oncology

1. Imaging,Diagnosis,Staging,Predi
ctive & Prognostic Factors in
Ca Breast

2. Ultrasound
• Breast ultrasound is an important modality in
breast imaging. It is the usual initial breast
imaging modality in those under 30 years of
age in many countries.

3. • Use of breast ultrasound
• to evaluate a young (usually under 30 years of
age) or pregnant patient who is symptomatic
• to evaluate a palpable lump with negative or
equivocal mammographic findings
• detect lesions in lower contrast field
• can help to distinguish between benign vs
malignant characteristics
• for guiding biopsy
• for evaluation of breast implants for rupture

4. Indications of Mammogram
-Screening
-evaluation of breast signs and symptoms:
pain, mass, discharge, thick skin, nipple
eczema
-Pre-op evaluation of palpable mass
-Follow up of Ca breast patient
-To assess contra lateral breast
-To determine size, extent and location of
lesion in breast

5. • Complete history of the patient
• Explain the procedure
• Look for previous records
• Rule out pregnancy
• Deodorant,talcum powder or lotion may show up on
Xray as calcium spots and women are discouraged from
applying these on the day of their exam.
Preparation of patient

6. Views In Mammography
Basic Views:
• Cranio-caudal View
• Medio-lateral Oblique View

7. SUPPLEMENTARY VIEWS:
These views are used in diagnostic breast workups in addition to the standard views.
-true lateral view - 90º view
mediolateral view - ML view
lateromedial view -LM view
-lateromedial oblique view - LMO view
-step oblique views
-spot view - spot compression view
- double spot compression view
-magnification view(s)
-exaggerated craniocaudal views
-axillary view - axillary tail view
-cleavage view
-tangential views
-reversed CC view - 180° CC view
-bulls eye CC view
-rolled CC view
-20° oblique projection

8. Reporting
• For reporting a mammogram,currently
BI-RADS…..,developed by the American college
of Radiology is used.
• It provides a standardised classification of
mammographic studies.
• This system demonstates good correlation with
the likelihood of breast malignancy.

9. 1 Mass lesion
Location, Size, Shape, Margin, Density and number
2 Architectural Distortion
3 Special cases
- Skin thickening, increased breast density, and
coarsening of stroma may be detected in patients with
inflammatory breast cancer.
4 Associated findings
Evalution of mammography

10. 5) calcifications:
- Calcifications may represent benign or malignant lesions.
- Linear and branching calcifications.
- The most specific mammographic feature of malignancy.
- Clustered microcalcifications (calcium particles 0.1-1mm
in diameter and numbering more than 4-5 per cubic
centimeter) are found in about 60% of mammographically
detected cancers)
- Smooth round or oval calcifications, rim-like
calcifications, large coarse calcifications, vascular
calcifications, cigar or rod-shaped calcifications, multiple
coarse "popcorn" calcifications are all considered benign.

11. • Adequate craniocaudal views
• all glandular tissue identified
• nipple in profile
• nipple in midline of image
• length of posterior nipple line (PNL) within one 1cm in size c.f PNL
on MLO
• images symmetric
• Adequate medio-lateral oblique views
• pectoral shadow seen down to level of nipple or lower
• inframammary fold well seen
• nipple in profile
• length of posterior nipple line (PNL) within one 1cm in size c.f PNL
on CC
• images symmetric

12. • BI_RADS CATEGORIES

13. • BI-RADS 0
Need Additional Imaging Evaluation and/or Prior
Mammograms For Comparison:
BI-RADS 0 is utilized when further imaging evaluation
(e.g. additional views or ultrasound) or retrieval of
prior films is required.
- When additional imaging studies are completed, a
final assessment is made.
- Always try to avoid this category by immediately
doing additional imaging or retrieving old film
before reporting.
- Even better to have the old films before starting the
examination.

