Cancer in Women - Cancer Chemotherapy Treatment

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Introduction - What is Cancer

Cancer is characterised by an abnormal, uncontrolled growth that may destroy and invade adjacent healthy body tissues or elsewhere in the body (secondary spread - secondary deposits secondaries - metastases).

Living organisms (all animals and plants) are made of cells. The simplest organisms consist of just a single cell. Each cell has a central control, the nucleus surrounded by cytoplasm (Fig. 21.2). The nucleus contains the genes, which are the biological blueprints that control the structure and function of the organism. The genes are the chromosomes each human cell has twenty-three pairs. Each chromosome is composed of DNA (Deoxyribose nucleic acid) and the DNA is a string of nucleotides. There are four nucleotides (A, C, G and T). The genetic code is a long string of these nucleotides grouped in threes e.g. ACG, TTT, CAG etc. The analysis of the human genetic coding has reached completion. It has been suggested that the full code would require 40 large volumes using a standard print size.

The human body has billions of cells (Q 2.1). Most cells have a limited life-span and need to be replaced. Cells are capable of duplicating themselves. Before birth and through childhood our bodies grow mainly through increase in cell numbers. The body's cells are dividing throughout life. The red blood cells, for example, only survive for 120 days about one per cent of the circulating red cells are therefore replaced each day. Little is currently known about how the cells are replaced in such an orderly and precise fashion. Fundamental to the process is the doubling of the chromosomes (mitosis) during cell replication so that each new cell has an exact copy of the chromosomes laid down in the original egg at the time of fertilisation. There are natural mechanisms that speed up the process if there has been an excessive amount of cell loss: for example, following blood loss the process of red blood cell replacement is temporarily increased.

Millions of cell divisions and replications occur daily in the body and it is astounding that the process occurs so perfectly most of the time every cell division requires replication of the 40 volumes of genetic coding. On rare occasions there is some defect in a division and a rogue (mutant), potentially malignant cell arises. The immune system seems to recognise such occurrences and is generally capable of removing the abnormal cells before they have an opportunity to proliferate. Rarely, there is a failure of the mechanism and a potentially malignant cell survives, replicates and cancer is the result.

The four more common female cancers have their origins in the ovaries, body of the uterus, cervix of the uterus and breast, and they strike at the heart of femininity and sexuality.

In general, the prevalence of cancer increases with age.

The Incidence of Cancer Increases With Age

http://info.cancerresearchuk.org/cancerstats/incidence/age/

Life expectancy is increasing and as a result cancer prevalence increases.

Increasing Trend In Life Expectancy - This example is from Australia. As cancer prevalence is related to age, cancer is increasing.

- Australia

Cancer Staging

Cancer staging is an agreed and defined classification of the spread of the disease determined around the time of the initial diagnosis. Stage I disease usually indicates that the tumour is confined to the organ of origin when surgical removal of the tumour or organ is likely to be associated with a good prognosis. Stage IV disease usually indicates that the tumour has spread widely and the prognosis is less favourable.

Prevalence Of Cancer In Women

Internationally, it has been estimated that one in four people will develop cancer during their life and one in five will die as a result. One in three British people will develop cancer.^2006-01 Whilst children can develop some malignancies such as leukaemia, cancer becomes increasingly common as we age. Table shows the increase in the incidence of cancer associated deaths in relation to women's cancers. More than 70% of cancers first appear after the age of 65 years. In the USA, there are 2.3 million deaths annually. The commonest cause of death is heart disease (732,000 deaths 32%) and cancer is the second most common cause (534,000 23.4%).Figure 32.1 shows the incidence of new cancer cases according to site of origin and the number of deaths in the USA for 1997 estimated by the National Cancer Institute. The cost for all healthcare in the USA in 1990 was $585 billion and 6% of this was for cancer. Figure 3 showing the major causes of mortality in the USA in 2002. (The American Cancer Society)

Lifetime Probability of Developing Cancer in Women

www.cancer.org/downloads/STT/Cancer_Statistics_Combined_2007. Ppt

Estimated Cancer Cases In Men and Women

New Cancer Cases in Women

New Genital Cancer Cases in Women

Cancer Incidence Rates For Women

Cancer Incidence Rates For Men And Women

http://info.cancerresearchuk.org/cancerstats/incidence/trends/

Related Medical Abstracts - Click on the paper title:-

Incidence of the major cancers, 2004, England (2006-01)

The incidence of new womens cancers in the United States in 1997 are indicated in Figure 32.2. In the United States the combined incidence rates of the three main s (uterine cervix, body of the uterus and ovary) is 43.6 per 100,000 women whereas the incidence of breast cancer is 109.5 per 100,000 women.

