CANCER

• In a cancerous cell, permanent gene alterations, or mutations, cause the cell to malfunction.
• For a cell to become cancerous, usually three to seven different mutations must occur in a single
cell.
• These genetic mutations may take many years to accumulate, but the convergence of mutations
enables the cell to become cancerous.

HOW CANCER DEVELOPS

A. Proto-oncogenes become onco-genes

• When the growth factor message reaches the cell nucleus, it activates genes called proto-
oncogenes. These genes produce proteins that stimulate the cell to divide.

• In cancerous cells, mutations in proto-oncogenes cause these genes to malfunction.

When a proto-oncogene mutates, it becomes an oncogene—a gene that instructs the cell
to grow and divide repeatedly without stimulation from neighboring cells.

• Some oncogenes overproduce growth factors, causing the cell to divide too often. Other
oncogenes stimulate the cell to reproduce even when no growth factor is present.

B. Tumor Suppresor genes Stop Working

• Tumor suppressor genes are like brakes for cell growth. When activated, these
genes halt the cell cycle, preventing further cell division.
• But if tumor suppressor genes malfunction due to mutations, the rapidly dividing cell
ignores messages from its neighbors telling it to stop dividing.
• Malfunctioning tumor suppressor genes are not enough to cause cancer—the cell
still must overcome a host of other safety mechanisms before it can cause truly
significant damage.

CAUSES OF CANCER

• Viruses
 Prolonged or frequent viral infections may cause breakdown of the immune system or
overwhelm the immune system (Failure of the Immune System Response Theory)
 Cancer-causing viruses include the human papilloma virus (HPV), a sexually
transmitted virus responsible for 70 to 80 percent of all cases of cancer of the cervix.
 Hepatitis B and C viruses cause almost 80 percent of all liver cancer in the world.
 Epstein-Barr virus can also be carcinogenic, causing cancer of the lymphatic system.
 Human immunodeficiency virus (HIV) or a type of herpesvirus can lead to rare
cancers of the lymphatic and circulatory systems.
 Helicobacter pylori, a bacterium associated with stomach ulcers, likely causes cancer of
the stomach.

• Chemical carcinogens
 Acts by causing cell mutation or alteration in cell enzymes and
proteins – altered cell replication
 Industrial compounds
 Vinyl chloride (plastic manufacture, asbestos factories,
construction works)
 Polycyclic aromatic hydrocarbons (burning, auto and
truck emissions, oil refineries), air pollution
 Fertilizers, weed killers
 Dyes
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  Analine dyes
 Hair bleach
 Tobacco, alcohol
 Drugs

 Food, preservatives
 Nitrites (bacon, smoked meat)
 Talc
 Food sweeteners
 Nitroamines (rubber baby nipples)
 Aflatoxins (mold in nuts and grains, milk, cheese, peanut
butter)
 Polycyclic hydrocarbons (charcoal burning)

• Physical agents
 Exposure to electromagnetic radiation, invisible, high-energy light waves such as
sunlight and X rays, accounts for about 2 percent of all cancer deaths
 Most cancer deaths from radiation are from skin cancer, which is triggered by too much
sun exposure. Sunlight that reaches the Earth’s surface contains two kinds of ultraviolet
(UV) radiation. UV-A and UV-B both contribute to sunburn and skin cancer as well as to
conditions such as premature wrinkling of the skin.
 Depletion of the ozone layer, which absorbs ultraviolet radiation in the upper
atmosphere, will continue to increase skin damage and skin cancer rates in the future.
 Physical Irritation

• Hormones
 In women, relatively high or long exposure to the female sex hormone estrogen seems
to increase the risk of breast and uterine cancers.
 Thus, early age at first menstruation, late age at menopause, having children after age
30, and never having children, all of which affect the duration of estrogen exposure in
the body, increase the risk for these cancers.
 Some evidence also suggests that estrogen replacement therapy (ERT), in which women
take estrogen to offset the unpleasant effects of menopause, may also increase the risk of
some cancers of the reproductive organs.
 The risk appears to go down significantly, however, when estrogen and another female
sex hormone, progesterone, are taken together. At one time studies showed a link
between birth control pills and cancer.
 Male sex hormones, particularly testosterone, also appear to play a role in cancers of the
male reproductive organs, but this role is not yet well understood.

• Genetics
 Some gene mutations associated with cancer are inherited. For example, inheritance of
the mutated tumor suppressor genes BRCA1 or BRCA2 greatly increases the risk of
breast cancer in young women.
 About 50 to 60 percent of women with inherited BRCA1 or BRCA2 mutations will
develop breast cancer by the age of 70. Inherited mutations in the genes MSH2, MLH1,
PMS1, and PMS2, all of which repair DNA, are especially prevalent in a rare form of
hereditary colon cancer.
 Scientists suspect that many other hereditary factors contribute to cancer. In addition to
inherited mutations, other genetic variations, particularly those influencing how the body
responds to carcinogens, may create a greater susceptibility to cancer. The identities of
the majority of these genetic variations are not yet known.

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PREDISPOSING FACTORS
• Age
• Sex
 Women – more prone to breast, uterus, cervix cancer
 Men – more prone to prostate, lung cancer
• Urban VS. Rural residence
 Cancer common among urban dweller than rural dwellers

• Geographic distribution
 Japan – cancer of the stomach, U.S. – breast cancer
 National diet, ethnic customs, type of pollution
• Occupational hazards
 Chemical factory workers, farmers, radiology department personnel
• Hereditary
• Stress
 Immunodeficiency
• Precancerous lesions
• Obesity

WARNING SIGNALS OF CANCER

 C – change in bowel or bladder habits
o pencil-thin stools with colon cancer.

o Occasionally, cancer exhibits continuous diarrhea.

o If any of these abnormal bowel complaints last more than a few days,
they require evaluation.
 A – sore that does not heal
 U – unusual bleeding or discharge
 U – unexplained sudden weight loss
 U – unexplained anemia
 T – thickening or lump in the breast or elsewhere
o Lumps may represent cancer or a swollen lymph gland related to cancer.

o A lump or gland that remains swollen for 3-4 weeks should be evaluated.
 I – indigestion or difficulty in swallowing
 O – obvious change in wart or mole
 N- nagging cough or hoarseness of voice
o Anyone with a cough that lasts more than a month or with blood in the
mucus that is coughed up should see a doctor.

Metastasis:

• Cancer cells divide and grow without control or order to form a mass of tissue, called a
growth or tumor. As the tumor grows, it can invade nearby organs and tissues. Cancer
cells can also break away from the tumor and enter the bloodstream or lymphatic system.
By moving through the bloodstream or lymphatic system, cancer can spread from the
primary site to form new tumors in other organs. The spread of cancer is called
metastasis.

GENERAL CONSIDERATIONS
Cancer can be considered a chronic disease requiring ongoing management, rather than a
terminal illness. It consists of more than 100 different conditions characterized by uncontrolled
growth and spread of abnormal cells. Normal mechanisms of growth and proliferation are
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disturbed which results in distinctive morphologic alterations of the cell and aberrations in tissue
patterns.

TABLE 8-1 Differences Between Malignant and Benign Tumors

CHARACTERISTIC BENIGN MALIGNANT

Growth Slow, expansive Invasive, grows rapidly

Differentiation Fully differentiated Immature, poorly differentiated

Metastasis Present
Absent
Recurrence Extremely unusual when Common following surgery
surgically removed
Capsule Encapsulated Not encapsulated

The malignant cell is able to invade the surrounding.

STAGING

Staging describes the extent or severity of an individual’s cancer based on the

extent of the original (primary) tumor and the extent of spread in the body.

Stages of cancer:

• Stage 0 or carcinoma in situ

Carcinoma in situ is very early cancer. The abnormal cells are found only in
the first layer of cells of the primary site and do not invade the deeper
tissues.
• Stage I
Cancer involves the primary site, but has not spread to nearby tissues.
• Stage II
Cancer has spread to nearby areas but is still inside the primary site.
o stage IIA: cancer has spread beyond the primary site.
o stage IIB: cancer has spread to other tissue around the primary site.
• Stage III
Cancer has spread throughout the nearby area.
• Stage IV
Cancer has spread to other parts of the body.
o stage IVA: cancer has spread to organs close to the pelvic area
o stage IVB: cancer has spread to distant organs, such as the lungs
• Recurrent
Recurrent disease means that the cancer has come back (recurred) after it
has been treated.

Once a stage is assigned and treatment given, the stage is never changed. For
example:

If a stage I cancer of the cervix is treated, and two years later a metastasis is found
in the lung, it is not now stage IV, but remains a "stage I, with recurrence to the
lung." However, some cancers may be re-staged.

4
The important thing about staging is that it determines the appropriate treatment,
provides a prognosis, and allows for comparison of treatment results between
different treatments.

The TNM Staging System

o In the TNM system, each cancer is assigned a T, N, and M category.

The T category describes the original (primary) tumor. The tumor size is usually measured in
centimeters (2 and 1/2 centimeters is about 1 inch) or millimeters (10 millimeters = 1
centimeter.)

 TX means the tumor can't be measured or evaluated.

 T0 means there is no evidence of primary tumor (the primary tumor cannot be found).
 Tis means the cancer is in situ (the tumor has not started growing into the structures
around it).
 The numbers T1–T4 describe the tumor size and/or level of invasion into nearby
structures. The higher the T number, the larger the tumor and/or the further it has grown
into nearby structures.

The N category describes whether or not the cancer has reached nearby lymph nodes.

