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BREAST CANCER-
DIAGNOSTIC WORKUP
PRESENTER- Dr ABHISHEK MEWARA
MODERATOR- Dr UPEN K MATHUR
DATE- 4.4.2024
1
OVERVIEW
I. HISTORY
II. EXAMINATION
III. INVESTIGATIONS
IV. HISTOPATHOLOGY
V. STAGING
2
TRIPLE ASSESSMENT OF BREAST LUMP
CLINICAL
EXAMINATION:
History and Physical
Examination
RADIOLOGICAL:
USG vs Mammography
vs MRI
H.P.E.
(Histopathological
Examination):
FNAC vs Tru Cut
Biopsy
Triple assessment
technique has a
positive predictive
value of 99.99%
3
I. HISTORY
4
1. PATIENT’S GENERAL INFORMATION-
o Name, age, gender, occupation, marital status, economic status, residence, hospital
registration number, etc.
2. CHIEF COMPLAINTS- In chronological order, with duration.
o Fever
o Lump
o Gross swelling
o Redness
o Ulceration
o Itching
o Nipple retraction
o Nipple discharge
o Weight loss
5
3. HISTORY OF PRESENTING ILLNESS-
o Above mentioned complaints in chronological order with their progression, associated complaints,
aggravating and relieving factors and whether or not any treatment was taken for the same.
4. PAST HISTORY-
o Of similar, or other illness, previous hospitalizations, surgeries, H/O acute/ chronic, systemic/
infectious diseases.
5. PERSONAL HISTORY-
o Smoking
o Drinking
o Tobacco
o Appetite
o Sleep
o Bowel/ Bladder habits
6
6. MENSTRUAL AND OBSTEATRIC HISTORY-
o Menarche/ Menopause
o Breast feeding
o Regularity of cycles/ Blood flow per cycle
o GPLA score
o Age at the time of first child birth.
7. FAMILY HISTORY-
o Of breast cancer or any other disease.
7
8.TREATMENT HISTORY-
o Includes history of past radiation therapy,
chemotherapy, surgery.
8
II. EXAMINATION
9
10
1. Inspection
2. Palpation with patient sitting
3. Palpation with patient lying down
1.INSPECTION-
o Assess for symmetry in shape, contour.
o Assess skin changes, particularly erythema,
ulceration, retraction, dimpling, nipple
changes viz retraction, discharge.
11
2. PALPATION WITH PATIENT SITTING-
o Check for position, size and shape, puckering/ dimpling, consistency,
surface, texture, margins, mobility.
o To check the fixity of lump over the underlying tissue, hands are placed
on hips, pressing tightly. This is done to fix the pectoralis major muscle.
o Also examine cervical, supraclavicular, axillary lymph nodes.
3. PALPATION WITH PATIENT LYING DOWN-
o Ipsilateral hand is placed overhead.
o Pattern- radial strips, concentric circles.
o Cover the entire breast.
o Use pads of fingers, i.e. the palmar surface of the hand.
12
13
14
15
16
III. INVESTIGATIONS
17
DIAGNOSTIC WORKUP 18
WORKUP DOGMA AT OUR INSTITUTE-
19
BIOPSY PROVEN CASE
1. IHC - to check ER/ PR/ HER 2 neu status - guides treatment and
narrates prognosis.
2. CLINICAL EXAMINATION – For clinical staging and gross idea
of metastasis.
3. WORKUP -
a. Hematological- CBC, LFT, RFT, Serum ALP
b. If stage I or II, go for CXR, USG of W/A And Pelvis, and if
suspicious of metastasis, do CECT W/A and Pelvis.
c. If stage III or IV, go for Bone Scan, as probability of bone
metastasis is > 14 – 20% in these stages.
d. 2D Echo- To check LVEF, which has to be > 50% for administration
of anthracyclines. (Lifetime dose of which is 550 mg/m2.)
20
RADIOLOGICAL
ASSESSMENT OF BREAST
LUMP
21
USG MAMMOGRAPHY MRI
1. USG
o Best investigation to
differentiate between solid
and cystic components.
o Sensitivity~ 73%,
Specificity~ 95%
o Best radiological test for
pregnant lady with breast
lump.
o Better imaging for dense
breasts in < 40 years.
o Disadvantage: Operator
dependent.
