Ovarian cancer has the highest mortality of all cancers of the female reproductive tract. In part this is due to the lack of an effective and proven screening test for ovarian cancer. It is also not helped by the fact that ovarian cancer is a ‘silent’ cancer. It has very few symptoms in its early stage and when symptoms appear, the cancer is usually quite advanced.

Ovarian cancer accounts for approximately 4 % of all cancers in women and is the fourth leading cause of cancer-related death among women in the United States. It is estimated that, in 2007, there will be 22,430 new ovarian cancer cases in USA and 15,280 women will die of the disease. In the United Kingdom, it is estimated that every year there will be 6,700 new cases of ovarian cancer and 4,600 women will die from it. The incidence of ovarian cancer rises in a linear manner from the age of 30 to 50 years but continues to increase thereafter, albeit at a slower rate. While ovarian cancer is more common and has higher mortality rates in white women than other racial / ethnic group, ovarian cancer does not discriminate between colour and creed.

HRT is used to reduce menopausal symptoms in some women. While short term usage of HRT may not have long term sequelae, persistent usage of HRT may be associated with increased risk of developing ovarian cancer. The UK Million Women Study Group has just reported its findings on ovarian cancer and HRT (Lancet 2007, 19th April epub). The researchers studied 948,576 postmenopausal women who had no previous cancer or surgery to remove the ovaries. These women were followed up for an average of 5.3 years for incident ovarian cancer and 6.9 years for death. Among these women there were 287,143 current users of HRT. The study showed that current HRT users were 20% more likely to develop ovarian cancer and 23% more likely to die from ovarian cancer when compared to women who had never used HRT. For current users of HRT, the incidence of ovarian cancer increased with increasing duration of HRT usage. This increased incidence was not affected by the type of preparation used, its constituents or the way it is administered. Interestingly, current users were more likely to develop the serous type of ovarian cancer (other types of ovarian cancers include mucinous, endometroid and clear cell tumour). Past users of HRT were not at an increased risk of ovarian cancer. Expressed in another way, there will be one extra ovarian cancer in approximately 2,500 HRT users (when compared to non-users) and one extra ovarian cancer death in approximately 3,300 HRT users.

Is there something that a woman can do to reduce the risk of developing ovarian cancer? Perhaps there is. Researchers from Harvard Medical School analysed the data on 149,693 parous women involved in the Nurses’ Health Study and Nurses’ Health Study II (Cancer Causes Control 2007; 21st April epub). Compared to women who never breastfed, women who did breastfeed (median duration of breast feeding was 9 months) had a reduction in their risk of developing ovarian cancer. This beneficial association did not reach statistical significance. When they compared women who breastfed for 18 months or more against those who never breastfed, they found that women who breastfed had a significantly reduced risk of developing ovarian cancer. These women who breastfed had a 34% reduction in ovarian cancer risk and for every month of breastfeeding the relative risk of developing ovarian cancer was decreased by 2%.

If you have breastfed for 18 months or more and are taking HRT, what would your risk of developing ovarian cancer? That would be an interesting question to ask but there is no published data to answer it yet. For some women taking HRT is ‘necessary’. For these women, taking the approach that “I will only take HRT for the shortest possible time necessary” is probably the best one. For those women who are contemplating breastfeeding but feel ‘alone’, you can get some encouragement and support by visiting this site.

Breast cancer is the most common cancer affecting women. Hormonal treatment for breast cancer is an important aspect as the cancerous tissue can be oestrogen receptor (ER) positive or ER negative. ER positive cancer can be influenced by altering the hormonal environment in the body by using medicine such as tamoxifen. Post-menopausal women have been prescribed HRT to help retard the onset and progression of osteoporosis. In some women HRT has been used to relieve menopausal symptoms. As HRT medicine contains oestrogen, it might not be illogical to think that it may play a role in encouraging breast cancer tissue to grow more readily.

In 2002, the result of the randomized trial of the Women’s Health Initiative looking at the risks and benefits of oestrogen and progestin in healthy post-menopausal women was published. The trial involving 16,608 postmenopausal women found that there was a significant increase in the risks of coronary heart disease and breast cancer associated with the use of oestrogen-progestin combination therapy. As a result of this report, the use of HRT in the United States dropped dramatically. The total number of prescriptions for the two most commonly prescribed forms of HRT in the United States – Premarin and Prempro – had their steepest decline beginning in 2002 and in particular in 2003. (In 2001, there were 61 million prescriptions, 47 million in 2002, 23 million in 2003, 21 million in 2004 and 18 million in 2005!) Has this drop in HRT use led to a corresponding drop in the number of breast cancer cases in USA in this period?

A recent report (NEJM 2007; 356: 1670 – 1674) from an analysis of the data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registries showed that the age-adjusted incidence rate of breast cancer in women in the United States fell sharply by 6.75 % in 2003 when compared to the rate in 2002! The decrease was found to have started in mid-2002 and began to level off in mid-2003. Data from 2004 showed a leveling off relative to the 2003 rate, with little additional decrease. The decrease in the breast cancer incidence was evident only in women who were ≥ 50 years old and in cancers that were ER positive. This drop in breast cancer incidence seems to be temporally related to the first report of the Women’s Health Initiative study and the ensuring drop in the use of HRT in post-menopausal women.