 NX means the nearby lymph nodes can't be measured or evaluated.

 N0 means nearby lymph nodes do not contain cancer.
 The numbers N1–N3 describe the size, location, and/or the number of lymph nodes
involved. The higher the N number, the more lymph nodes are involved.

The M category tells whether there are distant metastases (spread of cancer to other parts of
body).

 MX means metastasis can't be measured or evaluated.

 M0 means that no distant metastases were found.
 M1 means that distant metastases were found (the cancer had spread to distant organs
or tissues.)
 For example, breast cancer T3 N2 M0 refers to a large tumor that has spread outside the breast
to nearby lymph nodes, but not to other parts of the body.
 Prostate cancer T2 N0 M0 means that the tumor is located only in the prostate and has not
spread to the lymph nodes or any other part of the body.

Summary staging

 This system is used for all types of cancer. It groups cancer cases into five main categories:

• In situ is early cancer that is present only in the layer of cells in which it began.
• Localized is cancer that is limited to the organ in which it began, without
evidence of spread.
• Regional is cancer that has spread beyond the original (primary) site to nearby
lymph nodes or organs and tissues.
• Distant is cancer that has spread from the primary site to distant organs or
distant lymph nodes.
• Unknown is used to describe cases for which there is not enough information to
indicate a stage.

Grade
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 • The grade of the cancer reflects how abnormal the cancer cells look under the
microscope.
• Grade is important because cancers with more abnormal-looking cells tend to
grow and spread more quickly.
• Higher grade cancers (meaning that the cancer cells look very abnormal) usually
have a worse prognosis, and sometimes need different treatments.
• The American Joint Committee on Cancer (AJCC) recommends the following
cancer grading classifications:

 GX: Grade cannot be determined

 G1: Well-differentiated (the cancer cells look a lot like normal cells)
 G2: Moderately well-differentiated (cancer cells look somewhat like normal
cells)
 G3: Poorly differentiated (cancer cells don't look much like normal cells)
 G4: Undifferentiated (the cancer cells don’t look anything like normal cells)

 The lower the cancer grade the better the prognosis.

 G1 cancers are linked to the best outcomes. G4 is
associated with the worst outcomes and the others fall in
between.

The types of tests used for staging depend on the type of cancer.

• Physical exams are used to gather information about the cancer.

• Imaging studies produce pictures of areas inside the body. These studies are
important tools in determining stage. Procedures such as x-rays, computed
tomography (CT) scans, magnetic resonance imaging (MRI) scans, and
positron emission tomography (PET) scans can show the location of the
cancer, the size of the tumor, and whether the cancer has spread.

• Laboratory tests are studies of blood, urine, other fluids, and tissues taken from
the body. For example, tests for liver function and tumor markers (substances
sometimes found in increased amounts if cancer is present) can provide
information about the cancer. (PSA)

• Pathology reports may include information about the size of the tumor, the growth of the
tumor into other tissues and organs, the type of cancer cells, and the grade of the tumor
(how closely the cancer cells resemble normal tissue). A biopsy (the removal of cells or
tissues for examination under a microscope) may be performed to provide information
for the pathology report (Fine-needle aspiration (FNA) is used most commonly to
differentiate between solid and cystic masses. It is inexpensive, causes little discomfort,
and can be performed in an outpatient or office setting. ). Cytology reports also
describe findings from the examination of cells in body fluids.

• Surgical reports tell what is found during surgery. These reports describe the
size and appearance of the tumor and often include observations about lymph
nodes and nearby organs.

EFFECTS:
A. Proliferation of Cancer cells

 Pressure – due to increase in size of neoplastic growth

 Obstruction – as tumor continues to grow, hollow organs and
vessels become compressed and obstructed
 Pain
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  Pressure on nerve endings

 Distention of organs/vessels

 Lack of O2 to tissues and organs

 Release of pain mediators by the tumors

 Effusion

 When lymphatic flow is obstructed, there may be effusion

in serous cavities

 Ulceration and necrosis

 Results as the tumor erodes blood vessels and pressure

on tissues – causes ischemia – tissue damage and
bleeding – infection

 Vascular thrombosis, embolus, thrombophlebitis

 Tumors tend to produce abnormal coagulation factors

that causes increased clotting

B. Paraneoplastic Syndrome – malignant cells produce enzymes,

hormones and other substances

 Anemia

 cancer cells produce chemicals that interfere with rbc

production

 iron uptake is greater in the tumor than that deposited in

the liver

 blood loss may result from bleeding

 Hypercalcemia

 Tumors of the bone, squamous cell lung Ca, Ca of the

breast produce a parathyroid – like hormone that
increases or accelerates bone breakdown and release of
calcium

 Results from metastasis to the bones

 Enhance by immobilization and dehydration

 DIC

 Precipitated by the release of tissue thromboplastin or

endothelial injury

C. Anorexia-Cachexia Syndrome

 Malignant neoplasms deprive normal cells of nutrition

 Tumors revert to anaerobic metabolism – consume glucose –

deplete glycogen stores in the liver

 Protein depletion, serum albumin levels decrease

 Tumors take up sodium

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  Ca cells produce anorexigenic substances that act on the
satiety center of the hypothalamus, causing anorexia

 Taste sensation diminishes and the individual may have

aversion to eating

THERAPEUTIC MODALITIES

RADIATION THERAPY
 Radiation therapy is the use of high-energy ionizing rays to destroy a cancer cell's ability
to grow and multiply.
 The goal of radiation therapy is to deliver a precisely measured dose of irradiation to a
defined tumor volume with minimal damage to surrounding healthy tissue.
 This results in eradication of tumor, high quality of life, prolongation of survival, and
allows for effective palliation or prevention of symptoms of cancer, with minimal
morbidity.

Goals of Therapy

• Curative: When there is a probability of long-term survival after adequate therapy; some
adverse effects of therapy, although undesirable, may be acceptable.
• Palliative: When there is no hope of survival for extended periods, radiation can be
used to palliate symptoms, primarily pain. Lower doses of irradiation (75% to 80% of
curative dose) can control the tumor and palliate symptoms without excessive toxicity.

Principles of Therapy

• Higher doses of irradiation produce better tumor control. For every increment of
irradiation dose, a certain fraction of cells will be killed.
• A boost is the additional dose administered through small portals to residual disease.
• Radiosensitivity is the degree and speed of response. This measure of susceptibility of
cells to injury or death by radiation depends on cancer diagnosis and its inherent biologic
activity.
• Role of oxygen: Oxygen must be present at the time of radiation's maximal killing effect.
Poor circulation with resultant hypoxia can reduce cellular radiosensitivity.
• Cellular response can be modified by changing the dose rate, manipulating the process
of cell repair, and using hyperthermia (above 104° F , 40° C]).
• Radioresistance is the lack of tumor response to radiation because of tumor
characteristics (slow-growing tumor, less responsive), tumor cell proliferation, and
circulation. Radiation is most effective during the mitotic stage of the cell cycle.
• Radioresistant tumors: Many tumors are resistant to radiation, such as squamous cell,
ovarian, soft tissue sarcoma. Many other tumors can become resistant after a period of
time.
• Normal radioresistant tissues include mature bone, cartilage, liver, thyroid, muscle,
brain, and spinal cord.

Types of Radiation Therapy

A. Brachytherapy

 the radiation device is placed within or close to the target tissue.

8
  Radiation is delivered in a high dose to a small tissue volume with less radiation
to adjacent normal tissue, but requires direct tumor access.

o Interstitial therapy utilizes solid radioactive material such as seed implants.

These may be temporary (removed after several days) or permanent. The
permanent type remains in place with gradual decay. Implant procedure is
performed under local or general anesthesia. (Used in breast and prostate
disease)
o Intracavitary therapy utilizes radioactive material that is inserted into a cavity
such as the vagina, as in cancer of the uterine cervix.
o Other forms of brachytherapy are systemic irradiation (parenteral or I.V.), oral
131
I for thyroid cancer, or intraperitoneal radiation.

B. Teletherapy

 is external beam irradiation and uses a device located at a distance from the
patient.
 It produces X-rays of varying energies and is administered by machines a
distance from the body 31½ to 39 inches (80 to 100 cm).

Acute Adverse Effects

• Fatigue and malaise

• Skin: may develop a reaction as soon as 2 weeks into the course of treatment (Skin erythema
may range from mild to severe with possible dry-to-wet desquamation. Areas having folds, such
as the axilla, under the breasts, groin and gluteal fold, are at an increased risk because of
increased warmth and moisture.)
• GI effects: nausea and vomiting, diarrhea, and esophagitis
• Oral effects: changes in taste, mucositis, dryness, and xerostomia (dryness of mouth from lack of
normal secretions)
• Pulmonary effects: dyspnea, productive cough, and radiation pneumonitis (Usually occurs 1 to 3
months after radiation to the lung.)
• Renal and bladder effects: cystitis and urethritis
• Cardiovascular: damage to vasculature of organs, thrombosis
• Recall reactions: acute skin and mucosal reactions when concurrent or past chemotherapy
(doxorubicin [Adriamycin], dactinomycin [Actinomycin D])
• Bone marrow suppression: more common with pelvic or large bone radiation

Chronic Adverse Effects

After 6 months with variability in time of expression:

• Skin effects: fibrosis, telangiectasia, permanent darkening of the skin, and atrophy
• GI effects: fibrosis, adhesions, obstruction, ulceration, and strictures
• Oral effects: permanent taste alterations, and dental caries
• Pulmonary effects: fibrosis
• Renal and bladder effects: radiation nephritis, fibrosis
• Second primary cancer: patients who have received combined radiation and chemotherapy with
alkylating agents have a rare risk of developing acute leukemia

Nursing Assessment

• Assess skin and mucous membranes for adverse effects of radiation.

