Each mammary gland consist of 15-20 glandular lobes or acini, much like a bunch of grapes, with the stems representing the ramifying duct system, the duct are surrounded by specialized connective tissue, the periductal tissue, witch is under hormonal control.
Each lactiferous duct enlarges as it picks up more ductles and run toward the nipple, the nipple is surrounded by pigmented circular skin called the aerola, witch contains contractile smooth fibers to facilitate nipple contraction.
The lymphatic network of the breast is exceedingly rich, and drainage is extensive in many directions from the breast itself. The major and primary route of drainage is the axillary pathway, Lymphatics from the lobules and ducts pass through the axillary fascia along with the lateral thoracic vessels to the lateral or external mammary group of nodes, which are closest to the breast.
Scapular and lower axillary vein nodes are the next stop in the progression of flow toward the apex of the axilla. The central nodes are along the main portion of the axillary vein, and highest axillary nodes include the subclavicular lymph glands, lie beneath the clavicle on top of first rib and medital to the pectoralis minor muscle.
The internal mammary lymph nodes and the highest axillary nodes drain toward the medial end of the clavicle near the junction of the subclavian and internal jugular veins. Internal mammary modes also drain directly into the anterior mediastinum by multiple interlocking channels.
Less frequent pathways of lymphatic drainage are via lymphatic plexus on the rectis sheath from the lower and medial potions of the breast and in an anterolateral pathway to the opposite axilla.
From the time after puberty to menopause, breasts affected and altered daily by some of related endocrine hormones, such as ovary, pituitary, adrenal and placenta. especially affected by ovary.
Careful inspection of both breasts should be the initial procedure. Variation in symmetry, size, shape, skip color ,and venous patterns should be observed.
The examiner must pay special attention to the nipple, looking for excoriation, inversion, discharge, edema, or redness. The skin of the nipple should be critically examined, since papillomas, eczema, and infection can occur in the nipple. These must be differentiated from Paget’s disease of the nipple. Which always is associated with an underlying carcinoma, often undetected by palpation.
The skin of the breast may show diffuse edema, as seen with cellulitis; peaud’ orange or “pigskip” edema, as seen with underlying lymphatic obstruction; or dimpling tethering, or retraction due to contraction of Cooper’s ligament by tumor growth in the deeper portions of the breast.
Palpation of the breast is most efficient when the patient lies down, with her ipsilateral hand behind her head. Gentle palpation with fingertips is essential and a systematic examination, quadrant by quadrant, must be carried out . Changes in skin temperature, thickness should be noted. Breast palpation is completed with gentle squeezing of the nipple-areolar complex to detect subareolar masses and latent nipple discharge.
A mass that is smooth, movable, firm, and totally separable from the adjacent lobular tissue is easily identified and probably benign. It is much more difficult to decide whether firm, irregular areas, within a breast containing cystic hyperplasia , Such cystic changes are most common in the upper outer quadrants and in the axillary tail of the breast and are often symmetric.
Regional lymph node drainage sites should always be routinely evaluated at the time of breast examination.
It is advantageous to examine both the supraclavicular and the axillary areas bilaterally with the patient in both the sitting and the supine positions.
Special examination of breast
1. Nipple discharge
Nipple discharges always are abnormal except during lactation, but they do not always indicate malignancy. Serous, colorless discharge can occur during normal menstrual cycles, result from intraductal papilloma, or accompany early pregnancy.
A milk-white discharge, usually bilateral, not related to lactation or breast stimulation is galactorrhea. The presence of bilateral galactorrhea prompts evaluation for an endocrinopathy causing increased prolactin secretion by the pituitary gland
A bloody discharge is usually associated with either intraductal papilloma or ductal carcinoma. Milky discharge may persist after lactation has finished and is of no consequence in the diagnosis of breast cancer. Yellow discharge may indicate a cystic hyperplasia and is rarely associated with carcinoma. Bloody discharge is the most common type, present 50 to 75 percent of the time in most studies.
2.X-ray examination of breast.
