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BREAST CANCER Breast cancer is the most prevalent cancer among women and affects approximately one million women worldwide. Prevalence ( epidemiology) is the ratio for a given time period of the number of occurrences of a disease the number of units at risk in the population. Incidence is the number of new cases of a disease diagnosed in one year. Cancer incidence is the number of new cases of cancer diagnosed in one year. Breast cancer accounts for 30% of all female cancers in the UK and approximately 1 in 9 women in the UK will get breast cancer sometime during their life. Men can also develop breast cancer, accounting for 1% of cases diagnosed annually in the UK. Breast cancer is the most common cause of cancer in US women and the most common cause of death in women between the ages of 45 and 55. In most women, breast cancer is first noticed as a painless lump in the breast. Although most breast lumps are benign, they still need to be checked carefully to rule out the possibility of cancer. Also, if it is a cancer, the earlier the treatment is given, the more likely it is to be efficient. Pain in the breast is usually not a symptom of breast cancer. In fact, many healthy women find that their breasts feel lumpy and tender before a period. Most breast lumps are benign. Common causes of benign breast lumps are: Cysts – sacs of fluid that build up in the breast tissue. Breast cysts are quite common. Nearly 1 in 10 women will have a breast cyst at some time during her life. • Fibroadenomas – solid tumours made up of fibrous and glandular tissue. They are more common in women in their 20s and 30s. Benign breast lumps are easily treated.

Risk factors in breast cancer

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No one knows the exact causes of breast cancer. Research has shown that women with certain risk factors are more likely than others to develop breast cancer. A risk factor is something that may increase the chance of developing a disease. Studies have found the following risk factors for breast cancer: Age: The chance of getting breast cancer goes up as a woman gets older. Most cases of breast cancer occur in women over 50. This disease is not common before menopause. Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast. Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia) increases the risk of breast cancer. Gene changes: Changes in certain genes increase the risk of breast cancer. These genes include BRCA1, BRCA2, and others. Tests can sometimes show the presence of specific gene changes in families with many women who have had breast cancer. Reproductive and menstrual history: The older a woman is when she has her first child, the greater her chance of breast cancer. Women who had their first menstrual period before age 12 are at an increased risk of breast cancer. Women who went through menopause after age 55 are at an increased risk of breast cancer. Women who never had children are at an increased risk of breast cancer. Women who take menopausal hormone therapy with estrogen plus progestin after menopause also appear to have an increased risk of breast cancer. Race: Breast cancer is diagnosed more often in white women.

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Radiation therapy to the chest: Women who had radiation therapy to the chest (including breasts) before age 30 are at an increased risk of breast cancer. This includes women treated with radiation for Hodgkin's lymphoma Obesity after menopause: The chance of getting breast cancer after menopause is higher in women who are overweight or obese. Drinking alcohol: Studies suggest that the more alcohol a woman drinks, the greater her risk of breast cancer. Geographical variation There is quite a difference in incidence and death rate of breast cancer between different countries. The biggest difference is between Eastern and Western countries, (low to high rates). However, studies of women from Japan who emigrate to the US show that their rates of breast cancer rise to become similar to US rates within just one or two generations, indicating that factors relating to everyday activities are more important than inherited factors in breast cancer. High risk patients 1. 2. 3. 4. 5. 6. 7. 8. 9. Relative risk

Patients over the age of 50 >10 First kid in early 40s 3 Atypical hyperplasia 5 Cancer in other breast >4 Abnormal exposure to radiation after age 10 3 Current use of contraceptive pills 1,24 Use for more than 10 years of hormone replacement therapy 1,5 Breast cancer in first-degree relative >2 Developed country 5

SYMPTOMS AND SIGNS IN BREAST CANCER Breast cancer is now commonly diagnosed by breast screening in women who have no symptoms. Approximately 6 in every 1000 women between the ages of 50 and 64 who attend for screening will be found to have breast cancer the first time they attend screening. In many cases, the woman herself will first suspect the disease because she notices a lump or an area of lumpiness or irregularity in her breast tissue. Other signs of breast cancer include:

