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CANCER DATA
1
Gynecological Cancer

Five main types of cancer affect a woman's
reproductive organs:
1. cervical, 11,999 / 3,924 In 2005, 75,144 women
were told that they had
2. ovarian, 19,842 / 14,787
a gynecologic cancer,
3. uterine, 37,465
and 27,259 died from a
4. Vaginal*, and
gynecologic cancer.
5. Vulvar*.
*very rare
2
SOME STATS
2nd most common cause of death in the U.S.
1.4million new cases/559,000 deaths (2007)
Lifetime probability of developing cancer is:
46% for men, 38% for women.
Breast cancer- 1 in 7 women.
Prostate cancer- 1 in 6 men.
55% of all new cancers and over 50% of cancer deaths –
lung, prostate, breast, colon/rectum.
Leading cause of cancer death in the U.S. is lung.
3
Human carcinogens environmental
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Aflatoxins
Asbestos
Benzene
Cadmium
Coal tar
Creosote
DDT
Polycyclic aromatic hydrocarbons
Radon
Solar radiation
4
Physical Carcinogens
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Ultraviolet light
Ionizing radiation (X-rays)
Asbestos
Xenobiotics
5
6
XENOBIOTICS
 Chemical substances that are foreign to the biological
system. They include naturally occurring compounds,
drugs, environmental agents, carcinogens, insecticide,
etc
7
Viral Carcinogenesis
Viral infections account for an
estimated one in seven
human cancers worldwide
Majority of these are due to infection with two DNA viruses
HBV - linked to hepatocellular carcinoma
HPV - linked to cervical carcinoma
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EBV - Involvement in Human
Tumors
African Burkitt lymphoma
B-cell lymphomas of immunosuppressed patients
Some cases of Hodgkin lymphoma
Nasopharyngeal carcinomas
9
How Do Viruses like HPV and
HBV Cause Cancer?
Very small viruses
Can integrate their viral DNA into host genome
They code for viral proteins which block tumor suppressor
proteins in cells
10
Oncogenic Viruses
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Human papillomaviruses - HPV
Epstein-Barr Virus (EBV)
Human herpesvirus 8 (HHV8)
Hepatitis B virus - HBV
Hepatitis C virus - HCV
HTLV-I, HTLV-II
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Helicobacter pylori
Gastric infection linked to gastric lymphomas and
adenocarcinomas
Detection of H pylori in majority of
lymphomas
cases of gastric
Antibiotic treatment results in gastric lymphoma regression in
most cases
12
HOW CAN A PATIENT ACQUIRE
ONE OF THESE MUTATIONS?
1) Inheritance.
2) A spontaneous mutation.
3) A mutation induced by environmental exposure, infective agents,
“other factors.”
4) A mutation occurring as a result of accelerated cellular division.
13
BRCA 1 and 2
 Families with a history of multiple cases of breast cancer, cases of both breast and
ovarian cancer, one or more family members with two primary cancers (original
tumors at different sites), or an Ashkenazi (Eastern European) Jewish background.
 Increases risk of developing these cancers at a young age
 Breast:(36 to 85 percent (360-850 out of 1,000) of women with an altered
BRCA1 or BRCA2 gene) (13.2 percent (132 out of 1,000 individuals)
 Ovarian: 16 to 60 percent (160-600 out of 1,000) of women with altered BRCA1
or BRCA2 genes 1.7 percent (17 out of 1,000)
14
SOME EXAMPLES
PRIOR CHEMO OR RADIATION
 Associated with the development of a subsequent malignancy, especially
leukemia and solid tumors.
15
ESTROGEN & PROGESTERONE
 Combined estrogen & progesterone confers a markedly increased risk of
developing breast cancer.
 The Women’s Health Initiative (WHI)- showed an increased risk of breast
cancer, as well as heart disease, stroke, and blood clots, but a decreased risk
of colon cancer and hip fractures.
 The study was stopped early when the risk was found to be greater than the
benefit.
