Cancer – the EssentialsMichele Ritter, M.D.

Argy Resident – February, 2007

Risk Factors fo Cancer Breast

Early menarche, nulliparity, or late first full-term pregnancy

Exogenous estrogens Ionizing radiation Family History

Colon Family History Inflammatory Bowel Disease

Lung Tobacco Ionizing Radiation Asbestos (with tobacco)

Pleura/Mesothelioma Asbestos

Esophagus Tobacco Alcohol Barrett’s esophagus

Ovary Nulliparity

Pancreas Tobacco

Prostate Family history

Hepatocellular (liver) Hep. C, Hep. B Aflatoxin Vinyl chloride Alcohol (cirrhosis)

Urinary Bladder Tobacco Schistosoma haematobium Aromatic amine exposure

Cervical Human Papillomavirus

Endometrial Obesity Exogenous, unopposed estrogen Diabetes mellitus Low parity

Cancer Prevention Lung Cancer

Smoking cessation!!! Tobacco is related to lung, head and neck, esophagus,

pancreas, bladder, kidney, stomach and possibly ccolon and uterine cancers

Second hand smoke has been shown to be risk factor for lung cancer

Smoking Cessation The 5 “A’s” for smoking cessation

1. Ask: Systematically identify all tobacco users at every visit

2. Advise: Strongly urge all tobacco users to quit3. Assess: Determine a patient’s willingness to

attempt to quit4. Assist: Aid the patient in quitting.

1. Includes counseling, pharmacotherapy, social support

5. Arrange: Schedule follow-up contact.

Smoking Cessation (cont.) Pharmacotherapy

Nicotine Replacement Design to ameliorate symptoms of nicotine withdrawal: anxiety, dysphoria

or depressive symptoms, insomnia, increased appetite/weight gain, Includes gum, patches, nasal spray, inhaler

Bupropion (Zyban) Enhance noradrenergic, dopaminergic function Also used as an anti-depressant (Wellbutrin) Has been shown to significantly increase rate of smoking cessation

(especially when used in combination with nicotine replacement). Caution in anorexic/bulemics (increased rate of seizures)

Varenicline Is a partial agonist of nicotine acetylcholine receptor Has been shown to increase rate of quitting (may even be better than

bupropion)

Cancer Prevention (cont.) Breast Cancer

Tamoxifen therapy Shown to be beneficial in women who have at least a 1.7%

absolute risk of developing the disease over the subsequent 5-year period (http://bcra.nci.nih.gov/brc)

At 20 mg/day for 5 years , a decreased risk for invasive and noninvasive cancer of 50% was seen.

Caution: Increased risk for endometrial cancer Increased risk for life-threatening thromboembolic events

No evidence yet showing that prophylactic mastectomy, oophorectomy is beneficial woman with average risk.

Limit exposure to postmenopausal hormone replacement therapy

Cancer Prevention (cont.) Colon Cancer

Possible benefit with NSAID use (specifically in patients with familial adenomatous polyposis) – but not yet recommended routinely.

Gastric Cancer Antibiotic eradiation of Helicobacter pylori -carotene, vitamin E, selenium supplementation

(in Chinese)

Cancer Prevention Prostate Cancer

Finasteride A 5- reductase inhibitor, blocks conversion of

testosterone to dihydrotestosterone. Show to decrease the risk for prostate cancer in men

aged 55 years and older (but mortality was equal) Decreased urinary symptoms with finasteride

Cancer Prevention Diet

While increased fruits and vegetables have been found to decrease cardiovascular disease, there has been no significant benefit seen in cancer prevention with fruits/vegetables.

Cancer Screening Cervical Cancer

Pap Smear Beginning when patient becomes sexually active until

age 65 (or until total hysterectomy) At least every 3 years. Insufficient evidence to screen routinely for human

papillomavirus (HPV) HPV-DNA testing as follow-up if low-grade atypia or other

abnormalities found..

Cancer Screening (cont.) Breast Cancer

Mammogram Once every 1 to 2 years age 40-49 years Annual mammogram for age ≥ 50

Breast exam Either performed by patient or provider, has not been

found to have any effect on outcome.

Cancer Screening (cont.) Colon Cancer

Beginning at age ≥ 50 Colonoscopy, flexible sigmoidoscopy, feocal

occult blood testing, barium enema used alone or in combination are equally effective.

If family history of colon cancer in first degree relative, first colonoscopy 10 years prior to his/her age at diagnosis.

Cancer Screening (cont.) Prostate Cancer

USPSTF has not found evidence supporting the routine use of PSA. Also has not found that routine DRE is helpful.