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a change in the skin: there is often dimpling or indentation of the skin with the formation of wrinkles. The nipple might be pulled in or there may be a discharge from the nipple. occasionally the nipple itself changes. A rash can affect the nipple or the nipple may weep. the breast may swell and become red and inflamed or the skin may change and become like the skin of an orange. In some breast cancers this is due to a blockage of the drainage of fluid from the breast. patients sometimes present with a lump under the arm which is a sign that the cancer has spread to the lymph glands.

How is breast cancer diagnosed? If breast cancer is found at an early stage this improves the chances of recovery. Questions to be asked:
• • • •

Does the lump vary in relation to the menstrual cycle? What previous breast problems have you had? Is there any breast cancer in your family? How many children have you had? Questions are directed to depict the possible risk factors of the patient. Physical examination

Physical examination of the breast is done with the patient in different positions: first with the arms by her sides, then above her head and, finally, with the arms pressing on her hips. At this stage, the doctor can often see the changes in the shape of the breasts, and can identify the site and cause of the problem. Next, the breasts are examined while the patient is lying flat with her arms folded under her head. Palpation of the breast may reveal a lump, recording the characteristics: shape, size, site, surface, edge, consistency, tenderness, mobility to the skin and to the major pectoralis muscle. Palpation of the axilla may reveal a lump, assessing the characteristics: shape, size, site, surface, edge, consistency, tenderness, mobility.

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General physical examination should focused on possible distant metastases of a breast cancer: bones, liver, lungs, brain. Investigations 1. Mammograms If the patient is over 35 and has not had a breast X-ray within the past year, the doctor may arrange for one to be performed. Mammograms are a good way of identifying abnormalities in the breast, but they don't always tell whether they are benign or malignant. Mammograms are usually only used for women over the age of 35. In younger women the breast tissue is more dense, which makes it difficult to detect any changes on the mammogram. Mammograms are the best tool doctors have to find breast cancer early. However, mammograms are not perfect:

A mammogram may miss some cancers. (The result is called a "false negative.") A mammogram may show things that turn out not to be cancer. (The result is called a "false positive.")

2. Ultrasound scanning X-rays do not pass easily through the breasts of young women. Ultrasound scanning, which is familiar to many women by its use to look at babies during pregnancy, can also be used in the breast to tell whether a lump is fluid or solid. An ultrasound uses sound waves to build up a picture of the breast tissue. Ultrasound can often tell whether a lump is solid (made of cells) or a fluid-filled cyst. It can also often gives the information whether a solid lump is likely to be benign or malignant.

Ultrasound is not useful as a screening test. It is useful if an abnormal shadow is seen on the mammogram because ultrasound is an accurate way of judging whether any abnormality is benign and straightforward or whether it is more likely to be serious. 3. Needle tests (FNAC)

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Inserting a needle into the lump will show whether it is full of fluid (a cyst) or solid. The needle can allow a sample of cells to be removed for examination under the microscope –cytologic examination. This is a very accurate method of finding out whether the lump is benign or malignant. A fine needle aspiration (FNA) is a quick, simple procedure done in the outpatient clinic
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Core biopsy

Core biopsy can allow a breast tissue specimen for histological and immunohistochemistry examinations, obtaining such way a preoperative diagnosis resulting in more appropriate decision of therapy. Core biopsies are often done using ultrasound as guide to the lump. Local anaesthetic is injected into the area first to numb it

