Managing Breast Abnormalities in the Primary Care Practice

1
Managing Breast Abnormalities in the Primary Care
Practice

• Benjamin D. Li, MD, FACS
• Charles Knight Sr. Professor and Vice Chairman
• Department of Surgery
• Chief, Surgical Oncology
• LSUHSC-Shreveport and the Feist-Weiller Cancer
  Center

2
Outline - 1

• Clinical presentations of breast disease
• Nipple discharge
• Mastalgia
• Breast mass
• diagnostic imaging
• who to biopsy
• how to biopsy

3
Outline 2

• Treatment of breast cancer
• Local-regional control of breast cancer
• Surgery
• Modified Radical Mastectomy (MRM)
• Breast Conservation Therapy (BCT)
• Addressing nodal disease
• Axillary Lymph Node Dissection (ALND)
• Sentinel Lymph Node Biopsy (SLNB)
• Radiation therapy
• Postmastectomy Radiotherapy (PMRT)
• Whole breast irradiation versus Accelerated
  Partial Breast Irradiation (APBI)

4
Outline - 3

• Systemic adjuvant therapy
• Advances in chemotherapy
• Taxanes
• Dose dense regimens
• Evolving paradigms in hormonal manipulation
• Estrogen receptor inhibition
• Aromatase inhibitors

5
Outline - 4

• Breast cancer screening
• Guidelines for screening
• Risk Factors for breast cancer
• Family history
• Low relative risk
• High relative risk
• BRCA genes
• Who should be tested
• Breast cancer risk reduction
• Prophylatic surgery
• Chemoprevention

6
Clinical Presentation

• 3 most common breast complaints
• Mastalgia
• NIPPLE DISCHARGE
• MASS
• gt50 of patients presenting to surgeon with a
  breast condition will have benign disease
• Marchant, Surg Oncol Clinics of North
  America, 1998

7
Caution!

• Applying the correct diagnostic and/or
  therapeutic algorithm is critical
• Treat patient thoughtfully
• Look for a mass
• Image area as appropriate
• Ultrasound
• Mammogram
• Balance the need for diagnostic workup and avoid
  unnecessary procedure(s)

8
Breast Pain (Mastalgia)

• Almost all women will have experienced varying
  degree of breast pain in her lifetime ranging
• mild discomfort
• severe pain
• cyclical
• estrogen overstimulation
• methylxanthines

9
Mastalgia

• Mastalgia is a poor predictor for cancer risk
• lt5 of breast cancer are associated with pain
• gt95 of patients with some breast pain
• Beware!
• Though the association of breast pain and breast
  cancer is NOT strong, the fear is very REAL

10
Management of Mastalgia

• The most important questions
• Is there a dominant mass?
• Physical examination for dominant mass
• Follow the workup of a breast mass
• Is there associated nipple discharge?
• If there is bloody or serous discharge, follow
  nipple discharge workup
• Does patient have recent breast imaging
• Mammogram
• Ultrasound
• If abnormal, follow workup of a breast mass

11
Management of Mastalgia

• If the breast examination and mammograms are
  negative
• Discontinue caffeinated products
• Discontinue nicotine use
• Nonsteroidal anti-inflammatory agents (NSAIDs)
• Hormonal manipulation
• Danazol
• 6 month trial of 100 to 400mg daily
• Side effects
• Tamoxifen
• Vitamins
• A and E
• Repeat examination in 4 to 6 months

12
Nipple Discharge

• Less than 5 chance of cancer
• Leis, World J Surgery, 1999
• Differentiate between high versus low risk by
  history
• Higher risk Lower risk
• Spontaneous versus provoked
• Unilateral versus bilateral
• Bloody/serous versus cloudy and/or
  multicolored
• Post- versus pre-menopasual

13
Nipple Discharge

• Physical examination
• Is there a subareolar mass?
• Types of imaging
• Mammogram
• Ultrasound
• Duct ectasia
• Ductogram
• Intraductal defect

14
Nipple Discharge

• Determine the need for histologic diagnosis based
  on the following
• History
• Examination
• Imaging
• Causes of nipple discharge
• Most common cause for spontaneous nipple
  discharge is intraductal papiloma
• BUT intraductal (DCIS) and invasive ductal
  carcinoma can cause nipple discharge (5)

