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Breast Cancer

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									                                              Breast Cancer

• Breast cancer is the most common cancer in females, affecting 1 in 11-15 women in Australia
• It is uncommon in women under 30, however it increases exponentially to a maximum at the age of
60
• Breast lumps are common in women, with many of them areas of thickening of normal breast tissue
       Most common lump is mammary dysplasia (accounts for 32% of lumps)
       Only about 22% of lumps are cancerous
• Nevertheless, it is good practice to consider any lump in the breast as cancerous until proven
otherwise

Risk Factors for Breast Cancer

    i.         Age & Menopause
         Incidence of breast cancer increases with age (see previous not about exponential increase)
         About 1/3 of women who develop breast cancer are premenopausal and 2/3
          postmenopausal  therefore, increased risk when women hit menopause
         It should also be noted that women who start menstruating early in life or who have a late
          menopause have an increased risk of developing breast cancer (Women who have a natural
          menopause after age 55 are twice as likely to develop breast cancer compared to women
          who have a natural menopause before 45)

    ii.        Familial
         Up to 5% of cases of breast cancer are familial, with most being autosomal dominant
         Mutations in either of the two genes – BRACA1 and BRCA2 – result in a strong predisposition
          for both breast and ovarian cancer
         About 1 in 800 of the general population are carriers
         With the mutation, the risk of developing breast cancer is 10-fold and 40-80% of cases occur
          before the age of 70
         Other factors that contribute to familial risk are if two first-degree or second-degree relatives
          on one side of the family have cancer and if you are of Jewish ancestry (Ashkenazy Jews)

    iii.     Previous benign breast disease
     Women who have pre-existing benign breast lumps are 4-5 times likelier to develop breast
         cancer than women who do not have any proliferative changes

    iv.       Lifestyle
     Increased risk if on Hormone Replacement Therapy (HRT) for greater than 5 years. Women
        are doubling their risk after 5 years if have combined oestrogen and progestogen
     Increased risk has been associated with obesity, alcohol and smoking
     There is also an increased risk with ionising radiation exposure
     Increased risk if childless after 30 years. Risk of breast cancer with in women who have their
        first child after the age of 30 is about twice that of women who have their first child before
        the age of 20

Breast Cancer Classification
• Breast cancer can either be described as non-invasive or invasive
• A cancer that remains within the basement membrane of the duct lobular unit and draining duct are
classified as in situ or non-invasive
• An invasive breast cancer is one which there is dissemination of cancer cells outside the basement
membranes of the ducts and lobules into the surrounding tissue

Carcinoma in situ
• There are two types of breast carcinoma in situ: Lobular carcinoma in situ and Ductal carcinoma in
situ
    1.   Lobular carcinoma in situ (LCIS)
        A non-invasive cancer that has developed in the lobules of the breast and has not spread
        LCIS rarely distorts the underlying architecture and the underlying lobules remain
         recognisable

    2.   Ductal carcinoma in situ (DCIS)
        Most common type of non-invasive breast cancer and accounts for 20% of all breast cancers
        Ductal means that the cancer starts inside the milk-ducts
        With appropriate treatment, patients usually have excellent outcomes with low local
         recurrence rates and survival of at least 98%




    Invasive (or infiltrating) ductal carcinoma
     Most common type of breast cancer, accounting for about 80% of all breast cancers
     Starts in milk-ducts but breaks through duct walls and spreads into the breasts fatty tissue
     It can spread to other parts of the body through the lymphatic system and bloodstream

    Invasive (or infiltrating) lobular carcinoma
     Accounts for about 1 in 10 (10%) of breast cancers
     It originates in the lobules and like IDC, it can metastasize to other parts of the body

• Less common (very uncommon) types of breast cancer include:
     Inflammatory breast cancer – accounts for 1-3% of breast cancers, makes breast skin look
         red and warm, Doctors now know that these changes are not caused by inflammation or
         infection, but by cancer cells blocking lymph vessels in the skin.

• Most breast cancers (58%) are located in the upper lateral quadrant, then 15% in upper medial
quadrant, 12% in lower lateral quadrant and 5% in lower medial quadrant. 10% are on the nipple
• Breast cancers can metastasize to other parts of the body through either
    1. The bloodstream
    2. The lymphatic system
• However, breast cancers tend to metastasize through the lymph ducts where they will eventually
enter blood circulation and be carried to various major organs
• Once the primary cancer has been dislodged from its original position, they travel to other organs of
the body and begin to form secondary cancers (distant metastases is common in the lungs, liver,
bones, brain and adrenal glands)
• Breast cancer cells, however, do not always begin to form a secondary cancer as soon as they have
settled in a new place. Often they die or sometimes they may lie dormant for many years before they
start to grow again. It is not yet known why cancer cells lie dormant or what triggers them years later
to form secondary cancers.