Changing Incidence of Women's Cancer

The prevalence of major cancers changes with time:

Percentage change in the age standardised incidence rates - UK 1994 - 2004

There is evidence that the number of women dying from cancer in the under 65s has fallen in developed countries over the last 20 years. It is difficult to be certain why this has happened as there are likely to be a number of confounding factors. Screening for cancer and pre-malignancy and improvements in the treatment of cancer are thought to have played a significant part.Figure 32.5 shows the fall in the mortality rates in the USA (Data from The National Cancer Institute - Cancer Mortality Rates from 1973 to 1994 - age under 65 in the USA).

Table showing that the death rates for heart disease and strokes have improved since 1952, the overall death rates for cancer has remained static.

We know that there are certain risk factors for cancer although exactly how they work is not known. We do not know why some individuals or families seem more prone to cancer although this is presumed genetic (their chromosomes are more susceptible). In some cases it may be that mitosis has been abnormal and in others the immune system fails.

Some infections may be associated with subsequent malignant change. We now know that specific strains of the human papilloma (wart) virus can be linked to pre-malignant and malignant changes in the cervix. Sexual activity is almost invariably a factor with cervical cancer (neck of the womb); the younger sexual activity commences and the greater the number of partners, the higher the risk.

Hormones may alter the chance of cancer developing. Pregnancy seems to reduce the incidence of breast cancer and ovarian cancer. Hormone replacement therapy decreases the overall chance of cancer although there is a small (1.5%) increase risk of breast cancer if a woman starts the HRT at the age of 50 and continues to take it for 10 years (Q 27.15).

The incidence of cancer rises with age. This is possibly a reflection of the number of times that cells have been replicated from the time of conception or that the immune system has become less effective in removing the abnormal cells. As life-expectancy increases, the apparent incidence of cancer increases. Many women, who would have died relatively young from childhood illnesses, complications of childbirth or diseases such as tuberculosis just a century ago, now survive to an age where cancer is more likely to occur.

Carcinogens are chemicals that increase the risk of malignant change. The most publicised carcinogens are in tobacco and these increase the risk of lung cancer.

We understand that infection covers a multitude of illnesses ranging from a common cold, through malaria, tuberculosis and AIDS. Similarly, cancer covers a multitude of conditions that have different causations and they respond differently to treatment. A review of the causation of women's cancers provides an illustration (Cervix -cervical cancer ; Endometriumendometrial cancer ; Ovary -Q32.28 and8 breastQ 27.14).

Familial Cancer

One person in three will develop cancer so that even if one or two family members have developed cancer, it does not necessarily mean that other family members are more at risk. There are, however, some families with an even higher incidence and extra vigilance would be appropriate. Perhaps five to ten per cent of cancers are associated with faulty genes that run in families (Q32.39 /40).

Women's Cancers - Symptoms - Signs - Diagnosis

Irregular vaginal bleeding may be the first sign of cervical cancer or lining of the uterus and, therefore, recurrent bleeding between periods requires medical assessment particularly after the age of thirty-five. The first symptoms of cervical cancer include post-coital bleeding (bleeding after sexual intercourse) and blood stained vaginal discharge. The average age of presentation of cervical cancer is 45 and for endometrial cancer it is 55. Ovarian cancer may present with enlargement of the abdomen or abdominal pain. Vulval cancer may present as a swelling or an ulcer on the vulval skin.

It must be emphasised that most patients presenting with any of these symptoms will not prove to have cancer. Persistence of symptoms indicates the need for increased vigilance. It is for the doctor to assess from the story and examination findings, which investigations, if any, are required.

Preventing Women's Cancer

Questions relating to prevention or early diagnosis of the ?female? cancers require the fullest discussion. Cancer of the genital organs or breast is the greatest concern, if not fear, of many patients attending their gynaecologist. Initially patients may worry that their presenting symptoms indicate that they already have cancer. The possible treatments for gynaecological problems usually include the administration of hormones and there can be anxiety that these may increase the risk of cancer developing.

The best form of treatment is prevention. Screening programmes are targeted at those most at risk of developing a disease with the objective of early diagnosis before the disease becomes too advanced for curative treatment.