• Assess GI, respiratory, and renal function for signs of adverse effects.
• Assess patient's understanding of treatment and emotional status.

Nursing Diagnoses

9
 • Risk for Impaired Skin Integrity, Infection, Hemorrhage, Stomatitis related to radiation
effects
• Ineffective Protection related to brachytherapy

Nursing Interventions

Maintaining Optimal Skin Care

• Inform the patient that some skin reaction can be expected, but that it varies from patient
to patient. Examples include dry erythema, dry desquamation, wet desquamation, and
tanning.
• Do not apply lotions, ointments, or cosmetics to the site of radiation unless prescribed.
• Discourage vigorous rubbing, friction, or scratching because this can destroy skin cells.
• Avoid wearing tight-fitting clothing over the treatment field; prevent irritation by not using
rough fabric such as wool and corduroy.
• Take precautions against exposing the radiation field to sunlight and extremes in
temperature.
• Do not apply adhesive or other tape to the skin.
• Avoid shaving the skin in the treatment field.
• Use lukewarm water only and mild soap when bathing.

Preventing Infection

• Monitor blood counts weekly

• Good personal hygiene, nutrition, adequate rest
• Inform about signs of infection and report to physician

Preventing Hemorrhage

• Avoid physical trauma and use of aspirin

• Teach signs of hemorrhage
• Monitor stool and skin for signs of hemorrhage
• Use direct pressure over injection sites until bleeding stops

Ensuring Protection from Radiation

• To avoid exposure to radiation while the patient is receiving therapy, consider the
following:
o Time - exposure to radiation is directly proportional to the time spent within a
specific distance to the source. (limit contact for 5 minutes each time, a total of
30 minutes per shift)

o Distance - amount of radiation reaching a given area decreases as distance

increases. (maintain a distance of at least 3 feet when not performing nursing
procedures)
o Shield - sheet of absorbing material placed between the radiation source and the
nurse decreases the amount of radiation exposure.

• If exposed to penetrating radiation (X-ray or gamma rays), wear film badges on the front
of the body.
• Take appropriate measures associated with sealed sources of radiation implanted within
a patient (sealed internal radiation).
o Follow directives on precaution sheet that is placed on the charts of all patients
receiving radiotherapy.
o Do not remain within 3 feet (1 meter) of the patient any longer than required to
give essential care.
10
 • Do not linger longer than necessary in giving patient care, even though all precautions
are followed.
• Be alert for implants that may have become loosened (those inserted in cavities that
have access to the exterior); for example, check the emesis basin following mouth
care for a patient with an oral implant.
• Notify the radiation therapist of any implant that has moved out of position.
• Use long-handled forceps or tongs and hold at arm's length when picking up any
dislodged radium needle, seeds, or tubes. Never pick up a radioactive source with
your hands.
• Do not discard dressings or linens unless you are sure that no radioactive source is
present.
• After the patient is discharged from the hospital, it is a good policy for the radiologist to
check the room with a radiograph or survey meter to be certain that all radioactive
materials have been removed.
• Continue radiation precautions when a patient has a permanent implant, until the
radiologist declares precautions unnecessary.

CHEMOTHERAPY
 Chemotherapy is the use of antineoplastic drugs to promote tumor cell destruction by
interfering with cellular function and reproduction. It includes the use of various
chemotherapeutic agents and hormones.

 Principles of Chemotherapy Administration

• The intent of chemotherapy is to destroy as many tumor cells as possible with
minimal effect on healthy cells.
• Chemotherapeutic agents can be effective on one of the four phases of the cell
cycle or during any phase of the cell cycle. The cell cycle is divided into four stages:
o G1 (gap one) phase: RNA and protein synthesis (enzymes for DNA synthesis
are manufactured)
o S (synthesis) phase: During a long time period the DNA component doubles for
the chromosomes in preparation for cell division.
o G2 (gap two) phase: This is a short time period; protein and RNA synthesis
occurs, and the mitotic spindle apparatus is formed.
o M (mitosis) phase: In an extremely short time period, the cell actually divides
into two identical daughter cells.
• Routes of administration:
o Oral - capsule, tablet, or liquid
o I.V. - push (bolus) or infusion over a specified time period
o Intramuscular
o Intrathecal/intraventricular - given by injection by lumbar puncture
o Intra-arterial
o Intracavitary such as peritoneal cavity
o Intravesical into uterus or bladder
o Topical

• Dosage is based on surface area (mg/m2) in both adults and children.

• Most chemotherapeutic agents have dose-limiting toxicities that require nursing
interventions
• Chemotherapy predictably affects normal, rapidly growing cells (eg, bone marrow,
GI tract lining, hair follicles). It is imperative that these toxicities be recognized
early on by the nurse.

Safety Measures in Handling Chemotherapy

11
Personal Safety to Minimize Exposure via Inhalation

• Wrap gauze or alcohol pads around the neck of ampules when opening to decrease
droplet contamination.
• Wrap gauze or alcohol pads around injection sites when removing syringes or needles
from I.V. injection ports.
• Do not dispose of materials by clipping needles or removing needles from syringes.
• Use puncture- and leak-proof containers for non-capped, non-clipped needles.

Personal Safety to Minimize Exposure via Skin Contact

• Wear nitrile examination gloves at all times when preparing or working with
chemotherapeutic agents.
• Wash hands before putting on and after removing gloves.
• Change gloves after each use, tear, puncture, or medication spill or after every 60
minutes of wear.
• Wear a long-sleeve, nonabsorbent gown with elastic at the wrists and back closure.
• Eye and face shields should be worn if splashes are likely to occur.
• Use syringes and I.V. tubing with Luer locks (which have a locking device to hold needle
firmly in place).
• Label all syringes and I.V. tubing containing chemotherapeutic agents as hazardous
material.
• Place an absorbent pad directly under the injection site to absorb any accidental
spillage.
• If any contact with the skin occurs, immediately wash the area thoroughly with soap and
water.
• If contact is made with the eye, immediately flush the eye with water and seek medical
attention.
• Spill kits should be available in all areas where chemotherapy is stored, prepared, and
administered.

Personal Safety to Minimize Exposure via Ingestion

• Do not eat, drink, chew gum, or smoke while preparing or handling chemotherapy.
• Keep all food and drink away from preparation area.
• Wash hands before and after handling chemotherapy.
• Avoid hand-to-mouth or hand-to-eye contact while handling chemotherapeutic agents or
body fluids of the person receiving chemotherapy.

Safe Disposal of Antineoplastic Agents, Body Fluids, and Excreta

• Discard gloves and gown into a leak-proof container, which should be marked as
contaminated or hazardous waste.
• Use puncture- and leak-proof containers for needles and other sharp or breakable
objects.
• Linens contaminated with chemotherapy or excreta from patients who have received
chemotherapy within 48 hours should be contained in specially marked hazardous waste
bags.
• Wear non-sterile nitrile gloves for disposing of body excreta and handling soiled linens
within 48 hours of chemotherapy administration.
• In the home, wear gloves when handling bed linens or clothing contaminated with
chemotherapy or patient excreta within 48 hours of chemotherapy administration. Place
linens in a separate, washable pillow case. Wash separately in hot water and regular
detergent.

Adverse Effects of Chemotherapy

 Adverse effects of chemotherapy are graded on a scale of 0 to 4, with 0 being normal
and 4 indicating life-threatening. Scoring of adverse effects will determine if a delay in
therapy is necessary, dose modification is necessary, or cessation of therapy must
occur.

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Alopecia

• Most chemotherapeutic agents cause some degree of alopecia. This is dependent on

the drug dose, half-life of drug, and duration of therapy.
• Usually begins 2 weeks after administration of chemotherapy. Regrowth takes about 3 to
5 months.
• The use of scalp hypothermia and tourniquets is highly controversial.

Anorexia

• Chemotherapy changes the reproduction of taste buds.

• Absent or altered taste can lead to a decreased food intake.
• Concurrent renal or hepatic disease can increase anorexia.

Fatigue
The cause of fatigue is generally unknown but can be related to anemia, weight loss, altered
sleep patterns, and coping.

Nausea and Vomiting

• Caused by the stimulation of the vagus nerve by serotonin released by cells in the upper
GI tract.
• Incidence depends upon the particular chemotherapeutic agent and dosage.
• Patterns of nausea and vomiting:
o Anticipatory - conditioned response from repeated association between therapy
and vomiting.
o Acute - occurs 0 to 24 hours after chemotherapy administration.
o Delayed - can occur 1 to 4 days after chemotherapy administration.

Mucositis

• Caused by the destruction of the oral mucosa, causing an inflammatory response.

• Initially presents as a burning sensation with no changes in the mucosa and progresses
to significant breakdown, erythema, and pain of the oral mucosa.
• Consistent oral hygiene is important to avoid infection.

Anemia

• Caused by suppression of the stem cell or interference with cell proliferation pathways.
• May require red blood cell transfusion or injection of erythropoietin

Neutropenia

• Defined as an absolute neutrophil count (ANC) of 1,500/mm3 or less.

• Risk of infection is greatest with an ANC less than 500/mm3.
• Caused by suppression of the stem cell.
• Usually occurs 7 to 14 days after administration of chemotherapy.
• Patients should be taught to avoid infection through proper hand washing, avoiding
those with illness, proper hygiene.
• Patients need to be monitored and treated promptly for fever or other signs of infection.

