2. • SCREENING PRINCIPLES
• BREAST CANCER SCREENING
• SCREENING GUIDELINES
• SCREENING TECHNIQUES
• CANCER PREVENTION
CONTENTS
3. Screening
routine examination of asymptomatic women for disease
Appropriate for diseases having -
• High prevalence
• Known natural history, precursor lesion and course of progression
• If detected in early stage, amenable to cure
• Methods used must be simple, cheap, specific and sensitive, acceptable,
risk-free and accessible.
• High sensitivity
• High specificity
5. • Carcinoma of the breast - the commonest cancer of women worldwide
• Important public health strategy to reduce mortality
• Breast cancer screening -> early detection of this disease
• Decline in mortality due to :
• early detection
• increased awareness
• tremendous advances in the multimodal treatment.
• Incidence increasing in developing nations-
• more urbanisation
• lifestyle factors
Need for breast cancer screening
7. Recommended Screening Algorithm
Woman's Risk Level Mammography MRI
Normal Annual starting at age 40
LCIS, ADH, ALH Annual after diagnosis
Personal history of breast cancer Annual after diagnosis
BRCA+; multiple first-degree, second-degree
relatives; bilateral in first-degree premenopausal
relative; breast/ovarian cancer family history
Annual starting 10 years younger than youngest relative
but not younger than 25
Annual
Hodgkin's lymphoma treated with mantle radiation Annual mammogram starting 8 years after treatment Annual
NCCN GUIDELINE :BREAST CANCER SCREENING AND DIAGNOSIS 2021
10. GENETIC SCREENING
• Only 5% to 10% cancer caused by autosomal dominantly inherited cancer
predisposition genes
• In 1990s germline mutations in three important tumor suppressor genes were
discovered
• p53
• BRCA 1
• BRCA 2
• p53 gene :tumor suppressor gene aka “guardian of human genome”
• Breast cancer is most common malignancy in patients with Li -Fraumeni syndrome
(lifetime risk - 90%)
11. Ref: Perez and Brady principles and practice of radiation oncology, 7 ed
Increase risk of breast cancer with family history is known:
20- 25% diagnosed have positive family history
Category Relative risk
Single 1st degree relative
(Mother or sister)
1.7 to 2.5
Multiple 1st degree relatives 4-6
2nd degree relative
(Aunt or grandmother)
1.5
12. TABLE 34.1
Genes Associated with Hereditary Breast Cancer
Gene Syndrome
Relative Risk of Breast Cancer Relative
Risk (Age Range)
Breast Cancer Risk by
Age 70 Years (%)
High-Penetrance Genes
BRCA1
Hereditary breast and ovarian cancer
syndrome
17 (20–29 y) 32 (40–49 y) 14 (60–69 y) 39–87
BRCA2
Hereditary breast and ovarian cancer
syndrome
19 (20–29 y) 10 (40–49 y) 11 (60–69 y) 26–91
p53 Li-Fraumeni syndrome 1.46 overall 56 at 45 y; >90 at 70 y
PTEN Cowden disease 2–4 25–50
STK11 Peutz-Jeghers syndrome 1545–54
CDH1 Hereditary diffuse gastric carcinoma 3.25 39
Low- to Moderate-Penetrance Genes
ATM Ataxia-telangiectasia 3–4 NA
CHEK2 Li-Fraumeni variant 2 for women; 10 for men NA
BRIP1 Fanconi anemia 2NA
PALB2 None 2.3NA
Excerpt from Robson M, Offit K. Management of an inherited predisposition to breast cancer. N Engl J Med
2007;357:154–162.
