Tumor Markers in Oncology (211 Oncology) – Flashcards

Not really

A type of biomarker Cellular products that are helpful in detection, diagnosis, & therapeutic management of certain cancers Found in blood, other body fluids, and/or tumor tissue itself May be normal cell components that are over-expressed by malignant cells (higher # in cancer cells sometimes) May be produced by body in response to malignant cells Can be measured by various means in lab

A "blood test for cancer" in which only patients with cancer would test positive level of tumor marker would correspond exactly with staging, response to treatment, & prognosis of cancer easily measurable & reproducible in lab

More than a dozen markers have been identified No tumor markers are unique to cancer cells Different tumor markers are found in different types of cancer Levels of same tumor marker can be elevated in different cancers Markers have not been identified for every cancer Tumor markers are not elevated in all people with a given cancer

Help to confirm diagnosis you already suspect through history, physical exam, ; radiographic studies Provide important info about prognosis ; treatment Alert you to early recurrence in previously treated patients

Diagnose Cancer Identify a Specific Cancer Rule out Cancer

The way we diagnose cancer is not primarily with laboratory tests, but by listening carefully to our patients, doing meticulous physical examinations, and keeping the suspicion of malignancy in our differential until proven otherwise "See first, think later, then test. But always see first. Otherwise you will only see what you were expecting. Most scientists forget that."

History Systemic symptoms -Weight loss -Fatigue Local symptoms -Pain -SOB -Blood in stool, unusual vaginal bleeding Physical Exam Lumps, Bumps, Sounds, Reactions, Appearances Imaging X-ray CT MRI Pathology It's all about the tissue Everyone's tumor is unique

Tumor markers don't diagnose cancer... People diagnose cancer* * Those people are called pathologists!

% of people with cancer who will have an ABNORMAL test ability to IDENTIFY people who HAVE the disease

% of people w/o cancer whose test is NEG ability to IDENTIFY people who DO NOT have the disease

Probability that people with an ABNORMAL test ACTUALLY have cancer

Probability that a NEG test will predict that a person DOES NOT have cancer

prevalence of cancer in general population is so low as to make most screening efforts statistically futile

probability that a positive test is truly the result of cancer can be greatly improved if the test is performed in a population in which the prevalence of the cancer is high, such as: Patients with known cancer Patients with risk factors for the cancer Patients with suggestive imaging studies

In 2014, an estimated 1,665,540 people in United States will be diagnosed with cancer 585,720 will die of cancer Estimates of the percentage of these deaths that could be avoided through screening vary from 3-35%

PERSONAL history of cancer Strong family history of cancer (?2 first degree relatives)

Antigens Enzymes Hormones Oncogenes Tissue Receptors

Proteins normally found in larger amounts during fetal development Cancers contain undifferentiated cells that may carry surface markers of their fetal predecessors; these cells often manufacture antigen proteins in increased quantities Common Antigens -AFP -CEA -PSA -CA-125 -Bence Jones Proteins

Blood plasma levels of these proteins may be increased in malignant tissue Measured by immunoassay Common Enzymes -Prostatic Acid Phosphatase -Galactosyl transferase II

Either larger-than-normal amounts of hormone usually secreted by specific tissue Or hormonal production by tissue which does not normally produce that hormone "Ectopic Production" Often associated with cancers of endocrine glands Common in Paraneoplastic Syndromes Common Hormones -Beta-HCG -Human Calcitonin

Genes that are useful in fetal development but when activated in mature cells trigger tumor growth Common Oncogenes -BRCA 1 -BRCA 2 -Philadelphia chromosome

Cell surface proteins that affect rate of tumor development by binding to hormones ; growth factors Some of these tumor markers are measured in tissue itself Some are secreted into extracellular tissue ; can be measure in blood Common Tissue Receptors -ER Assay -PR Assay -EGFR

Screening Diagnosis and Staging Prognosis Directing therapy Evaluating treatment Surveillance

