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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.
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.
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.
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.
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.
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.
If breast cancer is found at an early stage this improves the chances of recovery.
Questions to be asked:
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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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 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.
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
4. 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
These investigations are requested for assessing the possible spread of the
cancer cells in other organs of the body.
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.
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 screen-
detected cancers (microcalcifications on mammogram).
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.
Tumors with distinct pattern of growth are classified as tumours of special type:
tubular, cribriform, mucinous, medullary and lobular.
Stage Information
TNM definitions
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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,
to other structures
pN1bi: Metastasis in 1 to 3 lymph nodes, any more than 0.2 cm and all
pN1bii: Metastasis to 4 or more lymph nodes, any more than 0.2 cm and
or to other structures
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
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 oestrogen-
receptor 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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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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3. 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.
4. 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. Bleeding wound
4. 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 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 neo-
adjuvant 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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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.
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 ?