Mammography is particularly useful in the older woman with large, fatty woman, Where bulky soft tissue makes palpation difficult but where the high fat content mades X-ray identification of a malignant lesion easier.
X-ray identification of a malignant lesion easier. The more definite radiologic signs of breast cancer are mass lesions with poorly defined margins, particularly when the edges are either speculated or irregular. Fine stippled soft tissue and periductal calcification or clustered microcalcifications, not vascular calcification, are also important findings.
Only about ¼ of nonpalpable lesions detected on mammograms are found to be malignant at biopsy. The following features suggest but are not diagnostic of cancer
Distortion of normal breast architecture
Skin or nipple distortion
1. Pathological examination
(1)Fine needle aspiration biopsy
A 22-to 25-gauge needle on a 10-mL syringe is advanced into the mass,and suction is applied. False-negative findings are caused by inadequate sampling or improper specimen processing.
With either a Tru-Cut or spring-loaded Monopty device,can be used to obtain more tissue. The needle is infiltrated into the mass and fired. Three to five cores are taken and placed in formalin. Invasion, grade, and receptor status can be determined.
Is performed in the operating room using local anesthesia and intravenous sedation. All incisions should be planned such that they can be incorporated into a mastectomy incision.Masses should be excised as a single specimen.
incisional biopsy---removes of a wedge of tissue from a palpable breast mass. frozen section is obtained and definitive operation is performed immediately.
(1)Other examination for breast
Thermography and ultrasonography are physical technique employed in early detection of breast cancer.
Malignant lesion has increased skin temperature and radiation of heat. Infrared camera equipment identifies the increased surface temperature and records the variations by scanning the breast.
A ductogram, also called a galactogram, is another test that is sometimes helpful in finding the cause of a nipple discharge. This is a type of x-ray test in which a fine plastic tube is placed into the opening of the duct into the nipple. A small amount of dye is injected, which outlines the shape of the duct on an x-ray picture and will show whether there is a mass inside the duct.
Acute mastitis due to bacterial infection most commonly occurs within the first few weeks of lactation.
1.Stasis of milk
(2)obstruction of milk ducts
(3)excess secretion of milk
1.Invasion of bacteria
2.Infection usually results from staphylococci or streptococci entering the breast
The patient usually has local pain and fullness accompanied by cold feel and fever initially. Then erythema, Tender mass and cellulitis are tended to be produced, often with systemic toxic manifestations. Infections develop rapidly, and abscess may form within 1~2 days with throbbing pain, pitting edema fluctuation.
The abscess may form in the following types.
(1)the abscess locates in peripheral breast
(2)subareolar abscess involving lactiferous duct that tends to recur.
The abscess is deep, has large single or multiple cavity and milk leakage may probably be present.
Treatment.1.In early stage, promote infection subside and absorption.
(1)Antibioties can be used generally,
(2)Cessation of nursing. Immobilization and local hot compression may control the infection. Moist compression by 25% magnesium sulphate or Traditional Chinese Herbs can be applied if edema is severe
1.Early and adequate drainage is essential if fluctuation occurs or pus is proved by needle puncture.
1) Direction of incision:
Radial incision, semicircular incision-subareolar abscess. For retromammary abscess, large beneath the breast. inframammary incision should be performed. (1)All septa should be broken down with finger and the incision should be large enough, or counter incision be made.
Occurs as a result of duct ectasia with periductal mastitis, infected cysts, infected hematoma. If the abscess is subareolar, anaerobes are the most common causative agent. Treatment is with the appropriate antibiotics or surgical drainage for an abscess. These abscesses have a high recurrence rate, treatment is a central duct excision.
.Mammary dysplasia usually occurs in the age of 25~40.
Hormonal imbalance to some degree probably excessive estrogen production and deficient corpus lutein activity, produces exaggerated responses in the breast.
The typical change in the breast is characterized by varying degree of proliferative change in epithelium and connective tissues. often with cystic dilatation of ducts and acini.
1.Distended pain occurs or accentuates just before menstrual period.
