Nerdy Science Blog

Breast Cancer is the most common cause of cancer in women and as per statistics, the second most common cause of death in women in the U.S. aged between 45 and 55. No one knows the exact cause of breast cancer but there are women with certain risk factors that are more likely to develop the disease. It should be mentioned that a even when a woman with risk factors develops breast cancer, it is hard to know just how much these factors contributed to her cancer. There are certain risk factors like gender, race and ethnicity, family history, aging and dense breast tissues that you cannot change. But there are certain lifestyle risk factors that you can keep track of to reduce the chances of the disease. Let us take a look at these lifestyle risk factors that can cause breast cancer.

1. Child-bearing factor. A woman who has her first child after the age of 35 stands a greater chance of getting breast cancer than a woman who has her first child around age 20. The older she is, the greater the risk of developing breast cancer. Further, having more than one child at an earlier age reduces her risk of the disease and having no children at all increases the risk. Pregnancy reduces a woman’s total number of lifetime menstrual cycles, which may be the reason for this effect.
2. Recent Use of Birth Control Pills. Women who are recent users of oral contraception have a higher risk of developing breast cancer. The risk is highest for women who start using oral contraceptives as teenagers. However 10 or more years after they have stopped taking oral contraceptives, the risk comes down considerably. Women who plan to take oral contraception must discuss the side-effect of breast cancer with their doctor.
3. Not Breast Feeding. Women that do not breast feed their babies stand a slightly higher chance of breast cancer than women that breast feed their babies for a long period of time like 1-2 years. This could be attributed once again to the reduced number of menstrual cycles that goes with breast feeding.
4. Lack of Physical Exercise. When women do not include exercise as a part of their daily routine, they elevate their risk of breast cancer. A sedentary life style with absolutely no physical activity makes them susceptible to the disease. An ideal exercise program to reduce the risk would be about 45-60 minutes, 5 days a week.
5. Alcohol Consumption. The more the alcohol intake of women, the higher the risk of breast cancer. Alcohol consumption is clearly linked to an increased risk and it has been found that women who have about 2-5 drinks daily have about 150 % higher chance of breast cancer than those that do not consume alcohol at all. It is suggested for women to limit their alcohol consumption to one drink a day if they have to drink at all.

There are other factors too like post menstrual hormone therapy, obesity and high fat diets that are said to expose women to breast cancer. Keeping a check on these factors after discussing them with your health team will help reduce the risk of the disease.

By-line:

This post was contributed by Holly McCarthy, who writes on the subject of the certification for geriatric nursing. She invites your feedback at hollymccarthy12 at gmail dot com

ADI-PEG 20 is a cancer drug that is developed by TDW Pharmaceuticals.  TDW Pharmaceuticals is the Taiwanese subsidiary of the US-based Polaris Group of pharmaceutical companies.  ADI-PEG 20 is a cancer drug for liver and cancer and metastatic melanoma, which is safer than Sorafenib.  It is ready for Phase III clinical trials to test on large patient groups.  The drug is promising for pancreatic, prostrate and kidney cancers treatment.  Unlike conventional cancer drugs which destroy cancer cells’ DNA, ADI-PEG 20 is a protein drug that breaks down arginine (required by cancer cells to grow and survive) in human blood, hence inhibit the proliferation and growth of cancer.  Another advantage of ADI-PEG 20 is that it only need to be injected once a week and won’t affect the survival of normal cells.  The drug is expected to release into market at the end of 2011.

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Chemotherapy had been used with one of the two intentions: the hope to cure cancer, and the hope to prolong life. Palliative chemotherapy/care means chemotherapy which is taken without expecting it to be curative. In other words, palliative chemotherapy is a form of medical treatment that concentrates on reducing the severity of the disease symptoms, rather than trying to provide a cure. This means that most of the time, palliative chemotherapy are only offered to patients with incurable cancer, preferably to patients with excellent performance status and a tumor sensitive to chemotherapy.

Just like treating cancer, cytotoxic drugs are also used in palliative chemotherapy. They attack cells during cell divisions. They could be phase specific and cycle specific. Phase-specific drugs kill cells only when they are given during a certain phase of cells’ cycle. By prolonging the treatment using such drugs, the number of cells killed increases because cells divide randomly. Cycle-specific drugs target cells during any phase of the cells’ cycle, thus the number of cells killed increases when the dosage of such drugs increase. Other Antimetabolites are given as well. These anti metabolites could interfere with the incorportation of nucleic acid bases into the DNA.Given the potential toxicities of the chemotherapeutic agents, it is important to educate patients about the side effects of the drugs consumed. The main challenge for both the doctors and patients would be balancing symptom relief and treatment’s side effects. It is also crucial for the doctors to maintain a holistic view of patients with cancer and help patients to achieve the best possible quality of life.