A test designed to detect cancer in an asymptomatic person Most tests lack enough sensitivity ; specificity given low prevalence of cancer in most population groups Even tests that are highly sensitive ; specific may have low predictive values Most tumor markers are not useful as screening tools -Levels may be elevated in nonmalignant conditions -Levels found in early malignancy often overlap with range of levels found in non-affected people Not all screening tests are helpful ; most have risks Important to know the risks of the test ; whether it has been proven to decrease chance of dying of cancer In some cancers, finding ; treating cancer early does not improve chance of a cure or that patient will live longer For a screening test to be efficacious: -Test or procedure must be able to detect cancer earlier than if cancer was detected as a result of development of symptoms -Evidence must be available that treatment initiated earlier as a consequence of screening improves outcomes Accuracy is less important than clinical outcomes in judging efficacy of screening weigh benefit of screening vs. harm of testing or treatment

abnormal level of a tumor marker increases suspicion of cancer over a similarly presenting non-malignant condition -A positive result must be confirmed with imaging and/or pathology studies -False positives may occur Extremely high values may be pathognomonic Can be helpful in narrowing differential in cancer of unknown primary

Some tumor markers are associated with a more aggressive course ; higher relapse rate ; can therefore be helpful in determining at least a general prognosis

Tissue receptors in particular can be helpful in guiding therapy choices Known oncogene expression may result in more aggressive treatment Value of a marker in a given malignancy depends also on effectiveness of treatment for that malignancy

Tumor marker levels should be low or undetectable after effective therapy Post-treatment levels provide a new baseline for surveillance Greatest value when used to monitor patients with widespread disease

Most tumor markers are used to monitor patients for recurrence of cancer following treatment Levels should be low to non-detectable after successful therapy A delayed rise raises concern for recurrence May alert you to a recurrence faster than clinical symptoms or radiographic findings

Alpha-Fetoprotein (AFP) Beta-HCG Bence Jones Proteins Cancer Antigen 19-9 (CA 19-9) Cancer Antigen-125 (CA-125) Carcinoembryonic Antigen (CEA) Prostate Specific Antigen (PSA)

ANTIGEN Normally found in fetal GI tract; biochemically related to albumin in adults Increased in 80-90% of patients with hepatocellular carcinoma (HCC) Higher AFP correlates with greater tumor burden Used to screen patients with a high risk of developing HCC -Patients with cirrhosis and active hepatitis should be screened with AFP every 3-4 months Increased in 60% of patients with non-seminoma germ cell cancers

ANTIGEN (immunoglobulins) Used primarily to detect ; monitor clinical course of Multiple Myeloma Found in urine -Does not show up on routine UA -Measured by protein electrophoresis -Amount of protein roughly correlates with extent of disease 2-20% of patients with multiple myeloma do not produce Bence Jones proteins Also found in patients with leukemia, lymphoma, ; bone metastases Considered 1st tumor marker Elucidated in 1845 by Henry Bence Jones "best chemical doctor in London" --Florence Nightingale

HORMONE Glycoprotein produced by placental tissue Normally negative except in pregnancy Used primarily to monitor the therapy and/or recurrence of these cancers in women: -Hydatidiform mole of the uterus -Choriocarcinoma of the uterus -Germ cell tumors of the ovaries Never found in normal males -High levels are almost always pathognomonic for germ cell neoplasm in men Also elevated in hepatoma, testicular cancer

ANTIGEN Useful in diagnosis, evaluation of therapy, ; surveillance in patients with pancreatic ; hepatobiliary cancer 70% of patients with pancreatic cancer have increased CA 19-9* -Very high levels at diagnosis indicate unresectable disease 65% of patients with hepatobiliary cancer have increased CA 19-9 Rapid increase can mean recurrence in treated patients - Recommendation to test every 1-3 months in patients with advanced or metastatic pancreatic cancer on active therapy 5% of people are unable to form the protein

ANTIGEN Elevated in 80-90% of women with ovarian cancer Blood levels correspond closely with extent of disease A precipitous fall in CA-125 after 2 cycles of chemotherapy is a good prognostic indicator Useful in post-treatment surveillance -Delayed rise is an early predictor of recurrence in 93% of patients -Can predate symptomatic or radiographic recurrence by 2-7 months High degree of specificity and sensitivity to ovarian cancer -Positive predictive value is only 2% in general population

