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Breast Cancer

Seyed Morteza Mahmoodi
Contents

Breast Cancer
OVERVIEW
WORK UP
TREATMENT
PROGNOSIS
Contents

Breast Cancer
OVERVIEW
WORK UP
TREATMENT
PROGNOSIS
OVERVIEW

 Anatomy
 Histology
 Physiology
 Pathology
 Presentation
Lymphatics of the Mammary Gland
Superficial lymphatics
From the skin except nipple and areola
a.

Upper marginal >>apical ...
Deep lymphatics
From the parenchyma and glandular tissue
+ Skin of nipple and areola
•75% to axillary nodes- anterior or p...
a
b&c
Sternum

From retromammary space
a. Upper part >>Apical
group

d

b. Upper lateral
parts>>pectoral
c. Lower lateral>...
Hormones


Estrogen
►



Progesterone
►



Development of the breast and lactiferous ducts
Secretory acinar tissue – lo...
The female breast:

Normal breast anatomy & anatomical location of
common breast lesions
Breast – Neoplastic diseases:
 Benign:
 Fibroadenoma.
 Phyllodes tumor.
 Papilloma.

Stromal
tumors

 Malignant:
 Ca...
In situ (noninvasive ) carcinoma – Morphology:

C
In situ (noninvasive) carcinoma – Morphology:
In situ (noninvasive) carcinoma – Morphology:
In situ (noninvasive) carcinoma – Morphology:
Invasive (infiltrating) carcinoma – Morphology:

Invasive ductal carcinoma
Invasive (infiltrating) carcinoma – Morphology:

Invasive lobular carcinoma.Parallel arrays of single files
of small, poor...
Invasive (infiltrating) carcinoma – Morphology:

Colloid carcinoma.
Invasive (infiltrating) carcinoma – Morphology:

Medullary carcinoma with lymphoid infiltrates,
Invasive (infiltrating) carcinoma – Morphology:

Tubular carcinoma.
Syndrome
Breast/ovarian

Gene
BRCA1

Inheritance

Cancers

Other Features

AD*

Breast, ovarian

Cancer syndrome BRCA2

AD...
Li-Fraumeni Syndrome
► Mutation


of p53 gene

Tumor suppressor

► Premenopausal





breast CA

Childhood sarcoma
Br...
Cowden Syndrome
►

Major criteria







►

Thyroid CA (follicular)
Marcocephaly
Cerebellar tumors
Endometrial CA
Br...
Tumor Grade


Histologic grade
 Well differentiated, >75% tubule
 Moderately differentiated, 10-75% tubule formation
 ...
Presentation & Assessment
 Symptoms
Lump

80%

Painful lump or lumpiness
Pain
Nipple discharge
Nipple change
Miscellaneou...
Symptoms & possible diagnosis
1.Lump

Fibroadenoma
Juvenile
Fibroadenoma
Giant fibroadenoma
Phyllodes tumours
Cysts
Galact...
Charecterestics of nipple discharges
Contents

Breast Cancer
OVERVIEW
WORK UP
TREATMENT
PROGNOSIS
Laboratory Studies
Genetic and molecular testing
 Oncotype DX
 Serum markers

BRCA
BRCA (breast cancer) tumor suppressor
gene,
 breast cancer type susceptibility protein
 Chromosome 17,
 Chromosome...
BRCA
► Account

to 25% of early-onset breast Ca
► 36%-85% lifetime risk of breast CA
► 16-60% lifetime risk of ovarian CA
...
BRCA is it a Screening tool
or a Prognostic tool?
Screening (Significant FH)
2 or more first-degree relatives
 2 or more second-degree relatives (on the
same side of the f...
BRCAPRO is a statistical model, with
associated software, for assessing the
probability that an individual carries a
germl...
BRCA +
► Management




Monthly BSE beginning18yo
6 mo CBE & annual mammo beginning 25yo
Discuss risk reducing options
...
Prognostic
Breast cancer age less than 40 years
 Males with breast cancer
 Two or more cancers

BRCA1
Has a medullary histology
 "triple negative"
 high nuclear grade
 Has a higher rate of proliferation
 Overexpres...
Hormone Receptor (HR) status


ER +
Indicator of growth not metastatic potential
 More likely to be well differentiated ...
Breast, adenocarcinoma, immunohistochemical stain for estrogen
receptor - Low and medium power
Antibodies used to stain a ...
Does ER- patients benefit from
tamoxifen?
Since tamoxifen can potentially affect
cellular functions by binding to calmodulin
or inhibiting protein kinase C , it has...
New prognostic factors