Staging of Breast Cancer
• Breast cancers can be staged from 0 to IV, with the staging grade indicating the degree of spread of
the cancer (if unsure of grade, classify it according to the degree of spread)
• Staging is the most powerful predictor of prognosis
Stage 0 – breast cancer is non invasive (cancer in situ)
Stage I – breast cancer is less than 2cm in size and has not spread from the breast
Stage II – breast cancer is 2-5cm in size and has spread to axillary lymph nodes
Stage III – breast cancer is greater than 5cm in size and has spread to more lymph nodes (more of the
axillary lymph nodes and some in parts of the chest)
Stage IV – breast cancer can be of any size and has spread beyond the local lymph nodes
(metastasizes to distant sites e.g. bone, liver, lungs and brain)

• The size, grading and staging of the tumour impact the outcome and type of treatment
• Prognosis is defined in terms of 5-year survival
     People with disease confined to the breast have a 97% 5-year survival rate
     Those with involvement of regional lymph nodes have a 75%-85% 5-year survival
     Those with stage III disease with more extensive local or lymph disease have approximately a
         50% 5-year survival.
     When the disease has already spread from the immediate area or metastasized, the 5-year
         survival rate is 20%.

Treatment

    1. Surgery
    • Surgery is usually the first treatment for breast cancer. It can either be:
             o Lumpectomy – removal of breast cancer and margin of surrounding normal tissue
                  (issue with this is that scans may underestimate the amount of cancer tissue, and
                  thus one may fail to achieve adequate cancer clearance; 20% of women require a
                  second operation)
             o Mastectomy – removal of all breast tissue. During a mastectomy, surrounding
                  lymph nodes may also be removed. A mastectomy is recommended when breast-
                  conservation surgery is not possible due to the size of the tumour in relation to the
                  size of the breast or when the cancer is not confined to one spot within the breast

    1a. Types of mastectomy
    • There are many types of mastectomy
     Radical mastectomy – removal of entire breast, axillary lymph nodes and muscle from the
        chest underlying the breast (it is rarely done nowadays)
     Modified radical mastectomy – no chest muscle is removed (most common mastectomy)
     Prophylactic mastectomy – mastectomy undertaken when there is no cancer present in
        breast (appropriate choice for women who are at particularly high risk of developing breast
        cancer)
     Bi-lateral mastectomy – removal of both right and left breast (usually performed for
        prophylactic reasons)

• The biggest issue to consider with surgical approach is the emotional affect on the women due to
the cosmetic effects, as well as psychological effects, of breast removal
    2. Radiotherapy
    • Uses high-powered radiation beams which deliver radioactive particles or X-rays to targeted
    tissue causing the death of cells
    • Is virtually always recommended after lumpectomy for invasive cancer
    • Lumpectomy plus radiotherapy have similar rates of cure as mastectomy for many patients
    • If patients are at high risk of recurrence, radiotherapy should also be considered for patients
    who have had a mastectomy
    • On the whole, it is very well tolerated and suitable for most women
    • Side effects = skin changes like sunburn, pigmentation of skin, woodiness of breast tissue,
    fatigue, depression, it rarely can damage other organs

    3. Chemotherapy
    • Is drug therapy, usually given through I.V, which targets dividing cells causing them to stop
    dividing and self destruct
    • Chemotherapy overall reduces the chance of breast cancer returning by about 1/3
    • Use of chemotherapy depends on how aggressive the patients tumour appears, the likeliness of
    tumour responding to other treatment besides chemotherapy, the patients age and the choice of
    the women herself based on the risks and benefits
    • Chemotherapy regimes usually last 4-6 months, require hospital stays and have various side-
    effects

    4. Hormone Therapy
    • It should be noted that 2/3 of breast cancers grow in response to the female hormone
    oestrogen (therefore risk factors include HRT > 5 years and the oral contraceptive)
    • Hormonal therapy works by either reducing overall amount of oestrogen in the body or by
    stopping the oestrogen present exerting its usual effect
    • Result is that for hormone-responsive breast cancer cells, they are starved of oestrogen, which
    they require to grow
    • Hormonal treatment usually given over 5 years and has side effects similar to that of
    menopause (hot flushes, sweats, mood and sleep disturbances, vaginal dryness, reduced labido)
    • Drug example = tamoxifen

    5. New Drug Treatments
    • Targeted drugs are those that attack the single part of a cancer cell and so selectively destroy
    these cells
    • Herceptin targets the 15% or so of breast cancers that have the growth of Her2 receptor
    • Around 15-20% of breast cancers make an excess of molecules on the cell surface which allows
    them to grow, invade and develop a blood supply of heir own. This is known as the Her2 growth
    factor receptor – cells with excess of Her2 are describes as ‘Her2 positive’. E.g of drug that targets
    this is Trastuzumab
    • Other targeted drugs affect other growth receptors and the tumour blood supply

Extra Information

Triple Test
     1. Clinical examination
     2. Imaging – mammography +/- ultrasound
     3. Fine-needle aspiration +/- core biopsy
• All three tests must be done if you are trying to identify whether a lump is cancerous

								
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