ANTIGEN Produced by fetal GI tract; present in small quantities in many cells of normal adults Used in determining extent of disease, prognosis, ; response to therapy in patients with GI cancers -Recommend postoperative levels every 3 months for 3 years Discovered in colorectal cancer, but also useful in other malignancies -Breast, pancreas, gastric, hepatobiliary, small cell lung cancer 20% of CRC ; breast cancer patients do not produce CEA Elevated baseline levels found in smokers

ANTIGEN Screening test for early detection of prostate cancer -High sensitivity -; low specificity When combined with digital rectal exam 90% of clinically significant cancers can be detected PSA level corresponds closely with tumor bulk ; is used to measure response to therapy in men with prostate cancer Clinical recurrence is associated with an increase in PSA in 90-100% of patients Efficacy of screening was questioned in light of lack of direct evidence that early detection ; treatment for prostate cancer improves outcomes Not all prostate cancer is clinically significant -30% of men over the age of 50 have histological evidence of tumor at autopsy Use of PSA for screening for prostate cancer are evolving quickly USPSTF Guidelines (May 2012): - Recommend against screening PSA-based screening for prostate cancer (Grade D recommendation). - Applies to men of any age

Not a tumor marker but a useful diagnostic tool for assessing risk of developing breast cancer in a woman in general population Based on a statistical model named after Dr. Mitchell Gail, Senior Investigator in Biostatistics Branch of NCI's Division of Cancer Epidemiology & Genetics Used to assess the risk of an individual woman developing an invasive breast cancer over the next five years as well as her lifetime probability of developing breast cancer Has been validated in several studies Gail model calculates risk by assessing several factors: History of breast cancer, DCIS or LCIS Current age Age at menarche Age at first live birth Family history of breast cancer in first-degree relatives Previous breast biopsies And whether any of those biopsies demonstrated atypical growth Race/ethnicity

Breast cancer oncogenes -BRCA 1 -BRCA 2 Estrogen receptor (ER) Assay* Progesterone receptor (PR) Assay* HER 2* Cancer Antigen 15-3 (CA 15-3)* Cancer Antigen 27.29 (CA 27.29)*

ONCOGENE Either mutation indicates an increased genetic susceptibility for development of breast cancer -More than 50% of women with a mutation will develop breast cancer by age 50 (compared with 2% of women without) -65% of women who have breast cancer and a BRCA mutation will develop contralateral disease Also confers an increased risk of developing ovarian cancer -44% of women with the mutation will develop ovarian cancer by age 70 (compared with <2% of women without) Men with a BRCA mutation carry a markedly increased risk of developing prostate cancer and/or colorectal cancer -May pass mutation to their daughters

TISSUE RECEPTOR Indicates sensitivity to hormonal therapy & helps determine prognosis of breast cancer ER+ tumors are more than twice as likely to respond to hormonal therapy: -Tamoxifen -estrogens -androgens -oophorectomy -adrenalectomy

TISSUE RECEPTOR Indicates sensitivity to hormonal therapy & helps determine prognosis of breast cancer More often positive in postmenopausal breast cancer patients

ER+/PR+ 75% ER-/PR+ 60% ER+/PR- 35% ER-/PR- 25%

ANTIGEN Performed on breast cancer tissue Increased levels of HER 2 protein are associated with more aggressive breast cancers Useful in making treatment decisions Can serve as a target for trastuzumab (Herceptin) So called "triple negative" tumors have no hormonal target for therapy -ER-/PR-/HER 2 -

ANTIGEN 1st breast cancer tumor marker available Rarely elevated in early stage disease Elevated in 70-80% of patients with metastatic disease

ANTIGEN 33% of early stage patients have elevated levels of CA 27.29 65% of patients with metastatic disease have elevated CA 27.29 levels Useful in monitoring response to therapy in metastatic breast cancer patients

Beta2 microglobulin BTA/NMP-22/Survivin Galactosyl transferase II Human Calcitonin Neuron Specific Enolase (NSE) Prostatic Acid Phosphatase (PAP) Thyroglobulin