HER-2/neu receptor status







+ relatively resistant to adjuvant endocrine
therapy
+ tumo...
Breast cancer, immunohistochemical stain for HER2/neu High power

Immunohistochemical detection of HER2 protein expression...
Molecular changes associated with breast cancer progression



Increased expression of
oncogenes




c-erb-B2, her2/neu...
Oncotype DX recurrence score


21 gene expression used to predict recurrence in early
stage invasive breast cancer




...
Hybridization signals are detected using a confocal laser scanner and downloaded to a computer
for analysis (red squares, ...
Serum Markers


CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen
(CEA), tissue polypeptide antigen, tissue polypepti...
Mammography
Mammography
Symmetry
 Size
 General density
 Glandular distribution
 Masses, densities, calcifications,
architectural ...
BI-RADS
BI-RADS
Classification

Features

0
1
2
3
4

Need additional imaging
Negative – routine in 1 yr
Benign finding – r...
Screening
► American

Cancer Society recommends
annual mammography and examination by
a physician beginning at age 40 year...
Calcification















Malignant
Greater density
Irregular and (usually) spiculated margins
small (<0....
Ultrasound
►
►
►
►
►
►
►
►
►

Not a screening tool
Palpable vs cystic
Mammographic detected lesion
Mammography has limitat...
Ultrasound
► Malignant





Hypoechoic, spiculated
Taller than wide
Duct extension
microlobulation

► Benign





...
MRI
►

►
►
►

High risk patients
 Personal history of breast ca
 LCIS, atypia
 1st degree relative with breast cancer
...
Digital Breast Tomosynthesis
Scintimammography
CT laser mammography (CTLM)
Positron Emission Mammography
Thermography
Diagnosis
► Fine


Cytology

► Core



needle aspiration
biopsy

Image guided
Stereotactic

► Excisional


biopsy

Nee...
Excisional Biopsy
► Atypical

lesions

► LCIS
► Atypical

papillary lesions
► Radiologic-pathologic discordance
► Inadequa...
Vacuum Assisted Biopsy
Sentinel Lymph Node Biopsy
How to assess axillary LN metastasis?
 Reports suggest that the sentinel lymph
node has a high...
lymphoscintography
Staging
AJCC
 Primary tumor = T











Tx - Primary tumor cannot be assessed
T0 - No evidence of primary tumo...
Staging
Regional lymph nodes N
 Nx - cannot be assessed
 N0 - No regional lymph node metastases
 N1 - Metastases to ips...
Staging
Distant metastases = M
 Mx - Cannot be assessed
 M0 - No metastases
 M1 - Distant metastases, including
ipsilat...
Stage

Primary tumor size (T)

Lymph node
involvement (N)

Metastatic disease (M)

0

Tis

N0

M0

1

T1

N0

M0

2a

T0

...
Stage 1

Tumor size less than 2 cm
Stage 2

2-5 cm with N1 or N0
More than 5cm but N0
Less than 2 cm or T0 but no more
than N3
Stage 3

Larger than 5 cm with any N
Less than 5 cm with nodal matting
Less than 5 cm with supraclavicular
LN involvement
Stage 3

Inflammatory breast
Stage 4

Metastatic breast cancer
Contents

Breast Cancer
OVERVIEW
WORK UP
TREATMENT
PROGNOSIS
Case 1


An annual screening mammogram in a 55year-old nurse administrator revealed
suspicious microcalcifications. The p...
What are reasonable options to reduce this
patient's risk of developing invasive breast
cancer?
 Re-excise the lesion unt...
Case 2








RG, a 77-year-old, white, former schoolteacher, presents
with a palpable mass in the right breast and 1...
Case Cont.










What would you recommend as the initial
management approach for this patient?
Neoadjuvant chemot...
Medical Therapy







Chemoprevention
Selective estrogen receptor modulators (SERM)
(tamoxifen)
Aromatase inhibitor...
Chemoprevention








Tamoxifen use for 5 years reduces risk for at least 10 years in
premenopausal women, particula...
Adjuvant Rx
► All

tumors > 1cm
► All postmenopausal women with positive
LN
► Postmenopausal women with lesion
greater tha...
Adjuvant Hormonal Rx
► All

premenopausal women with tumor >
1cm
► All postmenopausal unless a
contraindication
Adjuvant Radiation Rx
► All

pts. With conservative Rx
► When > 4 LN, radiation to axilla
Surgical Therapy










Ductal excision
Lumpectomy or wide local excision
Quadrantectomy
Completion Lymph Node...
Needle localization
Contraindications to Breast
Conservation
► Tumour

