Breast Cancer and screening Flashcards
Breast Cancer
general
Disease characterized by malignant transformation of the epithelial cells of the breast
Major types
Invasive
Non-invasive
Epidemiology:
Most common cancer in women
Incidence – 1 in 8 women
Risk increases with age, with 90% of cases occurring in women > 40 years of age; average age of onset 61 years
Male breast cancer accounts for < 1% of total cases
2nd-leading cause of cancer-related deaths in women in the United States
Early detection and improved treatments have reduced death rates
breast cancer
unmodifiable RF
Family history:
Breast cancer in 1st- or 2nd-degree relatives (mother, grandmother, sister, aunt) – 2-3x increased risk
Ashkenazi Jewish descent
Hormonal influences: long hormone exposure due to earlymenarche (before 12 yearsand/or latemenopause (after 55 years)
Genetic mutations:
BRCA1(onchromosome17q)
BRCA2(onchromosome13q)
p53(onchromosome17)
Increasing age
Dense breast tissue
Breast cancer on the contralateral side
breast cancer
Modifiable RF
Lifestyle factors:
High-fat diet
Obesity(especially aftermenopause)
Heavy alcohol use
Tobacco
Hormonal influences:
Higher age at 1st delivery (> 30 years of age)
Nulliparity
Exogenous hormone use:
Contraception
Hormone replacement therapy after menopause (> 5 years)
Breastfeedingfor at least 6 months decreases the risk for breast cancer
breast cancer
Patho
DNA damage and genetic mutations that can be influenced by exposure to estrogen
BRCA1(chromosome 17q21) and BRCA2 (chromosome 13q12.3)mutations (familial breast andovarian cancer)
TP53(tumor-suppressor gene (TSG))
Normal individual: the immune system attacks cells with abnormal DNA or abnormal growth
TSG inducescell cyclearrest anddeoxyribonucleic acid(DNA) repair in the setting ofDNA damage
Individual with breast cancer: Failure of the immune system leading to tumor growth and spread
Impaired function of TSGs → ↑DNA damage→ ↑ oncogenic mutations
breast cancer
S/Sx
Symptoms
Palpable lump/mass by the patient
Skinchanges (dimpling,erythema, thickening)
Nipplechanges (appearance, discharge)
Signs
Firm or hardmasswith poorly defined margins; fixed or immovable
Location:
Highest frequency: upper outer quadrant
Lowest frequency: lower inner quadrant
breast cancer
metastasis
Presentation depends on organ(s) involved
Most common sites:
Brain (headaches/head pressure, dizziness, balance problems, change in mood/personality/behavior)
Bone(back orleg pain)
Liver(jaundice, abdominal pain, nausea, abnormallivertests)
Lungs(shortness of breath, cough, abnormal chest imaging)
Non-invasive Breast Cancer
types
Ductal carcinomain situ(DCIS)
Proliferation of cytologically malignant cells within the mammary ductal system, with no invasion of the surrounding stroma
⅓ develop invasive cancer in 5 years
Frequently detected bymammography
Lobular carcinomain situ(LCIS)
Proliferation of malignant cells within thelobules, growing in an incohesive manner
Rarely with calcifications
Low risk for invasive breast cancer
Invasive Breast Cancer
Types
Infiltrating ductal carcinoma (IDC)
Most common invasive breast cancer(76% of all breast carcinomas)
Mostly unilateral
Gross appearance:
Firm,fibrous, “rock-hard”masswith irregular stellate shape
Often 2–3 cm in size
Metastasizes early
Infiltrating lobular carcinoma (ILC)
2nd most common invasive breast cancer (5%–10%)
Usually multicentric and present bilaterally
Gross appearance:
May not have a mass lesion
Difficult to palpate or detect bymammography
Metastasizes late
Paget’s disease of the breast
Gross appearance
1%–4% of cases
Gross appearance:
Unilateral eczematous, erythematous patcheson thenipple, andnipple retraction
With palpablemass (> 50% of cases) → invasive carcinoma, ER negative andHER2 overexpression
Without amass → DCIS
Breast cancer in men
general
Presents as a painless, firm subareolar mass
Associated findings
Change in breast size or shape
Nipple changes or discharge
Rash overlying the nipple area
Most common type
Invasive ductal carcinoma (IDC)