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CANCER PREVENTION
 PRIMARY PREVENTION
 SECONDARY PREVENTION
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PRIMARY PREVENTION
 1) LIFESTYLE MODIFICATION
a) SMOKING.
b) DIET / OBESITY.
c) OTHER.
 2) CHEMOPREVENTION
a) RETINOIDS.
b) ASPIRIN, NSAID’s.
c) BETA CAROTENE, VITAMIN E.
d) CALCIUM, SELENIUM.
e) TAMOXIFEN, RALOXIFENE.
f) ISOFLAVONES, FINASTERIDE.
18
LIFESTYLE MODIFICATION
SMOKING
 Linked to cancers of the: lung, head & neck, esophagus, pancreas, kidney,
and bladder, and a 30% increase in the risk of death from colon cancer, and
a higher mortality in breast cancer.
 Associated w/ # of years and # of packs smoked per day, the “pack-year.”
 Risk decreases every year after quitting, but may not approach that of those
who never smoked.
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LIFESTYLE MODIFICATION
DIET – FATS OR FRUITS?
 The data can be confusing, and please read them yourself, but it appears we should
be telling our patients to consume less fat, especially saturated/animal fat, and more
fruits and veggies.
 There may be confounding variables, ie persons w/ a diet high in fat tend to also be
obese, and it may be the obesity or other elements in the obese patient, rather than
the actual fat, that is associated with the increased risk of cancer.
20
LIFESTYLE MODIFICATION
DIET – FIBER
 Fiber is good, especially for things like smooth glycemic control and
prevention of diverticular disease, but the data do not show that a high-fiber
diet decreases the risk of colorectal cancer.
21
LIFESTYLE MODIFICATION
DIET – PHYTOESTROGENS
 Plant-derived substances such as isoflavones, lignans, and coumestans that have
weak estrogenic effects.
 Dietary data re phytoestrogens hindered by issues inherent in a recall-type study,
but a reduced incidence of breast cancer is seen in women in places such as Asia
where diets are high in phytoestrogens.
 Data re phytoestrogen supplements still being collected. There are no data to
suggest that phytoestrogen supplements increase the risk of breast cancer.
22
LIFESTYLE MODIFICATION
DIET –OBESITY
A risk factor for cancers of the:
 Breast, colon & rectum, and lung,
even in non-smokers.
 Increased BMI* and hypertension
associated w/ increased risk of renal
cell carcinoma in men.
 *BMI= body mass index
 kg/m2
 http://apps.usa.gov/bmi-app/
 2007 Survey: 63% of Americans
are overweight, with 26% now
in the obese category (a BMI of
30 or more)
Category
BMI range – kg/m2
Emaciation
less than 16.0
Underweight
from 16.0 to 18.5
Normal
from 18.5 to 25
Overweight
from 25 to 30
Obese Class I
from 30 to 35
Obese Class II
from 35 to 40
Obese Class III
Over 40
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LIFESTYLE MODIFICATION
OTHER
 Breast feeding for at least 1 year w/ 1 or more pregnancies is associated w/
a reduced risk of breast cancer.
 Korean women who breast feed for less than a year had a 20% lower risk of
breast cancer, 40% if more than 2 years, compared to women who’ve never
breast fed.
 In 1 study, 2 or more glasses of wine per day was associated with a 50%
increase in breast cancer.
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CHEMOPREVENTION
RETINOIDS
 Retinoids are modulators of epithelial cell differentiation, regulating
cellular growth and differentiation and apoptosis.
 Isotretinoin has been shown to suppress leukoplakia, a premalignant
squamous cell lesion in the “aerodigestive tract.”
 Also looked at in the prevention of second primaries in patients with early
malignancies of the head & neck. See text for details.
25
CHEMOPREVENTION
 “Prevention of cancer by administering chemical compounds that interfere with
the multi staged carcinogenic process.”
 Interventions aimed at:
 1) Patients with a Dx of malignancy- to prevent a second.
 2) Patients with a premalignant lesion (dysplasia).