>5cm
► Larger tumor to breast ratio
► Two large tumours in two separate...
Lymph Node Dissection
Patey modified radical
mastectomy
Complications
Seromas most frequent complication 30%
 Closed-system suction drainage <30 mL
per day
 Wound infections sk...
LCIS
LCIS chemoprevention with tamoxifen,
 Bilateral total mastectomy
 No benefit to excise LCIS

DCIS
DCIS and evidence of extensive disease
(>4 cm of disease or disease in more than
one quadrant) mastectomy
 Limited d...
Early Invasive Breast Cancer (I, II)
Mastectomy with axillary lymph node
status and
 Breast conserving surgery with axill...
Advanced Local-Regional Breast
Cancer (III)
Neoadjuvant chemotherapy for all
 Modified radical mastectomy,
 Adjuvant rad...
Distant Metastases (IV)
Hormonal therapies are preferred
 Systemic chemotherapy
 Role of Surgery is under investigation
...
Local-Regional Recurrence
Mastectomy vs. Lumpectomy
 Surgical resection of the local-regional
recurrence
 Chemotherapy a...
BSO
BSO has been used to reduce the risk for
breast cancer, as well as to decrease the
risk for ovarian cancers in women w...
Prophylactic Mastectomy






To date, PM as well as the use of CPM in breast
cancer patients have yet to show a decisi...
Contents

