Cancer Screening Flashcards
Describe the carcinogenic pathway
- initiation
- inherited acquired DNA change, immature response - promotion
- additional exposures, DNA mutations, epigenetic changes, immune response, pre-malignant dx, early malignant dx - progression
- additional exposures, DNA mutations, epigenetic changes, immune response, symptomatic dx
What is a risk factor?
characteristic associated with statistically significant likelihood of developing particular disease in a particular time
-risk increase with dose/exposure
Probability calculation
- average v high risk individual (or group)
- use of multifactorial risk calculators, if available
What are risk reduction interventions and why should/shouldn’t consider them?
- goal is to decrease cancer susceptibility, stop carcinogenesis, ideally evidence-based, not available for all cancers, is the individual willing and or able to follow?
- lifestyle modification, vaccination, chemoprevention, prophylactic surgeries
- do benefits exceed risks? Accept more risk from interventions if individual or group is higher risk for disease
What disease-specific characteristics are necessary to be considered for screening?
Early detection of sub-clinical disease
Asymptomatic
Disease
Be clinically relevant
High incidence, mortality, morbidity
Has an obvious pre-clinical stage before symptoms present
Has an effective treatment for early stage cancer
Improved outcome when treated at early stage
Shortening disease duration
Decreasing the severity of the disease
What are screening test examples and what characteristics must they have?
Cheap, simple, safe, minimally invasive, widely available, culturally acceptable
Includes Imaging Laboratory tests Exfoliative cytology Endoscopy Physical examinations Self examinations
What characteristics must a patient have to be considered for screening?
If positive
Likely to undergo treatment
Has access to care
Patients should know
primary risk reduction strategies
symptoms of cancers
What are symptoms of cancer?
unexplained weight loss extreme fatigue skin changes nagging cough/hoarseness lump thickening in breast fever, night sweats persistent pain change in bowel/bladder unusual bleeding/discharge difficulty swallowing
What are general screening recommendations for high risk patients?
Generally beginning screening earlier
FH but no genetic predisposition syndrome, start screening when patient 10 years YOUNGER than age affected family member diagnosed with cancer
Perform more often than for average risk patients
May do more invasive, riskier screening
What considerations are there of screening older adults for cancer?
“Screening in the elderly is not associated with a survival advantage”
Elderly frequently have life limiting co-morbid medical conditions
More indolent nature of some cancers in the elderly
“Die with or die of cancer” conundrum
But studies have not always Included older adults Adjusted for differences in frailty Accounted for groups at increased risk Addressed impact of screening on QOL, suffering, or functionality
More likely to be diagnosed at advanced stage than younger counterparts
** Never screened **
Many will benefit from treatment
But with advanced stage, more extensive treatments
Aging population, increased cancer burden, costs
Breast cancer lifetime risk
12.4%
age 40-70
median age 55
Most common cancers based on sex
- most likely to die, lung for both
- prostate most likely “men”
- breast most likely “women”
- colon is next for both
Discuss family history and risk assessment for screening
Family History If 1st degree relative with cancer Especially if diagnosed at younger age generally start screening for that cancer 10 yrs before the age of affected person when diagnosed Breast Cancer Family history First degree relative: RR 2.5 Second degree relative: RR 1.5
Red flags for cancer predisposition syndromes
Cancer in 2 or more close relatives on
same side family
Early age at diagnosis
Multiple primaries in the same individual
Bilateral cancers
Constellation of tumors associated with a specific cancer syndrome (ie. breast and ovarian)
Presence of congenital anomalies or syndrome associated benign lesions
Family History
Paternal and maternal, 2-3 generations
Dynamic and evolve over time
De novo
Discuss BRCA 1 lifetime risk
Breast cancer 50%-85% (often early age at onset)
Second primary breast cancer 40%-60%
Ovarian cancer 15-45%
Slightly increased risk of Uterine and Cervical cancer
Possible increased risk of other cancers:
Prostate Colon
Male breast cancer Fallopian tube
Pancreatic Gastric
Discuss BRCA2 lifetime risk
Breast Cancer (50%-85%) Male Breast Cancer (6%) Ovarian Cancer (10%-20%) Increased risk of other cancers: Prostate Laryngeal Pancreatic Melanoma Stomach
PMH/PSH risk for breast ca
Benign breast disease Proliferative without atypia: RR 1.5-2.0 Atypical hyperplasia: RR 4.0-5.0 Atypia with family history: RR 11 Other cancers Especially breast, and ovarian Previous therapeutic thoracic radiation therapy 2nd or 3rd decade - 56 fold increase
Reproductive risk factors for breast ca
Early menarche (<9 years): RR 1.2 Late menopause (>55 years): RR 2.0 Full-term pregnancy (> 30 years of age): RR 2.0 Nulliparity: RR 1.4 HRT: RR 2 OCP: RR 0.9
Social history risks for Breast ca
Obesity
Pre menopause: RR 0.6 - 1
Post Menopause: RR 1.16 - 1.74
ETOH
1-2/day: RR 1.04 - 1.19
2-4/day: RR 1.21 – 1.41
Smoking
Fruits/Vegetables
Exercise decrease risk
Family history risk for breast ca
1st Degree: RR 2.5
2nd Degree: RR 1.5
Genetic predisposition syndrome
What is the GAIL model for Breast cancer?