 3) Patients at high risk (family Hx).
 4) The general population.
 Need to be safe and well-tolerated.
26
CHEMOPREVENTION
ASPIRIN, NSAID’s
 In short, regular aspirin use (16 or more 325 mg doses per month for at least 1 year)
is associated with a reduced risk of fatal colon cancer by as much as 40-50%.
 Aspirin may also protect against cancers of the esophagus, stomach, and rectum.
27
CHEMOPREVENTION
BETA-CAROTENE & VITAMIN E ?
 Function as anti-oxidants.
 Studies do not support the role of supplementation with beta-carotene as a
means of reducing cancer risk.
 In fact, a couple of studies found a much higher rate (28%) of cancer in the
supplement group, as well as mortality from all causes (17%) and
cardiovascular disease(26%).
 Vitamin E may show more positive results, but data are still being gathered.
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CHEMOPREVENTION
CALCIUM AND SELENIUM
 On-going data collection via the “SELECT” study.
 Calcium is felt to lower colon cancer risk by binding bile salts and reducing
bile-induced mucosal damage.
 Selenium is already felt to reduce prostate and skin cancer risk.
29
CHEMOPREVENTION
TAMOXIFEN
 A “SERM” – selective estrogen receptor modulator. Depending on the
receptor, it has either estrogenic activity (uterus) or anti-estrogenic activity
(breast).
 Its use is well established in reducing the risk of developing a second
primary in the opposite breast in women with a diagnosis of breast cancer.
A form of adjuvant therapy.
 Works only for breast cancers that are estrogen receptor positive.
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CHEMOPREVENTION
FINASTERIDE
 See text.
 A 5-alpha reductase inhibitor, prevents the conversion of testosterone to
dihydro-testosterone.
 Reduces the risk of developing prostate cancer by 25%,
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SECONDARY PREVENTION
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Early detection by screening asymptomatic patients.
Shown to be effective at reducing mortality for cancers of the:
1) Breast.
2) Colon.
3) Cervix.
4) Prostate.
5) Oral cavity.
6) Skin.
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STAGING OF MALIGNANCY
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Useful for:
1) Prognosis.
2) Treatment.
3) Uniformity for purposes of comparing mortality rates, outcome of
treatment, etc.
TNM Classification:
T describes the size of the tumor and whether it has invaded nearby tissue,
N describes regional lymph nodes that are involved,
M describes distant metastasis (spread of cancer from one body part to
another).
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TREATMENT
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SURGERY.
RADIATION.
SYSTEMIC THERAPY.
ADJUVANT THERAPY.
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TREATMENT
SURGERY
 Useful for diagnosis, staging, and treatment.
 Potentially curable for early-stage lesions.
 Not all tumors are surgically resectable (spinal cord, brain stem), may be too
diffuse/multi-focal (Hodgkins, leukemia, or may be disfiguring, as for breast
cancer, osteosaracoma.)
 For these patients, some form of combined surgery-chemo-radiation or even
chemo and/or radiation may be possible.
35
TREATMENT
RADIATION
 More than 50% of all patients with cancer receive radiation at some point.
 Can be curative while allowing for organ conservation, such as carcinoma
of the larynx.
 Has the potential for radiation-induced side-effects/burns – skin, radiation
proctitis, etc.
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SYSTEMIC THERAPY
 USES:
 1) For cure.
 2) Adjuvant therapy- to decrease the rate of relapse or improve the disease-free
interval.
 3) For palliation and prolonging the survival in patients with incurable
malignancies.
 4) Preoperative or “neoadjuvant” therapy- to reduce the size and extent of a primary
tumor, making it more amenable to surgical removal with less local destruction,
even allowing for breast/organ-sparing surgery.
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SYSTEMIC THERAPY
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TYPES:
1) Cytotoxic drugs (chemotherapy).
2) Hormones.
3) Hormone antagonists.
4) Other agents.
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CYTOTOXIC DRUGS
 Curative for: Hodgkin’s Disease, lymphomas, carcinoma of the testis, some
leukemias, and embryonal cell carcinoma.
