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Managing Breast Abnormalities in the Primary Care Practice PowerPoint PPT Presentation


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. Outline - 1. Clinical presentations of breast disease

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Managing breast abnormalities in the primary care practice l.jpg

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


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Outline - 1

  • Clinical presentations of breast disease

    • Nipple discharge

    • Mastalgia

    • Breast mass

      • diagnostic imaging

      • who to biopsy

      • how to biopsy


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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)


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Outline - 3

  • Systemic adjuvant therapy

    • Advances in chemotherapy

      • Taxanes

      • Dose dense regimens

    • Evolving paradigms in hormonal manipulation

      • Estrogen receptor inhibition

      • Aromatase inhibitors


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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


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Clinical Presentation

  • 3 most common breast complaints:

    • Mastalgia

    • NIPPLE DISCHARGE

    • MASS

  • >50% of patients presenting to surgeon with a breast condition will have benign disease

    Marchant, Surg Oncol Clinics of North America, 1998


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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)


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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


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Mastalgia

  • Mastalgia is a poor predictor for cancer risk

    • <5% of breast cancer are associated with pain

    • >95% of patients with some breast pain

    • Beware!

      • Though the association of breast pain and breast cancer is NOT strong, the fear is very REAL


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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


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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


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Nipple Discharge

  • Less than 5% chance of cancer

    Leis, World J Surgery, 1999

  • Differentiate between high versus low risk by history

    Higher riskLower risk

    Spontaneous versus provoked

    Unilateral versus bilateral

    Bloody/serous versus cloudy and/or multicolored

    Post- versus pre-menopasual


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Nipple Discharge

  • Physical examination

    • Is there a subareolar mass?

  • Types of imaging

    • Mammogram

    • Ultrasound

      • Duct ectasia

    • Ductogram

      • Intraductal defect


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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%)


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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


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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


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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


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Management of a Breast Mass

  • 2 categories of biopsy

    • Excisional

      • Removes the whole lesion

    • Incisional

      • Removes part of the lesion


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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


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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


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Treatment for Breast Cancer


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Breast Cancer Outcome

  • Incidence211,240

  • Death40,410

  • 5 yr survival

    197575%

    198678%

    200088%

    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


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Breast Cancer Therapy

  • Local-regional control

    • Surgery

    • Radiation therapy (XRT)

  • Systemic control

    • Chemotherapy

    • Hormonal manipulation


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Surgical Therapy for Breast Cancer“The 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


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Systemic Therapy

  • Adjuvant therapy based weighing

    • Risk of recurrence

    • Sequelae of therapy

  • Chemotherapy

    • Node-positive patients

    • Tumors >1 cm

    • Age/Menopausal status

    • Overall health of patient

  • Endocrine therapy

    • Receptor status (ER and PR)

      • Anti-estrogen

      • Aromatase inhibitors (AIs)


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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


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What to do with the lymph nodes?


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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


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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


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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

    • < 4 cm

    • Included node- positive and negative patients

  • Establishes the efficacy and safety for BCT

    Fisher, NEJM Oct., 2002


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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 Paradigms:The 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


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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


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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% (p<0.0001)

      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


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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


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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


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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


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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


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Critical Issues with SLN Biopsy

  • NO SURVIVAL DATA

    • NSABP trial

    • ACOSOG Z00010 and Z00011

      • Await cancer cooperative groups results

  • Importance of Informed Consent


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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.


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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 > 6 cm

    • Avoid patients treated with neoadjuvant therapy

    • Avoid patients with previous axilla surgery

    • Avoid patients with gross nodal disease

      Anderson, JNCCN, 2003.


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Evolving Treatment Paradigms: Adjuvant Radiation Therapy

  • Accelerated Partial Breast Irradiation (APBI)

  • Postmastectomy radiotherapy (PMRT)


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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


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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 23:1726, 2005.


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Clinical Trial – NSABP B39

  • Partial breast irradiation trial

  • Tumor size < 3 cm

  • Unifocal tumor

  • After lumpectomy, randomized to

    • External beam radiation (EBRT)

    • Partial breast irradiation (PBI)

      • MammoSite

      • Intracavitary catheters

      • 3-D conformal EBRT


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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


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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 337:949, 1997.

      • Danish Breast Cancer Cooperative Group

    • Ragaz, et al., NEJM 337:956, 1997.

      • British Columbia

    • Postmastectomy radiotherapy became relevant


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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


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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


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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%


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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


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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


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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


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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


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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 23:1760, 2005.


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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%, p=0.0023

    • 5 yr OS:80% v 77%, p=0.0064

      Henderson, et al., J Clin Oncol 21:976, 2003


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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 22:4, 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 8:1073, 2002.


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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 21:36, 2002


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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

      • ATCevery 3 weeks

      • ATCevery 2 weeks + G-CSF

      • ACTevery 3 weeks

      • ACT every 2 weeks + G-CSF


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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 21:1431,2003.


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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


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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 30:96, 2001.


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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


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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


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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+%


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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


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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 (p=0.03)

    • Risk for 2nd primary in contralateral breast

      • Hazard Ratio of patients on AI = 0.56 that of Tamoxifen (p=0.04)

    • Combination of Arimidex and Tamoxifen did not appear to be superior

    • No overall survival difference to date


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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 359:2313, 2002.

      Baum, et al., Cancer 98:1802, 2003.


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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?


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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%, p<0.001

    • HR for recurrence 0.57 (p=0.00008)

  • Extending endocrine therapy beyond 5 yrs with an AI offers significant DFS benefit

    Goss, et al., NEJM 349:1793, 2003.


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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


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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


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Breast Cancer Screening


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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


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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


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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 populationNIH Consensus Statement, 1997


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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


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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


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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


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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


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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


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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


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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 Don’t Know If The Breast Cancer Reduction Translates into Cancer Death Reduction

      • Increased risk for

        • endometrial cancer (RR = 4 in age>50)

        • DVT (RR = 1.7)

        • PE (RR=3.0)

          Fisher, JNCI, 1999


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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


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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)


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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


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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


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Questions ????


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