5. Open biopsy A biopsy is the only way to tell for sure if cancer is present. An incisional biopsy takes a sample of a lump or abnormal area. An excisional biopsy takes the entire lump or area. This procedure is done either under local anaesthesia or general anaesthesia. If a lump is too small to be felt but has shown up on a mammogram or ultrasound, the radiologist may need to mark the area for the surgeon before the excision biopsy. This is done by inserting a very small wire (a guide wire) under local anaesthetic, using x-ray or ultrasound guidance. The procedure is known as wire localisation 6. Chest X ray, abdominal ultrasound, brain CT, bone scintigraphy. These investigations are requested for assessing the possible spread of the cancer cells in other organs of the body. Types of breast cancer Breast cancers are derived from the epithelial cells that line the terminal duct lobular unit. Cancer cells that remain within the basement membrane of the lactiferous duct are classified as in situ or non-invasive. An invasive cancer is one in which cells have moved outside the basement membrane into the surrounding tissue. Non-invasive breast cancer

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Two main types can be recognized on the basis of cell aspect. DCIS (ductal carcinoma in situ) is the most common form, making up till 25% of screendetected cancers (microcalcifications on mammogram). LCIS (lobular carcinoma in situ) is usually an incidental finding and is generally treated by observation. Invasive breast cancer The most commonly used classification of invasive cancers divides them into ductal and lobular types. This is now known to be incorrect, as almost all cancers arise in the terminal duct lobular unit. Invasive ductal carcinoma accounts for up 85% of all cancers. Tumors with distinct pattern of growth are classified as tumours of special type: tubular, cribriform, mucinous, medullary and lobular. Invasive lobular cancer, accounts for up to 10% of invasive cancers. These tumours are often large at diagnosis and have an increased rate of bilaterality. Grading of breast cancer When a cancer is examined under the microscope, it is usually possible to assess how aggressive it is: in other words how far and how fast it is likely to spread. The tumour may be assigned to one of three grades ranging from grade I to grade III in order of seriousness. For instance, a grade I (low-grade) cancer is non-aggressive and unlikely to cause harm. In contrast, grade III( high-grade) tumours are aggressive and likely to cause harm, but can sometimes be controlled with effective treatment. Stage Information The American Joint Committee on Cancer (AJCC) staging system provides a strategy for grouping patients with respect to prognosis. Therapeutic decisions are formulated in part according to staging categories but primarily according to lymph node status, estrogen- and progesterone-receptor levels in the tumor tissue, menopausal status, and the general health of the patient. The AJCC has designated staging by TNM classification.

TNM definitions

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Primary tumor (T): TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Tis: Carcinoma in situ; intraductal carcinoma, lobular carcinoma in situ, or Paget's disease of the nipple with no associated tumor. Note: Paget's disease associated with a tumor is classified according to the size of the tumor. T1: Tumor 2.0 cm or less in greatest dimension T1mic: Microinvasion 0.1 cm or less in greatest dimension T1a: Tumor more than 0.1 but not more than 0.5 cm in greatest dimension T1b: Tumor more than 0.5 cm but not more than 1.0 cm in greatest dimension T1c: Tumor more than 1.0 cm but not more than 2.0 cm in greatest dimension T2: Tumor more than 2.0 cm but not more than 5.0 cm in greatest dimension T3: Tumor more than 5.0 cm in greatest dimension T4: Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below. Note: Chest wall includes ribs, intercostal muscles, and serratus anterior muscle but not pectoral muscle. T4a: Extension to chest wall T4b: Edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast T4c: Both of the above (T4a and T4b) T4d: Inflammatory carcinoma

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*Note: Inflammatory carcinoma is a clinicopathologic entity characterized by diffuse brawny induration of the skin of the breast with an erysipeloid edge, usually without an underlying palpable mass.1 Radiologically there may be a detectable mass and characteristic thickening of the skin over the breast. This clinical presentation is due to tumor embolization of dermal lymphatics with engorgement of superficial capillaries.