Breast Cancer
OVERVIEW
WORK UP
TREATMENT
PROGNOSIS
Prognosis
Biological, and independent patient factors
 Genetic predisposition
 Tumor size
 receptor status
 Axillary n...
Prognosis
5-year survival rates for women in the
United States have improved to 98% for
disease localized to the breast
 ...
Male Breast Cancer
Rare disease, accounting for ∼1% of all
breast cancer cases
 Similar to breast cancer in females in it...
Breast Cancer Awareness Month
October 2010
THANK YOU
Contents
Acute Lymphoblastic
Leukemia
INTRODUCTION
CLASSIFICATION
EITIOLOGY
CLINICAL
PRESENTATION
DIAGNOSIS
TREATMENT
Contents
Acute Lymphoblastic
Leukemia
INTRODUCTION
CLASSIFICATION
EITIOLOGY
CLINICAL
PRESENTATION
DIAGNOSIS
TREATMENT
Awareness Ribbons 
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  • Extends(surface anatomy)
    Above to 2nd rib
    Below to 6th rib
    Medially to lateral sternal line
    Laterally to mid axillary line.
    Axillary tail of Spence is a part of the gland extending into the axilla.
    Passes through a foramen of Langer in the deep fascia(axillary).
    In relation to pectoral(anterior) group of lymph nodes.
    Sometimes confused for a tumor.
    Medial 2/3rd on fascia over P.major
    Lateral 1/3rd over S.Anterior.
    Below over external oblique and its aponeurosis.
  • The breast is bounded by the clavicle superiorly, the sternum medially, the lateral border of the latissimus muscle laterally, and the inframammary fold inferiorly. The axillary tail of Spence extends into the deep fascia superior and lateral to the breast. The deep pectoral fascia defines the deep margin.
    Fibrous bands, known as the suspensory ligaments of Cooper, divide the breast parenchyma into 12-20 separate lobules of glandular tissue. Separate branching lactiferous ducts drain each lobule. These ducts converge just beneath the nipple into sinuses that empty into a single terminal duct. Drainage from individual ducts can be localized for surgical excision.
    The lateral pectoral nerve passes medially around the medial pectoralis minor, and the medial pectoral nerve passes laterally around the pectoralis minor. The names are based on the origin of the nerves from the lateral and medial cords of the brachial plexus rather than their orientation to the muscle. Injuries to these nerves are rare.
    Injury to the brachial plexus can be avoided by keeping the superior extent of the axillary dissection inferior to the lower border of the axillary vein.
    The thoracodorsal nerve is identifiable medial to the thoracodorsal vein running along to enter the latissimus dorsi. Injury may result in slight, if any, clinically evident weakening of the latissimus.
    The long thoracic nerve is located more medially in the axilla. It runs just beneath the investing fascia of the serratus anterior, medial to the thoracodorsal complex. Injury to this nerve results in winging of the scapula on arm extension.
    The skin of the axilla and upper arm is supplied by the intercostobrachial nerve, which often is sacrificed in the dissection of axillary nodes. Transection may result in numbness in these areas.
  • Branches of axillary artery—
    sup. Thoracic A; lateral thoracic A and thoraco acromial A
    Branches of internal thoracic A-perforating arteries of 2nd-4th intercostal spaces
    Anterior intercostal arteries
    Lateral branches of posterior intercostal arteries of 2nd-4th spaces.
    All these enter the anterior surface of the gland –so posterior surface is relatively avascular and is called “Lake of Marcelli”
  • Venous drainage
    Run towards the base of the nipple to form circulus venosus
    End in the internal thoracic and axillary veins.
    Posterior intercostal veins may connect with the vertebral venous plexus.
  • Surgical classification
    The surgical classification is used in axillary dissection for breast cancer. It is entirely based on the relationship of the lymph nodes to pectoralis minor. The levels usually refer to a dissection, so a &apos;level 3 dissection&apos; will have removed nodes from levels 1, 2 and 3.
    Level 1 nodes
    Level 1 includes all those nodes inferior to the inferolateral border of pectoralis minor. It is usually comprised of the lateral, anterior and posterior nodes.
    Level 2 nodes
    Level 2 consists of those nodes posterior to pectoralis minor. It includes the central nodes and some of the apical nodes.
    Level 3 nodes
    Level 3 consists of those nodes beyond the superior border of pectoralis minor. It includes the remaining apical nodes and infraclavicular nodes.
    Sentinel node
    A sentinel node is the first node to drain from a particular area. In breast cancer, it refers to the first node to drain from that portion of the breast. This is usually an anterior node.
    Axillary lymph nodes receive most mammary lymphatic drainage. The internal mammary nodes also receive some drainage medially. Axillary nodes are referred to by levels, which are defined by the pectoralis minor muscle. Level I nodes are lateral, II behind, and III medial to the muscle.
  • Surgical classification
    The surgical classification is used in axillary dissection for breast cancer. It is entirely based on the relationship of the lymph nodes to pectoralis minor. The levels usually refer to a dissection, so a &apos;level 3 dissection&apos; will have removed nodes from levels 1, 2 and 3.
    Level 1 nodes
    Level 1 includes all those nodes inferior to the inferolateral border of pectoralis minor. It is usually comprised of the lateral, anterior and posterior nodes.
    Level 2 nodes
    Level 2 consists of those nodes posterior to pectoralis minor. It includes the central nodes and some of the apical nodes.
    Level 3 nodes
    Level 3 consists of those nodes beyond the superior border of pectoralis minor. It includes the remaining apical nodes and infraclavicular nodes.
    Sentinel node
    A sentinel node is the first node to drain from a particular area. In breast cancer, it refers to the first node to drain from that portion of the breast. This is usually an anterior node.