Breast cancerreceptortesting
99% are ER positive
81% are PR positive
97% are androgen receptor positive
Usually HER2 negative
Every member in an affected man’s family should be screened for BRCA expression
breast cancer
Clinical breast exam
Physical examination of the breasts performed by a healthcare provider on a yearly basis
Performed on average-risk, asymptomatic women
Every 1–3 years between ages 25–39 years
Every year ≥ 40 years
breast cancer
Screening mammography
First step to work up a breast change identified on physical examination
Most cases of cancer are diagnosed by having an abnormal mammogram
Signs of a malignant finding
Soft-tissue mass or density
Clustered microcalcifications
Spiculated high-densitymass(most specific for invasive cancer)
The presence of a breast lump with a negative mammogramstill warrants further investigation
breast cancer
Ultrasonography
Complementary test tomammography
Exception: Women under age 30 with a palpable breast mass because breast tissue tends to be dense and glandular
Advantages
Noradiationexposure
Differentiates solid from fluid-filledcystic lesions
Disadvantage
Highly operator dependent, not suited for screening on its own
under 30 do US first.
breast cancer
MRI
Screeningfor women at high risk for breast cancer
Advantage:
High soft-tissue contrast = high sensitivity
Disadvantage:
Low specificity, no detection of microcalcifications
breast cancer
Biospy
Biopsy (confirms diagnosis)
Fine-needle aspiration
Small sample, with a false-negative rate of 10%
Core needle biopsy(recommended)
Larger sample that allows for immunohistochemical testing
breast cancer - Post-Diagnostic Tools
Breast cancer receptor testing:
Determine ER/PR receptor expression
ER/PR-positive carcinoma is suitable for endocrine therapy → better prognosis
Aromatase inhibitors or tamoxifen
Determine expression ofHER2 receptor
HER2 positive → treatment with trastuzumab (HER2antibody)
Triple-negative breast cancer (~15% of breast cancers worldwide) are usually high-grade aggressive tumors with rapid progression in premenopausal women
breast cancer - Post-Diagnostic Tools
Additional imaging(for metastatic breast cancer):
Bonescan: forpatients withbone painor elevatedalkaline phosphatase
Computed tomography (CT) of the chest: forpatientswith pulmonary symptoms
CT of the abdomen andpelvisor MRI: forpatientswith abnormalpainand/or examination, elevated liver enzymes/alkaline phosphatase
Positron emission tomography-CT (PET-CT): for whole-body screening for metastasis (stage III or higher)
Breast Cancer - Post-Diagnostic Tools
Genetic testing
United States Preventive Services Task Force recommends the use of approved familial risk assessment tools for the following:
A personal orfamily historyof breast, ovarian, tubal, or peritoneal cancer
Ancestry associated with BRCA1 or 2 mutations
Positive assessment indicates the need forgenetic counseling and testing
DCIS
Tx
Surgery
Breast-conserving surgery (lumpectomy) or mastectomy
Radiationtherapy (RT) considered in those with high risk of recurrence
Endocrine therapy for ER-positive DCIS (for 5 years)
Tamoxifen:
ER antagonist
Option for all women
Aromataseinhibitors (anastrozole):
Inactivatesaromatase, reducing peripheral conversion ofandrogensto estrogens
Alternative for post-menopausal women
Early-stage Cancer
Tx
Surgery
BCS ormastectomy
Axillary lymph node assessment performed with sentinel lymph node biopsy (if positive, axillary dissection is done)
Radiation therapy in most cases (if BCS is done and for those at risk for local recurrence)
Adjuvantor systemic therapy given in addition to surgery
Endocrine therapy:
For hormonereceptor(ER/PR)–positivepatients → aromatase inhibitors or tamoxifen
HER2-targeted therapy:
For HER2-positive cancers → trastuzumab
Chemotherapy(doxorubicin +cyclophosphamide, thenpaclitaxel) based on tumor and receptor testing
Breast Cancer Screening
Includes
Includes
Breast examination
Mammography
Ultrasound (US)
Magnetic resonance imaging (MRI)