Regional lymph nodes (N): NX: Regional lymph nodes cannot be assessed (e.g., previously removed) N0: No regional lymph node metastasis N1: Metastasis to movable ipsilateral axillary lymph node(s) N2: Metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures N3: Metastasis to ipsilateral internal mammary lymph node(s) Pathologic classification (pN): pNX: Regional lymph nodes cannot be assessed (not removed for pathologic study or previously removed) pN0: No regional lymph node metastasis pN1: Metastasis to movable ipsilateral axillary lymph node(s) pN1a: Only micrometastasis (none larger than 0.2 cm) pN1b: Metastasis to lymph node(s), any larger than 0.2 cm pN1bi: Metastasis in 1 to 3 lymph nodes, any more than 0.2 cm and all less than 2.0 cm in greatest dimension

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pN1bii: Metastasis to 4 or more lymph nodes, any more than 0.2 cm and all less than 2.0 cm in greatest dimension pN1biii: Extension of tumor beyond the capsule of a lymph node metastasis less than 2.0 cm in greatest dimension pN1biv: Metastasis to a lymph node 2.0 cm or more in greatest dimension

pN2: Metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures pN3: Metastasis to ipsilateral internal mammary lymph node(s) Distant metastasis (M): MX: Presence of distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis present (includes metastasis to ipsilateral supraclavicular lymph nodes)

AJCC stage groupings Stage 0 : Stage I : Stage IIA: Tis, N0, M0 T1, N0, M0 T0, N1, M0 or T1, N1, M0 or T2, N0, M0 T2, N1, M0 or T3, N0, M0

Stage IIB: Stage IIIA:

T0, N2, M0 or T1, N2, M0 or T2, N2, M0 or T3, N1, M0 or T3, N2,

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M0 Stage IIIB: Stage IV: T4, Any N, M0 or Any T, N3, M0

Any T, Any N, M1

Staging of the breast malignant tumour Ductal carcinoma in situ (DCIS) is sometimes described as stage 0. DCIS is almost always completely curable with treatment. The following stages of breast cancer are known as invasive breast cancer: Stage 1 The tumour measures less than 2cm. The lymph nodes in the axilla are not affected and there are no signs that the cancer has spread elsewhere in the body. Stage 2 The tumour measures between 2 and 5cm. or the lymph nodes in the axilla are affected, or both. However, there are no signs that the cancer has spread further. Stage 3 The tumour is larger than 5cm. and may be attached to surrounding structures such as the muscle or skin. The lymph nodes are usually affected. Stage 4 The tumour is of any size, but the lymph nodes are usually affected and the cancer has spread to other parts of the body. This is metastatic breast cancer. Breast cancer that has come back after initial treatment is known as recurrent breast cancer. As well as describing the stage and grade of breast cancer, it is important also, to know whether the tumour has hormone and HER receptors. Knowing the stage, grade and receptor status helps us to choose the most appropriate treatment for the patient. Hormone and HER2 receptors Some breast cancer cells have receptors, which allow particular types of hormones or proteins to attach to the cancer cell. A sample of the breast tissue will usually be tested to see if it has these receptors. Whether particular receptors are present or not will affect the type of treatment. Hormone receptors

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Many breast cancers have receptors for the hormone oestrogen. When oestrogen attaches to these receptors, it causes the cancer cells to grow. If a breast cancer has a significant number of oestrogen receptors it is known as being oestrogen-receptor positive (ER+). If it doesn’t it is known as oestrogenreceptor negative (ER-). Knowing whether the tumour has oestrogen receptors or not helps the doctors to decide on the best treatment. A tumour that is ER+ is likely to respond to hormonal treatments, whereas a tumour that is ER- will not respond. Some breast cancers have progesterone receptors and are known as progesterone-receptor positive (PR-positive). Usually, cancers that are ER+ will also be PR+. Progesterone receptors are less important than oestrogen receptors in predicting the likely response to hormone treatment. HER2 receptors Some cancers have receptors for a protein known as HER2. Tumours that have high levels of these receptors are known as HER2-positive and may respond to treatment with drugs such as trastuzumab (Herceptin®). HER2 is a protein found on the surface of certain cancer cells. Some breast cancers have a lot more HER2 receptors than others. In this case, the tumour is described as being HER2-positive. Tumours that are HER2-positive tend to grow more quickly than other types of breast cancer. Knowing if a cancer is HER2-positive can sometimes affect the choice of treatment. Women with HER2-positive breast cancer can benefit from a drug called trastuzumab (Herceptin®). Herceptin only works in people who have high levels of the HER2 protein. Treatment overview The treatment of breast cancer is individual for each woman. The treatment depends on many factors, including: the stage and grade of the cancer • age • the size of the tumour • whether the cancer cells have receptors for certain hormones (such as oestrogen) or particular proteins (such as HER2).