5 year and lifetime risk, in women >35 1.7% = high risk
includes: age, reproductive history, benign breast disease history, atypical hyperplasia, breast cancer in mother or sisters, race in modified model
does not include: other cancers, 2nd deg relatives, paternal history, age at diagnosis in relatives, modifiable risks
What is the Claus Model?
Predictive model for breast cancer risk. predominantly based on family history (and number of family members) and age.
-20% or greater lifetime risk of breast cancer is high risk
Breast cancer risk reduction for average risk patients
- lean healthy weight 18.5-25 BMI
- diet (plant based); men 12-1600, women 10-1200, lean protein
- 30 minutes exercise daily
- ETOH max 1 drink per day, CAGE
- reproductive
- avoid/limit HRT, lowest dose, shortest time needed - pregnancy
- breastfeeding
Breast cancer risk reduction for high risk patients
- chemoprevention
- tamoxifen (Nolvadex)
- raloxifen (Evista) - Preventive Sx
- prophylactic mastectomy
- prophylactic oopherectomy (35-40 age, upon completion of childbearing)
Average risk mammogram recommendations
Mammography Regular, annually age 45-54 -biennial or annual >54
-opportunity for annual age 40-44
No age upper age limit
– good health status,
life expectancy >10 years
Willing to have diagnostic and therapeutic procedures
What are the birads scores mean?
Category 0: need additional imaging evaluation
Category 1: negative- no findings to comment on.
Category 2: benign finding - finding not consistent with mammographic evidence of malignancy.
Category 3: probably benign finding–short-term interval follow-up suggested to establish its stability over time.
Category 4: suspicious abnormality–biopsy should be considered
Category 5: highly suggestive of malignancy–appropriate action should be taken
Breast cancer screening high risk
Known or likely BRCA mutation carriers
Untested but 1st degree relative w/ BRCA mutation
Approximately 20% to 25% or greater lifetime
risk of breast cancer
Radiation to chest for Hodgkin disease between ages 10-30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or have first-degree relatives with one of these syndromes
Starting age 30
Annual mammogram
Addition of annual MRI
CBE
What are clinical presentations of breast cancer?
Painless lump in the breast: Solitary, unilateral mass Solid, irregular Non-mobile Stabbing or aching pain Less common symptoms are: nipple discharge, retraction, dimpling, inflammatory symptoms
What is the lifetime risk and median age of ovarian cancer?
1.3%
median age 62
Risk factors for developing ovarian cancer
Age 55-64 yrs Median Age is 63 Race Reproductive factors Nulliparity/Low parity Early Menarche (before 12) Late Menopause (after 50) Late Full-term Pregnancy (> 35) Infertility HRT > 5 years Protective: Use of OCPs >5 years 1st Pregnancy <25 Breast Feeding
PMH/PSH
Breast Cancer
Endometrial Cancer 10%
Social history
Obesity
High Fat Diet
Talcum Powder
Familial history 5% if 1 First Relative 7% if 2 First Relatives Hereditary cancer syndromes including: BRCA 1 – 15-45% BRCA 2 – 10-20%
Hereditary Non-Polyposis Colon Cancer Syndrome (HNPCC) 10-15%
Risk reduction for ovarian cancer for average risk people
lifestyle: pregnancy, breastfeeding, limit HRT, limit obesity
OCP for chemoprevention
Risk reduction for ovarian cancer for high risk people
OCPS???
surgery? BSO
TAH? (hysto?)