15
Management of a Breast Mass

• Questions that need to be addressed
• Is it dominant?
• What is the age of patient?
• How long has it been?
• Has it change in size?
• Any associated symptoms?
• discharge
• skin changes
• pain
• What is the relative risk for cancer?
• previous biopsy
• family history

16
Management of a Breast Mass

• Determine the type of imaging
• Diagnostic mammogram
• Reserved for older than 30 years of age
• Pleomorphic microcalcification
• Architectural distortion
• Ultrasound
• Diagnostic imaging
• Cystic versus solid
• NOT a screening test nonspecific
• MRI
• Dense breast tissue
• Post radiation therapy
• PET scan
• In house protocol for recurrent disease

17
Management of a Breast Mass

• Determine if histologic confirmation is necessary
• Cystic lesion
• Simple versus complex
• Is there any intra-cystic defect?
• Does it need drainage?
• Solid lesion
• Mammographic criteria
• BiRads
• Suspicious ultrasound characteristics
• Solid lesion with
• Low level internal echo
• Irregular margin
• Taller than in it is wide

18
Management of a Breast Mass

• 2 categories of biopsy
• Excisional
• Removes the whole lesion
• Incisional
• Removes part of the lesion

19
Excisional Biopsy

• Often used for palpable lesion
• Nonpalpable, mammographically detected lesion
• Needle localization
• Blue dye injection
• Benefits
• Removes lesion completely
• Reduces risk for sampling error
• If tumor-free margin is achieved
• Lumpectomy with curative intent

20
Incisional Biopsy

• By definition, samples the lesion
• Fine needle aspiration (FNA)
• Cytology
• Open wedge biopsy
• Tru-cut or core biopsy
• Image guided or by palpation
• Mammogram
• Stereotatic core biopsy (SCB)
• Mammotomy
• Ultrasound

21
Treatment for Breast Cancer
22
Breast Cancer Outcome

• Incidence 211,240
• Death 40,410
• 5 yr survival
• 1975 75
• 1986 78
• 2000 88
• Jemal, et al., CA Cancer J Clin 55(1)10,
  2005
• Improvement in breast cancer outcome
• Early detection
• Multimodal therapy
• Locoregional control
• Systemic adjuvant therapy

23
Breast Cancer Therapy

• Local-regional control
• Surgery
• Radiation therapy (XRT)
• Systemic control
• Chemotherapy
• Hormonal manipulation

24
Surgical Therapy for Breast CancerThe Gold
Standard

• Modified Radical Mastectomy (MRM)
• Total mastectomy
• Removal of all gross breast tissue
• including the nipple areolar complex
• Level I and II axillary node dissection (ALND)
• Breast Conservation Therapy (BCT)
• Excision of cancer with tumor-free margin
• lumpectomy
• ALND
• XRT

25
Systemic Therapy

• Adjuvant therapy based weighing
• Risk of recurrence
• Sequelae of therapy
• Chemotherapy
• Node-positive patients
• Tumors gt1 cm
• Age/Menopausal status
• Overall health of patient
• Endocrine therapy
• Receptor status (ER and PR)
• Anti-estrogen
• Aromatase inhibitors (AIs)

26
Breast Conservation Therapy

• Removal of breast cancer
• Lumpectomy
• Quadrantectomy
• Partial mastectomy
• Segmentectomy
• Must achieve tumor-free margins
• Axillary node dissection
• Breast irradiation
• 4500 to 5000 cGy
• 5 to 6weeks
• Whole breast irradiation

27
What to do with the lymph nodes?
28
Management of Axillary Lymph Nodes

• Infitrating ductal cell carcinoma (IDCA)
• Invasion of tumor cells beyond the basement
  membrane
• Nodal basin needs evaluation
• Gold Standard
• Complete ALND
• Sentinel Node Biopsy (SLNB)
• Early breast cancer

29
Axillary Node Dissection

• Staging
• Single best predictor for risk of systemic
  disease and cancer recurrence
• Therapeutic decisions
• Systemic therapy
• Radiation therapy
• May improve survival and cuure