Most primary breast cancers will be treated with surgery to remove the tumour. All or part of the breast tissue may be removed. If the whole breast is removed (mastectomy), breast reconstruction may be carried out, either at the same time as the initial surgery or later.

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Sometimes chemotherapy or hormonal therapy may be given to shrink a cancer before surgery. This is known as neo-adjuvant therapy. After surgery, radiotherapy will be given to any remaining breast tissue, and may be given to the chest wall if the breast has been removed. This is to make sure that any cancer cells that may be left in the area are destroyed. Further treatment includes hormonal therapies, chemotherapy and/or a drug called Herceptin®. After surgery, the stage and the grade of the cancer can be established. Factors which affect the chance of the cancer coming back include: the size of the tumour • lymph nodes status • the grade of the tumour • lymphatic or vascular invasion • hormone receptor content and markers of proliferation. Cancers with oestrogen receptors are less likely to recur in the short term, whereas those with HER2 receptors are more likely to come back unless Herceptin is given.

However, if there is a risk of recurrence, many women who have oestrogen receptor negative (ER-) breast cancer will be advised to have treatment with chemotherapy, and those with oestrogen receptor positive (ER+) breast cancer are usually advised to have hormonal therapy. This treatment is known as adjuvant therapy. Many women who are ER+ will have both treatments, but not at the same time. Surgery for breast cancer Most women with breast cancer will have surgery to remove the tumour. There are two main types of surgery for breast cancer: Surgery to remove the breast lump and some of the breast tissue surrounding it (a lumpectomy or segmental excision). This is known as breast-conserving surgery or breast-sparing surgery and is usually followed by radiotherapy aimed to destroy cancer cells that may remain in the breast.

Surgery to remove the whole breast (mastectomy) and sometimes the muscles underneath. Studies have found equal survival rates for breast-sparing surgery (with radiation therapy) and mastectomy for Stage I and Stage II breast cancer.

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Women who have a mastectomy may choose to have surgery to reconstruct the breast, either at the same time or later. • Part of any operation for breast cancer is axillary lymphadenectomy.

Types of surgery for breast cancer I. Breast-conserving surgery 1. Lumpectomy (wide local excision) This is the removal of a breast lump, together with some surrounding tissue. A lumpectomy is usually followed by radiotherapy treatment to the remaining breast tissue. Sometimes, if the lump is very small, a fine wire (guide wire) is used to mark the area so that the surgeon can find the lump more easily. A local anaesthetic is given, and the wire is then inserted by a radiologist, using x-ray or ultrasound guidance. This procedure is known as wire localisation. After a lumpectomy, the breast tissue that has been removed is sent to the laboratory to be examined under a microscope by a pathologist. The pathologist looks to see whether there is an area of healthy cells all around the cancer – this is known as a clear margin. If there are cancerous or precancerous (DCIS) cells at the edge of the area of breast tissue that has been removed, there is a higher chance that the cancer will come back in the breast. In this case, more breast tissue will need to be removed a few weeks later. Approximately 1 in 8 (12.5%) of women will need to have a second operation to remove more breast tissue. Sometimes, the results from the laboratory show that another lumpectomy is unlikely to remove all the cancer cells completely. In this situation, a mastectomy (removal of the whole breast) will need to be done. 2. Segmental excision (quadrectomy) This is similar to a lumpectomy but involves removing more of the breast tissue. It is only used if a larger area of the breast needs to be removed. The effect of this type of surgery is more noticeable than lumpectomy, particularly in women who have small breasts. In women with large breasts it is usually less noticeable. Radiotherapy to the breast is usually recommended after a segmental excision. II. Mastectomy Removal of the whole breast (mastectomy) may be necessary if: • The breast lump is large in proportion to the rest of the breast tissue.