 Combined with surgery and sometime irradiation, can increase the longterm control and cure of: breast cancer, cervical cancer, some lung cancers,
cancers of the colon and rectum, esophagus, stomach, and osteogenic
sarcoma.
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HORMONAL THERAPY
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BISPHOSPHANATESInhibit osteoclast activation.
Useful in reducing bone pain in patients with skeletal metastases.
Also being studied and used to reduce the frequency of skeletal metastases.
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ADJUVANT CHEMOTHERAPY
 To eradicate or suppress minimal residual disease after surgery or
irradiation (“micrometastases”).
 Effective in cancers of the breast, colon, stomach, esophagus, bladder,
prostate, ovary, osteogenic sarcoma, malignant melanoma.
 Tumor recurrence after adjuvant chemotherapy usually signifies
incurability.
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TOXICITY OF CHEMOTHERAPY
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BONE MARROW SUPPRESSION.
NAUSEA & VOMITING.
G.I., SKIN.
MISCELLANEOUS.
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TOXICITY OF CHEMOTHERAPY
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BONE MARROW SUPPRESSION
The most serious and limiting toxicity.
Treated with:
1) Bone marrow transplant for high dose chemo.
2) Myeloid growth factors to combat leukopenia, erythrocytopenia, and
thrombocytopenia in standard dose chemo.
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TOXICITY OF CHEMOTHERAPY
NAUSEA & VOMITING
 Common. CTZ actvity
 A variety of antiemetics.
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EVALUATION OF TUMOR
RESPONSE
 1) TUMOR SIZE.
 2) TUMOR MARKERS.
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EVALUATION OF TUMOR
RESPONSE
TUMOR SIZE
 Assessed by a variety of methods, most of which involve some sort of
imaging technique- X-Ray, CT, MRI, ultrasound, gallium scan, PET scan,
etc.
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EVALUATION OF TUMOR
RESPONSE
TUMOR MARKERS
EXAMPLES:
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HCG- in choriocarcinoma and testicular cancer.
PSA- in prostate cancer.
IMMUNOGLOBULINS- in multiple meyloma.
STEROIDS- in paraneoplastic Cushing’s.
Can measure the protein or its metabolite(s).
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EVALUATION OF TUMOR
RESPONSE
TUMOR MARKERS
EXAMPLES OF FETAL ANTIGENS:
 AFP- alpha-fetoprotein- in hepatocellular carcinoma, testicular cancer,
teratoembryonal carcinoma, gastric cancer.
 CA 125- in ovarian cancer.
 CEA- carcinoembryonic antigen- in cancers of the colon, lung, breast, pancreas.
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PARANEOPLASTIC SYNDROMES
 From production by the tumor cells of proteins/hormones, the genes for
which are generally suppressed in mature, differentiated cells.
 EXAMPLES: ACTH, PTH, ADH.
 These syndromes may be the 1st indication of an underlying malignancy,
present in up to 15% of patients w/ cancer.
 May be a more urgent hazard to life than the cancer.
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GENETIC DISORDERS
Downs
Homocysteine
Klinefelter
Marfan
Turner
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REVIEW
PATTERNS OF INHERITANCE
 Single gene / Mendelian inheritance-autosomal dominant and recessive, Xlinked.
 Multifactorial.
 Chromosomal- translocation, insertion, deletion, non-disjunction.
 Phenotype, genotype.
 Heterozygous, homozygous.
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DOWN SYNDROME
 From non-disjunction of chromosome #21, but can be due to an unbalanced
translocation from a parent with a balanced translocation.
 Incidence rises with increasing maternal age.
 Risk at age 40 = 1/40.
 Characteristic phenotype.
 Antenatal screening: AFP; AFP + HCG + ESTRIOL; Nuchal skin fold thickness
on sono.
 Dx: by amniocentesis and karyotype.