  • A mature breast is composed of three principal tissue types: (1) glandular epithelium, (2) fibrous stroma and supporting structures, and (3) fat. Infiltrating cells, including lymphocytes and macrophages, are also found within the breast.
    In youth, the predominant tissues are epithelium and stroma, which may be replaced by fat in postmenopausal women as they age. However, there is great variability among individual women of any age. Mammography in women younger than 30 years, whose breast tissue is dense with stroma and epithelium, may produce an image without much definition. Fat absorbs relatively little radiation and provides a contrasting background that favors detection of small lesions in older patients. Throughout the fat of the breast, coursing from the overlying skin to the underlying deep fascia, strands of dense connective tissue called Cooper&apos;s ligaments provide shape to the breast. Because they are anchored into the skin, tethering of these ligaments by a small scirrhous (scarring) carcinoma commonly produces a dimple or subtle deformity on the otherwise smooth surface of the breast.
    The glandular apparatus of the breast is composed of a branching system of ducts, roughly organized in a radial pattern spreading outward and downward from the nipple-areolar complex (see Fig. 34-1 ). It is possible to cannulate individual ducts and visualize the lactiferous ducts with contrast agents. Figure 34-3 shows such an image and demonstrates the arborizing tree of branching ducts, which end in terminal lobules. The contrast dye opacifies only a single ductal system and does not enter adjacent and intertwined branches from functionally independent ductal trees. At the summit of the arborizing ductal system, the subareolar ducts widen to form the lactiferous sinuses, which then exit through 10 to 15 orifices on the nipple. These large ducts close to the nipple are lined with a low columnar or cuboidal epithelium that abruptly meets the squamous epithelium of the nipple surface and invades the duct for a short distance.
  • In situ (Non invasive carcinoma):
    A: Gross appearance of comedo carcinoma showing typical white necrotic centres.
    B&amp;C: Comedo carcinoma showing intraductal proliferation of malignant cells with central necrosis and calcifications
  • Noncomedo DCIS:
    Cribriform DCIS with low grade nuclei the cells are forming round, regular (cookie cutter) spaces. The lumens are often filled with calcifying secretory material.
    Solid DCIS almost completely filled and distorted this lobule with only a few remaining luminal cells visible. This type of DCIS is not usually associated with calcifications.
  • Noncomedo DCIS:
    A: Papillary DCIS; delicate fibrovascular cores extend into a duct and are lined by a monographic population of tall columnar cells. Myoepithelial cells are absent.
    B: Micropapillary DCIS; the papillae are connected to the duct wall by a narrow base and often have bulbous or complex outgrowths. The papillae are solid &amp; do not have fibrovascular cores.
  • Lobular carcinoma in situ (LCIS):
    A monomorphic population of small, rounded, loosely cohesive cells fills and expands the acini of a lobule. The underlying lobular architecture can still be recognized.
    The cells never form a mass and calcification is uncommon.
    N.B.: The abnormal cells of ALH, LCIS, and invasive lobular CA are identical &amp; consist of small cells that have oval or round nuclei with small nucleoli. Signet- ring cells containing mucin are commonly present.
    LCIS almost always express ER &amp; PR while overexpression of HER2/neu is not observed.
  • Note the lakes of lightly staining mucin with small islands of tumor cells
  • Note lymphocytes infiltrating sheets of high grade tumor cells
  • Note the well-formed tubules lined by a single layer of cells with apocrine snouts
  • Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease.
  • Genetic testing for BRCA1 and BRCA2 can be performed in selected patients with a strong family history of breast or ovarian carcinoma. However, genetic counseling and discussion of subsequent management and treatment options should be performed prior to testing. The criteria for referral for genetic counseling and testing of high-risk individuals include the following:
    Any patient diagnosed with breast cancer who is aged less than 40 years
    Males with breast cancer, especially if they are of Jewish ancestry
    Any patient with 2 or more first-degree relatives, or 2 or more second-degree relatives (on the same side of the family) who meet any of the following conditions:
    Breast cancer diagnosed at in patient aged less than 50 years
    Breast and ovarian cancer in the same bloodline or in the same individual
    Male relative diagnosed with breast cancer when aged less than 50 years
    Family members with bilateral breast cancer
    According to the American Society of Clinical Oncology, serum markers that may be used in the workup for breast cancer include carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, and CA 27.29. These are not recommended routinely, and indications for their use have not been standardized.
    However, once a diagnosis of breast cancer has been made, additional testing may be performed to determine a patient&apos;s likelihood of response to chemotherapy. Specifically, the Oncotype DX assay is a 21-gene assay first announced in 2003 by NSABP researchers.5 The Oncotype DX provides a score that predicts the likelihood of distant recurrence in a select group of patients who have node-negative and estrogen-receptor–positive breast cancer. Resulting scores may assist in determining the potential benefit or necessity of chemotherapy in these patients.
  • BRCA1 gene copy number and protein expression analysis on breast tumor section. Tumor cells in a BRCA1 methylated sample are seen to have reduced BRCA1 gene copy numbers (red signal) compared with centromere 17 (green signal) by FISH.