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There are several areas of cancer cells in different parts of the breast- multicentricity of the tumour. • The lump is just behind the nipple. A simple mastectomy removes only the breast tissue.

2.

A simple mastectomy and sentinel node biopsy or node sampling removes the breast tissue and the lower lymph nodes, within the axilla. Sentinel lymph node biopsy is a new method of checking for cancer cells in the lymph nodes. A surgeon removes fewer lymph nodes, which causes fewer side effects. (If there are cancer cells in the axillary lymph nodes, an axillary lymph node dissection usually is done.)

3.

4.

A modified radical mastectomy removes all the breast tissue and all of the lymph nodes in the axilla. It may also be referred to as a total mastectomy and axillary clearance. A radical mastectomy removes all the breast tissue and the lymph nodes in the axilla, together with the muscles behind the breast tissue. This is only done if the cancer invaded the pectoralis muscles.

A new breast shape can often be created either at the same time as the mastectomy, or some months or years later. This is known as breast reconstruction. Postoperative complications: 1. Local pain and tenderness- pain relief with painkillers 2. Wound infection
3. 4.

Bleeding wound Numbness and tingling of the shoulder and upper arm due to nerve damage during axillary dissection

5. Lymphedema of the arm due to impaired lymph drainage following axillary dissection. Radiotherapy for breast cancer Radiotherapy treats cancer by using high-energy rays to destroy the cancer cells, while doing as little harm as possible to normal cells. The treatment is often used after surgery for breast cancer, most commonly after surgery to remove part of the breast (lumpectomy or segmental excision). It may occasionally be used before, or instead of, surgery.

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Radiotherapy can cause side effects such as skin soreness and tiredness, but most will improve once the treatment has finished. If part of the breast has been removed (lumpectomy or segmental excision), radiotherapy is usually given to the remaining breast tissue to reduce the risk of the cancer coming back in that area. The radiotherapy is normally given to the whole breast area, and may also include the axilla, and the area above the sternum and clavicle. After a mastectomy, radiotherapy to the chest wall may be given if your doctor thinks there is a risk that any cancer cells have been left behind. If a few lymph nodes have been removed and these contained cancer cells, or if no lymph nodes have been removed, radiotherapy may be given to the axilla to treat the remaining lymph nodes. If all the nodes have been removed from the axilla, radiotherapy to this area is not usually needed. Radiotherapy to the breast sometimes causes side effects such as: reddening and soreness of the skin • tiredness • feeling sick (nausea) These side effects gradually disappear once your course of treatment has finished. The tiredness may continue for some months.

Chemotherapy for breast cancer Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. The aim of chemotherapy is to do the maximum damage to cancer cells while causing the minimum damage to healthy tissue. Women with breast cancer may have chemotherapy: • Before surgery to shrink the cancer. This is known as neoadjuvant chemotherapy. • After surgery if doctors think there is a risk of the cancer coming back. This is known as adjuvant chemotherapy. There are many different chemotherapy drugs used to treat breast cancer, and they are often used in combinations (called a chemotherapy regimen). The commonly used chemotherapy drugs include:
• • • • • • •

cyclophosphamide epirubicin fluorouracil (5FU) methotrexate paclitaxel (Taxol) doxorubicin (Adriamycin®) docetaxel (Taxotere®).