13. • BRCA 1 was discovered in 1195 and BRCA 2 in 1996
• Accounts for approx 5 to 10% of all breast cancers
• Only in <1% population
• EMBRACE study showed that:
BRCA 1 AND BRCA 2
Genes RISK OF BREAST CA OVARIAN CA
CONTRALATERAL
BREAST CA
BRCA 1 60% 59% 83%
BRCA 2 55% 16.5% 62%
15. • About 20-35% of breast tumors are due to p53 mutant
• Point missense mutation leading to synthesis of malfunctioned protein
• Associated with aggressive type of breast cancer- triple negative
breast cancer
• Germline mutation of p53 -Li Fraumani syndrome :
• Rare autosomal dominant
• Involves breast ,colon ,osteosarcomas, soft tissue sarcoma, brain
tumors ,leukaemia and adrenocortical cancers
• 50% LFS pt will develop invasive cancer by 30 years and 90% by 70
years
• Mc cancer in LFS- BREAST CANCER
• lifetime risk of developing breast cancer in LFS - 90%
p53
16. Indications Of Genetic Testing
•Family history of known BRCA1/BRCA2 mutations
•Personal h/o breast cancer plus (one of following)
1. age 45 years or younger
2. age <= 50 years with :
•One or more close relatives with breast or prostate or pancreatic cancer
3. age <= 60 years with :
•triple negative (TN) BREAST CANCER
4. any age with :
• 2 or more close blood relative with breast pancreatic, or prostate ca
•>=1 close blood relative with breast cancer >= 50 years
•>= 1 close relative with ovarian cancer
•Close male blood relative with breast cancer
•Ethnicity ass. with huge mutation frequency (eg. Ashkenazi Jewish)
•Personal h/o epithelial ovarian/fallopian tube/ primary peritoneal cancer
•Personal h/o male breast cancer
REF:NCCN GUIDELINES FOR GENETIC SCREENING
18. Various screening approaches
• Physical examination:-
• Self-breast examination.
• Clinical-breast examination.
• Mammography:-
• Screen film mammography.
• Digital mammography.
• Ultrasound screening.
• Magnetic Resonance Imaging Screening.
19. SELF BREAST EXAMINATION
Stared as early as 20 years of age
Adv:
early detection esp in high risk women
Cost effective esp in developing resource limiting countries
Disadv:
Low specificity and sensitivity
Acc. To Breast Cancer Registry data ,Costana and Foster
Characteristics Control group
Study group
(Woman performing SBE)
DEATH DUE TO BREAST
CANCER
26% 14%
5 YEAR SURVIVAL RATES 59% 75%
22. Malignant masses Benign masses
Hard
Painless: painful in only 10-15% of patients.
Irregular
Possibly fixed to the skin or chest wall
Skin dimpling
Nipple retraction
Bloody discharge
Firm, rubbery mass
Frequently painful
Regular margins
Not fixed to skin or chest wall,
mobile
No skin dimpling
No nipple retraction
No bloody discharge
Malignant discharge Benign discharge
Unilateral
Spontaneous
One duct orifice
Bloody, serosanguineous, or serous
Bilateral
Spontaneous or induced
Multiple duct orifices
Thick green or yellow, induced and
bilateral (duct ectasia)
23. • Canadian National Breast Screening Study - Physical
examination of the breast by trained nurses useful and cost-
effective.
• Clinical breast examination (CBE) low sensitivity(54%) as a
screening tool .
• CBE has been recommended based on lack of conclusive
evidence against it and it can be used as a tool to discuss
early breast cancer detection and other breast cancer issues
26. routine mammographic images in asymptomatic women
• Two views: craniocaudal and mediolateral oblique of each breast.
• Sensitivity of Mammography - 90%
• specificity- 94%
• 85% - 90% in fatty replaced breasts
• 65% in dense breasts
• Positive predictive value- 10-14% for screened pts, but significantly
higher for symptomatic pts
• After mammography guided FNAC/Biopsy, detection rate of
malignancy about 30 %
Screening mammography
27. ADVANTAGES:
• Screening mammography has a considerable impact on
incidence and stage of presentation.
• Studies show
oShift to earlier stage
oDecrease in mortality
oEarly detection, followed by appropriate local, regional, &
systemic treatment is associated with reduced breast cancer
mortality rates in women 50 yrs of age & older.