14. • BI-RADS 1
Negative:
-There is nothing to comment on.
-The breasts are symmetric and no masses,
architectural distortion or suspicious
calcifications are present.

15. • BI-RADS 2
Benign Finding:
Involuting, calcified fibroadenomas, multiple
secretory calcifications, fat-containing lesions such as
oil cysts, lipomas, galactoceles,intramammary
LNs,architectural distortion due to previous surgery.

16. • BI-RADS 3
Probably Benign Finding - Initial Short-Interval Follow-Up
Suggested:
A finding placed in this category should have less than a 2%
risk of malignancy.
Lesions appropriately placed in this category include:
• Nonpalpable, circumscribed mass on a baseline mammogram
• Focal asymmetry which becomes less dense on spot
compression view.
• Cluster of punctate calcifications

17. • BI-RADS 4
Suspicious Abnormality - Biopsy Should Be Considered:
BI-RADS 4 is reserved for findings that do not have the classic
appearance of malignancy but have a wide range of probability
of malignancy (2 - 95%).

18. • BI-RADS 5
Highly Suggestive of Malignancy. Appropriate
Action Should Be Taken:
-BI-RADS 5 must be reserved for findings that are
classic breast cancers, with a >95% likelihood of
malignancy.
-A spiculated,irregular high-density mass, a segmental
or linear arrangement of fine linear calcifications or
an irregular spiculated mass with associated
pleomorphic calcifications are examples of lesions
that should be placed in BI-RADS 5.

20. • BI-RADS 6
Known Biopsy Proven Malignancy. Appropriate
Action Should Be Taken
BI-RADS 6 is reserved for lesions identified on the
imaging study with biopsy proof of malignancy prior
to definitive therapy.

21. LIMITATIONS
• Non specific results
• False negative results
• False positive results
• Breast implants
• Dense breasts

22. • Although direct digital mammography has
improved the sensitivity of the method,
especially in dense breasts, the number of
false negatives (FN) is still high.
• The theoretical solutions to the problem exist:
the main among them is MRI, but this is not
the radical solution because it is expensive,
time-consuming, and in most cases not
available in the same Department.

23. Digital breast tomosynthesis (DBT)
• Digital breast tomosynthesis (DBT) is an
imaging technique that allows a volumetric
reconstruction of the whole breast from a
finite number of low-dose two-dimensional
projections obtained by different X-ray tube
angles, with a geometric principle very similar
to that applied in stratigraphic technique.
- affordable ,fast, practical, simple

24. MRI
Indications for breast MRI
1) ACR guidelines screrening(> 25% lifetime risk based on genetic models )
- BRCA+ : BRCA 1 or BRCA 2
- 1st degree relative BRCA+ and untested
- those who have had prior radiotherapy to chest wall (based on expert opinion)
- Li-Fraumeni syndrome & first degree relatives
- Cowden syndrome & first degree relatives
not recommended if lifetime risk < 15 % because of high false positive rate
2) neo-adjuvant chemotherapy : to assess residual disease
3) metastatic axillary lymphadenopathy of unknown primary (75 - 80% sensitive) - can spare a patient
from having management because may be able to undergo BCT; management path only finds
cancer in two-thirds
• Other possible indications
• problem solving (e.g. post operative breasts with distortion)
• recurrent breast cancer / scar changes
• to assess for synchronous, multifocal or multicentric disease

25. • Breast MRI enhancement curves
• Following administration of Gadolinium there can be three
possible enhancement kinetic curves for a lesion on breast MRI.
These are sometimes termed the Kuhl enhancement curves.
• type I curve: progressive enhancement pattern
– typically shows a continuous increase in signal intensity throughout
time
– usually considered benign with only a small proportion of (~9%) of
malignant lesions having this pattern
• type II curve: plateau pattern
– initial uptake followed by the plateau phase towards the latter part of
the study
– considered concerning for malignancy
• type III curve: washout pattern
– has a relatively rapid uptake shows reduction in enhancement towards
the latter part of the study
– considered strongly suggestive of malignancy

26. Contraindications to performing
breast MRI
• Patient's inability to lie prone.
• Marked kyphosis or kyphoscoliosis.
• Marked obesity.
• Extremely large breasts.
• Severe claustrophobia.
• Inability to use gadolinium-based contrast media
(history of allergy to contrast media or
pregnancy).
• Other general contraindications to MRI.