Skin Cancer Routine screening for skin cancer using a total body skin exam not

recommended. Ovarian Cancer

Does not recommend vaginal ultrasound or CA-125 measurement Lung Cancer

No established guidelines yet for the use of screening CT of the chest

Oncologic Complications Hypercalcemia

The most common metabolic paraneoplastic syndrome

Seen in: Squamous cell carcinoma

(lung, head, neck) Frequently produce PTHrP

Multiple myeloma Breast carcinoma T-cell lymphoma Renal Cell carcinoma

Symptoms: Confusion Fatigue Constipation Nausea Polyuria

Management Vigorous hydration Lasix Bisphosphonates

Pamidronate Zoledronic acid

Oncologic Complications Superior Vena Cava

Syndrome Symptoms

Swelling face, neck, arms (especially when patient is supine)

Cough Dyspnea Hoarseness due to laryngeal edema Headaches (increased intracranial

pressure) Most commonly occurs in

Lung Cancer (small cell) Lymphoma (Hodgkin and non-

Hodgkin) Mediastinal germ cell tumors

Exam: Periorbital and arm

edema Elevated JVP Increased number of

collateral veins covering anterior chest wall

Diagnosed via: CT scan Should show right hilar

mass with SVC occlusion

An oncologic urgency Tissue diagnosis

recommended Radiation therapy (or

chemo. if small cell or lymphoma)

Oncologic Complications Spinal Cord Compression

Symptoms: New or significantly worsening

back pain/tenderness with neurologic deficits. Urinary incontinence, fecal

incontinence Lower extremity weakness

Exam: Point tenderness of spine Lower extremity weakness Decreased rectal tone

Evaluation: STAT MRI Of Spine (all

levels) Treatment:

Start Dexamethasone 4-8 mg IV q 6h (as soon as suspect)

Neurosurgery Consult Radiation Oncology

consult Radiation is most

frequent treatment.

Oncologic Complications Malignant Pleural

Effusions Can be:

Exudative Caused by metastases

to major lymphatic structures or pleural surface

Chylous Lymphatic/thoracic

duct obstruction Commonly caused by:

Lung Cancer Any other cancer with mets

to lung (Breast, Colon) Non-Hodgkins lymphoma

(chylous)

Evaluation: Thoracentesis

Send for cytology Pleural biopsy

Treatment: Therapeutic thoracentesis Chest-tube w/ talc

pleurodesis Pleurex catheter

Oncologic Complications Pericardial Effusion

Caused by local disease into the pericardium or hematogenous spread into pericardium

Most frequent cancers: Lung Breast Non-Hodgkins Lyphoma

Treatment: If signs of tamponade on

echocardiogram, may perform pericardial window.

Peritoneal metastases Ascites Peritoneal carcinomatosis

Frequent cause of bowel obstruction

Frequently seen in: Ovarian cancer Colon cancer Stomach cancer Breast Cancer Non-Hodgkins

Lymphoma Diagnosis:

Paracentesis – cytology Treatment

Symptomatic control

Breast Cancer Most common cause of cancer in females

215,000 women diagnosed with and 40,000 died from breast cancer in 2004.

Genetic Risk Factors: BRCA 1, BRCA 2

Risk of breast cancer > 50% by age 60 Very high risk of ovarian cancer as well Only present in ~ 5% of breast cancers Only women who have very strong, premenopausal family history of

breast cancer should be tested for BRCA 90% reduction in breast cancer after prophylactic mastectomy Oophorectomy may be ebeneficial

Number 1 risk factor for breast cancer is AGE!

Breast Cancer - Treatment Surgery

Lumpectomy Frequently Breast Conserving therapy, with radiation

Mastectomy Sentinel Node Mapping

Injecting blue dye or radioactive material into tumor site/breast – if sentinel node has no tumor, no further surgery needed.

If sentinel node positive, further axillary node biopsy needed Estrogen Receptor (ER) positive? Progesterone Receptor (PR)

Positive? If yes – overall prognosis better, endocrine therapy useful (tamoxifen,

aromatase inhibitors) Chemotherapy

May include Herceptin (traztuzumab) if Her2-positive.

Colon cancer Age is greatest risk factor (90% of cases in patients > 50 years) 75% occur in patients without risk factors.

Remaining cases have family history, familial hereditary cancer syndromes, inflammatory bowel disease.