29. Mammographic Manifestation of Breast Cancer
• Ill-defined mass -spiculated margins, rarely cancers may also be seen
with a knobby, lobulated, or even a smooth contour
• Architectural distortion of the breast . the appearance of linear,
radiated, or spiculated changes around a central focus should always be
considered suspect for carcinoma.
• The tumor may be hidden by dense parenchyma;
• Calcification can be associated with either benign or malignant
conditions.
• Malignant tumors:- are typically 100-300 micrometer in size & are rod
like, tubular, branching or punctate.
• Clusters of microcalcification are suggestive of intraductal disease.
31. Studies conducted were :-
1. Health Insurance Plan Study:-
• Health insurance plan study (HIP)-16 yr, 31000 pts’,40-64 yr old women
• Mortality decreased in all women in screening arm . More for > 50 age group.
2.Tabar et al:-
Tabar et al studied mammographic screening (29 yrs ,1863 pts )and found 63%
decrease in mortality from breast cancer.
3. Canadian study:-
But in a Canadian study and one by Miller et al addition of annual mammographic
screening to physical examination had no effect on breast ca. mortality .
4.Millar et al:- similar result as Canadian study was observed.
REASON FOR THIS DISCRIPENCY WAS:
• unbalanced allocation
• Poor quality of mammography
• Less sample size
32. Screening in women <50yrs
• Stockholm mammographic screening trial (40,000, 14,842 ).The RR of
breast cancer death in screened versus non screened women was 1.08 in
the 40- 49 year group.
A large trial conducted in United kingdom:-(age 40-64 yrs)
• One group:- annual screening by clinical examination &
mammography.
• 2nd group:- breast self-examination.
• 3rd group:- control group.
• 16 yrs follow-up:- mortality was 27% lower in the 2
. screening groups.
35% decrease in mortality was observed in mammographically screened
women
• No evidence of less benefit in women 45-49yrs at initial screening.
33. • Wald et al. (6 trials) observed 15% reduction in breast ca. mortality in
40-49 year old group as compared to 25% in 50 – 74 years
CONCLUSION
Screening mammography leads to increased use of breast conservation
techniques, significant reduction in breast ca. mortality and reduction in
cancer incidence.
34. Digital Mammography
• Transforms x-ray images into electronic digital images.
• System is equipped with a digital receptor and a computer
instead of film screen
• Advantage:-
• No film processing
• Faster image acquisition
• less call-backs
• Sensitivity is same as that of screen film techniques.
• At present time, resolution is better for film screen, but
studies have proved equal accuracy
35. Ultrasound screening
• Role in
➢High risk population
➢Young women with mammographically
dense breasts
• It is very helpful in differentiating cysts from solid
tumors.
• Early, curable invasive cancers not seen on
mammography can be found with sonography.
• Sensitivity of 73%
• specificity of 95%.
• Disadv: reproducibility, high false-positive rates,
operator dependency of the examination, inability to
image most ductal carcinoma in situ, and lack of
agreement on which solid or complex lesions require
biopsy
Usg breast in asymptomatic patient:DCIS
36. MRI SCREENING
• INDICATIONS:
• high risk women (BRCA+,strong family history)
• single screening MRI of the contralateral breast(detection rate -5%)
• HIGH sensitivity: 70-100%
• Specificity: 89.9%
• All trials have demonstrated a superiority for MRI screening for high risk
patients.