Is this drop due to a cessation of HRT use or a reduction in the number of patients going for mammography? A study from the Geneva University looked at two populations, Geneva and the Netherlands, with comparably high levels of screening mammography but with different prevalence of HRT use (Breast Cancer Res Treat 2007; Mar 13 Epub). The use of HRT in Geneva is high while its use in the Netherlands is rather low. In the period 2001 – 2003, the annual increase in lobular breast cancer incidence was sharper in Geneva (10 %) than in the Netherlands (5 %). Since the only difference between the 2 populations studied was the prevalence of HRT use, the researchers concluded that the higher incidence of lobular breast cancer in Geneva is likely to be driven by greater HRT usage.

No doubt there will be researchers who will doubt the results of the US study and want further, bigger studies to confirm or refute the link between HRT and breast cancer incidence, but for others they would caution the public on HRT usage.

If you are using HRT or considering its use, the best thing to do is to consult your doctor and discuss thoroughly before making a decision.

“What supplements should I take to help combat my cancer?” This is quite a common question that I get asked in my practice. While the question may seem logical and innocuous, it is actually not an easy question to answer. It is not easy to answer either because there is no available information on their use in cancer cases or evidence to support their use in cancer cases is conflicting.

CAM can be defined as products and practices that fall outside the realm of conventional medicine. When CAM is used in conjunction with conventional approaches, its use is termed complementary. When a patient shuns conventional medical therapy and uses CAM instead, it is then termed alternative medicine. In 2000, a US survey of patients with cancer showed that > 80% reported using CAM.

One of the main categories of CAM is antioxidants. Reactive oxygen species (ROSs) are produced in our body on a daily basis. These molecules can cause severe damage to DNA, proteins and lipids in the body when there are high or sustained levels of ROSs. This oxidative stress has been implicated in a number of diseases such as atherosclerosis, diabetes, cancer and in the aging process. As a result, the ingestion of CAM with antioxidant properties by cancer sufferers is a logical step. Examples of antioxidants taken as CAM includes astralagus (Astralagus membranaceus), β-carotene, coenzyme Q10 (ubiquinone), Essiac tea (a combination product that includes burdock root, sheep sorrel, slippery elm and Turkish rhubarb), garlic (Allium sativum), ginkgo (Ginkgo biloba), grape seed extract (Vitis vinifera), milk thistle (Silybum marianum), selenium, Siberian ginseng (Eleutherococcus senticosus), superoxide dismutase, vitamin A, vitamin C (ascorbic acid), vitamin E (α-tocopherol) and zinc.

Life becomes difficult for a conventional physician to recommend or endorse CAM use either because of a lack of efficacy or a lack of information on its use. An observed beneficial effect of a particular supplement may turn out to be false when it is tested in a formal study. One good example is the hypothesis that β-carotene can be used for cancer prevention. The Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) trial and the Beta-Carotene and Retinol Efficacy Trial (CARET) were 2 large trials designed to determine the chemopreventive efficacy of β-carotene on lung cancer risk. Surprisingly, both studies demonstrated an increased cumulative rate of lung cancer and cancer mortality (ATBC) or all-cause mortality (CARET) in the treatment groups compared to controls. Another example is the potential use of lycopene, a powerful antioxidant present in tomato, supplement to influence the level of prostate cancer tumour marker. Researchers from Mayo Clinic found that the lycopene-rich tomato supplement did cause a > 50% decline in the tumour marker level in one patient. However, when the whole group was considered, the supplement did not have a significant effect on the tumor marker level in the whole study population (Urology 2007; 69: 289 – 294).

On a more cheerful note, a research group from San Francisco performed a meta-analysis on the potential benefit of taking oral vitamin D in reducing cancer mortality in Europe and the United States of America (Recent Results Cancer Res 2007; 174: 225 – 234). (Sunlight ultraviolet B exposure and / or vitamin D have been found to be inversely correlated with incidence, mortality and / or survival rates for breast, colorectal, ovarian and prostate cancer and lymphoma.) Based on their estimation, a daily intake of 1000 IU/day of vitamin D could lead to a reduction of cancer mortality rate of 7% for males and 9% for females in USA and 14% for males and 20% for females in Western European countries below the 59 degrees latitude. In America, while the cost of providing 1000 IU of vitamin daily to all adult Americans would cost about $1 billion, the expected benefits from reducing cancer mortality would amount to $16-25 billions.

When a cancer patient considers taking or is taking CAM, as clinicians we need to be aware of 6 characteristics of the CAM: antioxidants, anticoagulants or procoagulants, immunosuppressives or immune-modulating agents, hormonal properties, known safety issues and known or theoretical drug interactions. If we know that the supplement is toxic to the body then we have to advise the patient against taking it. If there is a lack of information on risk and benefit of the supplement, it is hard for the doctor to be dogmatic about its use or not. Even if there is evidence that the CAM is ineffective, should the doctor object to its use?

My personal philosophy is that as long as the CAM is known to be not toxic or harmful, even if it has been shown to be ineffective, I would have no objection to its consumption by the patient. If the patient feels better taking the CAM it is fine with me. We must not forget that the power of suggestion can be strong and may benefit the patient psychologically and emotionally. After all, the role of a doctor is to help alleviate suffering.