Thrombocytopenia

• Caused by suppression of megakaryocytes.

• Incidence depends on the agent being used.
• Risk of bleeding is present when platelet count falls below 50,000/mm3.
• Risk is high when count falls below 20,000/mm3.
• Risk is critical when count falls below 10,000/mm3.

13
 • Patient should be taught to avoid injury, eg, no razors, avoid vaginal douches and rectal
suppositories, and avoid dental floss during the period of thrombocytopenia.
• May require platelet transfusions if count drops below 20,000/mm3.

Hypersensitivity Reactions

• The mechanism is unknown for most of the chemotherapeutic agents in use.

• Signs and symptoms include hives, pruritus, back pain, shortness of breath,
hypotension, and anaphylaxis.
• All unexpected drug reactions should be reported to the manufacturer.

Nursing Assessment

Integumentary System

• Inspect for pain, swelling with inflammation or phlebitis, necrosis, or ulceration.

• Inspect for skin rash, characteristics, whether pruritus, general or local.
• Assess areas of erythema and associated tenderness or pruritus. Instruct patient to
avoid irritation to skin, sun exposure, or irritating soaps.
• Assess changes in skin pigmentation.
• Note reports of photosensitivity, tearing of the eyes.
• Assess condition of gums, teeth, buccal mucosa, and tongue.
o Determine whether any taste changes have occurred.
o Check for evidence of stomatitis, erythematous areas, ulceration, infection, or
pain on swallowing.
o Determine whether the patient has any complaints of pain or burning of the oral
mucosa or on swallowing.

GI System

• Assess for frequency, timing of onset, duration, and severity of nausea and vomiting
episodes before and after chemotherapy.
o Usually occurs from 1 to 24 hours after chemotherapy but may be delayed.
Anticipatory vomiting may occur after first course of therapy. Can be initiated by
various cues, including thoughts, smell, or even sight of the medical personnel.
• Observe for alterations in hydration, electrolyte balance.
• Assess for diarrhea or constipation.
o Ascertain any changes in bowel patterns.
o Discuss the consistency of stools.
o Consider the frequency and duration of diarrhea (the number of stools each day
for the number of days).
• Assess for anorexia.
o Discuss taste changes and changes in food preferences.
o Ask about daily food intake and normal eating patterns.
• Assess for jaundice, right upper quadrant abdominal pain, changes in the stool or urine,
and elevated liver function tests that indicate hepatotoxicity.
• Monitor liver function tests and total bilirubin.

Hematopoietic System

• Assess for neutropenia - ANC less than 500/mm3.

o Assess for any signs of infection (pulmonary, integumentary, central nervous
system, GI, and urinary).
o Auscultate lungs for adventitious breath sounds.
o Assess for productive cough or shortness of breath.
o Assess for urinary frequency, urgency, pain, or odor.
o Monitor for elevation of temperature above 101° F, chills.
• Assess for thrombocytopenia - platelet count less than 50,000/mm3 (mild risk of
bleeding); less than 20,000/mm3 (high risk of bleeding).
o Assess skin and oral mucous membranes for petechiae, bruises on extremities.

14
 o Assess for signs of bleeding (including nose, urinary, rectal, or hemoptysis).
o Assess for blood in stools, urine, or emesis.
o Assess for signs and symptoms of intracranial bleeding if platelet count is less
than 20,000/mm3; monitor for changes in level of responsiveness, vital signs, and
pupillary reaction.
• Assess for anemia.
o Assess skin color, turgor, and capillary refill.
o Ascertain whether patient has experienced dyspnea on exertion, fatigue,
weakness, palpitations, or vertigo. Advise rest periods as needed.

Respiratory and Cardiovascular Systems

• Assess lung sounds.

• Assess for pulmonary fibrosis, evidenced by a dry, nonproductive cough with increasing
dyspnea. Patients at risk include those over age 60, smokers, those receiving or having
had pulmonary radiation, those receiving cumulative dose of bleomycin (Blenoxane), or
those with any preexisting lung disease.
• Assess for signs and symptoms of heart failure or irregular apical or radial pulses.
• Verify baseline cardiac studies before administering doxorubicin (Adriamycin) or high-
dose cyclophosphamide (Cytoxan).

Nursing Diagnoses

• Risk for Infection related to neutropenia

• Risk for Injury related to bleeding from thrombocytopenia
• Fatigue related to anemia
• Imbalanced Nutrition: Less Than Body Requirements related to adverse effects of
therapy
• Ineffective protection and risk for hypersensitivity reaction related to chemotherapy
• Impaired Oral Mucous Membranes related to stomatitis
• Disturbed Body Image related to alopecia and weight loss

Nursing Interventions

Preventing Infection

• Monitor vital signs every 4 hours; report occurrence of fever greater than 101° F (38.3°
C) and chills.
• Provide patient education.
o Instruct patient to report signs and symptoms of infection:
 Fever greater than 101° F and/or chills
 Mouth lesions, swelling, or redness
 Redness, pain, or tenderness at rectum
 Change in bowel habits
 Areas of redness, swelling, induration, or pain on skin surface
 Pain or burning when urinating or odor from urine
 Cough or shortness of breath
o Reinforce good personal hygiene habits (routine bathing [preferably a shower],
clean hair, nails, and mouth care).
o Avoid contact with people who have a transmissible illness.
o Encourage deep breathing and coughing to decrease pulmonary stasis.
• Avoid performing invasive procedures - rectal temperatures, enemas, or insertion of
indwelling urinary catheters.
• Monitor white blood cell count (WBC) and differential.
• Administer prophylactic antibiotics as prescribed (if WBC is less than 500).

Preventing Bleeding

• Avoid invasive procedures when platelet count is less than 50,000/mm3, including I.M.
injections, suppositories, enemas, and insertion of indwelling urinary catheters.
• Apply pressure on injection sites for 5 minutes.
15
 • Monitor platelet count; administer platelets as prescribed.
• Monitor and test all urine, stools, and emesis for blood.

Provide patient education.

o Instruct patient to avoid straight-edge razors, nail clippers, vaginal or rectal

suppositories.
o Avoid intercourse when platelet count is less than 50,000/mm3.
o Encourage patient to blow nose gently.
o Avoid dental work or other invasive procedures while thrombocytopenic.
o Avoid the use of NSAIDs, aspirin, and aspirin-containing products.

Minimizing Fatigue

• Monitor blood counts (hemoglobin and hematocrit).

• Administer blood products as prescribed.
• Provide patient education and counseling
o Information about fatigue
o Reassurance that treatment-related fatigue does not mean your cancer is worse
o Why fatigue and shortness of breath may occur
o Suggestions for ways to cope with fatigue
 Energy conservation
 Caution the patient about physical overexertion; encourage rest
frequently and warn patient to expect a tired feeling
 Plan frequent rest periods between daily activities; take naps that do not
interrupt nighttime sleep
 Set priorities and delegate tasks to others
o Stress management
o Explain that blood transfusions, if given, are a part of therapy and not necessarily
an indication of a setback
o Observe skin color
o Monitor nutritional status

Promoting Nutrition

• Administer antiemetics before chemotherapy and on a routine schedule (not as needed).

• Be aware that certain antiemetic combinations are more effective than single agents.
• Consider alternative measures for relief of anticipatory nausea, such as relaxation
therapy, imagery, and distraction.
• Encourage small, frequent meals appealing to patient preferences.
• Encourage patient to eat a diet high in calories and proteins. Provide a high-protein
supplement as needed.
• Discourage smoking and alcoholic beverages, which may irritate mucous membranes.
• Encourage fluid intake to prevent constipation.
• Monitor intake and output, including emesis.
• Consult dietitian about patient's food preferences, intolerances, and individual dietary
interventions.
• Recognize that the patient may have alterations in taste perception, such as a keener
taste of bitterness and loss of ability to detect sweet tastes.

Minimizing Stomatitis

• Encourage good oral hygiene.

o Soft nylon bristled toothbrush, brush 2 to 3 times daily, rinse frequently
o Floss once daily

16
 • Encourage the use of oral agents to promote cleansing, debridement, and comfort.
Mouthwashes with more than 25% alcohol should be avoided.
• Assess the need for antifungal, antibacterial, or antiviral therapy (each infection has a
different appearance).
• Administer local oral therapy such as combinations with viscous lidocaine (Xylocaine) for
symptomatic control and maintenance of calorie intake.

Preventing and Managing Hypersensitivity Reactions

• Be alert for signs of allergic reactions such as pruritus, urticaria, and difficulty breathing,
as well as back pain. Situation may worsen suddenly to hypotension and anaphylaxis.
• Stop the medication or infusion immediately, notify the health care provider, and monitor
the patient closely. Treatment is supportive and dependent on type of reaction and its
severity.
o Do not administer the agent again if there was a severe reaction resulting in
significant hypotension.
o Premedicate the patient with antihistamine or corticosteroid as directed if there is
a history of moderate reaction.

Strengthening Coping for Altered Body Image

• Reassure patient that hair will usually grow back; however, it may grow back a different
texture or different color.
• Suggest wearing a turban, wig, or headscarf, preferably purchased before hair loss
occurs. Many insurance companies will pay for a wig with a prescription.
• Encourage patient to stay on therapeutic program.
• Be honest with the patient.