2.Tender lumps are frequently in many locations. multiple lumps or nodules are frequently scattered about both breasts
3.The disease may have a long course and develops slowly
Attention must be paid to rule out early carcinoma as 2~3% of mammay dysplasia may have malignant change.
(1)Surport the breast with brassiere
(2)Give drugs to soften the lump and subside symptoms , such as Lugol’s solution and Traditional Chinese herbs.
(3)In extreme cases , androgen may be benifitial .
Excision biopsy should be done on those over 40 years old ,with solid ,hard lumps and family history. If biopsy shows excessive epithelial ductal hyperplasia, excision of mammary lobe or simple mastectomy should be performed .If malignancy is proved, radical mastectomy should be done.
TUMORS OF BREAST
1.benign tumors (85%);include fibroadenoma and intraductal papiloma.
2.Malignant tumors (15%)include :
(1)Primary: carcinoma, intraductal carcinoma, Paget’s disease of nipple and fibrosarcoma.
The peak age incidence is 18~25 years.
Characters: freely movable ,smooth, and independent of the surrounding breast tissue. These lesions are usually painless but can be tender to palpation and do not regress after a menstrual cycle.
Fibroadenomas are best treated by excisional biopsy.
They most commonly produce a bloody nipple discharge.
These papillomas may be soft ,small ,and difficult to palpate. Ductograms can also be very useful in idetifying such papillomas.
If no mass can be felt, the duct from which blood is expressed should be gently probed and excision carried out along the prob until the papilloma is identified.
Intraductal papillomas are always benign, but 6% to 8% of the cases may have malignant change.
CARCINOMA OF BREAST
It causes more deaths than any other disease or injury in women ages 45~49 and 60~64, cancer of the breast is second only to lung cancer as a cause of death from cancer among women
Risk factors for breast cancer Benign proliferative changes with atypia Noninvasive carcinoma( ductal or lobular carcinoma in situ) Personal history of contralateral breast cancer Low dose radiation Family history(mother, sister, or daughter with premenopausal or bilateral breast cancer Late nenopause(after age 50) Age older Early menarche(<12) Gender (female>male) ninor major
If diagnosed at an early stage, breast cancer has an encouraging cure rate: up to 97% of women diagnosed with localized breast cancer will survive five years after their diagnosis. Even if the cancer is found at a more advanced stage, new therapies have enabled many people with breast cancer to experience the same quality of life as before their diagnosis. About 90% of all breast cancers originate in the ducts or lobes. Almost 75% of all breast cancers begin in the cells lining the milk ducts and are called ductal carcinomas. Cancers that begin in the lobules are called lobular carcinoma. Lobular carcinoma has a higher chance of occurring in the contralateral (the other) breast either at the time of diagnosis or in the future.
Breast cancer cells may spread to other sites in the body by migrating through the blood vessels and/or lymph vessels. The lymph nodes can be located under the arm (axillary), in the neck (cervical), or just above the collarbone (supraclavicular). The most common sites of distant metastasis are the bones, lungs, and liver. The cancer can also recur locally in the skin or tissues of the chest.
Doctors may also test the tissue obtained during a biopsy to help guide treatment decisions. The tests include:
Tumor features: Examination of the tumor under the microscope determines whether it is invasive or in situ; ductal or lobular; well, moderate, or poorly differentiated; and whether it detects the presence of vascular or lymphatic invasion.
Estrogen receptor (ER) and progesterone receptor (PR) tests: These help determine both the prognosis (chance of recovery) and whether the cells respond to hormone therapy. Generally, ER or PR positive (+) tumors will respond to hormone therapy. The ER/PR status helps guide treatment decisions.
HER-2/neu tests: This is a protein that is overexpressed (too much of it) in about 25% of breast cancers. The HER-2 status helps guide treatment decisions.
Alkaline phosphatase levels: High levels of this enzyme could signify disease in the liver, bone cells, or bile ducts.
Tumor markers: Carcinoembryonic antigen (CEA), CA 15-3, or CA 27.29 may indicate the presence or degree of cancer.