The main goals of palliative chemotherapy are:

1. To relieve symptoms. By reducing a tumor, symptoms like shortness of breath and pain could be reduced. The effects of palliative chemotherapy in relieving symptoms vary, depending on the location of the tumor..
2. To improving quality of life. There are studies and clinical trial data showing that such chemotherapy could improve the quality of life of the patients, and unlikely to result in any major survival advantage
3. To slow the progress of cancer.

The survival benefits of palliative chemotherapy tend to be modest, and are usually measured in months rather than years. Even though such treatment could support the patients but usually there are always a wide gap between the patient’s hope and what is achievable. A United Kingdom based study shows that palliative chemotherapy could help to extend a patient’s life, who is suffering from non-small-cell lung cancer, for up to 2 months. 3 to 6 months for those suffering from pancreatic cancer. 5 to 9 months for those suffering from colorectal cancer.

In most countries, palliative care is provided by a team, consisting of doctors, nurses, nursing assistants, physiotherapist, social workers, volunteers and family members. The team would focus on optimizing the patient’s comfort. In the UK, palliative care includes inpatient care, day care, home care, and outpatient services. Palliative care may range from managing physical signs and symptoms of the patients, to treating depressions, to the care of patients during their last days and hours.

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Chemotherapy – in the general sense, means using chemical agents to kill cells, and in most cases, specifically those of cancer. In its non-oncological use, the term may also refer to antibiotics, used to kill micro-organisms.

Brief History
History of chemotherapy can be traced back to the discovery of nitrogen mustard (used as a chemical warfare agent), as an effective treatment of cancer. Two pharmacologists, Louis S. Goodman and Alfred Gilman had discovered lymphoid and myeloid suppression on people exposed to the mustard gas. Soon after that, they tried to inject a related agent, called mustine, into a patient with non-Hodgkin’s lymphoma. They then documented the significant reduction in the patient’s tumor masses. After World War II, Sidney Farber, a pathologist at Harvard Medical School, together with Harriett Klite and Lederle Laboratories chemists, used folate analogues (now methotrexate), which is antagonistic to folic acid, to block the function of folate-requiring enzymes. This analogue became the first drugs to induce remission in children with Acute Lymphocytic Leukemia.

What is cancer?
Before we proceed into knowing how chemotherapy works, types of chemotherapy and its side effect, it is important to know the definition of cancer. Cancer can be defined as the uncontrolled growth of certain group of cells with malignant behavior like invasion and metastasis. Metastasis is the spread of a cancer from one organ or part to another non-adjacent organ or part. Invasion is the spread of a cancer to another adjacent organ.

Mechanism of action of chemotherapy
Chemotherapeutic drugs damage cell divisions, called mitosis, and effectively affecting cells which are dividing in a fast pace. The drugs are termed cytotoxic because they cause damage to the cells. Some of them cause apoptosis of cells (programmed cell death). As chemotherapy affects cell division, high growth fractions tumors are more sensitive to chemotherapy. Malignancies with slower growth rates tend to respond to chemotherapy much more modestly. The same concept can be used to explain why chemotherapy affect ‘younger tumors’ more effectively. It is because the mechanisms regulating cell growth are usually still preserved. With succeeding generations of tumor cells, the differentiation is typically lost and growth become less regulated, and tumors become less responsive to most chemotherapeutic agents.

Objectives of Chemotherapy
There are few kinds of strategies in the administration of chemotherapeutic drugs for desired effects:

1. Combined modality chemotherapy – chemotherapeutic drugs are used together with other cancer treatments like radiation therapy or surgery. Most of the cancer patients receive this kind of treatment now. Combination chemotherapy also involves treating the patient with a number of different drugs simultaneously. The advantage of this type of strategy would be the ability to minimize the chances of resistance developing to any one agent.
2. Neoadjuvant chemotherapy – chemotherapeutic drugs are used with the aim to shrink the primary tumor, so that local therapy like surgery or radiotherapy will be less destructive and more effective. This strategy is also one kind of preoperative treatment.
3. Adjuvant chemotherapy – chemotherapeutic drugs are used when there is little evidence of cancer present, but there is risk of recurrence. Adjuvant chemotherapy is usually given postoperatively. During this period, the newly growing tumors are fast-dividing, and therefore very susceptible. This can also help to reduce chances of resistance developing if the tumor does develop.
4. Palliative chemotherapy – chemotherapeutic drugs are given without curative intent but simply to decrease tumor load and increase life expectancy.