30
NSABP B-06 20 Year Update

• Randomized trial initiated in 1976
• 3 arms (all patients underwent ALND)
• Total mastectomy (MRM)
• Lumpectomy
• Lumpectomy and XRT (BCT)
• Accrued 2,163 patients with tumors
• lt 4 cm
• Included node- positive and negative patients
• Establishes the efficacy and safety for BCT
• Fisher, NEJM Oct., 2002

31
Breast Conservation Versus Mastectomy

• For most women, breast conservation therapy is as
  good as mastectomy
• Contraindications remain
• Multicentric disease
• Inability to obtain negative margins
• Breast lesion and breast size
• Contraindication to radiation therapy
• Patients preference
• Compliance

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Evolving Treatment ParadigmsThe Sentinel Node
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Sentinel Lymph Node Biopsy (SLNB)

• Definition
• gate-keeper or first echelon node to drain a
  tumor, i.e. primary breast cancer
• Focuses on
• Identify node-negative patients
• avoid unnecessary node dissection
• Identify node-positive patients
• Complete node dissection
• Systemic therapy
• XRT

34
Identifying the Sentinel Node

• Injection material
• Technetium-99m sulfur colloid
• Isosulfan blue
• Site of injection
• Intra-tumoral
• Intra-parenchymal
• Intra-dermal/peri-areolar
• Embryological axilla
• May miss internal mammary nodes

35
Potential Benefits

• Risk reduction for lymphedema
• Group 1 117 patients SLNB and node dissection
• Group 2 303 patients SLNB without node
  dissection
• Lymphedema 17.1 versus 3 (plt0.0001)
• Sener, Cancer, 2001
• Higher degree of scrutiny of SLN by pathologists
• Cursory examination of 10 to 25 nodes
• Extensive evaluation of a few nodes
• Application of molecular techniques

36
Potential Risks

• Risk of not finding the sentinel node 5
• In clinical trials after training
• Higher in early part of learning curve
• FALSE negative rate (FNS) 5 to 10
• Technical error
• Injection site
• Type of contrast used
• Learning curve
• Alternate lymphatic drainage

37
Risks of False Negative SLN

• Implications for the patients
• Leaving behind nodal disease
• Local-regional recurrence
• Systemic implications
• Understaging of disease will lead to
  under-treatment
• Small tumor, node-negative disease
• Impacts choice of adjuvant
• Chemo regimen
• Postoperative axillary XRT

38
False Negative SLN

• To reduce the number of missed node-positive
  patients
• Select patients with less likelihood of
  node-positive disease
• Practical application based on 1,000 patients
• FNR 5
• Applied to a 10 node-positive risk group
• You will miss 5 node-positive patients
• Applied to a 40 node-positive risk group
• You will miss 20 node-positive patients

39
Critical Issues with SLN Biopsy

• Technical competence
• Learning curve
• Mapping accuracy
• Blue dye plus Tc-sulfur colloid
• Maintain quality control
• False negative rate must be 5 or less
• Validated by performing completion ALND in the
  initial experience
• Surveillance of patients for cancer recurrence

40
Critical Issues with SLN Biopsy

• NO SURVIVAL DATA
• NSABP trial
• ACOSOG Z00010 and Z00011
• Await cancer cooperative groups results
• Importance of Informed Consent

41
Is SLNB Safe?

• Prospective, randomized trial in Milan
• Over 250 patients in each arm
• SLNB with completion ALND versus SLNB alone (if
  SLNB is negative)
• In the SLNB followed by ALND
• Accuracy 96.9
• False negative rate 8.8
• SLNB alone group (median follow-up 46 months)
• No overt axillary metastasis
• No difference in rate of cancer events
• 16.4 per 1,000 per year in ALND
• 10.1 per 1,000 per year in SLNB

Veronesi, et al., NEJM, 2003.
42
Take Home Message

• ALND remains the gold standard
• Quality control
• Careful patient selection for SLNB alone
• T1 and small T2 lesion
• Unicentric lesion
• Avoid patients with excisional breast biopsy gt 6
  cm
• Avoid patients treated with neoadjuvant therapy
• Avoid patients with previous axilla surgery
• Avoid patients with gross nodal disease
• Anderson, JNCCN, 2003.