2. MAMMOGRAPHY
o Screening IOC,
performed during first
half of menstrual cycle.
o Sensitivity~ 90%,
Specificity~ 94%
o Radiation exposure: 0.1-
0.2 cGy.
o Sensitivity increases with
age.
o Now-a-days, advanced 3-D
full field mammogram
known as Tomosynthesis is
used.
22
3. MRI
o IOC to detect multifocal and multi-centric breast
cancer.
o IOC in ladies with breast implant.
o Best imaging to identify local recurrence after
surgery (scar recurrence).
o Most sensitive investigation for DCIS.
o Best screening modality in young and high risk
patients (first degree relative of BRCA mutation
patients, Li FRAUMENI syndrome, COWDEN
syndrome).
23
SIGNS OF MALIGNANCY ON
MAMMOGRAPHY
o Irregular margins: Stellate,
Spiculate, Comet tail.
o Heterogeneous.
o High density.
o Wide halo around lesion.
o Microcalcifications (<0.5mm):
Cluster, Linear, Segmental,
Diffuse.
24
SIGNS OF MALIGNANCY ON USG
o Hypo echoic lesion.
o Irregular margins, disruption
of tissue plains.
o Posterior acoustic shadowing.
o Lesion is more taller than wider
(in vertical orientation).
o Increased cellular vascularity.
25
BIRADS (BREAST IMAGING REPORTING
AND DATA SYSTEM)
0 Incomplete assessment Additional imaging required
1 Negative
(0% chance of malignancy)
Annual screening mammography
2 Benign Annual screening mammography
3 Probably benign ; <2% chance of
malignancy
6 monthly follow up for 2 years
4 Malignancy suspicious Biopsy required
4a 2-10%
4b 11-50%
4c 51-94%
5 Highly suggestive (>/=95%) Biopsy + Intervention
6 Biopsy proven Intervention
26
IV. HISTOPATHOLOGY
27
2 MAIN MODALITIES
FNAC
o 23-30 G needle used.
o Cannot differentiate
between invasive and
in-situ carcinoma.
o High false negative
rates.
TRU-CUT BIOPSY
o 8-18 G needle used.
o Incisional biopsy
technique is used.
o ER/ PR/ HER2neu
status can be known.
o IOC for
histopathological
examination.
28
PATHOGENESIS
1. SPORADIC – 90% (M/C gene mutated: p53)
2. FAMILIAL – 10% (M/C gene mutated: BRCA 1, present on 17q)
29
EXTENSIVE INTRADUCTAL COMPONENT-
 It means >/= 75% involvement of lumen of the
duct, and is associated with a comparatively
bad prognosis.
 It is also an indication of early radiation
therapy administration.
30
TYPES OF BREAST CANCER
BASED ON
HISTOPATHOLOGY
31
1. PAGET’S DISEASE OF NIPPLE-
o Paget’s disease of nipple is a
superficial manifestation of an
underlying breast carcinoma.
o Clinical presentation: presents as an
eczema like condition of the nipple and
areola associated with itching and
burning, slow progression towards
crusting eczematoid appearance.
o Microscopically: large ovoid cells with
abundant, clear, pale staining cytoplasm
in malpigian layer of the epidermis.
32
2. DUCTAL CARCINOMA IN SITU
(DCIS)-
o Clinical Presentation - Mostly
asymptomatic palpable mass, associated
with nipple discharge.
o Micro-calcifications are seen on
mammogram.
 Linear & Branching pattern– High Grade
 Fine & Granular– Low Grade
o 40-80% chance of being multicentric.
o Mostly unilateral.
o Most sensitive imaging investigation:
MRI.
o DCIS is a precursor lesion to invasive
ductal carcinoma.
33
3. INVASIVE/ INFILTRATIVE
DUCTAL CARCINOMA (IDC)-
o M/C histological type, constituting
>50% of all cases.
o It appears as solid cords or groups
of ductal tumor cells varying in size
& cytoplasmic content and degree
of differentiation. (Image B & D )
o Necrosis is rare, but lymphatic
invasion may be present.