Patient Education and Health Maintenance

• Make sure that patient uses good hygiene, knows symptoms of infection to report, and
avoids crowds and people with infection while neutropenic.
• Advise patient to avoid using a razor blade to shave, contact sports, manipulation of
sharp articles, use of hard bristle toothbrush, and passage of hard stool to prevent
bleeding while thrombocytopenic.
• Advise women to report symptoms of vaginal infection due to opportunistic fungal or viral
infection.
• Encourage patient participation in plan for chemotherapy and to set realistic goals for
work and activities.
• Assure patient that changes in menses, libido, and sexual function are usually temporary
during therapy.

Cancer Screening Recommendations

• Most cancers are treatable if they are detected before they have spread to other
parts of the body. For this reason, the American Cancer Society recommends the
following regular screening tests for people who have no apparent symptoms. People
who have certain risk factors, such as a family history of cancer, may elect to consult
with their doctor to determine a more aggressive cancer screening program.

Type of Screening Frequenc

Cancer Procedure y

Cancers of the thyroid, oral cavity, skin, lymph nodes, testes, and ovaries
General cancer-related Every three years for people aged 20 to 40; yearly after age 40
physical examination

Colorectal cancer
Stool examination for the Yearly after age 50
presence of occult (hidden)
blood

17
One of the following:
Sigmoidoscopy Every five years after age 50
examination and digital
rectal examination
Colonoscopy and digital Every ten years after age 50
rectal examination
Double-contrast barium Every five to ten years after age 50
enema and digital rectal
examination

Prostate cancer
Digital rectal examination Yearly after age 50

Blood test measuring Yearly after age 50

levels of prostate-specific
antigen

Cervical cancer
Pelvic examination and Pap Yearly for women who are or have been sexually active or have
smear reached age 18. After three or more consecutive normal exams,
a Pap smear may be performed less frequently at the
physician's discretion.

Breast cancer
Breast self-examination Monthly after age 20
Breast examination by a Every three years for women aged 20 to 40; yearly after age 40
physician
Mammography Yearly after age 40
Source: American Cancer Society.

18
 BREASR CANCER

The breasts are made of fat, glands, and connective (fibrous) tissue. The breast has several
lobes, which are divided into lobules that end in the milk glands. Tiny ducts run from the many
tiny glands, connect together, and end in the nipple.

• These ducts are where 80% of breast cancers occur. This condition is called ductal
cancer.

• Cancer developing in the lobules is termed lobular cancer. About 10-15% of breast
cancers are of this type.

• Other less common types of breast cancer include inflammatory breast cancer,
medullary cancer, phyllodes tumor, angiosarcoma, mucinous (colloid) carcinoma, mixed
tumors, and a type of cancer involving the nipple termed Paget's disease.

Precancerous changes, called in situ changes, are common.

• In situ is Latin for "in place" or "in site" and means that the changes haven't spread from
where they started.

• When these in situ changes occur in the ducts, they are called ductal carcinoma in situ
(DCIS). DCIS may be identified on routine mammography.

• When in-situ changes happen in the lobules, it is called lobular carcinoma in situ (LCIS).

When cancers spread into the surrounding tissues, they are termed infiltrating cancers. Cancers
spreading from the ducts into adjacent spaces are termed infiltrating ductal carcinomas.
Cancers spreading from the lobules are infiltrating lobular carcinomas.
The most serious cancers are metastatic cancers. Metastasis means that the cancer has spread
from the place where it started into other tissues distant from the original tumor site. The most
common place for breast cancer to metastasize is into the lymph nodes under the arm or above
the collarbone on the same side as the cancer. Other common sites of breast cancer metastasis
are the brain, the bones, and the liver.

Breast Cancer Causes

Many women who develop breast cancer have no risk factors other than age and sex.

• Gender is the biggest risk because breast cancer occurs mostly in women.

• Age is another critical factor. Breast cancer may occur at any age, though the risk of
breast cancer increases with age. The average woman at age 30 years has one chance
in 280 of developing breast cancer in the next 10 years. This chance increases to one in
70 for a woman aged 40 years, and to one in 40 at age 50 years. A 60-year-old woman
has a one in 30 chance of developing breast cancer in the next 10 years.

19
 • White women are slightly more likely to develop breast cancer than African American
women in the U.S.

• A woman with a personal history of cancer in one breast has a three- to fourfold greater
risk of developing a new cancer in the other breast or in another part of the same breast.
This refers to the risk for developing a new tumor and not a recurrence (return) of the
first cancer.

Genetic Causes
Family history has long been known to be a risk factor for breast cancer. Both maternal and
paternal relatives are important. The risk is highest if the affected relative developed breast
cancer at a young age, had cancer in both breasts, or if she is a close relative. First-degree
relatives, (mother, sister, daughter) are most important in estimating risk. Several second-
degree relatives (grandmother, aunt) with breast cancer may also increase risk. Breast cancer
in a male increases the risk for all his close female relatives. Having relatives with both breast
and ovarian cancer also increases a woman's risk of developing breast cancer.
There is great interest in genes linked to breast cancer. About 5-10% of breast cancers are
believed to be hereditary, as a result of mutations, or changes, in certain genes that are passed
along in families.

• BRCA1 and BRCA2 are abnormal genes that, when inherited, markedly increase the risk
of breast cancer to a lifetime risk estimated between 40 and 85%. Women with these
abnormal genes also have an increased likelihood of developing ovarian cancer. Women
who have the BRCA1 gene tend to develop breast cancer at an early age.

• Testing for these genes is expensive and may not be covered by insurance.

• The issues around testing are complicated, and women who are interested in testing
should discuss this with their health-care providers.

Hormonal Causes
Hormonal influences play a role in the development of breast cancer.

• Women who start their periods at an early age (11 or younger) or experience a late
menopause (55 or older) have a slightly higher risk of developing breast cancer.
Conversely, being older at the time of the first menstrual period and early menopause
tend to protect one from breast cancer.

• Having a child before age 30 years may provide some protection, and having no children
may increase the risk for developing breast cancer.

• Oral contraceptives have not been shown to definitively increase or decrease a woman's
lifetime risk of breast cancer.

• A large study conducted by the Women's Health Initiative showed an increased risk of
breast cancer in postmenopausal women who were on a combination of estrogen and
progesterone for several years. Therefore, women who are considering hormone
therapy for menopausal symptoms need to discuss the risk versus the benefit with their
health-care providers.

Lifestyle and Dietary Causes

Breast cancer seems to occur more frequently in countries with high dietary intake of fat, and
being overweight or obese is a known risk factor for breast cancer, particularly in
postmenopausal women.

• This link is thought to be an environmental influence rather than genetic. For example,
Japanese women, at low risk for breast cancer while in Japan, increase their risk of
developing breast cancer after coming to the United States.

20
 • Several studies comparing groups of women with high- and low-fat diets, however, have
failed to show a difference in breast cancer rates.

Benign Breast Disease

• Fibrocystic breast changes are very common. Fibrocystic breasts are lumpy with some
thickened tissue and are frequently associated with breast discomfort, especially right
before the menstrual period. This condition does not lead to breast cancer.

• However, certain other types of benign breast changes, such as those diagnosed on
biopsy as proliferative or hyperplastic, do predispose women to the later development of
breast cancer.

Environmental Causes
Radiation treatment increases the likelihood of developing breast cancer but only after a long
delay. For example, women who received radiation therapy to the upper body for treatment of
Hodgkin disease before 30 years of age have a significantly higher rate of breast cancer than
the general population.

Breast Cancer Symptoms

Early breast cancer has no symptoms. It is usually not painful.

Most breast cancer is discovered before symptoms are present, either by finding an abnormality
on mammography or feeling a breast lump. A lump in the armpit or above the collarbone that
does not go away may be a sign of cancer. Other possible symptoms are breast discharge,
nipple inversion, or changes in the skin overlying the breast.

• Most breast lumps are not cancerous. All breast lumps, however, need to be evaluated
by a doctor.

• Breast discharge is a common problem and is rarely a symptom of cancer. Discharge is

most concerning if it is from only one breast or if it is bloody. In any case, all breast
discharge should be evaluated.

• Nipple inversion is a common variant of normal nipples, but nipple inversion that is a
new development can be of concern.

• Changes in the skin of the breast include redness, changes in texture, and puckering.
These changes are usually caused by skin diseases but occasionally can be associated
with breast cancer.

How to Perform a Breast Self-Exam

Women older than 20 years should perform monthly breast self-examinations (BSE). If you still
have menstrual periods, you should perform the examination a few days after your period has
ended. During this time, your breasts are not tender. If you are not menstruating (such as in
menopause), BSE should be performed on the same day each month.
Use the following techniques to perform a BSE. Choose the method that is best for you.
Facing a mirror
Stand before a mirror and compare both breasts for differences in size, nipple inversion (turning
in), bulging, or dimpling. Note any skin or nipple changes, such as a hard knot or nipple
discharge.

• Inspect your breasts in the following 4 steps:

o With your arms at your sides

o With your arms overhead

21
 o With your hands on hips - Press firmly to flex your chest muscles.

o Bent forward - Inspect your breasts.

• In these positions, your pectoral muscles are contracted, and a subtle dimpling of the
skin may appear if a growing tumor has affected a ligament.

Lying down

• Right breast

o Place a pillow under your right shoulder.

o Put your right hand under your head.

o Check the entire breast area with the finger pads of your left hand.

o Use small circles and follow an up-and-down pattern.

o Use light, medium, and firm pressure over each area of the breast.

o Feel the breast with the surfaces of the second, third, and fourth fingers, moving
systematically and using small, circular motions from the nipple to the outer
margins.

o Gently squeeze the nipple for any discharge.

• Left breast

o Repeat these steps on your left breast using your right hand.