43
Evolving Treatment Paradigms Adjuvant Radiation
Therapy

• Accelerated Partial Breast Irradiation (APBI)
• Postmastectomy radiotherapy (PMRT)

44
Postoperative XRT after BCT

• External Beam Radiation Therapy (EBRT)
• Whole breast therapy
• Daily treatment for 5 to 6 weeks
• Total dosage 5000 cGy
• Compliance issue
• Non-compliance 50
• Local failure 50
• Li, Ann Surg, 1999

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Accelerated Partial Breast Irradiation (APBI)

• Limit the volume of breast to be treated
• Within 2 cm border of lumpectomy
• XRT completed in 4 to 5 days after lumpectomy
• Multicatheter interstitial brachytherapy
• Balloon catheter brachytherapy (MammoSite)
• 3-D conformal external beam radiotherapy
• Intraoperative radiotherapy

46
Summary of APBI Results

• Multicatheter interstitial brachytherapy
• Longest follow-up (median FU 27 to 91 months)
• 5 yr local recurrence (LR) rate 5 (0 to 37)
• Balloon catheter brachytherapy (MammoSite)
• LR rate 0 (F/U11 to 29 months)
• Infection rate 16
• 3-D conformal external beam radiotherapy
• LR rate 0 to 25
• Arthur, et al., J Clin Oncol 231726, 2005.

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Clinical Trial NSABP B39

• Partial breast irradiation trial
• Tumor size lt 3 cm
• Unifocal tumor
• After lumpectomy, randomized to
• External beam radiation (EBRT)
• Partial breast irradiation (PBI)
• MammoSite
• Intracavitary catheters
• 3-D conformal EBRT

48
Take Home Message

• The role of APBI is evolving
• This is NOT the standard of care
• Must be considered in the context of
• Clinical trial
• Careful patient selection
• Informed consent

49
Radiotherapy After Mastectomy

• Pre-1997 NOT indicated except for
• Positive margins
• High risk for local failure
• Locally advance breast cancer
• Inflammatory breast cancer
• Post-1997
• Overgaard, et al., NEJM 337949, 1997.
• Danish Breast Cancer Cooperative Group
• Ragaz, et al., NEJM 337956, 1997.
• British Columbia
• Postmastectomy radiotherapy became relevant

50
Postmastectomy Radiotherapy (PMRT)

• ASCO Expert Panel
• Reviewed data from 18 randomized clinical trials
  (RCTs)
• Reduction in risk for local failure (LF)
• By two thirds to three quarters, proportionally
• In practical terms
• Reduction of LF from 8 per 100 patients
• To 2-3 per 100 patients

Recht, et al., J Clin Oncol19(5)1539, 2001
51
Controversies with PMRT

• Sparked debates regarding routine use of PMRT
• Complications of XRT include
• Lymphedema
• Brachial plexopathy
• Radiation pneumonitis
• Rib fractures
• Cardiac toxicity
• Radiation-induced 2nd primaries

52
ASCO Expert Panel

• Specific review of the British Columbia and
  Danish trials
• First to report improvement in DFS and OS
• Relative reduction in risk for death
• Danish trial 29
• British Columbia Trial 26

53
Controversies with PMRT

• Limitations of the Danish and BC trials
• No other trials demonstrating similarly
  significant benefits
• Benefits only apparent after 12 years of
  follow-up
• Number of nodes recovered after mastectomy were
  low

54
Take Home Message

• ASCO Guidelines for PMRT
• Patients with 4 or more positive nodes
• Patients with T3 or Stage III Disease
• Insufficient data to PMRT
• Patients with 1 to 3 positive nodes
• All patients treated with neoadjuvant therapy and
  mastectomy
• Other tumor characteristics
• HER2, ER, vascular and lymphatic invasion, etc
• Recht, et al., J Clin Oncol19(5)1539, 2001

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Advances in Systemic Adjuvant Therapy
Chemotherapy and Endocrine Therapy
56
Adjuvant Chemotherapy