• Disadv:
• recall rates and biopsy rates 2-3 times higher than mammography
• expensive
• Thus limited to high risk patients only
Characteristic Cbe Mammography MRI
SENSITIVITY 17.9% 33.3% 79.5%
SPECIFICITY 98.1% 95% 89.9%
Kriege et al
38. ANNUAL MRI
BASED ON
EVIDENCE
ANNUAL MRI BASED
ON EXPERT OPINION
INSUFFICIENT EVIDENCE FOR
OR AGAINST MRI
• BRCA mutation
•Untested first degree
relative of BRCA
carrier
• Lifetime risk of
breast cancer 20 -
25%
•Radiation to chest
between age 10 and 30
• Li-Fraumeni syndrome
and first-degree relatives
• Lifetime breast cancer risk 15%
to 20%
•LCIS
•Atypical hyperplasia (lobular or
ductal)
•Extremely or heterogeneously
dense breasts on mammogram
•Personal history of breast cancer,
including DCIS
•American Cancer Society Guidelines.MRI
39. Conclusions
•Film screen mammography – modality of choice for screening
•Negative screening mammogram never replaces need for
diagnostic mammogram
•Ultrasound essential in majority of (but not all) women for
complete work up of palpable abnormality
•MRI & other newer modalities- evaluating extent of disease in
women with current breast cancer diagnosis
41. High-risk patients requiring cancer prevention strategies are :
(1) those with a strong family history of breast cancer
(2) those with a >20% lifetime risk of developing breast cancer
defined by a risk assessment tool like GAIL/National Cancer
Institute (NCI), Tyrer-Cuzick, Claus, and BRCAPRO risk
assessment tool
(3) those who have tested positive for a deleterious genetic
mutation.(BRCA1/2 , PTEN, TP53,STK11,CDH1)
(4)Young women treated for Hodgkin lymphoma with mantle
radiation between the ages of 10 and 30 years
(5)patients with a previous breast biopsy of lobular carcinoma in situ
(LCIS)
43. •Indications: high to average risk women with breast cancers
ACR recommendations:
Includes annual MRI and annual mammogram (combined
modality has better sensitivity than single) done by two
schedules:
Staggering MRI and mammography screening every 6 months :
reduce the rate of interval cancers diagnosed
MRI and mammogram at the same time: simultaneous
interpretation and comparison of both imaging modalities
BRCA1/2 mutation carriers: screening with MRI begin by age 30
years (not before 25 years )
HIGH RISK SURVEILLANCE
44. • patients with a >20% lifetime risk of breast cancer: screening with
MRI to begin at age 30 years.
• patients with Hodgkin lymphoma who were treated for cancer before
age 30 years with ≥20 Gy of chest irradiation: annual mammography
and breast MRI start at age 25 years or 8 years after radiation
treatment .
• women with LCIS with other risk factors such as a family history of
breast cancer or a previous abnormal breast biopsy
• Routine screening of patients with a <15% lifetime risk of breast
cancer is not supported by the ACS.
45. • lowers the risk of developing breast cancer.
• High risk patient receives tamoxifen (20 mg/dL) or raloxifene (60 mg/dL) for
5 years
• STAR trial : the benefit of chemoprevention in postmenopausal women with
a 5-year breast cancer risk of >1.66%
• American Society of Clinical Oncology (ASCO) suggested in high risk
women tamoxifen (in premenopausal women) and tamoxifen, raloxifene, or
exemestane (in postmenopausal women) be considered for risk reduction of
hormone-sensitive breast cancers.
• King et al. : 10-year cumulative breast cancer incidence to be 7% in patients
with LCIS who used chemoprevention, compared to 21% in those that did
not.
Chemoprevention
46. Invasive options
• Invasive options are :
• risk-reducing mastectomy (RRM) :-
• simple or total mastectomy (TM)
• skin-sparing mastectomy (SSM)
• nipple-sparing mastectomy (NSM).
• risk-reducing salpingo-oophorectomy (RRSO),
• The Prevention and Observation Surgical End Points (PROSE) study
group showed that RRM reduced the risk of breast cancer by 99% in
BRCA1/2 patients with prior oophorectomy and 90% in women with intact
ovaries.
• Timing of prophylactic surgeries is highly individualized ;studies shown
younger people benefits more.
47. The first step in management is to identify high-risk patients by taking a
detailed history or with the help of a risk assessment tool. High-risk
surveillance with MRI as an adjunct to mammography,
chemoprevention, and RRSs are all options that require a nuanced
conversation regarding management between patients and their
clinicians.
Conclusion