy. What had proven to be an unsuccessful contraceptive pill, seemed to slow down and halt the growth of breast cancer cells in the laboratory. The drug was Tamoxifen and it proved to be a major advance by improving the chances of long-term survival.

Beware of your diet

Tamoxifen is a very weak artificial oestrogen which interferes with the cancer cells' receptor for the much stronger woman's oestrogen hormone. Tamoxifen belongs to a fairly new group of drugs called selective oestrogen receptor modulators (SERMs). Aromatase inhibitors are even newer drugs which block natural oestrogen production in all organs and are more powerful anti-oestrogenic drugs than Tamoxifen, but more expensive.

Newer chemotherapeutic agents which prevent cancer cells from multiplying or induce them to commit suicide, are taxanes (originally of plant origin but now copied pharmaceutically) and Herceptin. The latter is one of a new series of clever molecularly-targeted (and very expensive) anti-cancer drugs; it works by blocking one of the cancer cell's genes which makes a growth factor receptor. Trials suggest that if these new drugs are given to the right patients immediately after surgery, rather than wait for recurrence to appear, long-term survival improves. Another group of new drugs are so-called anti-angiogenic. These block the ability of the cancer to attract a new blood supply, thus starving it of nutrients and stopping its growth.

Some of these new drugs may produce dramatic disappearance of disseminated breast cancer. However, the emergence of these new very expensive drugs (not just for breast cancer) is posing a huge financial problem for modern health delivery worldwide. In Malta, for example, the prospect of such expensive drugs was not even on the horizon when the decisions to build a new hospital, and then double its size, were taken. It appears that the huge expenditure on the new hospital might be interfering with free provision of these new very expensive cancer drugs as part of the claimed free and comprehensive NHS. A recent European health consumer audit (The Times, October 3) confirmed this, giving the Maltese NHS poor marks for "new cancer drugs deployment speed and access to new drugs".

If the causes of breast cancer were known, prevention might be possible. Like many other cancers and chronic diseases, breast cancer is now thought to be caused by a combination of inheritance, hormonal, dietary and lifestyle factors. Very strong inherited predisposition is thought to account for a relatively small minority (probably less than 10 per cent) of breast cancers; the majority of patients have, in fact, no family history of the disease. One of the most illuminating observations is that Asian countries, like Japan and Korea, have very little breast cancer, and when these people emigrate to the US, their breast cancer rate rises to almost that of other Americans within one to two generations. This indicates that heredity is not the main factor. The traditional diets of Asian peoples are mainly vegetable-based. We now appreciate that the plant kingdom contains a vast array of compounds some of which might have health benefits to humans.

Apart from the fact that some of our pharmaceutical compounds originated from plants, we now know that some plants contain natural occurring SERMs with a similar anti-breast cancer action to that of Tamoxifen; these are found highly concentrated in legumes (the bean/lentil family). The staple diet in Asian countries is based on soya beans, which might therefore have a lot to do with their low rates of breast cancer. How many Maltese still have minestra full of favetta and other lentils several times a week? Other plant compounds may help prevent cancers because of anti-angiogenic properties, while others contain compounds which slow down or prevent the multiplication of cancer cells. Still other plant compounds may improve one's immunity to early cancer cells. These compounds appear to be mainly present in brightly-coloured vegetables like broccoli and tomatoes.

This is not to say that some vegetables and fruit will cure you of disseminated cancer, but some plant compounds might halt the early stages of cancer. They might also interfere with the establishment of cancer colonies in other organs, thus preventing recurrent disseminated cancer. Although these claims for plant products are unproven, statistics have long established that mainly vegetarian populations suffer less cancer (like breast) than populations eating mainly animal products.

Statistics also show a significant relationship between obesity and a number of cancers, including breast. Insulin is a growth hormone which encourages cancer when we have too much of it for many years, and overweight people tend to have higher blood insulin (hyperinsulinaemia). Lack of exercise and a diet rich in strong carbohydrates mainly in white flour, potato, white rice and sugar) increase the risk of hyperinsulinaemia. Lack of exercise and fast foods are major contributors to obesity. The danger of fast foods is in their fat and sugar/ carbohydrate (and salt) content. There is a misconception that fast foods consist of only burgers and chips; white bread, white pasta, pizza and pastries are fast foods that have similar carbohydrate and fat content to burgers and chips. Another misconception is that sweets and puddings are the only sources of sugar; all foods made from refined white flour, potato and white rice produce lots of blood sugar within an hour of eating them. Still another misconception is the notion that loads of white bread and white pasta are a healthy Mediterranean diet. The main healthy elements in the Mediterranean diet are vegetables, fruit, fish, nuts, olive oil and some red wine. Our staple diet of foods made from white flour, potato, margarine and lard is a dangerous, unhealthy Mediterranean one. No wonder we appear to have the highest rates of cardiovascular disease and breast cancer in the Mediterranean. Our fast foods make our high rates of diabetes worse, and diabetics have higher risk of cardiovascular disease and some cancers including breast.

