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Cancer breast

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Cancer breast Dr. Adnan Merdad Professor of General & Thoracic Surgery Faculty of Medicine King Abdulaziz University Cancer breast The problem : Common disease In ... – PowerPoint PPT presentation

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Title: Cancer breast


1
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2
Cancer breast
  • Dr. Adnan Merdad
  • Professor of General Thoracic Surgery
  • Faculty of Medicine
  • King Abdulaziz University

3
Cancer breast
  • The problem
  •  Common disease
  • In Saudi Arabia
  • Younger patients
  • Advanced disease
  • Poor documentation of data
  • Management is not standardized
  • The suggested solutions

4
Probability of Developing Breast Cancer Before a
Given Age( U.S. Women born in 1990)
5
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7
Cancer Breast Patients at KAUH
  • lt 60 years 85.1
  • lt 50 years 64.5
  • lt 40 years 30.6
  • WHY???

8
Late presentation in our country may be due to
  • Lack of health education
  • Difficult access to specialized medical centers
  • Lack of screening programs

9
Breast lumpiness
  • Fibrocystic changes
  • Benign lumps
  • Nodularity, cysts
  • Fibroadenoma, .etc.
  • Malignant lumps

10
Signs and Symptoms
  • Lumpiness
  • Pain (mastalgia)
  • Nipple discharge
  • Nipple erosion
  • Cutaneous erythema
  • Skin dimpling
  • Lymphadenopathy
  • Metastasis

11
How to reach a diagnosis ?
  • History physical examination
  • Ultrasonography (lt40 years)
  • Mammogram /- U/S (gt40 years)
  • MRI ???

12
BI-RADS Assessment Categories
13
  • FNA (Breast)
  • False ve 10

14
Breast biopsy
  • FNA
  • Trucut (core)
  • Open (Excisional or incisional)
  • Needle localization Bx
  • Stereotactic computerized biopsy

15
Breast cyst
  • Aspirate if symptomatic suspicious
  • Biopsy if
  • Bloody aspirate
  • Residual lump after aspiration
  • Recur within 2 weeks after aspiration

16
Factors associated with increased risk of cancer
 
Race, weight, fat diet, alcohol
 
17
Screening
  • AsymptomaticPhysical exam mammogram
  • Identify 6 cancers 1000 women
  • 80
    axill nod. ve

  • ( 50 in asymptomatic)
  • 85
    survive 5 years and more

18
Screening
  • 20-40 years SBE monthly 6-7 d after
    period
  • 40 50 years 1-2 years mammogram
  • gt 50 years yearly mammogram
  • gt 70 years Individualize

19
Screening mamogram
  • lt 0.4 cGY / breast / view
  • Only approved screening modality
  • Reduce mortality lt 30 (women gt50 years)

20
Mammographic abnormalities associated with cancer
  1. Cluster of polymorphic micro calcification
  2. Mass density
  3. Architectural distortion

21
Cancer breast
  • Most cases are sporadic
  • 10-15 ve family history
  • 5 have familial Ca breast

22
  • Introduction
  • Monoclonal.
  • Doubling time (average 100 days).
  • One cell ? 1 cm lump (8-10 years).
  • At 2nd or 3rd year Hematogenous and lymphatic
    invasion by cancer cells.

23
  • Introduction
  • Women die from breast cancer because of
    metastasis.
  • Local surgical treatment to control local disease
    and may prevent further metastasis.
  • Systemic treatment should be considered in all.

24
  • 1950 - 60 Halstedian concept
  • Enbloc radical resection
  • 1970 - 80s Fischer and Veronesi
  • Systemic disease (Micro metastasis)
  • Axillary dissection staging more than
  • therapeutic
  • 1990 - 00s Spectrum hypothesis
  • Some are systemic at diagnosis, others
    are still loco-regional

25
  • Pre-operative evaluation of patients with primary
    operable breast cancer
  • Complete history and physical exam.
  • Bilateral mammography.
  • Chest radiograph.
  • Liver function studies.
  • Further studies only when indicated by symptoms.

26
Prognostic Factors
  • May be at higher risk to develop metastasis
  • high risk group (many ve factors) may benefit
    from systemic therapy
  • Proven factors
  • Tumor size
  • Axillary lymph node status
  • Estrogen receptor status

27
Prognostic Factors
  • Questionable value
  • Breast mucin markers (CA 15-3, CA 549, CAM 26,
    CAM 29)
  • CEA
  • Oncogene protein C-erbB-2 (HER-2/neu), Ha-ras
  • Mutation of tumor suppressor gene TP 53 (P53)
  • S-phase fraction
  • Ki-67 antibody
  • Thymidine labeling index (mitotic index)

28
  • Treatment of Stages I II Breast Cancer
  • Breast conservation treatment
  • (Lumpectomy with -ve margins Axillary
    dissection(?sentinel LN Bx)
  • Irradiation to breast).
  • OR
  • Modified radical mastectomy

29
  • Factors favoring breast conservation in Stages I
    II Breast cancer
  • Patient preference.
  • Tumor location and size are favorable for
    aesthetic result.
  • Unifocal tumor.
  • High risk for general anesthesia.