34
4. INVASIVE LOBULAR
CARCINOMA (ILC)-
o Microscopically: Tumor cells
arranged in small clusters in a
targetoid or Single file pattern.
(Image A & C)
o Mutation in E-cadherin (lack of
expression on membrane).
o It is often mammographically
silent.
o ILC are much more commonly
ER+ than IDC.
o Usually multifocal and/ or
bilateral.
35
V. STAGING
TNM AJCC 2018
36
PATHOLOGICAL & CLINICAL T
STAGING
T0 NO TUMOUR
Tis Carcinoma in situ
T1 mic < 0.1 cm
T1a 0.1-0.5 cm
T1b > 0.5-1 cm
T1c > 1-2 cm
T2 > 2 cm – 5 cm
T3 > 5 cm
T4a Involvement of chest wall (Ribs, Serratus anterior, Intercostal muscles)
T4b Involvement of skin (Peau d’orange, ulceration, satellite nodules)
T4c T4a+T4b
T4d Inflammatory breast cancer ( >1/3 breast shows Peau d’orange)
37
N0 No lymph node involved
cN1 Mobile Axillary lymph node
cN2a Fixed/ matted Axillary lymph node
cN2b Internal Mammary lymph node
cN3a Infraclavicular lymph node
cN3b Internal Mammary + Axillary lymph nodes
cN3c Supraclavicular lymph node
M0 No metastasis
M1 Mets (contralateral breast involvement is
also considered as metastasis)
38
CLINICAL N STAGING
N0 No lymph node involved
pN1 Micro-metastases; or metastases in 1–3 axillary lymph nodes; and/ or clinically
negative internal mammary nodes with micro-metastases or macro-metastases by
sentinel lymph node biopsy
pN1mic Micro-metastases (approximately 200 cells, larger than 0.2 mm, but none larger
than 2.0 mm)
pN1a Metastases in 1–3 axillary lymph nodes, at least one metastasis larger than 2.0 mm
pN1b Metastases in ipsilateral internal mammary sentinel nodes, excluding ITCs
pN1c pN1a and pN1b combined
pN2 Metastases in 4–9 axillary lymph nodes; o positive ipsilateral internal mammary
lymph nodes by imaging in the absence of axillary lymph node metastases
pN2a Metastases in 4–9 axillary lymph nodes (at least one tumor deposit larger than 2.0
mm)
pN2b Metastases in clinically detected internal mammary lymph nodes with or without
microscopic confirmation; with pathologically negative axillary nodes
39
PATHOLOGICAL N STAGING
pN3 Metastases in 10 or more axillary lymph nodes or in infraclavicular (Level III
axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by
imaging in the presence of one or more positive Level I, II axillary lymph
nodes;
or in more than three axillary lymph nodes an micro-metastases or macro-
metastases by sentinel lymph node biopsy in clinically negative ipsilateral
internal mammary lymph nodes or in ipsilateral supraclavicular lymph nodes
pN3a Metastases in 10 or more axillary lymph nodes (at least one tumor deposit
larger than 2.0 mm);
or metastases to the infraclavicular (Level III axillary lymph) nodes
pN3b pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by
imaging);
or pN2a in the presence of pN1b
pN3c Metastases in ipsilateral supraclavicular lymph nodes
40
MOLECULAR CLASSIFICATION OF BREAST
CANCER, BASED ON GENE EXPRESSION
PROFILING
LUMINAL A ER+ PR+ HER2 neu- Ki67 low Best
prognosis
LUMINAL B
(TRIPLE +)
ER+ PR+ HER2 neu+ Ki67 high/
low
Good/ bad
prognosis
BASAL
(TRIPLE -)
ER- PR- HER2 neu- Ki67 high Worst
prognosis
HER2 neu
ENRICHED
ER- PR- HER2 neu+ Ki67 high/
low
Poor
prognosis
41
N0 N1 N2 N3 M1
T1 I IIA IIIA IIIC IV
T2 IIA IIB IIIA IIIC IV
T3 IIB IIIA IIIA IIIC IV
T4 IIIB IIIB IIIB IIIC IV
COMPOSITE STAGING 42
RAPID REVIEW 43
5 YEAR SURVIVAL RATE FOR
BREAST CANCER BY STAGE-
STAGE 5-YEAR SURVIVAL
(PERCENTAGE OF
PATIENTS)
EARLY INVASIVE BREAST CANCER I 92
IIA 82
IIB 65
LABC (LOCALLY ADVANCED BREAST CANCER) IIIA 47
IIIB 44
METASTATIC BREAST CANCER IV 14
REFERENCES-
1. S. DAS
2. ROBBINS
3. PEREZ
4. DEVITA
5. HARRISON
6. NCCN
7. AJCC 2018
45
THANK YOU, AND
HAVE A NICE DAY.