In the shower

• A BSE can easily be performed while you're in the bath or shower. Some women
discover breast masses when their skin is moist.

o Raise your right arm.

o With soapy hands and fingers flat, check your right breast.

o Use the same small circles and up-and-down pattern described earlier.

22
 o Repeat on the left breast.

When to Seek Medical Care

Breast cancer develops over months or years. Once it is identified, however, a certain sense of
urgency is felt about the treatment, because breast cancer is much more difficult to treat as it
spreads. You should see your health-care provider if you experience any of the following:

• Finding a breast lump

• Finding a lump in your armpit or above your collarbone that does not go away in two
weeks or so

• Developing nipple discharge

• Noticing new nipple inversion or skin changes over the breast

Redness or swelling in the breast may suggest an infection of the breast.

• You should see your health-care provider within the next 24 hours because infection
should be treated promptly.

• If you have redness, swelling, or severe pain in the breast and are unable to reach your
health-care provider, a trip to the nearest emergency department is warranted.

If an abnormality is found on your mammogram, you should see your health-care provider right
away to make a plan for further evaluation.

Exams and Tests

Diagnosis of breast cancer usually is comprised of several steps, including examination of the
breast, mammography, possibly ultrasonography or MRI, and, finally, biopsy. Biopsy is the only
definitive way to diagnose breast cancer.
Examination of the Breast

• A complete breast examination includes visual inspection and careful palpation (feeling)
of the breasts, the armpits, and the areas around your collarbone.

• During that exam, your health-care provider may palpate a lump or just feel a thickening.

Begin by looking at your breasts in the mirror with your shoulders straight and your arms on
your hips.

23
Here's what you should look for:

• Breasts that are their usual size, shape, and color.

• Breasts that are evenly shaped without visible distortion or swelling.

If you see any of the following changes, bring them to your doctor's attention:

• Dimpling, puckering, or bulging of the skin.

• A nipple that has changed position or become inverted (pushed inward instead of
sticking out).

• Redness, soreness, rash, or swelling.

Raise your arms and look for the same changes.

While you're at the mirror, gently squeeze each nipple between your finger and thumb and
check for nipple discharge (this could be a milky or yellow fluid or blood).

Feel your breasts while lying down, using your right hand to feel your left breast and then your
left hand to feel your right breast. Use a firm, smooth touch with the first few fingers of your
hand, keeping the fingers flat and together.

Cover the entire breast from top to bottom, side to side—from your collarbone to the top of your
abdomen, and from your armpit to your cleavage.

Finally, feel your breasts while you are standing or sitting. Many women find that the easiest
way to feel their breasts is when their skin is wet and slippery, so they like to do this step in the
shower. Cover your entire breast, using the same hand movements described in Step 4.
24
Mammography

• Mammograms are x-rays of the breast that may help define the nature of a lump.
Mammograms are also recommended for screening to find early cancer.

• Usually, it is possible to tell from the mammogram whether a lump in the breast is breast
cancer, but no test is 100% reliable. Mammograms are thought to miss as many as 10-
15% of breast cancers.

• A false-positive mammogram is one that suggests malignancy (cancer) when no

malignancy is found on biopsy.

• A false-negative mammogram is one that appears normal when in fact cancer is present.

• A mammogram alone is often not enough to evaluate a lump. Your health-care provider
will probably request additional tests.

• All breast lumps need to be clearly defined as benign or should be biopsied.

25
A. Normal left mammogram with motion blur. Compression of the breast is
necessary in order to minimize the chance of blurring or fuzziness that may
hide a cancer.

B. Normal left mammogram without motion blur. This is the same view of the
same patient, performed with adequate breast compression that has
immobilized the breast. The image is sharp and therefore cancer is easier to
detect.

Note: Image shown for illustrative purposes. Do not attempt to draw

conclusions by comparing this image to others on the site. Only qualified
radiologists should interpret images.

Biopsy
• The only way to diagnose breast cancer with certainty is to biopsy the tissue in question.
Biopsy means to take a very small piece of tissue from the body for examination and
testing by a pathologist to determine if cancer is present. A number of biopsy techniques
are available.

• Fine-needle aspiration consists of placing a needle into the breast and sucking out
some cells to be examined by a pathologist. This technique is used most commonly
when a fluid-filled mass is identified and cancer is not likely.

• Core-needle biopsy is performed with a special needle that takes a small piece of tissue
for examination. Usually the needle is directed into the suspicious area with ultrasound
or mammogram guidance. This technique is being used more and more because it is
less invasive than surgical biopsy. It obtains only a sample of tissue rather than
removing an entire lump. Occasionally, if the mass is easily felt, cells may be removed
with a needle without additional guidance.

• Surgical biopsy is done by making an incision in the breast and removing the piece of
tissue. Certain techniques allow removal of the entire lump.

• Regardless of how the biopsy is taken, the tissue will be reviewed by a pathologist.
These are physicians who are specially trained in diagnosing diseases by looking at
cells and tissues under a microscope.

• If a cancer is diagnosed on biopsy, the tissue will be tested for hormone receptors.
Receptors are sites on the surface of tumor cells that bind to estrogen or progesterone.
In general, the more receptors, the more sensitive the tumor will be to hormone therapy.

Breast Cancer Treatment

26
Surgery is the mainstay of therapy for breast cancer. The choice of which type of surgery is
based on a number of factors, including the size and location of the tumor, the type of tumor and
the person's overall health and personal wishes. Breast-sparing surgery is often possible.
The cancer is staged, using the information from surgery and from other tests. Staging is a
classification that reflects the extent and spread of a tumor and has an impact on treatment
decisions and also the prognosis for recovery.

• Staging in breast cancer is based on the size of the tumor, which parts of the breast are
involved, how many and which lymph nodes are affected, and whether the cancer has
metastasized to another part of the body.

• Cancers may be referred to as invasive if they have spread to other tissues. Those that
do not spread to other tissues are called noninvasive. Carcinoma in situ is a noninvasive
cancer.

Breast cancer is staged from 0 to IV.

• Stage 0 is noninvasive breast cancer, that is, carcinoma in situ with no affected lymph
nodes or metastasis. This is the most favorable stage of breast cancer.

• Stage I is breast cancer that is less than 2 cm (3/4 in) in diameter and has not spread
from the breast.

• Stage II is breast cancer that is fairly small in size but has spread to lymph nodes in the
armpit OR cancer that is somewhat larger but has not spread to the lymph nodes.

• Stage III is breast cancer of a larger size, greater than 5 cm (2 in), with greater lymph
node involvement, or of the inflammatory type.

• Stage IV is metastatic breast cancer: a tumor of any size or type that has metastasized
to another part of the body. This is the least favorable stage

Medical Treatment

Many women have treatment in addition to surgery, which may include radiation therapy,
chemotherapy, or hormonal therapy. The decision about which additional treatments are
needed is based upon the stage and type of cancer, the presence of hormonal and/or HER-
2/neu receptors, and patient health and preferences.
Radiation therapy is used to kill tumor cells if there are any left after surgery.

• Radiation is a local treatment and therefore works only on tumor cells that are directly in
its beam.

• Radiation is used most often in people who have undergone conservative surgery such
as lumpectomy. Conservative surgery is designed to leave as much of the breast tissue
in place as possible.

• Radiation therapy is usually given five days a week over five to six weeks. Each
treatment takes only a few minutes.

• Radiation therapy is painless and has relatively few side effects. However, it can irritate
the skin or cause a burn similar to a bad sunburn in the area.

External Radiation

The most common type of radiation is known as external beam. In this technique, a large
machine called a linear accelerator delivers high-energy radiation to the affected area. The
linear accelerator creates high-energy radiation to treat cancers, using electricity to form a
27
stream of fast-moving subatomic particles. You'll receive this form of radiation as an outpatient
in daily sessions over five to seven weeks, depending on your particular situation.

Woman in position for external beam radiation treatment, from the front. Middle radiation
beam is shown.

A Bright yellow: breast being treated

B Light yellow: beam in air, not touching woman

C Opening of the linear accelerator

D Arm holder supports woman's right arm

Woman in position for radiation treatment, from the side. Side radiation treatment beam
is shown.

A Bright yellow: breast being treated

B Light yellow: beam in air, not touching woman

C Opening of the linear accelerator

D Arm holder

Cross-sectional view of a woman receiving radiation to the breast area

A Middle radiation beam

B Side radiation beam

C Bright yellow: place where radiation is given to the breast

D Rib cage/chest wall

E Heart

F Lungs

G Backbone

H Sternum/breastbone

28
As indicated in these photos, radiation to the whole breast is delivered from two different
treatment fields. The two fields come from opposite directions, which face each other:

• One starts from the side of the breast and faces the middle of the chest (where the
breastbone is).
• One starts in the middle of the chest and faces the side.

The radiation oncologist can maximize the amount of radiation delivered to the breast area and
avoid or minimize radiation to other parts of the body by:

• treating the breast area with angled fields that skim across the chest, just catching the
breast area,
• placing the back edges of the two fields as close to the breast area as possible,
• using special blocks in the head of the machine to avoid radiation to normal tissue, and
• placing special devices, called wedges, in the path of the beam to bend the dose of
radiation away from normal tissues under the breast.

Woman lying on the table of a linear accelerator

Photo courtesy of Varian Medical Systems, Inc.

Partial-breast Radiation

Most women with early-stage breast cancer are able to have breast-conserving surgery
(lumpectomy) followed by radiation instead of mastectomy—with the same chances of a good
long-term outcome.