• Treatment of patients at risk for disease
  dissemination prior to the diagnosis and
  initiation of therapy of the primary cancer
• Goal
• Reduce risk for recurrence and death
• Only helps those who recur
• May harm those that do not

57
After 200 RCTs -

• Combination therapy is superior to single agents
• 4 to 6 months produced optimal results
• Longer treatment with the same regimen did NOT
  provide incremental gains
• Hormone receptor-positive patients benefit from
  sequential chemotherapy plus endocrine therapy
• Additive therapeutic effect

58
What have we learned?

• Standard regimens are CMF and CAF
• Anthracycline (e.g. Adriamycin) containing
  regimens are superior to those that lacks it
• High dose therapy did not improve overall
  survival
• Increased morbidity and mortality
• Hamilton, et al., J Clin Oncol 231760, 2005.

59
Taxanes

• 1st Trial CALGB 9344 AC placlitaxel(T)
• 3,121 node-positive patients
• Median follow-up of 69 months
• 5 yr DFS 70 v 65, p0.0023
• 5 yr OS 80 v 77, p0.0064
• Henderson, et al., J Clin Oncol 21976, 2003

60
Supporting Data

• NSABP B28 Trial
• 3,060 node-positive patients
• AC X4 T X4
• Relative risk for recurrence reduced by 13
• Mamounas, et al., Proc ASCO 224, 2003.
• MDACC 94-002
• 524 patients
• T X4 FAC X4 v FAC X8
• Relative risk for recurrence reduced by 22
• Buzdar, et al., Clin Cancer Res 81073, 2002.

61
Docetaxel (Taxotere) Trial

• BCIRG 001 Trial
• 1,491 node-positive patients
• TAC X6 v FAC X6
• 5 yr outcome
• DFS 75 v 68
• OS 87 v 81
• Increased morbidity
• Febrile neutropenia 10X control arm
• Neurotoxicity
• Nabholz, et al., Proc ASCO 2136, 2002

62
Dose-dense Regimen

• Theoretical premise
• Full doses of drug, given at the highest
  possible frequency, will produce the highest
  degree of cell kill
• CALGB 9741
• 2,005 node-positive patients
• 2 X 2 factorial design
• A T C every 3 weeks
• A T C every 2 weeks G-CSF
• AC T every 3 weeks
• AC T every 2 weeks G-CSF

63
CALGB 9741

• Median follow-up of 36 months
• Dose dense regimen
• 4 yr DFS 82 v 75
• Significant OS in favor of dose-dense arm
• Low rate of neutropenic fever and cardiac
  toxicity
• Increased rate of anemia
• Citron, et al., J Clin Oncol 211431,2003.

64
Neoadjuvant Chemotherapy

• NSABP B-18 pre- versus post-operative adjuvant
  therapy
• 1,523 women
• operable breast cancer
• AC X 4 pre v post
• No survival benefit

65
Advantages

• Higher rate of breast conservation
• Convert some inoperable breast cancer to
  potentially curative surgical candidates
• Response in real time
• Lack of response change regimen
• Prognosis can be refined by degree of residual
  disease
• Pathologic clinical response had much higher DFS
  and OS
• Wolmark, et al., JNCI 3096, 2001.

66
Take Home Message

• Node-positive breast cancer patients with high
  likelihood of a long life span should be offered
  taxane systemic therapy in addition to
  anthracycline-based chemotherapy
• Dose-dense regimen may play a more significant
  role in chemotherapy administration in the near
  future
• Neoadjuvant therapy should be considered for late
  stage disease and/or for larger lesions in women
  who are to be considered for BCT

67
Endocrine Therapy

• Gold Standard Tamoxifen (Nolvadex)
• Anti-estrogen receptor
• 5 years treatment of ER/PR breast cancer
• Relative risk reduction of 25
• Node-positive 10 improvement in 10-yr survival
• Node-negative 5 improvement in 10-yr survival
• Lower toxicity profile compared to chemotherapy

68
Aromatase Inhibitors (AIs)

• Conversion of androgenic substrates to estradiol
• Enzyme complex - aromatase
• Highly expressed in ovarian follicles in
  premenopausal women
• AIs blocks aromatase activity
• Postmenopausal women
• Residual estrogen production by peripheral
  conversion
• Subcutaneous fat, liver, muscle
• AIs suppress circulating estrogen by 98