Total bilirubin count, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT) levels: These tests evaluate liver function. High levels can indicate liver damage, a signal of possible spread to that organ
Pathologic classification of carcinoma of breast
1. Noninvasive carcinoma
A.Intraductal carcinoma or ductal carcinoma in situ(DCIS) . These lesions comprise malignant cells that have not penetrated the basement membrane.
B.Lobular carcinoma in situ (LCIS)
2.Invasive breast cancer
A.Invasive ductal carcinoma(75%-80%)
B invasive ductal carcinoma with a prodominant intraductal component
C.Invasive lobular carcinoma(5-10%)
D.Mucinous carcinoma (3%)
E. medullary carcinoma(5-7%)
G. Tubular carcinoma(1-2%)
H. Adenoid cystic carcinoma
I. Sectory caecinoma.
J. Apocrine carcinoma
Kcarcinoma with metaplasia
Special clinical forms of breast cancer
Paget’s disease of the nipple
The first symptoms is often itching or burning of the nipple, with superficial erosion or ulceration. The diagnosis is established by biopsy of the erosion
Paget’s carcinoma is not common( about 1% of all breast cancers).
It is frequently diagnosed and treated as dermatitis or bacterial infection, leading to unfortunate delay in detection. When the lesion consists of nipple change only, the incidence of axillary metastases is about 5%, and the prognosis excellent.
This is the most malignant form of breast cancer and constitute less than 3% of all cases. The clinical findings consist of a rapidly growing, sometimes painful mass that enlarges the breast. The overlying skin becomes erythmatous, edematous, and warm. Often there is no distinct mass, since the tumor infiltrates the involved breast diffusely.
The inflammatory changes often mistaken for an infection process, are caused by carcinoma invasion of the dermal lymphatics, with resulting edema,and hyperemia, if the physicin suspects infection but the lesion does not respond rapidly( 1-2 weeks) to antibiotics, biopsy examination must be performed. Metastases tend to occur early and widely, and for this reason inflammatory carcinoma is rarely curable. Mastectomy is seldome, if ever, indicated. Radiation, hormone therapy, and antcancer chemotherapy are the measures more likely to be of value.
Pathway of spread
1.the patient may complain of a painless solitary ,firm lump in the breast.
2.The lump may not be tender with ill defined margin, It may have poor mobility or even be fixed.
3.The shape of the breast and nipple may change. The skin may show redness, ulceration, retraction and orange skin change.
1.The regional lymphnodes may be enlarged.
2.The patient has corresponding distal metastatic change such as in lung, bone, and liver.
3.Special type breast cancer
(1)The TNM system is described as follows
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 tumor.
T1 Tumor of 2cm or less; skin not involved
T2 Tumor 2 to 5cm in size
T3 Tumor greater than 5cm in size
T4 Tumor of any size with any of the following : skin infiltration, ulceration, peau d’orange, skin edema, pectoral muscle or chest wall attachment.
Nx. Reginal lymph node cannot be assessed
N0. No reginal lymph node metastasis
N 1 Clinically palpable but movable axillary nodes
N 2 Clinically palpable, fixed, axillary nodes.
N 3 Homolateral supra-or infraclavicular nodes considered to contain metastasis; edema of the arm. metastases to ipsilateral internal mammary lymph nodes
Mx. Presence of distant metastasis cannot be assessed
M 0 No distant metastasis
M 1 Clinical and radiographic evidence of distant metastasis( including ipsilateral supraclavicular nodes )
AJCC/UICC Stage Group American joint committee on cancer
Stage I T 1 -T 2 ,N 0 ,M 0
Stage II T 1 -T 2 ,N 1 ,M 0
Stage III T 1 -T 2 , N 2 -N 3 , M 0 or T 3 -T 4 , N 0 -N 3 , M 0
Stage IV Any T Any N , M 1 .
According to the clinical, pathological findings and patients condition, operation, radiation, hormone and chemotherapy can by applied, Yet early operation still remains the most satisfactory method. Surgical operation
Axillary lymph node dissection(ALND)
Involves removal of level 1 ( lateral to the pectoralis minor muscle) and level 2 lymph nodes (posterior to the pectoralis minor muscle) and if grossly involved, possibly level 3 nodes. An adequate dissection should remove at least eight lymph nodes.