  • History
    PE
    Screeeninig
    Biopsy
    Previous history
  • or has a high rate of estrogen-receptor (ER) negativity, progesterone-receptor negativity, and Her2/neu negativity
    Management of BRCA + breast cancer
  • Selected Targeted Anticancer Therapies Using Small Molecules
    Hormonal Therapy for Breast Cancer
    Arguably the first type of targeted therapy in oncology (Table 4) was the development of antiestrogen therapies for patients with breast cancer that expressed the estrogen receptor (ER) protein.[87] Originally developed as a competitive dextran-coated charcoal (DCC) radioligand binding assay performed on fresh tumor protein extracts and used to select patients for ablative endocrine surgery, the ER and progesterone receptor (PR) test format converted to an immunohistochemical platform when the decreased size of primary tumors associated with mass screening programs yielded insufficient tumor tissue for the DCC assay.[88]
    ER and PR testing has guided the use of the drug tamoxifen (Nolvadex), the most widely prescribed antiestrogen for the treatment of metastatic breast cancer and for chemoprevention of the disease in high-risk women.[89,90] Although ER and PR testing is the front line for predicting tamoxifen response, additional biomarkers have been used to further refine therapy selection.[91] The introduction of specific estrogen response modulators and aromatase inhibitors such as anastrozole (Arimidex), letrozole (Femara), and the combination chemotherapeutic, exemestane (Emcyt)[92-96] have added new strategies for evaluating tumors for hormonal therapy.
  • How to determine the ER status in non-breast cancer patients?
    Does it have a screening role?
  • Trastuzumab (Herceptin)
    During the mid 1980s, the discovery of the HER-2/neu (c-erb-B2) gene and protein and subsequent association with an adverse outcome in breast cancer provided clinicians with a new biomarker that could be used to guide adjuvant chemotherapy.[51] The development of trastuzumab (Herceptin), a humanized monoclonal antibody designed to treat advanced metastatic breast cancer in which first- and second-line chemotherapy had failed, caused rapid, wide adoption of HER-2/neu testing of the patients&apos; primary tumors.[52] Since its launch in 1998, trastuzumab has become an important therapeutic option for patients with HER-2/neu-positive breast cancer.[53-56]
    Reports that fluorescence in situ hybridization (FISH) could outperform immunohistochemical analysis in predicting trastuzumab response[23] and the well-documented lower response rates of tumors staining immunohistochemically as intermediate (2+) vs intense (3+)[57] has resulted in a variety of approaches for patient testing (Figure 1), including immunohistochemical analysis as a primary screen with follow-up FISH testing of 1+ cases, 2+ cases, or both, or primary FISH-based testing. Trastuzumab has achieved notable results in the treatment of HER-2/neu-positive advanced metastatic disease and is under extensive evaluation in major clinical trials for its potential efficacy when used in earlier stages of breast cancer.
    Figure 1. HER-2/neu testing in breast cancer. A, Immunohistochemical analysis using the HercepTest system (DAKO, Carpinteria, CA) with continuous membranous 3+ positive immunostaining for HER-2/neu protein (×400). B, HER-2/neu gene amplification detected by fluorescence in situ hybridization (PathVysion, Vysis, Downers Grove, IL). Note individual signals and clusters of red signals indicating the presence of numerous additional copies of the HER-2/neu gene against the 1 or 2 green chromosome 17 centromere signals (×1,000). (Image courtesy of Kenneth J. Bloom, MD.)
    Bevacizumab (Avastin)
    Bevacizumab (rhuMAb-VEGF) is a humanized murine monoclonal antibody targeting the vascular endothelial growth factor (VEGF). VEGF regulates vascular proliferation and permeability and functions as a survival factor for newly formed blood vessels.[65-67]
    In clinical trials for advanced metastatic breast cancer, the initial results of the combination treatment of bevacizumab and paclitaxel showed antitumor activity,[68] but the results of follow-up studies were not convincing that the targeting of VEGF in this clinical setting would be effective. Bevacizumab also has been combined with trastuzumab in a 2-antibody therapeutic strategy for HER-2/neu-overexpressing breast cancer.[69]
    The phase 2 study evaluating bevacizumab in metastatic renal cell carcinoma reached its prespecified efficacy endpoint earlier than expected. Although late-stage clinical trials using bevacizumab with 5-fluorouracil, leucovorin, and CPT-11 in third-line treatment for advanced colorectal cancer did not achieve all of the major endpoints,[70] when bevacizumab was used in first-line combination with 5-fluoruracil, a 5.5 month improvement in overall survival was observed.[71-73] These data led to the FDA approval of bevacizumab for the treatment of metastatic colorectal cancer in February 2004. Unlike cetuximab, the development of bevacizumab has not included a diagnostic eligibility test. To date, neither direct measurement of VEGF expression nor assessment of tumor microvessel density has been incorporated into the clinical trials or linked to the rates of response to this antibody.
  • Microarray technology provides simultaneous measurement of several thousands of genes or proteins
    Gene expression array profiling distinguishes distinct subtypes of cancer
    HER-2/neu (+)
    Two different types of ER+
    luminal A
    luminal B
    Basal-like breast cancer including BRCA1 mutation tumors (triple negative, poor outcome)