Multiple organizations provide recommendations regarding screening for specific age and risk groups
Early detection and improved pathology-specific treatments have resulted in a decrease in death rates
breast cancer screening
Initial risk assessment
Medical and personal history of the patient are needed to determine risk:
Personal andfamily history of breast, ovarian, tubal, or peritoneal cancer
Ancestry (associated withBRCA1and2)
Knowncarrierof agene mutationfor breast or ovarian cancer
Mammographic breast density
High-risk lesion on a previous breast biopsy
History of chest radiotherapy
breast cancer
Classification of Risk
A patient’s risk for developing breast cancer
Average:
None of the previously mentioned risks (mostpatients)
Lifetime risk < 15%
Moderate:
Most women with a family history of breast cancerin a 1st-degree relative, but no known genetic syndrome
Lifetime risk 15%‒20%
High:
Patientswith a known genetic predisposition, a personal history ofbreast cancer, or radiotherapy
Lifetime risk > 20%
breast cancer - Strategies for Screening
breast exams and localizing lesions
Breast examination
Self-examination:
Generally discouraged
Can lead to unnecessary procedures (mammograms and biopsies)
Clinical examination:
Generally not recommended for average-risk women
Utilized in the case of:
Women with a high risk (initial age differs depending on risk factors)
Any breast complaints or abnormalities
Low-resource settings
Localizing breast lesions:
If there is a vague or large area, then the area may be localized by a quadrant
If there is a focal area, then the area will be localized by the clock face position and distance from thenipple
breast cancer - Strategies for Screening
Mammography
Most effective method of detecting earlybreast cancer
Screeningmammogram: performed on a woman with no symptoms or signs ofbreast cancer
Diagnosticmammogram: performed on a woman who has a breast lesion suspicious for cancer either on clinical grounds or by findings on ascreeningmammogram
Types:
Screen film mammography: mostly replaced by digital mammography in the United States
Digital mammography: preferred for densebreasts(approximately 50% of all women)
Digital breast tomosynthesis (BDT, “3-D mammography”):
Takes images from many angles to obtain a 3-dimensional picture
Improves thesensitivity and specificityof mammography
Preferred modality by the American College of Breast Surgeons
Computer-aided detection (CAD):
Artificial intelligence (AI) technique that uses pattern recognition to highlight suspicious features and marks the features for the radiologist to review
breast cancer - Strategies for Screening
Breast imagingreporting and data system (BI-RADS):
Standardizes the mammography report
Indicates categories and corresponding recommendations
BI-RADS 1 and 2 will continue with routine screening
breast cancer - Strategies for Screening
Magnetic resonance imaging (MRI)
Indicated as supplementary screening along with mammography in women with a high risk ofbreast cancer
BRCA1or2mutations
Strong family histories of breast and/orovarian cancer
Used to follow up an abnormal or inconclusive mammogram result
Higher false-positive rates in women with densebreasts, leading to unneeded biopsies
Increased sensitivity formalignancy
Breast Cancer - Strategies for Screening
Ultrasonography
Not routinely used forscreeningdue to a high false-positive rate
Primarily used for diagnostic follow-up of an abnormalmammogram
Can be considered as an adjunct inpatientswith densebreasts
breast cancer
Screening for Average-risk Patients
USPSTF: U.S. Preventive Services
Task Force (Updated 2023)
Mammography
Age 40–74: every 2 years
Age > 75: insufficient evidence
Clinical breast exam
Insufficient evidence
ACOG: American College of
Obstetricians and Gynecologists
Mammography
May offer at age 40
Start no later than age 50: every 1–2 years
Age > 75: Assess health, longevity, and discontinuation options
Clinical breast exam
Age 29–39: every 1–3 years
Age ≥ 40: annually