46

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8. Breast Cancer Diagnostic Workup .pptx

  • 1. BREAST CANCER- DIAGNOSTIC WORKUP PRESENTER- Dr ABHISHEK MEWARA MODERATOR- Dr UPEN K MATHUR DATE- 4.4.2024 1
  • 2. OVERVIEW I. HISTORY II. EXAMINATION III. INVESTIGATIONS IV. HISTOPATHOLOGY V. STAGING 2
  • 3. TRIPLE ASSESSMENT OF BREAST LUMP CLINICAL EXAMINATION: History and Physical Examination RADIOLOGICAL: USG vs Mammography vs MRI H.P.E. (Histopathological Examination): FNAC vs Tru Cut Biopsy Triple assessment technique has a positive predictive value of 99.99% 3
  • 5. 1. PATIENT’S GENERAL INFORMATION- o Name, age, gender, occupation, marital status, economic status, residence, hospital registration number, etc. 2. CHIEF COMPLAINTS- In chronological order, with duration. o Fever o Lump o Gross swelling o Redness o Ulceration o Itching o Nipple retraction o Nipple discharge o Weight loss 5
  • 6. 3. HISTORY OF PRESENTING ILLNESS- o Above mentioned complaints in chronological order with their progression, associated complaints, aggravating and relieving factors and whether or not any treatment was taken for the same. 4. PAST HISTORY- o Of similar, or other illness, previous hospitalizations, surgeries, H/O acute/ chronic, systemic/ infectious diseases. 5. PERSONAL HISTORY- o Smoking o Drinking o Tobacco o Appetite o Sleep o Bowel/ Bladder habits 6
  • 7. 6. MENSTRUAL AND OBSTEATRIC HISTORY- o Menarche/ Menopause o Breast feeding o Regularity of cycles/ Blood flow per cycle o GPLA score o Age at the time of first child birth. 7. FAMILY HISTORY- o Of breast cancer or any other disease. 7
  • 8. 8.TREATMENT HISTORY- o Includes history of past radiation therapy, chemotherapy, surgery. 8
  • 10. 10 1. Inspection 2. Palpation with patient sitting 3. Palpation with patient lying down
  • 11. 1.INSPECTION- o Assess for symmetry in shape, contour. o Assess skin changes, particularly erythema, ulceration, retraction, dimpling, nipple changes viz retraction, discharge. 11
  • 12. 2. PALPATION WITH PATIENT SITTING- o Check for position, size and shape, puckering/ dimpling, consistency, surface, texture, margins, mobility. o To check the fixity of lump over the underlying tissue, hands are placed on hips, pressing tightly. This is done to fix the pectoralis major muscle. o Also examine cervical, supraclavicular, axillary lymph nodes. 3. PALPATION WITH PATIENT LYING DOWN- o Ipsilateral hand is placed overhead. o Pattern- radial strips, concentric circles. o Cover the entire breast. o Use pads of fingers, i.e. the palmar surface of the hand. 12
  • 13. 13
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  • 19. WORKUP DOGMA AT OUR INSTITUTE- 19
  • 20. BIOPSY PROVEN CASE 1. IHC - to check ER/ PR/ HER 2 neu status - guides treatment and narrates prognosis. 2. CLINICAL EXAMINATION – For clinical staging and gross idea of metastasis. 3. WORKUP - a. Hematological- CBC, LFT, RFT, Serum ALP b. If stage I or II, go for CXR, USG of W/A And Pelvis, and if suspicious of metastasis, do CECT W/A and Pelvis. c. If stage III or IV, go for Bone Scan, as probability of bone metastasis is > 14 – 20% in these stages. d. 2D Echo- To check LVEF, which has to be > 50% for administration of anthracyclines. (Lifetime dose of which is 550 mg/m2.) 20