An excessive influence of oestrogen (possibly also progesterone) on the breast seems to increase the risk of cancer. This explains why childless women, and women who have early menstrual periods and late menopause, have increased risk - their breasts have been exposed to more menstrual cycles in their lifetime. Obese ladies tend to have higher oestrogen blood levels because their fat cells convert other hormones into oestrogen.

Hormone replacement therapy for more than 10 years for menopausal changes also increases the risk somewhat. This risk varies from one individual to another and is difficult to quantify for a specific woman, but extra caution is used if she has a family history of breast cancer.

Although alcohol consumption (and red wine in particular) in moderation has been statistically shown to be associated with increased longevity, excessive consumption is linked to several cancers, including breast, possibly because it raises blood insulin and oestrogen. Women in industrialised countries now consume ever increasing amounts of alcohol. Other factors, such as breast-feeding and environmental pollution are thought to be of only minor significance in the causation of breast cancer. For breast-feeding to reduce breast cancer risk, it would probably have to continue for a few post-natal years and be associated with a significant length of cessation of menstrual periods, as may happen in Asian countries.

OCP doesn't boost breast cancer death risk

Survival is no better or no worse among breast cancer patients who have used the birth control pill, according to a report in the journal Obstetrics and Gynecology.

The findings are "broadly reassuring", Herbert R. Peterson of the University of North Carolina at Chapel Hill, one of the study's authors, said. "There just doesn't appear to be any concern about women using the pill at younger ages from the standpoint of breast cancer."

Concerns had been raised about oral contraceptives and breast cancer by an analysis of 54 studies, published in 1996, which found an increased risk of the disease among women currently on the pill, Dr Peterson noted.

Researchers hypothesised that women on birth control might have more consistent access to healthcare, and thus be more likely to have breast cancers detected early, which would mean they would have a corresponding reduced risk of being diagnosed with advanced disease.

To investigate, Dr Peterson and his team looked at use of oral contraceptives and the risk of dying from breast cancer among 4,292 women aged 20 to 54 who had been diagnosed with the disease.

The researchers found no increased risk of death associated with use of the pill, duration of use, or any specific oral contraceptive formulation. Women currently taking oral contraceptives were actually at 10 per cent lower risk of dying from the disease, but this finding may have been due to chance.

Another large study conducted in 2002 found no increased risk of breast cancer among women currently on the pill, Dr Peterson pointed out.

"There are now dozens and dozens of studies looking at the pill and breast cancer risk, and when you pull them all together they're broadly reassuring, both in terms of the risk and in terms of the risk of mortality," he said in an interview.

The one unanswered question remains the safety of the pill for women approaching menopause, given the increased risk of breast cancer recently identified for menopausal women taking hormone replacement therapy, Dr Peterson said.

"For healthy women over 40 who don't smoke, oral contraceptives continue to be an option for contraception, and for many a good option," he added. Nevertheless, Dr Peterson said, more research needs to be done to confirm that the pill is safe for older women.

Bristol breast cancer drug aims at sickest women

A new type of treatment for advanced breast cancer could win US approval this week and offer an option for patients whose cancer has continued to spread despite treatment with existing therapies.

The medicine, called ixabepilone, could generate annual sales of $500 million by 2012 and help Bristol-Myers Squibb reclaim a leadership role in oncology, according to industry analysts.

An estimated 160,000 women, and a relatively small number of men, in the US are diagnosed with breast cancer each year. About 40,000 die of the disease despite treatment with leading current drugs such as Taxol, Taxotere and Xeloda.

"Although three-fourths of breast cancer patients are responding well to existing tools, many are developing very advanced and protracted cancer because their have developed resistance to existing drugs," Renzo Canetta, a senior Bristol-Myers research official, said.

The New York-based company has asked the US Food and Drug Administration to approve ixabepilone as a stand-alone treatment, or in combination with Xeloda, for patients whose breast cancer has spread despite prior treatments.

Among patients taking it with Xeloda in clinical trials, tumours either shrank or did not grow for an average of 5.8 months. That was a statistically significant improvement compared to the 4.2 months seen for patients taking only Xeloda.

Two ongoing trials are expected to determine by late 2008 whether ixabepilone actually prolongs survival, Mr Canetta said.

"If the data show a survival benefit, that would make it more compelling to use against earlier-stage breast cancer," he said.

"In the past, when we were No. 1 in oncology, we were known for developing other people's drugs, but we are now discovering and developing our own," Mr Canetta said.

For instance, Bristol discovered and tested the company's recently approved Sprycel leukaemia drug and is studying a number of other compounds from its own laboratories, he said.

"A very clear strategic decision was made five to eight years ago to recommit ourselves to oncology, with a goal of dramatically increasing our ability to discover drugs," Mr Canetta said.

• Prof. Cilia-Vincenti is director of surgical pathology services at St Philip's Hospital. He is a former London University recognised teacher at Charing Cross and The Middlesex Hospital Medical Schools, and a former deputy dean of Malta's Medical School.

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