69
AIs and Breast Cancer

• Estrogen and receptor positive breast carcinoma
• Tamoxifen binds estrogen receptors and exerts
  anti-estrogenic effect
• AIs block peripheral estrogen conversion in
  postmenopausal women
• Reduction in estrogen results in cancer growth
  inhibition
• AIs have minimal effect on breast cancer in
  premenopausal women in clinical trials

70
AIs in the Adjuvant Setting

• ATAC Trial
• Arimidex, Tamoxifen, Alone or in Combination
• 9,366 postmenopausal patients
• After median follow-up of 47 months
• Risk for recurrence
• Hazard Ratio of patients on AI 0.86 that of
  Tamoxifen (p0.03)
• Risk for 2nd primary in contralateral breast
• Hazard Ratio of patients on AI 0.56 that of
  Tamoxifen (p0.04)
• Combination of Arimidex and Tamoxifen did not
  appear to be superior
• No overall survival difference to date

71
Adverse Effects AIs v Tamoxifen

• Lower incidence
• Hot flashes
• Vaginal bleeding and discharge
• Venous thromboembolism
• Endometrial cancer
• Higher risk for
• Musculoskeletal symptoms
• Fractures associated with osteoporosis
• ATAC Trialists Group Lancet 3592313, 2002.
• Baum, et al., Cancer 981802, 2003.

72
Use of AIs Beyond Year 5

• ER patients treated with tamoxifen fail between
  5 to 15 years after surgery
• Tamoxifen therapy beyond 5 yrs NOT useful
• Question
• Does adding AI to beast cancer patients after 5
  years of Tamoxifen therapy help?

73
MA.17 Trial

• 5,187 women after 4.5 to 6 yrs of Tamoxifen
• Randomized to placebo v letrozole (Femera)
• Median follow-up of 2.4 yrs
• Trial terminated
• DFS 93 v 87, plt0.001
• HR for recurrence 0.57 (p0.00008)
• Extending endocrine therapy beyond 5 yrs with an
  AI offers significant DFS benefit
• Goss, et al., NEJM 3491793, 2003.

74
Clinical Trial ACoSOG Z1031

• Stage II and III breast cancer patients
• Neoadjuvant hormonal manipulation trial comparing
  the 3 aromatase inhibitors
• Anastrozole
• Letrozole
• Exemestane
• Estrogen receptor positive
• Postmenopausal women
• Endpoints
• Response
• Toxicity profile

75
Take Home Message

• In postmenopausal women, AIs appears to be
  superior to Tamoxifen
• Reducing/delaying cancer recurrence
• Lowering contralateral second primary cancer
• Slightly better adverse effects profile except
  for osteoporosis
• Should be considered for women having
  difficulties with Tamoxifen
• Should be considered in addition to 5 years of
  Tamoxifen

76
Breast Cancer Screening
77
Breast Cancer Screening

• General population guideline
• Age 50 and above
• Breast examination
• Annually by healthcare professional
• Monthly breast self examination
• Annual mammogram
• Age 40 to 49
• Guidelines based on risk assessment
• More controversial
• More false positives
• More procedures
• Higher risk for interval cancer

78
Cancer Screening in Young Women

• Controversies
• High false positive rates
• 3 of 10 women will have a positive mammogram
• Unnecessary procedures and anxiety
• Non-invasive cancer (DCIS)
• No statistically significant difference in breast
  cancer mortality
• 0-10 lives in 10,000 screened from 40 - 49
• Canadian National Breast Cancer Screening Study,
  Can Med Assoc J, 1992
• Reserved for high risk women

79
NIH Consensus Panel

• Risk reduction in cancer death by breast cancer
  screening
• women over 50
• 33 risk reduction in death in the screened
  population
• NIH Consensus Statement, 1977
• women between 40 and 49
• 17 risk reduction in death in the screened
  population NIH Consensus Statement, 1997