  • 22. 1. USG o Best investigation to differentiate between solid and cystic components. o Sensitivity~ 73%, Specificity~ 95% o Best radiological test for pregnant lady with breast lump. o Better imaging for dense breasts in < 40 years. o Disadvantage: Operator dependent. 2. MAMMOGRAPHY o Screening IOC, performed during first half of menstrual cycle. o Sensitivity~ 90%, Specificity~ 94% o Radiation exposure: 0.1- 0.2 cGy. o Sensitivity increases with age. o Now-a-days, advanced 3-D full field mammogram known as Tomosynthesis is used. 22
  • 23. 3. MRI o IOC to detect multifocal and multi-centric breast cancer. o IOC in ladies with breast implant. o Best imaging to identify local recurrence after surgery (scar recurrence). o Most sensitive investigation for DCIS. o Best screening modality in young and high risk patients (first degree relative of BRCA mutation patients, Li FRAUMENI syndrome, COWDEN syndrome). 23
  • 24. SIGNS OF MALIGNANCY ON MAMMOGRAPHY o Irregular margins: Stellate, Spiculate, Comet tail. o Heterogeneous. o High density. o Wide halo around lesion. o Microcalcifications (<0.5mm): Cluster, Linear, Segmental, Diffuse. 24
  • 25. SIGNS OF MALIGNANCY ON USG o Hypo echoic lesion. o Irregular margins, disruption of tissue plains. o Posterior acoustic shadowing. o Lesion is more taller than wider (in vertical orientation). o Increased cellular vascularity. 25
  • 26. BIRADS (BREAST IMAGING REPORTING AND DATA SYSTEM) 0 Incomplete assessment Additional imaging required 1 Negative (0% chance of malignancy) Annual screening mammography 2 Benign Annual screening mammography 3 Probably benign ; <2% chance of malignancy 6 monthly follow up for 2 years 4 Malignancy suspicious Biopsy required 4a 2-10% 4b 11-50% 4c 51-94% 5 Highly suggestive (>/=95%) Biopsy + Intervention 6 Biopsy proven Intervention 26
  • 28. 2 MAIN MODALITIES FNAC o 23-30 G needle used. o Cannot differentiate between invasive and in-situ carcinoma. o High false negative rates. TRU-CUT BIOPSY o 8-18 G needle used. o Incisional biopsy technique is used. o ER/ PR/ HER2neu status can be known. o IOC for histopathological examination. 28
  • 29. PATHOGENESIS 1. SPORADIC – 90% (M/C gene mutated: p53) 2. FAMILIAL – 10% (M/C gene mutated: BRCA 1, present on 17q) 29
  • 30. EXTENSIVE INTRADUCTAL COMPONENT-  It means >/= 75% involvement of lumen of the duct, and is associated with a comparatively bad prognosis.  It is also an indication of early radiation therapy administration. 30
  • 31. TYPES OF BREAST CANCER BASED ON HISTOPATHOLOGY 31
  • 32. 1. PAGET’S DISEASE OF NIPPLE- o Paget’s disease of nipple is a superficial manifestation of an underlying breast carcinoma. o Clinical presentation: presents as an eczema like condition of the nipple and areola associated with itching and burning, slow progression towards crusting eczematoid appearance. o Microscopically: large ovoid cells with abundant, clear, pale staining cytoplasm in malpigian layer of the epidermis. 32
  • 33. 2. DUCTAL CARCINOMA IN SITU (DCIS)- o Clinical Presentation - Mostly asymptomatic palpable mass, associated with nipple discharge. o Micro-calcifications are seen on mammogram.  Linear & Branching pattern– High Grade  Fine & Granular– Low Grade o 40-80% chance of being multicentric. o Mostly unilateral. o Most sensitive imaging investigation: MRI. o DCIS is a precursor lesion to invasive ductal carcinoma. 33
  • 34. 3. INVASIVE/ INFILTRATIVE DUCTAL CARCINOMA (IDC)- o M/C histological type, constituting >50% of all cases. o It appears as solid cords or groups of ductal tumor cells varying in size & cytoplasmic content and degree of differentiation. (Image B & D ) o Necrosis is rare, but lymphatic invasion may be present. 34