  • The main disadvantages of existing serum markers for breast cancer are a lack of sensitivity for low-volume disease and a lack of specificity. Consequently, the available markers are of no value in either screening or diagnosing early breast cancer. Although of little use for early diagnosis, however, CA 15-3 may be the first independent circulating prognostic marker described for breast cancer. Preoperative CA 15-3 concentrations may thus be combined with established prognostic factors for use in deciding which lymph node-negative breast cancer patients should receive adjuvant chemotherapy. Currently, one of the most widely used applications of tumor markers in breast cancer is in the follow-up of patients with diagnosed disease. In the absence of data from a large randomized trial, however, the clinical value of this practice is unclear. Finally, markers are potentially useful in monitoring therapy in advanced disease, particularly in patients who cannot be assessed by standard modalities.
  • Mammography has become the standard tool for screening and initial evaluation of breast cancer. Multiple prospective randomized controlled trials have demonstrated that mammography can reduce the mortality from breast cancer in women aged 50-74 years. A great deal of controversy surrounds the use of mammography in younger women, particularly those aged 40-49 years. Currently, the American Cancer Society recommends annual mammography and examination by a physician beginning at age 40 years with no maximum upper age limit. Obviously, this should be taken with the caveat that patients who fall outside these guidelines need to be assessed individually.For instance, women younger than 40 years who have extensive family histories for breast cancer may benefit from beginning screening earlier. Conversely, older women with significant comorbidities, which may be prohibitive in the treatment of breast cancer, may not derive any benefit from mammography. In addition, the sensitivity of mammography is decreased significantly in young patients with dense breast tissue and possibly with augmentation prosthesis. Mammography seldom is recommended in patients younger than 30 years.
    The American College of Radiology established the standard for classification of radiographic abnormalities, known as the Breast Imaging Reporting and Data System (BI-RADS), as follows:
    0. Incomplete examination - Usually requiring further imaging or evaluation
    I. Normal - With follow-up study recommended in 1 year
    II. Benign - Follow-up study in 1 year
    III. Likely to be benign - Follow-up mammogram in 6 months
    IV. Suspicious - Consider biopsy
    V. Highly suspicious for malignancy - Biopsy recommended
    In addition to evaluating parenchymal masses, mammography can be useful in evaluating the breast for calcifications, architectural distortion, skin thickening, nipple changes, and axillary adenopathy. Enlargement, stellate shape, irregular or spiculated margins, and the presence of pleomorphic calcifications less than 0.5 mm in a given lesion all are suggestive of malignancy.
  • The quality of the mammograms should be assessed, and if not optimal, repeat examinations may be ordered. Mammograms of the right and left breasts are first placed back to back (mirror images) for comparable projections. Lighting should be homogeneous, and adequate viewing conditions should be maintained. The mammograms are inspected carefully. The search is done systematically through similar areas in both breasts.
    First, breast symmetry, size, general density, and glandular distribution are observed. Next, a search for masses, densities, calcifications, architectural distortions, and associated findings is performed. For masses, the shape, margins, and density are analyzed. Malignant lesions tend to have irregular and (usually) spiculated margins. Malignancies, especially scirrhous cancers, also tend to have density greater than that of the normal breast tissue. Very low density, such as that of fat, is seen in benign lesions (eg, oil cyst, lipomas, galactoceles, hamartomas).
    Benign calcifications are usually larger than calcifications associated with malignancy. They are usually coarser, often round with smooth margins, and more easily seen. Benign calcifications tend to have specific shapes: eggshell calcifications in cyst walls, tramlike in arterial walls, popcorn type in fibroadenomas, large and rodlike with possible branching in ectatic ducts, and small calcifications with a lucent center in the skin.
    Calcifications associated with malignancy are usually small (&lt;0.5 mm) and often require the use of a magnifying glass to see them well. They tend to have a pleomorphic or heterogeneous shape or a fine granular, fine linear, or branching (casting) shape.
    The distribution of the calcification should be specified as grouped (clustered), linear, segmental, regional, or diffuse.
    Special findings may be encountered, such as a linear density that might represent a duct filled with secretions or reniform shape of intramammary lymph nodes (with a radiolucent center).
    Associated findings are then taken into account. These include skin or nipple retraction, skin thickening (which may be focal or diffuse), trabecular thickening, skin lesions, axillary adenopathy, and architectural distortion.
    The lesion seen is located by using the views to either of the inner or outer or the lower or upper quadrants. It may also be central or retroareolar. The lesion can be described in a clock-shape position. The breast is viewed as the face of a clock with the patient facing the observer. The depth of the lesion is assigned to the anterior, middle, or posterior third of the breast.
    If previous examination results are available, their comparison is useful in assessing disease progress.
    All of these findings are considered together, a final impression is formed, and a BI-RADS category is assigned.
  • Normal mammograms in a 40-year-old woman show dense breast parenchyma
  • Screening mammogram depicts malignant ductal-type microcalcifications
  • Image shows a malignant-type lesion: an invasive ductal carcinoma. This stellate (spiculated) lesion has ductal-type microcalcifications.
    Image shows a malignant-type lesion: an invasive ductal carcinoma. This stellate (spiculated) lesion has ductal-type microcalcifications.