80
Defining High Risk Patients

• What exactly is the relative risk when there is a
  family history of breast cancer?
• One family member with postmenopausal breast
  cancer
• 2-3 fold relative risk elevation
• high risk family
• Multiple 1st degree relatives
• Pre-menopausal breast cancer
• Bilateral breast cancer
• Male breast cancer
• Ovarian cancer

81
The BReast CAncer (BRCA) Genes

• 5 to 10 of breast cancer are hereditary
• BRCA1
• BRCA2
• 50 to 80 lifetime risk
• Tumor suppressor genes
• Involved in cell cycle control
• In addition to breast cancer
• BRCA1 mutation is associated with 50 risk for
  ovarian cancer
• BRCA2 mutation is associated with increased risk
  for male breast CA

82
BRCA Genes

• Who should be considered for BRCA testing?
• 2 first degree relatives
• One first degree relative
• Premenopausal
• Bilateral
• Ovarian cancer
• Multiple breast cancer, including male breast
  cancer
• Offered with complete genetic/social counseling

83
Other Risk Factors

• Personal history of breast cancer
• 10 to 15 lifetime risk for contralateral breast
  cancer
• Previous biopsy with the diagnosis of in situ
  carcinoma
• Lobular Carcinoma In Situ (LCIS)
• Ductal Carcinoma In Situ (DCIS)
• Proliferative breast disease
• Without atypia
• With atypia
• Estrogen
• Unopposed stimulation versus prolonged exposure
• Replacement therapy

84
Prophylatic Surgery for Breast Cancer

• Bilateral mastectomies
• 639 patients with family history of breast cancer
• 90 risk reduction
• Hartman, NEJM, 1999
• Women with BRCA1 or BRCA2 mutations
• 76 underwent prophylatic mastectomies
• 63 surveillance only
• At 3 years follow-up
• 0 patients with breast cancer in 76 treated with
  prophylatic mastectomies
• 8 patients with breast cancer in the surveillance
  group
• Meijers-Heiboer, NEJM, 2001

85
Prophylatic Surgery for Breast Cancer

• Prospective trial of 131 BRCA carriers
• 69 underwent prophylatic bilateral oophorectomies
• 3 developed breast cancer subsequently
• 62 patients were in the surveillance group
• 8 developed breast cancer
• Median follow-up of 2 years
• Kauff, NEJM, 2002

86
Chemoprevention

• NSABP BPCT-1
• 13,388 women randomized to receive tamoxifen
  versus placebo
• At median follow-up of 54 months
• 49 reduction of invasive breast cancer
• 50 reduction of non-invasive breast cancer
• Caveats
• No reduction in ER negative carcinomas
• Overall survival was not a measured outcome
• We Dont Know If The Breast Cancer Reduction
  Translates into Cancer Death Reduction
• Increased risk for
• endometrial cancer (RR 4 in agegt50)
• DVT (RR 1.7)
• PE (RR3.0)
• Fisher, JNCI, 1999

87
Summary - 1

• Management of the 3 most common clinical
  presentations for breast disease
• Nipple discharge
• Mastalgia
• Breast mass
• diagnostic imaging
• who to biopsy
• how to biopsy

88
Summary 2

• Treatment of breast cancer
• Local-regional control
• Surgery
• Modified Radical Mastectomy (MRM) versus Breast
  Conservation Therapy (BCT)
• Addressing nodal disease
• Axillary Lymph Node Dissection (ALND)
• Sentinel Lymph Node Biopsy (SLNB)
• Radiation therapy
• Whole breast irradiation versus Accelerated
  Partial Breast Irradiation (APBI)
• Postmastectomy Radiotherapy (PMRT)

89
Summary - 3

• Systemic adjuvant therapy
• Advances in chemotherapy
• Anthracycline-based therapy
• Taxanes
• Dose dense regimens
• Evolving paradigms in hormonal manipulation
• Estrogen receptor inhibition
• Tamoxifen
• Aromatase inhibitors
• Femara, Aromasin, Arimidex

90
Outline - 4

• Breast cancer screening
• Guidelines for screening
• NIH consensus statement women over 40
• Breast examination
• Risk Factors for breast cancer
• Family history
• BRCA genes
• Who should be tested
• Breast cancer risk reduction
• Surgical prophylaxis
• Tamoxifen

91
Questions ????