Intraoperative complications of axillary dissection include damage to the long thoracic, medial pectoral, thoracodorsal and intercostobrachial nerves. Postoperatively , the most frequent complications include wound infections and seromas.
Sentinel lymph nodes biopsy(SLNB)
It involves introperative lymphatic mapping using lymphazurin blue dye or technetium labeled sulfur colloid ( or both ) to identify the primary draining lymph nodes in the nodal basin. If the SLN is negative, a more extensive lymph node dissection can be avoided.
If the SLN is positive, a standard axillary dissection is performed or radiation therapy is givens to the axilla.
A blue dye in lumpectomy site B axillary lymph nodes: levels I C axillary lymph nodes: levels II D axillary lymph nodes: levels III E large lymphatic channels F small lymphatic channels G sentinel lymph nodes taking up dye
When planning the treatment for a person's breast cancer, the doctor will consider many factors, including:
The stage and grade of the tumor
The tumor's hormonal status (ER, PR)
The patient's age and general health
The patient's menopausal status
The presence of known mutations to breast cancer genes
Factors that may signify an aggressive tumor, such as HER-2/neu amplifications
(1)Standard radical mastectomy: involves en bloc excision of the breast, pectoral muscles, and axillary lymph nodes, sometimes with a skin graft to cover the defect.
(2)Modified radical mastectomy: is the same operation except that the pectoralis major muscles are preserved.
(3)extended radical mastectomy: involves removal of internal mammary lymb nodes in addition to standard radical mastectomy. Stage I&II.
(4)Simple mastectomy: is removal of just the breast, Leaving the pectoralis muscles and axillary nodes. It is indicated for those of stage III and poor medical risk.
(5)Local excision or “Lumpectomy”
Surgical treatment options include the following:
Lumpectomy and radiation therapy
Partial mastectomy and radiation therapy
Modified radical mastectomy
Adjuvant means "in addition to," and these therapies are given in addition to surgery or surgery plus radiation therapy to decrease the risk of the breast cancer returning. Adjuvant therapies include radiation therapy, chemotherapy, and hormonal therapies. They are intended to eliminate any breast cancer cells lingering in the body. Adjuvant therapy decreases the risk of recurrence but does not necessarily eliminate it.
It is used to reduce local recurrence and sterilize internal mammary lymph nodes in postoperative patients. It is also the first choice therapy in advanced cases.
Radiation therapy is given regularly for a number of weeks following a lumpectomy or partial mastectomy in order to eliminate remaining cancer cells near the tumor site. Radiation therapy is also recommended for many women after a mastectomy depending upon the size of their tumor, number of involved lymph nodes under the arm, and width of the margin of resection obtained by the surgeon. Sometimes radiation therapy is given before surgery to shrink a large tumor and make it easier to remove.
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy drugs travel through the bloodstream to cancer cells throughout the body and destroy cancer cells that have migrated from the original site of the tumor. It may be given orally or intravenously and is usually given in cycles. Chemotherapy generally does not require a hospital stay; women are usually treated in an outpatient setting.
An oncologist may administer chemotherapy before surgery (neoadjuvant therapy) to shrink a large tumor, or after surgery (adjuvant therapy). The goal is to remove the entire tumor during surgery.
It is and adjuvant therapy to increase survival and reduce the incidence of recurrence alone or in combinations.
Chemotherapy for node-positive patient. Six months of CMF or CAF therapy, typically giving nine cycles of CMF, is a stantard regiman given to women with node-positive breast cancer who are less than 50 years of age.
Different chemotherapy drugs are useful for different cancers, and research has shown that combinations of certain drugs are more effective than individual drugs. Some common regimens for breast cancer include combinations of two or three of the following chemotherapy drugs: cyclophosphamide (Cytoxan or Neosar) (C), methotrexate (M), fluorouracil (5-FU) (F), doxorubicin (Adriamycin) (A), epirubicin (Ellence) (E), paclitaxel (Taxol), and docetaxel (Taxotere) (T).