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HOMOCYSTEINURIA
 A deficiency of cystathionine β-synthase, an enzyme involved in the
metabolism of homocysteine (from methionine).
 Inheritance: autosomal recessive.
 Results in accumulation of homocysteine.
 Body habitus similar to Marfan’s, ectopia lentis, mental retardation,
hypercoagulability.
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MARFAN’S SYNDROME
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Autosomal dominant.
A systemic connective tissue disorder.
Tall, arachnodactyly, ectopia lentis (similar to homocysteinuria).
Pectus excavatum, joint dislocations.
Cardiac- mitral v. prolapse w/ regurg, chordae tendonae rupture.
Aorta- dissecting aortic aneurysm w/ rupture.
See text for Dx criteria.
54
Marfan’s
55
TURNERS SYNDROME- XO
1 out of every 2,500 female live births worldwide.
Short neck with a webbed appearance
A low hairline at the back of the neck, and low-set ears.
Hands and feet of affected individuals may be swollen or puffy at birth,
have soft nails that turn upward at the ends when they are older.
Due to developmental due to obstruction of the lymphatic system
Short stature/ short fingers and toes
Loss of ovarian function early in childhood, and thus do not enter puberty
5-10%- coarctation of the aorta
30%-bicuspid aortic valves
High blood pressure
High incidence of osteoporosis
Type II diabetes/ hypothyroidism
learning math/
visual-spatial coordination loss
Growth hormone & Estrogen therapy
56
Klinefelter’s Syndrome-XXY
 Male hypogonadism and infertility
 somatic and cognitive development are more likely to be affected.
Mental Retardation
 1 in 500-1,000 males is born with an extra sex chromosome; more than
3,000 affected males are born yearly
 Weak muscles and reduced strength
 Affect different stages of physical, language and social development
57
GERIATRIC MEDICINE
CHAPTER 4
58
GENERAL PRINCIPLES
 By age 2030, 20% of the U.S. population will be > age 65.
 Because co-morbidities are common, a disorder in one organ system may lead to
symptoms in another, especially one compromised by preexisting disease, most
commonly of the heart, urinary system, and musculoskeletal system.
 As such, regardless of the presenting symptom (confusion, falls, etc) the differential
Dx is often the same
 Diseases present atypically.
 Symptoms are often multifactorial.
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ASSESSMENT OF OLDER ADULTS
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1) FUNCTIONAL ASSESSMENT.
2) VISION.
3) HEARING.
4) FALLS, IMPAIRMENT OF GAIT.
5) COGNITION.
6) URINARY CONTINENCE.
7) DEPRESSION.
8) DECISION-MAKING.
60
ASSESSMENT OF OLDER ADULTS
FUNCTIONAL ASSESSMENT
 IADL’s- instrumental activities of daily living- bills, shopping, cooking,
transportation, medication, etc.
 ADL’s- activities of daily living- bathing, dressing, eating, etc
 Degree of impairment in IADL’s and ADL’s often dictates the degree to
which THE OLDER PERSON can, and can not, live independently.
61
ASSESSMENT OF OLDER ADULTS

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FALLS, IMPAIRMENT OF GAIT
Falls- the leading cause of non-fatal injuries in older persons.
Complications from falls are the leading cause of death in persons over age
65.
1/3 of people over 65 fall each year, this increases w/ each year of age.
Fear of falling causes many to restrict their activity.
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ASSESSMENT OF OLDER ADULTS
COGNITION
 Prevalence of dementia doubles every 5 years after age 60.
 Some degree of impairment present in 30-50% by age 85.
 Screening can allow for: identification of reversible causes (Vit B12 def); provision
of support services; planning (advance directives, living wills, etc); other
interventions as appropriate (simplification of medication regimens, etc).
 “Draw a clock” test, 3 item recall. Pg 52.
63
COMMON PROBLEMS OF THE
OLDER PERSON
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1) DEMENTIA.
2) URINARY INCONTINENCE.
3) PAIN.
4) CHRONIC ARHTHRITIS
5) POLYPHARMACY
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