27. Advantages of breast MRI
• No ionizing radiation.
• Multiplanar capability.
• Capability of imaging the entire breast volume and
chest wall.
• 3-dimensional (3D) lesion mapping with techniques
such as maximum intensity projection (MIP) slab 3D
reconstruction.
• Detection of occult, multifocal, or residual malignancy.
• Accurate size estimation for invasive carcinoma.
• Ability to image regional lymph nodes (axillary as well
as internal mammary).

28. • MRI sensitivity
• IDC / ILC : > 90%
• DCIS : 80 – 90%

29. • not good at detecting DCIS
• leads to many false-positive findings
• may not show all calcifications
• may cause claustrophobia
• requires use of injected contrast agent
• more expensive than mammogram
• not widely available
• slower than mammogram (30 – 60 minutes)
Breast MRI disadvantages

30. Elastography
• Elastography is a newer technique that
exploits the fact that a pathological process
alters the elastic properties of the involved
tissue. This change in elasticity is detected and
imaged using elastography.

31. • The term elasticity refers to the physical property
of the tissue to change shape when a mechanical
force is applied and to regain the original shape
when the force is withdrawn.
• Elastography is a non invasive imaging which is
based on the principle - when a mechanical
compression or vibration ( stress ) is applied, the
tumor deforms ( strain ) less than the
surrounding tissue.

32. Types
• Ultrasound elastography
• CT elastography
• MR elastography

33. Strain Elastography
stiffness=stress/strain

34. Transient Elastography
velocity of shear waves=stiffness

35. What to look for
• Size
• Colour
• heteogeneity
• stiffness
• Strain ratio

38. Clinical Applications Breast cancer
1. Detection of breast tumors
2. Distinguish benign and malignant breast
lesions
3.Helps in differentiating benign from malignant
lymphnodal pathology.

39. Advantages of sonoelastography
• Non invasive
• Cost effective
• Non radiation imaging
• Less time consuming
• Reduces false negative biopsies
• Complements USG findings

40. Limitations
• Extent of tissue compression influences the
elasicity image.
• Need to establish exact cut off to distinguish
between benign and malignant tissues.
• Reproducibility and Quantification still under
scanner.
• Learning curve.

41. INVESTIGATIONS

42. • Routine blood investigations(CBC , LFT , RFT,
Cagulation profile, viral markers)
• ECG, 2D-ECHO
• CXR-PA

43. • Metastatic Work-up:
- ALK Phosphatase , S.Ca
-CXR-PA
-USG Abdomen
-CECT, Bone scan , PET-scan

44. Tissue diagnosis
• A biopsy remains the standard technique for diagnosing
both palpable and non-palpable breast abnormalities.
• The available biopsy techniques for the diagnosis of
palpable breast masses are fine needle aspiration (FNA),
core cutting needle biopsy, and excisional biopsy.

45. fnac
• FNA is easily performed, but requires a trained
cytopathologist for accurate specimen
interpretation.
• The sensitivity of FNA ranges from 80% to 95%,
and false-positive aspirates are seen in fewer than
1% of cases in most series.

46. Core biopsy
• Core cutting needle biopsy has many of the advantages of
FNA, but provides a histologic specimen suitable for
interpretation by any pathologist.
• Estrogen and progesterone receptor status and the
presence of HER-2 overexpression can be routinely
determined from core biopsy specimens, making core
needle biopsy the diagnostic technique of choice for
patients who will receive preoperative systemic therapy.