Common combinations of drugs include: CMF, CAF, CEF, T (docetaxel [in this case]) AC and AC followed by T (paclitaxel [in this case]). Chemotherapy drugs are powerful and affect both healthy and cancerous cells in the body. Normal cells that grow quickly, such as those lining the gastrointestinal tract or hair follicles, may be damaged or killed along with cancer cells.
Side effects can include fatigue, nausea, and vomiting, lowered white blood cell count, and a corresponding increased risk of infection, mouth sores, hair loss, and premature menopause. Most of these side effects go away once treatment is stopped and are not long term. However, long-term toxicities may occur including heart damage, nerve damage, or secondary cancers.
Hormonal therapy is useful to manage tumors that test positive for either estrogen or progesterone receptors. These tumors use hormones to fuel their growth. Blocking the hormones limits the growth of these types of tumors. .
If it is determined that the tumor uses estrogen or progesterone to grow than hormonal treatment may be used alone or together with chemotherapy. Examples of hormonal therapy used as adjuvant therapies are tamoxifen, anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin)
Preliminary evidence suggests that cancers with a high level of estrogen receptors are more responsive to hormonal manipulation. Tamoxifen is a competitive antagnist of estrogen and will bind to estrogen receptors, preventing the binding of estrogen. 10mg bid at least 5 years.
Tamoxifen is a drug that researchers have studied the longest for its use as a hormonal therapy. It blocks estrogen from binding to tumor cells. It has been shown effective in reducing the risk of recurrence in the treated breast, the risk of developing cancer in the opposite breast, and the risk of developing cancer in women with no history of the disease but who are at higher than average risk of developing breast cancer. Current research shows that there is no benefit for taking tamoxifen longer than five years
Aromatase inhibitors decrease the production of estrogen and are effective in postmenopausal women. They work by blocking the aromatase enzyme, which is necessary for production of estrogen. They are emerging as the preferred treatment for women with hormone-sensitive cancers. Several of these drugs include anastrozole, letrozole, and exemestane.
Targeted drug therapy.
Several promising new breast cancer drugs work by stopping the action of abnormal proteins that cause cells to grow and divide out of control. Monoclonal antibodies target proteins that are present in unusually large amounts in breast cancer cells.
Trastuzumab (Herceptin) is already approved for the treatment of advanced breast cancer for tumors that overexpress HER-2/neu. Trastuzumab is under evaluation for early stage breast cancer as well.
Bevacizumab (Avastin) blocks angiogenesis (the formation of new blood vessels), which is necessary for tumor growth and metastasis (spreading); it is under evaluation in clinical trials.
Recurrent breast cancer
Breast cancer is called recurrent if the cancer has come back after it was first diagnosed and treated. It may come back in the breast (a local recurrence), in the chest wall, or in another part of the body, including distant organs (such as the lungs, liver, and bones) called distant metastases.
Breast cancer may also spread to other organs such as the brain, the opposite breast, adrenal glands, spleen, and ovaries. If the tumor is metastatic (spread outside of the breast or local lymph nodes) it is generally not curable. The goal of treatment for advanced disease is to achieve remission (temporary or permanent absence of disease) or slow the growth of the tumor. Some patients live years after a recurrence of breast cancer and may undergo many different treatments. With the advent of earlier detection methods and new therapies, breast cancer may be considered a chronic disease for some patients.
Once metastatic disease is detected, a woman may undergo surgery to remove the metastases, or have chemotherapy, hormone therapy, radiation therapy, or targeted therapy (such as trastuzumab) to control it. Signs and symptoms depend on the site of the recurrence and may include:
A lump under the arm or along the chest wall
Bone pain or fractures, which may signal bone metastases
Headaches or seizures, which may signal brain metastases
Chronic coughing or trouble breathing, which may signal lung metastases
A biopsy of the recurrent site is often recommended to be certain of the diagnosis and to check for ER, PR, and HER-2/neu status. Often hormone therapy is used first if possible. Chemotherapy and targeted therapies are also used. Radiation therapy and surgery may be used in certain situations.