Lumpectomy removes the cancer. Then radiation is given to get rid of any cancer cells that
might be left behind after the main cancer has been removed.

The current standard of care is to treat the whole breast with radiation after lumpectomy. But
another option is available: partial-breast radiation. It's also known as partial-breast irradiation
(PBI) or limited-field radiation therapy. Researchers are studying partial-breast radiation to see
how the benefits compare to whole-breast radiation.

Partial-breast radiation was developed to reduce recurrence, shorten the length of time it takes
to get radiation treatment, and limit the dose of radiation (and associated side effects) to
surrounding normal tissue. Partial-breast radiation also MAY be able to be given again— but
only to another part of the breast—if a new breast cancer is diagnosed in the future. Whole-
breast radiation usually can't be given again to the same breast.

Background

A number of studies on women with early-stage breast cancer have compared lumpectomy
alone to lumpectomy and whole-breast radiation. The results showed that whole-breast
radiation after lumpectomy reduces the risk of recurrence by about two thirds.

The area that's very close to the site of the original cancer is the area that's at highest risk of
recurrence. The risk of cancer coming back in a different part of the same breast is quite low.
This is true whether you have lumpectomy alone or lumpectomy followed by whole-breast
radiation.

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Based on these findings, doctors created a new radiation approach: focus the radiation only on
the area near where the cancer was. Treating an area smaller than the whole breast can be
done in less time (one week versus six to seven weeks).

The early results from the first small studies on partial-breast radiation look very promising.
These results have led to the next step: comparing partial-breast radiation to whole-breast
radiation, which is the current standard of care. The NSABP B-39 clinical trial, which is
comparing these two treatments, is looking at:

• overall survival (how long the women lived, with or without the cancer coming back)
• recurrence-free survival (how many women lived with the cancer never coming back)
• distant disease-free survival (how long the women lived before the cancer came back)

The study is also looking at quality of life issues, including fatigue, treatment-related side
effects, and convenience of the treatments.

How Does Partial-breast Radiation Work?

There are different ways to deliver partial-breast radiation. It is usually given internally (from the
inside). But it can also be given externally (from the outside) during or after surgery.

In the past, the most common way to give partial-breast radiation was to put very tiny pieces of
radioactive material called seeds into hollow tubes that were placed in the treatment area. Now
the most popular methods are internal radiation using the MammoSite balloon device, and
external radiation using small fields from a linear accelerator (a large machine that creates the
radiation for treatment). Internal radiation delivered at the time of surgery, called intraoperative
radiation, is done in relatively few treatment centers.

Internal Partial-breast Radiation

Internal radiation is also called brachytherapy. "Brachy" means slow delivery using radioactive
seeds (compared to regular external beam radiation, which delivers radiation faster using a
machine). There are two kinds of brachytherapy: multi-catheter brachytherapy and balloon-
catheter brachytherapy.

In multi-catheter brachytherapy tiny tubes (catheters) are sewn under your skin in the area
where the cancer was. The ends of the tubes stick out through little holes in the skin. Tiny
stitches hold the tubes in place.

Radioactive seeds are then placed into the tubes just long enough to deliver the prescribed
dose. If slow-delivery radiation seeds are used, the treatment can take a few days. During
treatment, you stay in the hospital because there is radioactivity inside you. Special precautions
are taken to keep you and everyone else safe. Your nurses, doctors, and visitors are allowed to
be with you for only a short time while the radiation seeds are in the tubes. No one will be able
to be very close to you. Once the treatment is done, the radioactive seeds, the stitches, and the
tubes are removed. Then you can go home.

If high-dose radioactive seeds are used, each seed might be left in for up to 10 minutes. Once
treatment is done, the tubes are removed.

In balloon-catheter brachytherapy (the MammoSite system), a special tube with a balloon on the
end is used. The balloon is placed into the area where the cancer was. The tube comes out
through a little hole in the skin. Stitches aren't needed because the balloon is filled with fluid to
hold the balloon and tube snugly in place. The MammoSite can be inserted in an operating
room or in a surgeon's office. The balloon stays in place about a week and a half.

Careful planning is done to make sure that the balloon fits into the breast properly. During each
treatment, a radioactive seed is placed into center of the balloon for about 5 to 10 minutes—just
long enough to deliver the prescribed dose of radiation. A total of 10 treatments usually are

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given over five days. That means two treatments per day, about six hours apart. When the final
treatment is done, the balloon is removed through the small hole in the skin.

Intraoperative Partial-breast Radiation

Partial-breast radiation can be given during lumpectomy surgery, after the cancer has been
removed. While the underlying breast tissue is still exposed, a single dose of radiation is given
directly to the area where the cancer was.

One way uses the linear accelerator to deliver electron beam radiation to the area where the
cancer was. Radiation with electrons only goes a short distance and can be concentrated on the
area at risk. Special techniques are used to protect the underlying tissue. The procedure takes
about two minutes and then the surgery is completed as usual.

The other technique is known as the high-dose rate remote afterloading intraoperative radiation
technique. This procedure uses a small tube to deliver a high dose of radiation to the area
where the cancer was. The tube is put into position and then connected to a computerized
radiation machine. The procedure takes about 5 to 10 minutes. For safety reasons, all the
doctors and nurses must leave the room while the radiation is delivered. But a special patient
monitoring station is located outside the operating room so your doctors watch and check on
you the whole time.

Only a few treatment centers offer radiation during surgery. There are several reasons why:

• Using intraoperative radiation for partial-breast radiation is very new. Only small studies
with short follow-ups have been done so far.
• Intraoperative partial-breast radiation hasn't been compared to the standard of care:
whole-breast radiation after lumpectomy.
• It's very expensive to have a radiation machine and proper shielding in an operating
room. Most radiation therapy departments are far away from the operating rooms, so the
equipment can't be shared or moved.

External Beam Partial-breast Radiation

Only a few very small studies with very little follow-up have been done on giving partial-breast
radiation externally after surgery. This treatment approach starts with a planning session
(simulation). A special CAT scan of the breast is done and is used to map out small treatment
fields for the area at risk. The type and distribution of radiation is designed to maximize the dose
to the area that needs to be treated and avoid or minimize radiation to tissue near the area. The
radiation is delivered with a linear accelerator, twice a day for one week.

External radiation therapy consists of beams of high-energy radiation directed to

• the affected area. It is painless, and the treatments are usually given once a day over
• a period of weeks. The area for radiation therapy is often marked with tiny tattoos
• smaller than a freckle so that the treatment site is consistent throughout the therapy
• sessions.

Internal radiation (sometimes called brachytherapy) involves small amounts of

• radioactive material placed into the tissue where the cancer has been detected. This
• can be delivered by radioactive seeds or wires or by radioactive material placed into a
• body cavity. Brachytherapy allows delivery of higher doses of radiation over a shorter
• period because it stays in a small area near the cancerous tissue.

What is brachytherapy and how is it used?

Brachytherapy is one type of radiation therapy used to treat cancer. Radiation therapy is the use
of a type of energy, called ionizing radiation, to kill cancer cells and shrink tumors.

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Unlike external beam therapy (EBT), in which high-energy x-ray beams generated by a machine
are directed at the tumor from outside the body, brachytherapy involves placing a radioactive
material directly inside the body.

Brachytherapy, also called internal radiation therapy, allows a physician to use a higher total
dose of radiation to treat a smaller area and in a shorter time than is possible with external
radiation treatment.

Brachytherapy is used to treat cancers throughout the body, including the:

 Prostate - see the "Prostate Cancer" page

 Cervix
 Head and neck - see the "Head and Neck Cancer" page
 Ovary
 Breast - see the "Breast Cancer" page
 Gallbladder
 Uterus
 Vagina

Brachytherapy may be either temporary or permanent:

In temporary brachytherapy, the radioactive material is placed inside or near a tumor for a
specific amount of time and then withdrawn. Temporary brachytherapy can be administered at a
low-dose rate (LDR) or high-dose rate (HDR). Low-dose rate brachytherapy is also used in the
treatment of coronary artery disease to prevent restenosis after angioplasty. (For more
information, see "Radiation of the Heart: A Novel Treatment for Coronary Artery Narrowing After
Balloon Angioplasty.")

Permanent brachytherapy, also called seed implantation, involves placing radioactive seeds or
pellets (about the size of a grain of rice) in or near the tumor and leaving them there
permanently. After several weeks or months, the radioactivity level of the implants eventually
diminishes to nothing. The seeds then remain in the body, with no lasting effect on the patient.

• COMPLICATIONS OF RADIATION THERAPY

These depend on the site of the body being treated but may include
• Skin redness near the radiated site
• Fatigue
• Infertility from radiation of the reproductive organs
• Nausea, vomiting, or loss of appetite
• Hair loss and dry mouth (if therapy is directed to the head or neck)
• Diarrhea when the bowel is treated

Chemotherapy consists of the administration of medications that kill cancer cells or stop them
from growing. In breast cancer, three different chemotherapy strategies may be used:
1. Adjuvant chemotherapy is given to people who have had curative treatment for their
breast cancer, such as surgery and radiation. It is given to reduce the possibility that the
cancer will return.

2. Presurgical chemotherapy is given to shrink a large tumor and/or to kill stray cancer
cells. This increases the chances that surgery will get rid of the cancer completely.

3. Therapeutic chemotherapy is routinely administered to women with breast cancer that

has spread beyond the confines of the breast or local area.