47. EXCISION BIOPSY

48. • Non palpable lesions can be biopsied with image-guided
core needle biopsy or surgical excision after wire
localization.
• Ultrasound guidance is used for lesions that are visualized
with this modality; most calcifications require stereotactic
mammographic guidance for biopsy.

49. Technique Advantages Disadvantages
Fine needle aspiration
cytology
Rapid, painless, inexpensive.
No incision prior to selection
of local therapy.
Does not distinguish
invasive from in situ cancer.
Markers (ER, PR, HER-2) not
routinely available. Requires
experienced
cytopathologist. False
negatives and insufficient
specimens occur.
Core cutting needle biopsy Rapid, relatively painless,
inexpensive. No incision.
Can be read by any
pathologist, markers
routinely available.
False-negative results,
incomplete lesion
characterization can occur.
Excisional biopsy False-negative results rare.
Complete histology before
treatment decisions. May
serve as definitive
lumpectomy.
Expensive, more painful.
Creates an incision to be
incorporated into definitive
surgery. Unnecessary
surgery with potential for
cosmetic deformity in
patients with benign
abnormalities.

52. TNM STAGING

53. • T Staging
• TXPrimary tumor cannot be assessed
• T0No evidence of primary tumor
• TisCarcinoma in situ
• Tis(DCIS) Ductal carcinoma in situ
• Tis (LCIS) Lobular carcinoma in situ
• Tis (Paget’s) Paget’s disease of the nipple NOT associated with invasive carcinoma and/or
carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma. Carcinomas
in the breast parenchyma associated with Paget’s disease are categorized based on the
size and characteristics of the parenchymal disease, although the presence of Paget’s
disease should still be noted
• T1Tumor ≤ 20 mm in greatest dimension
T1mi Tumor ≤ 1 mm in greatest dimension
T1a Tumor >1 mm but ≤ 5 mm in greatest dimension
T1b Tumor >5 mm but ≤ 10 mm in greatest dimension
T1c Tumor >10 mm but ≤ 20 mm in greatest dimension
• T2 Tumor >20 mm but ≤ 50 mm in greatest dimension
• T3Tumor >50 mm in greatest dimension
• T4 Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin
nodules).

54. • T4a- Extension to the chest wall, not including only pectoralis muscle
adherence/invasion
• T4b- Ulceration and/or ipsilateral satellite nodules and/or edema
(including peau d’orange) of the skin, which do not meet the criteria for
infl ammatory carcinoma
• T4c- Both T4a and T4b
• T4d- Inflammatory carcinoma .

55. • Clinical N Staging
• NXRegional lymph nodes cannot be assessed (e.g.,previously removed)
• NoNo regional lymph node metastases
• N1Metastases to movable ipsilateral level I, II axillary lymph node(s)
• N2Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fi xed or matted; or in
clinically detected ipsilateral internal mammary nodes in the absence of clinically evident
axillary lymph node metastases
N2a Metastases in ipsilateral level I, II axillary lymph nodes fi xed to one another (matted) or to
other structures
N2b Metastases only in clinically detected ipsilateral internal mammary nodes and in the
absence of clinically evident level I, II axillary lymph node metastases
• N3Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I,
II axillary lymph node involvement; or in clinically detected ipsilateral internal mammary
lymph node(s) with clinically evident level I, II axillary lymph node metastases; or metastases in
ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph
node involvement
N3a Metastases in ipsilateral infraclavicular lymphnode(s)
N3b Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)
N3c Metastases in ipsilateral supraclavicular lymph node(s)

56. • Pathologic (pN)*
• pNX Regional lymph nodes cannot be assessed
(e.g., previously removed, or not removed
for pathologic study)
• pN0 No regional lymph node metastasis
identified histologically.
• Isolated tumor cell clusters (ITC) are defined as
small clusters of cells not greater than 0.2 mm, or
single tumor cells, or a cluster of fewer than 200
cells in a single histologic cross-section. ITCs may
be detected by routine histology or by
immunohistochemical (IHC) methods.