Most of the chemotherapeutic drugs today can be divided into antimetabolites, topoisomerase inhibitors, anthracyclines, plant alkaloids, alkylating agents and other antitumor agents. These mentioned groups of drugs affect DNA synthesis or cell division in some way. Some newer chemotherapeutic agents like monoclonal antibodies and the tyrosine kinase inhibitors (e.g. imatinib mesylate) do not directly interfere with DNA. They target a molecular abnormality in some types of cancer for example gastrointestinal stromal tumors and chronic myelogenous leukemia.

Different types of chemotherapeutic drugs

Alkylating antineoplastic agent
Alkylating agnets are active under conditions which are present in cells. The mechanism makes them toxic and allows them to be used as anti-cancer drugs. They stop the growth of the tumor by cross-linking some of the nucleobases in the double-helix strands of the DNA., directly destroying the structure of DNA. This makes the strands separated and thus unable to divide. Examples: Busulfan, Cyclophosphamide, Mechlorethamine, Cisplatin and etc.

Antimetabolites
An antimetabolite is a similar structure required for normal biochemical reactions, yet different enough to interfere with cell division. They masquerade as purine or pyrimidine – which are the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during S phase of the cell cycle and thus stopping normal development and division.

Anthracycline
Antrhacycline inhibits DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, inhibits topoisomerase II enzyme, preventing the relaxing of supercoiled DNA thus blocking DNA transcription and replication, and creates iron-mediated free oxygen radicals that damage the DNA and cell membranes. However, their main adverse effects are heart damage (cardiotoxicity) and vomiting. These adverse effects limit their usefulness. Some of the available agents include: Daunorubicin, Epirubicin and etc.

Topoisomerase inhibitor
These isomerase enzymes act on the topology of DNA. There are 3 kinds of topology: supercoiling, knotting and catenation. When outside of replication or transcription, DNA is kept as compact as possible. Topoisomerases upsets the proper DNA supercoiling during transcription and replication. Examples: irinotecan, amsacrine, etoposide and etc.

Monoclonal antibodies
By creating monoclonal antibodies that bind only to specific antigens of the cancer cell, immunological response could be induce, against the target cancer cell. Example: trastuzumab (anti-cancer therapy for a specific kind of breast cancer), alemtuzumab (used in B cell leukemia), gemtuzumab (use during relapsed acute myeloid leukemia).

The side effects of chemotherapy differ for each drugs, drug’s doses and individuals.
Some of the common side effects of chemotherapy are: nausea, vomiting, hair loss, fatigue, anemia, mouth sores, taste and smell changes, infection, diarrhea, infertility, fluid retention, rashes, irritated bladder, swelling, soreness of mucous membranes, numbness, aching joints and etc. Thus, it is important for each individual to research on each drug before trying them as side effects varies for each of them. Even though chemotherapy is designed to kill cancerous cells, it is so aggressive that it works against healthy cells as well. Since chemotherapeutic drugs travel everywhere in the body, damage of healthy cells can occur at various places in the body.

Proper diagnosis of cancer and careful administration of chemotherapy should be practised to ensure that the benefits of the therapy outstrip its unwanted effects.

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Radiation therapy (also called x-ray therapy, irradiation, radiotherapy) is the use of ionizing radiation to kill cancer cells and shrink tumors (to relieve symptoms). It destroys cells in the targeted area by damaging their genetic material. The radiation will ionize atoms which make up the DNA chain, damaging them and causing them to die or reproduce more slowly.

Radiation therapy has been in use as a cancer treatment for more than 100 years. The concept of therapeutic radiation was invented by German physicist Wilhelm Conrad Rontgen. With the discovery of computed tomography (CT), physicians are able to directly measure the dose delivered to the patient’s anatomy based on axial tomographical images. With the creation of magnetic resonance imaging (MRI) and positron emission tomography (PET), radiation therapy now have better treatment outcomes and fewer side effects.

Radiation therapy can be used alone or in combination with other cancer treatments such as chemotherapy or surgery.

The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissues.

The amount of radiation absorbed by the tissues is called the radiation dose, which is measured in a unit called ‘gray’(Gy). Different tissues of the body could tolerate various amounts of radiation (measured in centigrays). For example the kidneys can tolerate around 1800 cGy. The total dose of radiation is usually divided into smaller doses (called fractions) that are given daily over a specific time period.