Ovarian cancer screening recs
Average risk: no recommendations
High risk: 2 1st degree relatives, BRCA and HNPCC mutations
Starting age 25
Pelvic exam
Trans-vaginal ultrasound
CA 125
Annual until childbearing completed or at least age 35 and undergo prophylactic bilateral oophorectomy
(NIH Consensus Conference, JAMA 1994)
Transvaginal and CA 125 at discretion of provider starting age 30-35
(NCCN)
Clinical presentations for ovarian cancer
Early Signs Daily Symptoms Lasting More Than a Few Weeks Abdominal Bloating Difficulty Eating or Early Satiety Urinary Urgency Pelvic or Abdominal Pain Increased Abdominal Size Pain During Intercourse Change in Bowel/Bladder Habits Indigestion, Dyspepsia Early Satiety Back Pain Palpable Adnexal Mass In Pre-Menopausal Women – 5% Represent Cancer In Post-Menopausal Women - Requires Surgical Exploration
Late Signs Ascites Pleural Effusion Anorexia Nausea/Vomiting Masses Abdominal Pelvic Ovarian Omental
Uterine cancer risk factors
Lifetime risk 2.9%
Age
Median Age 61
Racial
Caucasian - Highest Incidence
Rising in African Americans and Hispanics
African Americans - Higher Mortality
Reproductive factors
Nulliparous RR 2.5
Late Menopause (> 52 yrs.) RR 2.4
Obesity
>50 lbs RR 10.0
>20-30 lbs RR 3.0
PMH/PSH Endometrial Hyperplasia 50% Diabetes RR 2.7 HTN RR 1.5 Unopposed Estrogen RR 6.0 PCOS RR 3.0 Tamoxifen RR 2.2 Ovarian Cancer 5% Breast Cancer Pelvic Radiation 1-3% OCP Reduction
FH
1st degree relative RR 1.82
BRCA 1 – Small Increased Risk
Hereditary Non-Polyposis Colon Cancer Syndrome (HNPCC) (40-60% chance)
Risk reduction for endometrial cancer for average risk
lifestyle - prevent obesity, prevent metabolic syndrome, diet, exercise, pregnancy
OCPs
Limit unopposed HRT
Risk reduction for high risk endometrial cancer
surgery
- hysto
- BSO
Endometrial cancer screening recs
At time of menopause, educate average and high risk women about risks and symptoms
Very high risk: known HNPCC mutation, substantial likelihood of having mutation Beginning age 35 Transvaginal ultrasound Endometrial biopsy Annually until TAH (? BSO)
Expert opinion
Clinical presentation of endometrial cancer
Post-Menopausal Bleeding (>90%)
Only 5-20% Have Endometrial Cancer
Bleeding MUST BE WORKED UP for Cancer
Longer Time Period Since Menopause = Higher Risk
Pyometria
Abnormal Cervical Cytology (Direct Extension)
Pain
Lumbosacral
Hypogastric
Pelvic
Unexplained Weight Loss
Change in Bowel/Bladder Habits
Prostate cancer risk factors
Lifetime risk approx 11.2% Age Median age 66 Race African American Highest Incidence & Mortality RR 1.8 PMH/PSH Other Cancers (?GU) FH One 1st Degree Relative > 2 Fold Risk 2 or 3 1st Degree Relatives 5 to 11 Fold Risk BRCA (Especially 2) HNPCC SH Vitamin E Agent Orange
Prostate Ca risk reduction, average risk
Unknown????
Prostate Ca high risk risk reduction
NO VITAMIN E, SELENIUM, DM
-5 alpha reductase inhibitor (ie finasteride) 50% decrease in PC
ACS prostate cancer screening guidelines
Asymptomatic men with a >10 year life expectancy
PSA should be discussed, beginning at:
50 average risk
Men with hypogonadism, should have DRE
45 high risk (PSA and DRE)
1st degree relative diagnosed < 65, African American’s .
40 higher risk (PSA and DRE)
Multiple 1st degree relatives diagnosed < 65
If abnormal DRE (size, symmetry, nodule)
Refer to urology for biopsy
If PSA
<2.5, can repeat every 2 years
>2.5, repeat annually
2.5 -4.0 consider referral to urology for biopsy if high risk (e.g. AA, FHX, increasing age)
PSA > 4.0, generally refer for biopsy if average risk
Talk about PSA results and what they mean/risk for prostate cancer
Not prostate cancer specific
Total PSA
~22% of men with PSA 2.5 -4 will have PC
30% of men with PSA >4 will have PC
67% of men with PSA >10 will have PC
PSA velocity - Rate of change over time
- 35 ng/mL/year increase in PSA <4
- 75 ng/mL/year in PSA 4-10
Age, Prostatitis, sexual activity, DRE, bike riding, finesteride, saw palmetto
Talk about Free PSA
Free PSA
- More PSA bound to protein in prostate cancer
- % of free PSA is lower in prostate cancer
is %free 0-10%, biopsy
free 10-15% consider biopsy
15-20% 20% chance cancer
What is the clinical presentation of PC?
Localized Disease Symptoms May Mimic Symptoms of BPH or UTI Advanced Disease Bone Pain Pelvic Pain Fatigue LUTS Lymphadenopathy Since Availability and Application of PSA, Most Patients are Asymptomatic at Presentation!