30
  • Factors favoring Modified Radical Mastectomy in
    Stages I II Breast cancer
  • Patient preference.
  • Multifocal tumor.
  • Difficulty with follow-up anticipated.
  • Inability to achieve negative margin at
    lumpectomy.
  • Contraindication to radiation therapy.

31
Treatment Stage III Breast Cancer
  • Induction chemotherapy (Neoadjuvant) regimens
    include a Taxane (Paclitaxel, docetaxel) and
    Doxorubicin (80 of tumors shrinks 50 or more)
  • Conservation treatment vs. Modified radical
    mastectomy
  • Local radiotherapy
  • Additional chemotherapy depends on number of
    involved nodes size of residual tumor

32
Treatment Stage IV Breast Cancer
  • Cure is rare but durable complete remission
    attainable
  • Local treatment in 10-20 is palliative (should
    be individualized )
  • If visceral disease absent or minimal and ER
    and/or PR ve Hormonal treatment
    (Tamoxifen,Aromatase inhibitors, Progestins,
    Oophorectomy for pre-menopausal)
  • If visceral disease present or ER and PR -ve,
  • Combination chemo
  • Doxorubicin
  • C M F
  • Taxol

33
Current Recommendations for Adjuvant Systemic
Therapy
34
Carcinoma in situ
35
Carcinoma in Situ
  • Ductal Carcinoma in Situ (DCIS)
  • Precursor lesion
  • If untreated - potentially fatal invasive cancer
    cytologic
  • Size of tumor, histologic, cytologic factors
    (grade) nuclear grade, presence of absence of
    necrosis (Comedo necrosis)

36
Carcinoma in Situ
  • Treatment of DCIS (NSABP B-17 B-24)
  • Breast conservation
  • Lumpectomy ? RT if ? 1 cm clear margin
  • If close or ve margin skin sparing
    mastectomy or simple mastectomy ? reconstruction
    Tamoxifen
  • Axillary LN dissection and systemic therapy NOT
    indicated

37
Carcinoma in Situ
  • Lobular carcinoma in situ (LCIS)
  • Marker lesion (in itself may not be dangerous)
  • Identifies higher risk group of patients to
    develop cancer BILATERALLY.

38
Carcinoma in situLCIS is a Risk Factor
  • Close observation (physical exam every 6-12
    months and annual mammograms, monthly breast
    self-examination)
  • Consider prophylactic Tamoxifen
  • OR
  • Bilateral, prophylactic simple mastectomies with
    or without reconstruction

39
Post Treatment Follow-up of the patient with
Stage I and Stage II Breast Cancer
40
Tamoxifen
  • Activity A result of anti-estrogenic and other
    biologic
  • properties
  • Effectiveness Proven effective in pre- and
    post-menopausal women with ER breast cancer,
    for both adjuvant treatment and metastatic
    disease. Possibly effective as a chemo
    preventive agent and to prevent osteoporosis and
    cardiovascular disease.
  • Toxicity menopausal symptoms, increased risk of
    thromboembolic events and endometrial cancer,
    possible increased risk of colorectal cancer

41
Tamoxifen
  • Activity A result of anti-estrogenic and other
    biologic
  • properties
  • Effectiveness Proven effective in pre- and
    post-menopausal women with ER breast cancer,
    for both adjuvant treatment and metastatic
    disease. Possibly effective as a chemo
    preventive agent and to prevent osteoporosis and
    cardiovascular disease.
  • Toxicity menopausal symptoms, increased risk of
    thromboembolic events and endometrial cancer,
    possible increased risk of colorectal cancer

42
ChemotherapyMost Common Regimens
  • Cytoxan
  • Methotrexate
  • Fluorouracil
  • Cytoxan
  • Adriamycin (doxorubicin)
  • Fluorouracil
  • Adriamycin
  • Cytoxan
  • Generally given monthly for 4-6 months