Pre-malignant changes of the cervix begin several years before invasive disease. Screening is designed to pick up the pre-malignant areas so that they can be destroyed before cancer occurs.

Cancer of the endometrium similarly passes through a pre-malignant phase (hyperplasia with severe atypia) before cancer develops.

A 42 year old lady presented with bleeding between her periods. Hysteroscopy with D and C (hysteroscopy D and C) were performed. The histopathology (11) showed endometrial cancer. Hysterectomy was performed and the histopathology showed residual hyperplasia only the tissue that had become malignant had been removed by the curettage. The prognosis for this lady is excellent.

Endometrial carcinoma is more common in those who have had relatively high oestrogen levels particularly if the endometrium has little protection from progesterone. Anovulation (menstrual cycles where no egg is released) is characterised by low progesterone levels. Obese women are more prone to high oestrogen levels and anovulation is one cause of heavy periods. Pre-malignant and malignant changes of the endometrium are very uncommon before the age of forty years. Endometrial sampling, usually by curettage, should be considered if periods are heavy in a lady over forty (hysteroscopy D and C). Irregular bleeding between periods (intermenstrual bleeding) may be a symptom of endometrial cancer and is another important indication for sampling the endometrium in the same age group and in women in their later thirties. Bleeding after the menopause, which is called postmenopausal bleeding, could be due to an endometrial cancer. After the menopause, the endometrial thickness should be 5 mm or less on ultrasound examination. Endometrial sampling is no longer mandatory in the investigation of postmenopausal bleeding provided ultrasound is reassuring.

Ovarian cancer is relatively silent so that the majority of ovarian cancers are diagnosed relatively late. Unlike the cervix and endometrium, the ovaries have no surface that is amenable to sampling. Ultrasound and tumour markers are under evaluation for early identification of ovarian cancer. If the disease could be identified early, the chance of successful treatment would be greatly enhanced.

In common with the ovaries, the breasts do not have a surface that can be sampled for identification of pre-malignant or malignant changes. You can examine your breasts for the presence of small lumps. Mammography and ultrasound of the breasts provide screening to identify early disease and thus improve the chance of cure. Some genes have been identified that are associated with increased risk for cancer of the breast and ovaries (Q32.40).

General health measures may reduce the risk of certain cancers. Obese women, for example are more likely to develop endometrial cancer.

With the exception of breast cancer, little is known about the effect of moderate intakes of alcohol, or of particular types of alcohol, on cancer risk in women. A total of 1,280,296 middle-aged women in the United Kingdom enrolled in the Million Women Study were routinely followed for incident cancer.A quarter of the cohort reported drinking no alcohol; 98% of drinkers consumed fewer than 21 drinks per week, with drinkers consuming an average of 10 g alcohol (1 drink) per day. During an average 7.2 years of follow-up per woman 68,775 invasive cancers occurred.

Increasing alcohol consumption was associated with increased risks of cancers of the breast (12%), and total cancer (6%, 95% CI = 4% to 7%, Ptrend < .001). The trends were similar in women who drank wine exclusively and other consumers of alcohol. For every additional drink regularly consumed per day, the increase in incidence up to age 75 years per 1000 for women in developed countries is estimated to be about 11 for breast cancer, 1 for cancers of the oral cavity and pharynx, 1 for cancer of the rectum, and 0.7 each for cancers of the esophagus, larynx and liver, giving a total excess of about 15 cancers per 1000 women up to age 75.⁰⁹⁰¹

Screening For Women's Cancers

The objective of screening is to detect evidence of increased risk of disease development or to pick up disease at an early stage when the chance of successful treatment is optimised. Screening may include clinical examination by your doctor, blood tests, x-ray (e.g. mammography), ultrasound (e.g. ovaries, uterus, breasts), and cervical smears.

A. The effectiveness of a screening test must be judged on several criteria:-
B. The condition sought should be an important health risk.
C. The disease should have a well understood natural history (course).
D. The disease being screened should have an effective treatment when found early.
E. The test should be inexpensive so that the majority of those at risk can have the test.
F. The false negative rate should be low (high specificity) the disease should not be missed.
G. The false positive rate should be low (high sensitivity) few patients should be given unnecessary anxiety.
H. The test should be acceptable to the population.
I. Screening should be repeated at intervals depending on the natural history of the disease.
J. The risks of the test should be low.