57. pN0(i−) No regional lymph node metastases histologically, negative IHC
pN0(i+) Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC
including ITC)
pN0 (mol−) No regional lymph node metastases histologically, negative molecular fi ndings (RT-PCR)
pN0 (mol+)Positive molecular fi ndings (RT-PCR), but no regional lymph node metastases detected by
histology or IHC
pN1 Micrometastases; or metastases in 1–3 axillary lymph nodes; and/or in internal mammary nodes
with metastases detected by sentinel lymph node biopsy but not clinically detected
pN1mi Micrometastases (greater than 0.2 mm and/ or more than 200 cells, but none greater than
2.0 mm)
pN1a Metastases in 1–3 axillary lymph nodes, at least one metastasis greater than 2.0 mm
pN1b Metastases in internal mammary nodes with micrometastases or macrometastases detected
by sentinel lymph node biopsy but not clinically detected
pN1c Metastases in 1–3 axillary lymph nodes and in internal mammary lymph nodes with
micrometastases or macrometastases detected by sentinel lymph node biopsy but not
clinically detected

58. • pN2 Metastases in 4–9 axillary lymph nodes; or in clinically detected internal mammary lymph
nodes in the absence of axillary lymph node metastases
pN2a Metastases in 4–9 axillary lymph nodes (at least one tumor deposit greater than
2.0 mm)
pN2b Metastases in clinically detected internal mammary lymph nodes in the
absence of axillary lymph node metastases
• pN3 Metastases in ten or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph
nodes; or in clinically detected ipsilateral internal mammary lymph nodes in the presence
of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph
nodes and in internal mammary lymph nodes with micrometastases or macrometastases
detected by sentinel lymph node biopsy but not clinically detected ; or in ipsilateral
supraclavicular lymph nodes
pN3a Metastases in ten or more axillary lymph nodes (at least one tumor deposit greater than 2.0
mm); or metastases to the infraclaviculr (level III axillary lymph) nodes
pN3b Metastases in clinically detected ipsilateral internal mammary lymph nodes in the
presence of one or more positive axillary lymph nodes; or in more than three axillary lymph
nodes and in internal mammary lymph nodes with micrometastases or macrometastases
detected by sentinel lymph node biopsy but not clinically detected
pN3c Metastases in ipsilateral supraclavicular lymph nodes

59. • Distant Metastases (M)
• M0 No clinical or radiographic evidence of distant
metastases
• cM0(i+) No clinical or radiographic evidence of distant
metastases, but deposits of molecularly or
microscopically detected tumor cells in circulating
blood, bone marrow, or other nonregional nodal tissue
that are no larger than 0.2 mm in a patient without
symptoms or signs of metastases
• M1 Distant detectable metastases as determined by
classic clinical and radiographic means and/or
histologically proven larger than 0.2 mm

60. STAGING

61. PROGNO STIC AND PREDICTIVE
FACTOR S
IN BREAST CANCER
• TNM stage—particularly the extent of axillary lymph
node involvement by breast cancer—is the most
established and reliable prognostic factor for
subsequent metastatic disease and survival.
• Patient age has also consistently been shown to be a
prognostic factor.
-Very young breast cancer patients (≤35 years) have a
poorer prognosis than older patients.
-The cancers in these patients tend to be higher grade,
less often ER/PR+, and more likely to have
lymphovascular invasion than cancers in older patients.

62. • Involvement of lymphovascular spaces is
associated with a greater likelihood of lymph
node metastases and is an independent
adverse prognostic factor in both node-
negative and node positive patients. Rigid
pathologic criteria are required for this factor
to be reliable.
• Tumor size and histologic grading also have
established prognostic significance.