43
  • Post-operative irradiation in operable
  • breast cancer
  • After lumpectomy
  • reduce local recurrence rate so
    increase success of
  • breast conservation
  • After modified radical mastectomy
  • 1. 4 or more ve axillary nodes and Stage
    III
  • 2. ve or close margins
  • 3. Extensive extra nodal disease
  • 4. ? Lobular type
  • 5. ? Lymphatic or vascular invasion in
    primary tumor
  • 6. -ve Estrogen receptors

44
  • Herceptin
  • Used for metastatic breast cancer in HER2 ve
    (score
  • 3) patients
  • Single or with combination chemo
  • Side effects
  • - Fever /- chills
  • - Weakness, nausea, vomiting
  • - Cardiac and respiratory failure
  • Clinical trials (non-metastatic Ca breast)
    chemo vs
  • chemo Herceptin
  • NSABP trial patients divided
  • a. AC followed by Taxol
  • b. AC followed by Taxol Herceptin

45
  • Herceptin (Trastuzumab)
  • Monoclonal antibody (I.V.)
  • Target cell over express HER-2 (erb B2)
    (Protein
  • found on surface of cancer cells)
  • 25 of Ca breast over express HER- 2. These
    tumors grow faster and recurs more than HER 2 -ve

46
  • Aromatase inhibitors
  • Estradiol (most potent endogenous estrogen
    biosynthesized from androgens by the cytochrome
    P-450 enzyme complex called Aromatase
  • Aromatase present in breast tissue
    Intra-tumoural aromatase local estrogen
    production
  • Steroidal aromatase inhibitors
  • (build on andostenedione nucleus)
  • Non-steroidal aromatase inhibitors
  • Aminoglutethimide-like molecule
  • Imidazole / Triazole derivatives
  • Flavonoid analogs

47
  • Aromatase inhibitors
  • Third generation aromatase inhibitors
    anastrozole,
  • letrozole, exemestane
  • Potent
  • Selective
  • Used as a second line endocrine therapy in
    post-menopausal patients failing Hormonal
    treatment

48
Conservative Breast Surgery
  • In Saudi Arabia 15.7
  • In U.S.A. 45.7
  •  
  • Due to
  • Late presentation.
  • No standard protocols for treatment.
  • Neoadjuvant chemotherapy in Stage III (not widely
    used).

49
Poor documentation
  • 9.9 of patient
  • site of tumor was not mentioned
  • Cancer registries
  • Hospital
  • Region
  • The Kingdom
  • are not well-developed
  •  
  • Pathology reports
  • Grade ???
  • L.N. status
  • Hormone receptors

50
Suggested solutions
  • Multi-disciplinary approach
  • Public health education
  • Screening mammogram programs
  • Breast clinics (team of all concerned
    specialties)

51
Suggested solutions
  • Proper utilization of available resources
  • Accurate documentation of data
  • Proper follow-up (nearest appropriate hospital)
  •  

52
There is a Lot to be Done !!
So we all should agree ,
53
  • Angiogenesis inhibitors (anti-Angiogenesis)
  • Current trials ongoing
  • Drugs that block matrix breakdown
  • - Marimastat (Phase III, Breast)
  • Drugs that inhibit endothelial cell directly
  • - Thalidomide
  • - Endostatin
  • Drugs that block activators of Angiogenesis
  • - SU 5416 (Phase I, Breast)
  • Drugs that inhibit endothelial-specific
    integrin /
  • survival signaling
  • - END 121974
  • Drugs with non-specific mechanisms of action
  • - CAI

54
High dose chemotherapy
  • High dose chemotherapy Bone Marrow Transplant
    (MBT) Peripheral Blood Stream Cells Transplant
    (PBSCT)
  • Randomized trial results are not better than
    standard regimen of chemotherapy in advanced or
    high risk Ca. breast patients
  • Used ONLY in clinical trials (most likely will be
    past history)

55
Sentinel lymph node(s) SLN forms
  • A limited set of regional lymph nodes which form
    the first step along the route of lymphatic
    drainage from a primary tumor
  • Dyes
  • Radioactive tracers
  • Radiographic contrast agents

used to identify SLN
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57
Is axillary LN dissection therapeutic ?
  • May be there is a small survival benefit.
  • Will be answered by ongoing trial of ACS
    observation vs dissection if SLN ve

58
Limitations of SLN biopsy
  • Age (older pts. L.N. replaced by fat)
  • Medial tumor Internal mammary L.N.
    radioactive material overlap LN, dye cant be
    seen)
  • Lateral tumor (radioactive tracer counts in
    diffusion area more on SLN)
  • 8 of SLN are outside axilla
  • ve predictive value 100
  • -ve predictive value 96
  • Sensitivity 89 (11 false -ve)

59
Consider axillary Sentinel lymph node (SLN)
biopsy in
  • 1. Stage I - II tumors (primary breast cancer)
  • 2. Clinically negative axillary lymph nodes
  • 3. Axillary node dissection ia part of the
    treatment
  • plan

60
Technique
  • Injection of radio colloid same day (up to 24
    hrs. before surgery) around tumor, intra avitory,
    ? sub dermal)
  • Pre-operative lymphoscintigrapgy or handheld
    gamma probe intraoperatively
  • The hotspot is identified and the skin above it
    is marked.