Sign/Symptoms: Abdominal pain, bloating, constipation, diarrhea, hematochezia, melena Iron deficiency anemia: Need to rule out colon cancer in anyone over age

50 presenting with iron-deficiency anemia! Clinical features

Liver is most frequent site of metastases Elevated CEA ( > 5 ng/mL) – higher value = worse prognosis

Treatment Surgery Radiation Chemotherapy – 5-Fluoruracil based regimens

Lung Cancer Number one cause of cancer death

1 million new cases a year, and 900,000 deaths per year Symptoms

Asymptomatic “solitary pulmonary nodule” A lesion < 3cm seen on chest X-ray/chest CT Malignant features include older age, tobacco use, irregular border, low

density on CT, doubling time < 1 year If suspicion high, should biopsy If suspicion low, should be monitored with subsequent studies

3-4 months for first CT scan, 6 to 8 months for second, third scan at a year

New or worsening Cough – most common symptom Hoarse voice – left recurrent laryngeal nerve involvement Hemoptysis

Lung Cancer – Small-Cell Small-Cell

Central Location Almost 100% smokers Almost 100% metastases Chemotherapy only, no surgery Paraneoplastic syndromes:

Eaton-Lambert Syndrome SIADH Ectopic ACTH

Lung Cancer – Non-Small Cell Squamous Cell

Central Location 95% smokers 60% metastases Paraneoplastic Syndrome:

Hypercalcemia

Large Cell Peripheral location 90% smokers 80% metastases

Adenocarcinoma Peripheral location 50% smokers 80% metastases Hypercoagulability Hypertrophic pulmonary

osteoarthropathy

Lung Cancer Treatment:

Surgery Only way to cure lung cancer is to perform surgical excision of

Stage I

Chemotherapy Works best in Small Cell Carcinoma (also the only option!)

Special Cases: Pancoast tumor

Apical tumor lower brachial plexopathy, shoulder pain, Horner’s syndrome

(unilateral constricted pupil, facial dryness, ptosis)

Prostate Cancer Incidence has doubled sinced PSA testing began. The lifetime risk of developing prostate cancer is 17.8% The lifetime risk of dying from prostate cancer is 3%. Risk factors:

Age (vast majority > 50 years of age) African-American race

Diagnosis Gold standard – prostate biopsy

Performed in patients with abnormal digital rectal exam or elevated serum PSA Gleason score helps determine prognosis

PSA Some labs say abnormal if > 4 ng/mL; NOT diagnostic of cancer Rate of change in PSA is most helpful. Age specific Most patients with metastatic prostate cancer have PSA well above 10 There are some patients with colon cancer with PSA < 4.

Prostate Cancer Treatment:

Nothing Prostatectomy Radiation Endocrine therapy

Bilateral orchiectomy GNRH-agonists

Can cause impotence, hot flushes, gynecomastia, and loss of libido Androgen-deprivation therapy

Need to watch for osteopenia

Question # 1 A 59-year old man presents with cough,

dyspnea and facial edema of 2 weeks’ duration. He has a 40-pack year smoking history. Except for an anteroseptal myocardial infarction 4 years ago, he has been healthy.

Question # 1 (cont.) Physical examination reveals a blood pressure of

130/85 mmHg and normal heart sounds with a pulse rate of 72/min., but there is reduced air entry in the right middle chest, dilated veins in the upper chest, and a slightly tender liver palpable 3 cm below the costal margin. The results of hematology and chemistry screens (including liver function tests) are normal, but a chest CT scan shows a central right upper lobe mass, with collapse and extensive mediastinal adenopathy. Blodd gases are within normal limits, but spirometry shows an obstructive pattern.

Question #1 (cont.) The next step in management of this patient

would be:(A) Immediate radiotherapy

(B) Immediate chemotherapy

(C) Bronchoscopy

(D) Mediastinoscopy

(E) Intravenous furosemide

Question # 2 A 36-year old woman with no previous

medical history presents with an eczematoid scaly eruption on her left nipple. She says that she has recently taken up jogging and this has irritated her breast.

Question # 2 (cont.) On physical examination, she has a 1-cm reddened

and slighlty crusty lesion on the left nipple. There is no discharge or masses or other abnormalities on either breast. Topical skin treatment with emollients and corticosteroids is prescribed, and she is told to return for re-examination in 2 weeks. At return 2 weeks later, the crust is somewhat decreased, but the scaly eruption on the nipple is still present, although somewhat diminished. She has continued to jog.

Question # 2 (cont.) Which of the following is the best course of

management?(A) Continue topical therapy

(B) Continue topical therapy, and recommend she wear a running bra or consider stopping her jogging program

(C) Continue topical therapy, but add an antifungal agent

(D) Order a mammogram, and refer her to a surgeon for biopsy

(E) Order a mammogram, and if negative, continue topical therapy.

Question # 3 A 70-year old male with advanced hormone-

refractory prostate cancer presents with multifocal pain, especially in hiss back. He has been treated by bilateral orchiectomy and radiotherapy to the hemipelvis. His PSA is 100 ng/mL, and a recent bone scan showed multiple “hot spots”. He states that he also has noticed increasing weakness of the lower limbs and severe constipation despite the use of stool softeners.

Question # 3 (cont.) The next step in management should be:

(A) Cytotoxic chemotherapy

(B) Referral for physical therapy

(C) MRI of the spine

(D) Increased laxatives

(E) Referral for radioactive strontium