  • 35. 4. INVASIVE LOBULAR CARCINOMA (ILC)- o Microscopically: Tumor cells arranged in small clusters in a targetoid or Single file pattern. (Image A & C) o Mutation in E-cadherin (lack of expression on membrane). o It is often mammographically silent. o ILC are much more commonly ER+ than IDC. o Usually multifocal and/ or bilateral. 35
  • 37. PATHOLOGICAL & CLINICAL T STAGING T0 NO TUMOUR Tis Carcinoma in situ T1 mic < 0.1 cm T1a 0.1-0.5 cm T1b > 0.5-1 cm T1c > 1-2 cm T2 > 2 cm – 5 cm T3 > 5 cm T4a Involvement of chest wall (Ribs, Serratus anterior, Intercostal muscles) T4b Involvement of skin (Peau d’orange, ulceration, satellite nodules) T4c T4a+T4b T4d Inflammatory breast cancer ( >1/3 breast shows Peau d’orange) 37
  • 38. N0 No lymph node involved cN1 Mobile Axillary lymph node cN2a Fixed/ matted Axillary lymph node cN2b Internal Mammary lymph node cN3a Infraclavicular lymph node cN3b Internal Mammary + Axillary lymph nodes cN3c Supraclavicular lymph node M0 No metastasis M1 Mets (contralateral breast involvement is also considered as metastasis) 38 CLINICAL N STAGING
  • 39. N0 No lymph node involved pN1 Micro-metastases; or metastases in 1–3 axillary lymph nodes; and/ or clinically negative internal mammary nodes with micro-metastases or macro-metastases by sentinel lymph node biopsy pN1mic Micro-metastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm) pN1a Metastases in 1–3 axillary lymph nodes, at least one metastasis larger than 2.0 mm pN1b Metastases in ipsilateral internal mammary sentinel nodes, excluding ITCs pN1c pN1a and pN1b combined pN2 Metastases in 4–9 axillary lymph nodes; o positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases pN2a Metastases in 4–9 axillary lymph nodes (at least one tumor deposit larger than 2.0 mm) pN2b Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary nodes 39 PATHOLOGICAL N STAGING
  • 40. pN3 Metastases in 10 or more axillary lymph nodes or in infraclavicular (Level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive Level I, II axillary lymph nodes; or in more than three axillary lymph nodes an micro-metastases or macro- metastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes or in ipsilateral supraclavicular lymph nodes pN3a Metastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (Level III axillary lymph) nodes pN3b pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging); or pN2a in the presence of pN1b pN3c Metastases in ipsilateral supraclavicular lymph nodes 40
  • 41. MOLECULAR CLASSIFICATION OF BREAST CANCER, BASED ON GENE EXPRESSION PROFILING LUMINAL A ER+ PR+ HER2 neu- Ki67 low Best prognosis LUMINAL B (TRIPLE +) ER+ PR+ HER2 neu+ Ki67 high/ low Good/ bad prognosis BASAL (TRIPLE -) ER- PR- HER2 neu- Ki67 high Worst prognosis HER2 neu ENRICHED ER- PR- HER2 neu+ Ki67 high/ low Poor prognosis 41
  • 42. N0 N1 N2 N3 M1 T1 I IIA IIIA IIIC IV T2 IIA IIB IIIA IIIC IV T3 IIB IIIA IIIA IIIC IV T4 IIIB IIIB IIIB IIIC IV COMPOSITE STAGING 42
  • 44. 5 YEAR SURVIVAL RATE FOR BREAST CANCER BY STAGE- STAGE 5-YEAR SURVIVAL (PERCENTAGE OF PATIENTS) EARLY INVASIVE BREAST CANCER I 92 IIA 82 IIB 65 LABC (LOCALLY ADVANCED BREAST CANCER) IIIA 47 IIIB 44 METASTATIC BREAST CANCER IV 14
  • 45. REFERENCES- 1. S. DAS 2. ROBBINS 3. PEREZ 4. DEVITA 5. HARRISON 6. NCCN 7. AJCC 2018 45
  • 46. THANK YOU, AND HAVE A NICE DAY. 46