An evaluation of screening tests for breast cancer has been applied to these criteria in Q32.35 The majority of cancers can be successfully treated if they are caught early. In an ideal world, screening tests would be 100% successful with no false positive results causing unnecessary anxiety. Sadly, no screening test is perfect. Screening has undoubtedly reduced the risks but there is still room for improvement.

The majority of blood screening tests have a cut-off limit as there is rarely a test where the chemical being measured is not present to some degree in healthy people. The ability of a blood screening test to diagnose a disease process (F - specificity) and its sensitivity (G) will often depend on the cut-off level (Figure 32.4). If the cut-off level is arbitrarily decreased specificity will be increased but sensitivity will fall leading to unnecessary anxiety for some. The reverse would apply if the cut-off level is increased the test would miss the disease more often but there would be less unnecessarily worried people.

Emotional Effects Of Cancer

Very bad news leads to a number of ‘shock’ reactions including depression. A diagnosis of cancer is likely to result in initial numbness and a feeling of unreality. There may be anger. Some go into denial and others may start to blame themselves and at times those who have been caring for them. Fear of the disease and treatment are likely to follow. There may be bereavement with feeling of loss of an organ if hysterectomy (hysterectomy)for example is required and perhaps grief for the potential loss of valuable years. Family and friends are also likely to go through this emotional turmoil.

Cancer Counselling

When cancer is diagnosed it is a most traumatic experience and there is usually need for the patient and her family to discuss their emotions. Many hospitals have counsellors trained to provide support at this difficult time. The general practitioner has an important role to play in supervising the situation when the patient is at home. Often the general practitioner will know the family well, almost as a family friend. Specialist doctors are best placed to advise on treatment.

Personality and Cancer

A study was carried out in 1982 by a psychologist at King's College Hospital. Those with a fighting spirit lived twice as long as those who had a negative outlook.

However, a review of the literature found no benefit in survival relating to the patient's spirit.

Holistic Approach To Cancer In Women

The treatment of cancer is developing rapidly and the success of orthodox medicine is beyond dispute. The holistic approach to treatment is a current buzz word often used by those without medical qualification who wish to advertise there own brand of treatment. Doctors are highly trained to understand disease processes. We learn a logical approach to diagnosis and the application of appropriate treatments. The importance of treating each patient as an individual person is emphasised throughout medical school and postgraduate training. Some patients may feel the need for complementary medicine. In my view this should never be recommended without exhausting conventional medical treatment. Disease processes such as cancer may run an unpredictable course and success stories could have occurred by chance rather than as a result of an unproven treatment.

Cancer of the Vulva Vagina and Fallopian Tubes

Cancer arising from these sites is uncommon. They occur mainly after the menopause and they are best treated by a gynaecologist with special interest in cancer.

There are four main treatment options to try to remove or destroy cancer. Surgery aims to remove the growth completely or otherwise as much as is safely possible (debulking). Radiation destroys cells and its effect is more marked on some malignant tissues than healthy tissues. Similarly, the objective of chemotherapy treatment is to use drugs that kill malignant cells selectively. Some tumours are inhibited by hormone therapy. Cancer specialists (oncologists) may recommend additional treatment after surgery to improve cure rates even if there is a high chance that surgery has completely removed the tumour.

A: Surgery

Surgery is increasingly undertaken by those with a special interest in the subject. Similarly, surgery on the breast is usually undertaken by a general surgeon with a corresponding special interest. The surgeon is always balancing the potential benefits of the operation and the risk of complications (surgery risks). Some patients are anxious about surgery for cancer as they fear that the operation can accelerate the disease. There is no evidence that this happens. There are times when the cancer is found to be more advanced at surgery than expected and the outcome is less favourable.

Surgical removal of the tumour is the primary treatment for endometrial cancer, ovary and breast. In the early stages of cervical cancer surgery is the first line of treatment particularly in younger healthy women. Extensive surgery for cancer is termed ‘radical’. A Wertheim’s hysterectomy, employed for the surgical treatment of early cervical cancer, involves removal of lymph glands and tissue on either side of the uterus and it is, therefore, more extensive than the usual abdominal hysterectomy. The pendulum swung initially towards radical surgery but recently back towards less extensive surgery. With early cervical cancer, some specialists are now removing the lymph glands laparoscopically and removing the cervix whilst leaving the uterus and fertility intact. Similarly, removal of the whole breast (mastectomy) is no longer as frequently employed. Removal of the lump (lumpectomy) and dissection of lymph glands has become more popular. Ovarian cancer is an indication for surgical removal of all of the tumour if possible or otherwise as much as possible. There is still some debate as to the advantages of radical surgery for ovarian cancer as complication rates are increased with more aggressive surgery. Beyond the age when fertility is an issue, hysterectomy with removal of both ovaries is usually the objective. In a young woman with tumour confined to one ovary, removal of that ovary alone may be all that is required.