61
IF SLN ve
  • No further axillary dissection
  • False ve is negligible
  • Little risk of axillary failure in SLN ve
    patients with no axillary dissection

62
SLN. ve
  • Complete axillary dissection or NOT ACS
    randomized trial ? ongoing, observation vs
    axillary dissection (if ve SLN)

63
Sentinel lymph node (SLN) role in cancer breast
management
  • Primary breast cancer
  • Clinically ve axilla
  • High identification rate SLN
  • Very low false ve rate of axilla (if ve)
  • ?? could eliminate axillary node dissection in
    Stage I-II.

64
SLN ve
  • Axillary dissection is necessary if
  •  1. Significant probability of additional tumor
    bearing nodes (ve nodes)
  • 2. Axillary dissection has therapeutic value

65
Taxanes
  • Paclitaxel (Taxol)
  • Docetaxel (Taxotere)
  • Microtubules

66
How often is the SLN the only ve axillary node?
  • Stage I Ca breast 67
  • (Albertini et al JAMA 1996)
  • Stage I-II Ca breast 38
  • (Veronesi et al
  • Lancet et al, 1997)

67
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68
Sentinel lymph node(s) SLN forms
  • A limited set of regional lymph nodes which form
    the first step along the route of lymphatic
    drainage from a primary tumor
  • Dyes
  • Radioactive tracers
  • Radiographic contrast agents

used to identify SLN
69
Technique of Sentinel LN dissection using
A. Isosulfan
  • 1 Isosulfan Blue dye (Lymphazurin)
  • 3-5 ml around tumor
  • Gentle massage to breast
  • Dissect 3-10 minutes after injection
  • Transverse incision 1cm below hairline
  • Look for blue L.N. (? partial blue)

70
B. Radio pharmaceuticals
  • Using radio pharmaceutical colloid
  • Particular size
  • Method and volume of injection
  • Detection technique

71
The radioisotope most commonly used
  • Technetium 99m (a high energy radioisotope that
    delays by pure gamma emersion)
  • Short half life (6 hours)
  • Ideal for SLN detection by gamma camera or probe

72
Colloid radio pharmaceuticals labeled with 99mTc
most commonly used for SLN
  • Antimony sulphide colloid (5-30 nm)
  • Nanocolloid (human albumin colloid ) (lt80 nm)
  • Sulfur colloid (commonly used in USA) (100-1000
    nm)

73
Micro metastases in SLN lt 2mm by HE stain
  • T1a T1b lt 2mm ? 6 had additional ve axillary
    nodes.
  •  
  • T1a T1b gt 2mm ? 50 had additional ve
    axillary nodes.
  •  
  • SLN ve by Immunohistochemistry ? 0 had
    additional ve axillary nodes.

74
Limitations of SLN biopsy
  • Primary lymphatic drainage to internal mammary LN
    in 20 to 86 depends on the quadrant involved
  • Exclusive metastasis to Internal mammary LN is
    5-10
  • Using radioactive tracer 3 of cases only
    non-axillary SLNs (ve)

75
Complications of axillary node dissection
76
Breast Reconstruction
  • Options
  • Immediate vs. delayed
  • Autogenous vs. prosthetic
  • Indications
  • All women undergoing mastectomy who desire
    reconstruction and who are not likely to require
    postoperative radiation therapy

77
  • Outside clinical trial
  •  
  • Axillary dissection is the role if ve SLN

78
Sentinel lymph nodeIts role in cancer breast
surgery
  • Dr. Adnan Merdad
  • Professor of General Thoracic Surgery
  • Faculty of Medicine
  • King Abdulaziz University

79
Buserelin
  • Used in prostate cancer
  • Patient on tamoxifen - develop high levels of
    Estradiol (ovaries) - Buserelin blocks this
    ovarian production
  • European study (EORTC) Tamoxifen vs Buserelin vs
    Tamoxifen Buserelin
  • Stage III IV patients
  • Better overall survival and progression free
    survival
  • Combined 5 year survival 34
  • Single 5 year survival 15-18

80
Breast Cancer
  • Dr. Adnan Merdad
  • Professor of Surgery
  • King Abdul Aziz University, Jeddah
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