Lung cancer risk
lifetime risk 6.2%
median age at diagnosis is 70
Smoking—>80% of cases
-Active
-Passive
Occupational/environmental carcinogens
-Asbestos, radon, arsenic, air pollutants
Family history
Dietary deficiencies
COPD
History of lung cancer/other aerodigestive cancersRisk reduction for lung cancer
Smoking cessation
ETS
Occupational
Chemoprevention
-No studies to date have identified any effective agents
-Beta carotene supplements increased the risk of lung cancer in one study
ACD lung cancer screening recs
Ages 55 -74
Current and former (quit within last 15 years) heavy smokers (30 ppy)
General health exclusions:
Metallic implants or devices in the chest or back
Requirement for home O2
Prior history of lung cancer or other lung cancer symptoms
Willing to undergo diagnostic and curative therapies
Annual LDCT at high volume lung centers
Smoking cessation
Clinical manifestations of lung cancer
Cough—most commonly presenting symptom Dyspnea Chest pain Hoarseness Pain Fatigue Anorexia/Cachexia
Risk for colon cancer
Lifetime risk 4.2%
Median age at dx 67
Risk increases with age
91% new colon cancer cases occur in patients over age 50
Risk increases with a personal or family history of colon cancer, polyps or inflammatory bowel disease
Inherited genetic syndromes
Familial adenomatous polyposis (FAP)
Hereditary nonpolyposis colon cancer (HNPCC)
Discuss FAP
Familial Adenomatous Polyposis Syndrome (FAP)
APC Gene Colorectal Cancer Epidermoid Cysts Osteomas Desmoid Tumors CHRPE
Discuss HNPCC
Hereditary Non-Polyposis Colon Cancer Syndrome (HNPCC)
MSH2, MLH1, PMS1, PMS2, MSH6
Increased Risk of Colorectal Cancer
Increased Risk of Gastric Cancer
40-60% Chance of Developing Endometrial Cancer
10-15% Chance of Developing Ovarian Cancer
“Lynch Syndrome”
What are modifiable risk factors for colon cancer?
Obesity (BMI >30) Diet high in fat Diet high in red meat (> 7 servings/week) Diet high in processed foods Diet low in fruits and vegetables Alcohol consumption (>1 drink/day) Smoking Physical Inactivity ASA
What does the colorectal GAIL risk assessment tool look at, and what does it neglect?
used: age 50-85, AA, asian american, pacific islander, hispanic/latino, white
can not be used: american indians, IBD, HNPCC, FAP, personal history of CRC
CRC Risk reduction for average risk
Healthy Weight Physical Activity 30-60 Minutes/Day of Moderate to Strenuous Activity 5 or More Fruits and Vegetables/Day Whole Grains Limit Red Meats Don’t Smoke
CRC risk reduction for high risk
Chemoprevention
ASA
NSAIDS
Cox 2 Inhibitors
Prophylactic Surgery
Colectomy
Cancer risks in HNPCC
CRC 82% endometrial 60% stomach 13% ovarian 12% urinary tract 7% biliary tract 2%
When to screen with FAP
Begin at puberty
Early surveillance with endoscopy and counseling to consider genetic testing
When to screen with HNPCC
begin age 21
Colonoscopy and counseling to consider genetic counseling
When to screen with Inflammatory bowel disease
Chronic ulcerative colitis
Chrohn’s disease
Cancer risk begins to be significant 8 years after the onset of pancolitis, or 12-15 y after the onset of left-sided colitis
Colonoscopy with biopsies for dysplasia
Cervical cancer risk factors
Age
Mean Age 45-50
Peaks at 35-39 and 60-64
Race
Lifestyle
More Sexual Partners
No Condoms
Smoking
PMH/PSH: HPV STDs HIV DES Mothers
ACS cervical cancer screening recs
Even if HPV vaccinated
21-29 every 3 years with Pap tests. (HPV only if abnormal Pap)
30-65 every 5 years with Pap tests and HPV DNA test (preferred); OR every 3 years with Pap alone
> 65 can stop if had 3 or more normal Pap tests or 2 consecutive negative HPV and Pap tests w/in last 10 years
Total hysterectomy may stop screening
History of CIN2 or CIN3 should continue to have testing for at least 20 years after the abnormality was found.
Cervical cancer screening with higher risk
DES exposure in utero
Same protocol as average risk women < 30 years
Continue with protocol >30 years
Immunosuppressed
HIV, Immunosuppressives for organ transplant, chronic corticosteroids, chemotherapy
Screened twice during 1st year of diagnosis and annually there after
No specific upper age to stop. Continue as long as in reasonably good health, likely to benefit from treatment
Clinical presentation of cervical cancer
Vaginal Bleeding Usually Post-coital Menorrhagia Vaginal Discharge Blood Tinged Bowel Obstruction Urinary Obstruction