In the majority of cases the surgical objectives for ovarian tumours are straightforward but there are times when there are confounding factors. For example, the patient may be keen to conserve at least one ovary and her uterus but the surgeon may be concerned about leaving undiagnosed malignancy. A frozen section (a representative sample removed at operation and examined microscopically during the operation providing a provisional answer within a few minutes) is only of value in a small number of cases.

A 32 year old lady attended for her initial pregnancy assessment at 12 weeks. This was her second pregnancy. In her first pregnancy her AFP (Q32.25) level was low, at that time indicating further investigation (amniocentesis – obtaining a fluid sample from around the baby) to exclude Down syndrome. That test proved negative and she went on to deliver a healthy baby.

At the first examination in the second pregnancy the uterus seemed to be larger than would have been expected for her dates. The two more likely causes would have been twins or that the pregnancy was more advanced than the dates indicated. An ultrasound examination was re quested and this demonstrated just one baby with a size consistent with the dates. The right ovary was enlarged and our radiologist was suspicious of ovarian malignancy. A blood test was sent for tumour markers and the AFP was extremely high. Now the most likely diagnosis was a yolk sac tumour, which is an extremely rare occurrence. Advice was taken from several experts. At 16 weeks into the pregnancy a laparotomy was performed. The tumour was confined to the right ovary which was removed. It proved to be a malignant teratoma which is even more rare than a yolk sac tumour. The pregnancy continued and serial scans and AFP tests were reassuring. At 38 weeks an elective Caesarean section was performed. A healthy baby was delivered and the opportunity taken to confirm that there was no evidence of tumour. Mother and child have done well and 11 years later there remains no sign of the original tumour returning.

This tumour has almost certainly been cured by surgery alone. Radical surgery, chemotherapy or radiotherapy were never required. Malignant teratomas are highly malignant but in recent years the prognosis has improved as they tend to be sensitive to chemotherapy if required. This case is interesting for a number of reasons not least being that it was detected early because of clinical examination simply to assess early pregnancy.

Some malignancies, such as cervical cancer may be particularly sensitive to radiotherapy. There are a variety of radiation sources and the treatment requires careful planning by doctors and physicists specialising in this mode of treatment. Traditionally, special applicators were introduced into the uterus and vagina and radium was inserted into these applicators. They were kept in place for up to 48 hours and during this time the patient was kept still to prevent movement of the applicators. There have been significant advances and radiotherapy is faster, less painful and associated with less complications than even a few years ago. The applicators are introduced under general anaesthetic and the radioactive sources are after loaded to protect staff. The modern sources provide stronger radioactive output so that treatment has been reduced to less than 30 minutes. Pelvic radiotherapy can cause troublesome diarrhoea.

Cancer chemotherapy treatment employs cytotoxic (toxic to cells) drugs that interfere with the cell division of malignant cells. There is a fine balance between the maximum dose of these drugs that can be safely given and the risk of damaging healthy tissues. Cytotoxic drugs affect cells that are dividing rapidly. Common side effects, therefore, include anaemia, reduced resistance to infection, ulcers, and hair loss. Some cytotoxic agents are given by mouth although most are given though a vein (intravenously). They may be given over the course of a few days and are often repeated at three or four week intervals. Treatment of ovarian cancer has improved the short and medium term survival. New chemotherapeutic agents are being developed and evaluated by clinical trials. Chemotherapy is particularly effective against ovarian germ cell tumours.

Some cancers, particularly endometrial cancer and breast are hormone sensitive. There is evidence that breast cancer outcome is more favourable for some women who are given tamoxifen, which is an anti-oestrogen. Cancer of the uterus seems to be inhibited by progestogens and it is our policy to commence medroxyprogesterone if the diagnosis is suspected at curettage; it is continued for one year.

Age Standardised Mortality Rates For Cancer In General And Breast Cancer, Cervical Cancer and Ovarian Cancer In Particular.

Mortality Statistics for England And Wales. Death Rates Increase With Age And Cancer Is Increasing As Life Expectancy Increases.

The Age Adjusted Death Rates From Breast Cancer And Uterine Cancer Have Fallen But It Has Risen For Ovarian Cancer.

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