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Other drugs may also be used. Commonly used chemotherapy combinations are: FEC – 5FU, epirubicin and cyclophosphamide • AC – doxorubicin (Adriamycin®) and cyclophosphamide • CMF – cyclophosphamide, methotrexate and 5FU • E-CMF – epirubicin and CMF • FEC-T – FEC plus docetaxel (Taxotere®). Chemotherapy drugs can cause unpleasant side effects, but these can usually be well controlled with medicines. The side effects might be: nausea and vomiting, tiredness , sore mouth , increased risk of infection , hair loss

Hormonal therapies for breast cancer Hormonal therapies are treatments to reduce the levels of hormones in the body or block their effects on cancer cells. They are often given after surgery, radiotherapy, and chemotherapy for breast cancer, to reduce the chance of the cancer coming back. Hormonal therapies are only effective in women whose cancer cells have receptors for oestrogen and/or progesterone on their surface. This is known as being oestrogen-receptor positive (ER+) or progesterone-receptor positive (PR+). It means that the breast cancer cells are affected by oestrogen or progesterone. These are female hormones that the body produces naturally and that can stimulate breast cancer cells to grow. Hormonal therapy for postmenopausal women Postmenopausal women may be offered hormonal treatment with either an antioestrogen (such as tamoxifen) or an aromatase inhibitor (such as Arimidex®), or a combination of the two different types, where one type is given after the other. Tamoxifen has been the most widely used hormonal therapy for breast cancer and has been shown to be highly effective in reducing the chance of the cancer coming back. Research has shown that for some women, giving aromatase inhibitors instead of tamoxifen, or after a period of tamoxifen treatment, can further reduce the chance of the cancer coming back. Hormonal therapy for premenopausal women Premenopausal women may be offered hormonal treatment with: an anti-oestrogen medicine (such as tamoxifen) • treatment to stop the ovaries from producing oestrogen (ovarian ablation). This can be done using surgery, radiotherapy, or a drug called goserelin (Zoladex® ).

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Unfortunately, ovarian ablation by surgery or radiotherapy brings on an early menopause, which can be very upsetting, especially for women who were hoping to have children. The effects of medicines are usually temporary. Biological therapy Herceptin® (trastuzumab) for breast cancer Trastuzumab (also known as Herceptin®) is a treatment that may be given to some women with breast cancer. It is a type of drug known as a monoclonal antibody. It works by attaching to HER2 receptors (proteins) on the surface of breast cancer cells. This stops the cancer cells from dividing and growing. It may also allow the body’s defences to fight better against the cancer cells. Herceptin can reduce the chance of breast cancer coming back after initial treatment for early breast cancer. However, it is only effective for women whose breast cancer cells have a large number of the HER2 receptors on their surface. This is known as being HER2-positive. Around 1 in 5 women (20%) with breast cancer are HER2-positive. Side effects are usually mild, but some women may have: flu-like symptoms, diarrhoea , headaches , an allergic reaction. In some women, Herceptin may cause damage to the heart muscle, which could lead to heart failure. If this happens the Herceptin® will be stopped. Usually, the effect on the heart is mild and reversible. Study questions I.45 years old lady gives a 2 months history of a painless lump in the right breast. On physical examination the lump is located in the UOQ, maximum size is of 2,5 cm, mobile, hard, not well defined. In the right axilla there is at the lateral border of the major pectoralis muscle another lump of 2 cm., mobile and not tender. 1. What is your clinical diagnosis? 2. What is clinical stage after TNM classification? 3. What investigations would you plan? 4. Having documented the diagnosis of breast carcinoma, what are the treatment modalities, you would advise? II.What treatment would you suggest for a 82 years old female with breast cancer, stage IV (T4, N2, M1- liver metastases) with serious comorbidities such as: moderate cardiac failure, chronic atrial fibrilation, pulmonary disfunction and obesity?

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III.It is efficient the treatment with Herceptine in breast cancer with positive ER/PR and negative Her2neu ?

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