Most chemotherapy agents are given through an IV line, but some are given as pills.
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 • Chemotherapy is usually given in "cycles." Each cycle includes a period of intensive
treatment lasting a few days or weeks followed by a week or two of recovery. Most
people with breast cancer receive at least two, more often four, cycles of chemotherapy
to begin with. Tests are then repeated to see what effect the therapy has had on the
cancer.

• Chemotherapy differs from radiation in that it treats the entire body and thus may target
stray tumor cells that may have migrated from the breast area.

• The side effects of chemotherapy are well known. Side effects depend on which drugs
are used. Many of these drugs have side effects that include loss of hair, nausea and
vomiting, loss of appetite, fatigue, and low blood cell counts. Low blood counts may
cause patients to be more susceptible to infections, to feel sick and tired, or to bleed
more easily than usual. Medications are available to treat or prevent many of these side
effects.

Hormonal therapy may be given because breast cancers (especially those that have ample
estrogen or progesterone receptors) are frequently sensitive to changes in hormones. Hormonal
therapy may be given to prevent recurrence of a tumor or for treatment of existing disease.

• In some cases, it is beneficial to suppress a woman's natural hormones with drugs; in

others, it is beneficial to add hormones.

• In premenopausal women, ovarian ablation (removal of the hormonal effects of the

ovary) may be useful. This can be accomplished with medications that block the ovaries'
ability to produce estrogens or by surgically removing the ovaries, or less commonly with
radiation.

• Until recently, tamoxifen (Nolvadex), an antiestrogen (a drug that blocks the effect of
estrogen), has been the most commonly prescribed hormone treatment. It is used both
for breast cancer prevention and for treatment.

• Fulvestrant (Faslodex) is another drug that acts via the estrogen receptor, but instead of
blocking it, this drug eliminates it. It can be effective if the breast cancer is no longer
responding to tamoxifen. Fulvestrant is only given to women who are already in
menopause and is approved for use in women with advanced breast cancer.

• Toremifene (Fareston) is another anti-estrogen drug closely related to tamoxifen.

• Aromatase inhibitors, which block the effect of a key hormone affecting the tumor, may
be more effective than tamoxifen in the adjuvant setting. The drugs anastrozole
(Arimidex), exemestane (Aromasin), and letrozole (Femera) have a different set of side
effects and risks than tamoxifen.

• Aromatase inhibitors are rapidly moving into first line hormonal therapy regimens. In
addition, they are frequently used after two or more years of tamoxifen therapy.

• Megace (megestrol acetate) is a drug similar to progesterone which may also be used
as hormonal therapy.

Monoclonal antibodies are antibodies against proteins in or around a cancer cell. Antibodies
recognize an "invader"—in this case, a cancer cell—and attack it.

• Trastuzumab (Herceptin) is an antibody against the HER-2 protein, a protein responsible

for cancer cell growth in many women with breast cancer (about 15-25% of breast
cancers). Adding treatment with trastuzumab to chemotherapy given after surgery has
been shown to lower the recurrence rate and death rate in women with HER2/neu-
positive early breast cancers. Using trastuzumab along with chemotherapy has become
standard adjuvant treatment for these women.

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 • Lapatinib (Tykerb) is another drug that targets the HER2/neu protein and may be given
combined with chemotherapy. It is used in women with HER2-positive breast cancer that
is no longer helped by chemotherapy and trastuzumab.

• Another monoclonal antibody, Bevacixumab (Avastin) has been shown to have activity in
the treatment of breast cancer and is used in combination with chemotherapy. This drug
targets the ability of cancers cells to form new blood vessels.

Surgery
Surgery is generally the first step after the diagnosis of breast cancer. The type of surgery is
dependent upon the size and type of tumor and the patient's health and preferences.

• Lumpectomy involves removal of the cancerous tissue and a surrounding area of normal
tissue. This is not considered curative and should almost always be done in association
with other therapy such as radiation therapy with or without chemotherapy or hormonal
therapy.

• At the time of lumpectomy, the axillary lymph nodes (the glands in the armpit) need to be
evaluated for the spread of cancer. This can be done by either removing the lymph
nodes or by sentinel node biopsy (biopsy of the closest lymph node to the tumor).

• If a sentinel node biopsy is done at the time of lumpectomy, it may allow the surgeon to
remove only some of the lymph nodes. In this procedure, a dye is injected into the area
of the tumor. The path of the substance is then followed as it travels to the lymph nodes.
The first node reached is the sentinel node. This node is considered most important to
biopsy when evaluating the spread of the tumor.

• If the sentinel node biopsy is positive, the surgeon will usually remove of all of the lymph
nodes found in the axilla (armpit).

• Simple mastectomy removes the entire breast but no other structures. If the cancer is
invasive, this surgery alone will not cure it. It is a common treatment for DCIS, a
noninvasive type of breast cancer.

• Modified radical mastectomy removes the breast and the axillary (underarm) lymph
nodes but does not remove the underlying muscle of the chest wall. Although additional
chemotherapy or hormonal therapy is almost always offered, surgery alone is
considered adequate to control the disease if it has not metastasized.

• Radical mastectomy involves removal of the breast and the underlying chest wall
muscles, as well as the underarm contents. This surgery is no longer done because
current therapies are less disfiguring and have fewer complications.

Mastectomy Overview

Mastectomy is an operation in which the entire breast, usually including the nipple and the
areola, is removed. Mastectomy is usually performed as a treatment of breast cancer.
In general, women with breast cancer can decide whether to be treated with a lumpectomy or a
mastectomy.
A lumpectomy is the removal of the cancerous breast tissue as well as a surrounding rim of
healthy breast tissue. A lumpectomy is a breast-conserving surgery that is usually followed by
radiation therapy (high-dose x-rays or other high-energy rays to kill cancer cells).
A woman may decide to have a mastectomy versus a lumpectomy based on the following:

• If the tumor is big and, after the lumpectomy, very little breast tissue would remain
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 • If she does not want to undergo radiation therapy after the surgery

• If she believes she will have less anxiety about a recurrence of breast cancer with a
mastectomy

If the woman has tumors in more than one quadrant of the breast, most cancer doctors
recommend a mastectomy.
Historically, a mastectomy for breast cancer included an axillary lymph node dissection (removal
of many of the axillary lymph nodes). Over the last decade, the approach has changed slightly
in that many women can undergo a sentinel lymph node biopsy (removal of the first few lymph
nodes draining the tissue of the breast) rather than an axillary lymph node dissection. The
nomenclature is such that a modified radical and a radical mastectomy include an axillary lymph
node dissection as part of the overall procedure. With the adoption of sentinel lymph node
biopsy in the treatment of early breast cancer, the nomenclature for mastectomy has also
changed. Depending on the characteristics of the tumor, the breast, and the patient, the
surgeon may choose one of the following types of mastectomies:

• Simple or total mastectomy: The surgeon removes the entire breast tissue but does not
remove the muscle tissue under the breast. This mastectomy can be combined with a
sentinel lymph node biopsy in any case of an early invasive cancer and in some cases of
ductal carcinoma in-situ when a mastectomy is chosen as the treatment option. Any of
these can also be combined with an axillary lymph node dissection (which by convention
turns the total mastectomy into a "modified radical mastectomy"). There are several
subtypes of simple or total mastectomy depending on how much skin is removed.

o Traditional: The surgeon removes an ellipse of skin that includes the skin of the
nipple/areolar complex. This is the most commonly performed mastectomy. If the
woman doesn't want immediate reconstruction or is not offered immediate
reconstruction, the end result is a flat chest with a scar about 8 inches in length,
usually oriented transversely.

o Skin-sparing: In addition to the breast tissue as noted, the only skin removed is
that of the nipple and areola, usually through a circular incision around the
areola. If the breast is large, the surgeon may have to make a "keyhole" incision
(one that includes a straight incision in one direction, generally down) to allow
removal of the breast tissue.

o Nipple-sparing: The surgeon makes an incision around the nipple but leaves the
areola intact. Again, in order to remove all of the breast tissue, the incision will
need to be bigger than what is achieved with removal of the nipple. This is often
an S-shaped incision.

o Total skin-sparing: The surgeon removes the breast tissue but leaves all the skin
(including the skin of the nipple and areola) behind. The incision can be place in
the outer part of the breast, in the inframammary fold or around the areola.

In general, if leaving the skin of the areola and or nipple, some surgeons recommend that the
woman have a tumor that is less than 2 centimeters in size and that is more than 2 centimeters
away from the nipple. The skin-sparing mastectomies are ideal for patients undergoing
prophylactic mastectomy. The skin-sparing, nipple-sparing, and total skin-sparing mastectomies
are generally done in combination with immediate breast reconstruction. The benefit of these
procedures is that more of the breast skin envelope is preserved to make it easier to recreate
the breast. No randomized trial has been undertaken to evaluate if there is an increased risk of
local (in the breast skin or on the muscle) recurrence with the skin-sparing techniques. Most
surgeons estimate that preserving more skin increases the risk of local recurrence of the tumor
by 1% or 2 % over 20 years (from 3%-5% for traditional to 5%-7% for skin-sparing).

• Modified radical mastectomy: This combines a simple or total mastectomy, including the
skin of the nipple and the areola, and includes removal of most of the lymph nodes in the
armpit (axillary nodes) using a 6- to 8-inch incision. A woman undergoing a modified
radical mastectomy can have immediate or delayed breast reconstruction.
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• Radical mastectomy: The surgeon removes the entire breast tissue, all the lymph nodes
in the armpit, and the muscles of the chest wall (pectoral muscles) that lie under the
affected breast. Radical mastectomy was common in the past; however, it is rarely
performed now.

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