Low-dose palliative treatments usually cause minimal or no side effects. Long-term treatment causes medium and long-term side effects, for example:

1. Fibrosis of the tissues – tissues become less elastic due to diffuse scarring process
2. Hair loss – usually seen in patients who receive radiotherapy to the brain. The radiation could spoil the matrix of the hair follicles thus producing permanent hair loss.
3. Fatigue
4. Cancer and secondary malignancies – this side effect is seen in a very small minority of patients, generally many years after they have received a course of radiation treatment.
5. Shortness of breath – radiation could decrease the levels of the substance called surfactant, which helps keep the air passages open. Low surfactant levels keep the lungs from fully expanding, thus causing shortness of breath or cough. These symptoms are sometimes treated with steroids. Lung fibrosis is also a possible side effect.
6. Digestive tract – radiation to the esophagus, stomach or intestine can cause pain, nausea, vomiting or diarrhea.

Treatment using higher doses causes acute side effects:

1. Damage of the epithelial tissue – for example skin, oral, pharyngeal and bowel mucosa, etc. The skin starts to become pink and sore several weeks into treatment. Although this desquamation is uncomfortable but it usually recovers quickly. There might be temporary soreness and ulceration in the mouth (mucositis) and throat if radiation is given to the head and neck area. Dry mouth and a loss of taste can be caused by radiation damage to the salivary glands and taste buds. Patients might need painkillers and nutritional support.
2. Swelling – as part of the general inflammation.
3. Infertility – the gonads are very sensitive to radiation. They may be unable to produce gametes following direct exposure of radiation.
4. Generalized fatigue.

There are 3 main types of radiotherapy. They are:

1. External radiation therapy – ‘external’ means that the radiation source is outside the body. It is used to treat most types of cancer including cancer of the bladder, brain, breast, cervix, larynx, lung, prostate, and etc. It also includes intraoperative radiation therapy (IORT) which is given during surgery to treat localized cancers that cannot be completely removed or that have a high risk of recurring in nearby tissues. External radiation therapy usually is given on an outpatient basis.
2. Internal radiation therapy / brachytherapy – uses radiation that is placed very close to or inside the tumor. The radiation is usually sealed in a small holder called an implant. Implants can be in the form of thin wires, plastic tubes, catheters, capsules, or seeds. They are put directly into the body. Brachytherapy is commonly used to treat localized prostate cancer, cervical cancer and cancers of the head and neck.
3. Systemic radiation / unsealed radiation therapy – uses radioactive materials which may be taken by mouth or injected into the body. For example, radioactive iodine (iodine-131) which is used to treat thyroid disease like thyrotoxicosis and malignant conditions like papillary thyroid cancer.

Conventional external beam radiotherapy is delivered via 2D beams using linear accelerator machines. Conventional refers to the way the treatment is planned or simulated. The aim of simulation is to accurately target or localize the volume which is to be treated. This technique is well established and reliable. The worry is that some high-dose treatments may be limited by the radiation toxicity capacity of healthy tissues which lay close to the target tumor volume. Some refinement had been done and with the help of computed tomorgraphy (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET), or single photon emission computed tomography (SPECT), a 3-D image of a tumor can be obtained. Using the information from the image, special computer programs design radiation beams that conform to the shape of the tumor. These revolutions allows more accurate placement of radiation beams, thus causing less radiological effects on the nearby healthy tissues.

Intensity-modulated radiation therapy (IMRT) is another type of 3-D conformal radiation therapy that uses radiation beams (usually x-rays) of varying intensities to deliver different doses of radiation to small areas of tissue at the same time. The technology allows the delivery of higher doses or radiation within the tumor and lower doses to nearby healthy tissue. The equipment can be rotated around the patient so that radiation beams can be sent from the best angles. The beams conform as closely as possible to the shape of the tumor.

Certain chemicals can be used to modify a cell’s response to radiation. These are called the radiosensitizers and radioprotectors. Some anticancer drugs, such as 5-flurouracil and cisplatin, make cancer cells more sensitive to radiation therapy. Radioprotectors are used to protect normal (noncancerous) cells from the damage caused by radiation therapy. These agents promote the repair of normal cells that are exposed to radiation, for example Amifostine. It helps to reduce the dry mouth that can occur if the parotid glands receive a large dose of radiation.

Although radiation therapy is not 100% safe and effective for cancer treatment, it could be some cancer patients’ only hope for survival or longer lifespan. Radiation therapy will continue to play a major role in cancer treatment until more effective and safe drugs and treatments are found.

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