63. • Estrogen and progesterone receptor
expression are important and useful predictive
factors.
- Assays for ER and PR are performed using IHC
techniques.
-ER and PR negative- do not derive benefit from
hormonal treatment.

64. • HER2 amplification or overexpression
• Approximately 20% of patients with breast cancer
have HER2/neu gene amplification, which results
in glycoprotein overexpression.
• HER2 amplification or overexpression has been
associated with higher tumor grade, lower
expression or lack of hormone receptors, higher
levels of tumor proliferation, heavier nodal tumor
burden, and poorer prognosis.

65. • Numerous other prognostic and predictive
factors have been evaluated, but have not been
widely adopted in routine clinical use in the
United States and include
(1) markers of proliferation, such as S-phase
fraction or cellular expression of Ki-67 or MIB-1
(2) measures of the plasminogen activator system,
(3) the detection of occult micrometastases in the
bone marrow using IHC techniques

66. Molecular and Genomic Factors
• Breast cancer is a heterogeneous disease, and
it has long been appreciated that tumors with
different biologic features have different
clinical outcomes and responses to therapy.

67. • prognosis and treatment selection in breast
cancer are based on characterization of tumor
growth factor receptor status—ER, PR, and HER2.
• These markers can be used to define four
functional groups of tumors:
• hormone receptor-positive with HER2−,
• Hormone receptor-negative with HER2− (“triple-
negative” tumors), and
• HER2-overexpressing tumors with or without
hormone receptor expression

68. • Recent advances in molecular biology have
resulted in further refinement of these breast
cancer subsets.
• The subtypes are;
luminal A,
luminal B,
HER2/neu, and
basal-like (or basaloid, or triple-negative).

69. • Subgroup affects both the likelihood and
timing of cancer recurrence.
• Triple-negative/basal-like, HER2-associated,
and luminal B breast cancers are at greater
risk for early recurrence relative to luminal A
cancers, which have a longer latency period of
possible recurrence.

70. • In addition to defining biologic tumor subsets,
gene expression profiling has been used to
stratify tumors as having good-risk or poor-risk
prognostic signatures.
• Several of these assays are now commercially
available.
• MammaPrint is a 70-gene signature developed in
the Netherlands.
• Prosigna (NanoString Technologies,Seattle, WA) is
a 50-gene intrinsic subtype classifier that
categories cancers into luminal A, luminal B,
HER2, or basal-like subtypes.

71. • Retrospective analyses suggest that these
gene signatures contribute independent
prognostic information above and beyond
thatachieved with use of traditional
pathologic markers, such as stage, grade,
lymphovascular invasion, and ER/PR/HER2
status.

72. • One molecular test that is of use clinically is
the Oncotype DX recurrence score.
• The recurrence score is based on a
quantitative assessment of 21 genes thought
to be relevant to breast cancer biology.

73. • In contrast to gene expression profiles that classify tumors into
specific subsets, the recurrence score calculates a continuous,
numeric result that correlates with distant metastatic recurrence.
• Oncotype DX assay was a strong predictor of benefit from CMF in
NSABP-B20, with little or no benefit from chemotherapy for
patients with low or intermediate recurrence scores but substantial
benefit for those with high recurrence scores.
• Conversely, in NSABP-B14, the benefit from tamoxifen versus
observation was confined to the low and intermediate risk
categories.

74. • Oncotype DX has been applied to a common clinical
question:
-whether a patient with ER+ breast cancer should receive
chemotherapy in addition to hormonal therapy?
• Retrospective analyses from NSABP B-20—a trial of
tamoxifen alone versus tamoxifen plus chemotherapy
for ER+, node-negative patients—demonstrated that
the recurrence score was a predictive factor for benefit
from chemotherapy.
• Patients with tumors that had a low recurrence score
had a very favorable overall prognosis that was not
meaningfully improved by chemotherapy, while
patients with high recurrence scores derived a
substantial benefit from chemotherapy.

75. • Thank You.