  • Image shows a benign lesion: a fibroadenoma with well-defined edges and a halo sign.
    Image shows a benign lesion: a fibroadenoma with well-defined edges and a halo sign.
    Partial translucency around a mass halo sign
  • Egg shell in cyst
  • Train track
  • Popcorn calc in fibroadenoma
  • Rod like
  • Malignant lesions tend to have irregular and (usually) spiculated margins. Malignancies, especially scirrhous cancers, also tend to have density greater than that of the normal breast tissue. Very low density, such as that of fat, is seen in benign lesions (eg, oil cyst, lipomas, galactoceles, hamartomas).
    Benign calcifications are usually larger than calcifications associated with malignancy. They are usually coarser, often round with smooth margins, and more easily seen. Benign calcifications tend to have specific shapes: eggshell calcifications in cyst walls, tramlike in arterial walls, popcorn type in fibroadenomas, large and rodlike with possible branching in ectatic ducts, and small calcifications with a lucent center in the skin.
    Calcifications associated with malignancy are usually small (&lt;0.5 mm) and often require the use of a magnifying glass to see them well. They tend to have a pleomorphic or heterogeneous shape or a fine granular, fine linear, or branching (casting) shape.
    The distribution of the calcification should be specified as grouped (clustered), linear, segmental, regional, or diffuse.
  • Media file 30: Breast cancer, ultrasonography. This 49-year-old woman was found to have a mass in the right breast on screening mammography (not shown). Sonography demonstrated a well-circumscribed, oval mass with internal echoes and equivocal posterior acoustic enhancement (arrow) beneath it. To determine if this was a solid mass or complex cyst containing echogenic debris, sonography-guided aspiration was performed with an 18-gauge needle. Nonbloody fluid was aspirated. The cyst completely disappeared on aspiration; this finding was consistent with a benign cyst. It is a benign cyst. In rare cases, a carcinoma can have an identical sonographic appearance, though it would not resolve after aspiration.
  • At present, US is accepted as complementary to clinical examination and mammography with a primary role in distinguishing cystic from solid masses. US is not considered reliable in screening for asymptomatic breast cancer, and its role in differentiating between benign and malignant solid breast masses has been controversial (88-90). Morphologic US criteria for differential diagnosis have, however, been presented recently (90-91). US can be a useful tool when mammography has limitations, as in the identification and evaluation of palpable or nonpalpable masses not visible in mammographically dense breasts (89,90,92). It is also helpful in the case of extremely peripherally located masses, where adequate positioning for mammography may be impossible, as well as in the evaluation of axillary node status and in examining breasts recently operated or acutely inflamed (60). During pregnancy, US is the primary imaging method because mammography has an unacceptably high false-negative rate, probably due to the high radiographic density, and ionizing radiation may be harmful for the developing fetus (93). US also plays an important role in the guidance of diagnostic interventional procedures, including core- and fine-needle aspiration biopsies (94-97).
    On sonograms, hypoechoic lesions with irregular and poorly defined margins and with shadowing and vertical orientation are considered probably malignant. The lesions may show infiltration into the surrounding fatty tissue or other associated features of malignancy.14,15,13,16 Some cancers can mimic benign tumors and appear well defined. A normal sonogram does not exclude breast cancer, especially in the early stages.
    Benign solid lesions with smooth or lobulated margins that are sharply defined, with homogeneous hypoechoic contents and a horizontal orientation, are assumed to be fibroadenoma and are classified as probably benign. Solid, hypoechoic lesions with irregular margins and an indeterminate or horizontal orientation but without a definite probability of being malignant or benign are classified as equivocal.
  • A ductogram, or galactogram, is sometimes helpful for determining the cause of nipple discharge. In this x-ray procedure, a fine plastic tube is placed into the opening of the duct in the nipple. A small amount of contrast medium is injected, which outlines the shape of the duct on an x-ray image and shows whether a mass is present inside the duct
  • With its 3D lesion localization capability, digital breast tomosynthesis (DBT) can get around mammography&apos;s overlapping tissue problem
  • Currently, 3 radiotracers are commonly used for breast imaging or scintimammography in either clinical practice or research: technetium-99m (99m Tc) sestamibi,99m Tc-tetrofosmin (2 agents used for myocardial perfusion imaging), and99m Tc–methylene diphosphonate (MDP, used for bone scintigraphy).99m Tc sestamibi was the first radiopharmaceutical to be approved by the FDA for use in scintimammography.17
    Although not indicated as a screening procedure for the detection of breast cancer, may play a useful and significant role in various specific clinical indications, as in cases of nondiagnostic or difficult mammography and in the evaluation of high-risk patients, tumor response to chemotherapy, and metastatic involvement of axillary lymph nodes.
    In several prospective studies, overall sensitivity of99m Tc-sestamibi scintimammography in the detection of breast cancer was 85%, specificity was 89%, and positive and negative predictive values were 89% and 84%, respectively. Similar numbers have been demonstrated for99m Tc-tetrofosmin and99m Tc-MDP scintimammography.17
  • examines blood flow to the breast, based on the idea that a tumour is more metabolically active than healthy tissue, and this metabolic activity can be detected by the laser technology. CTLM is not affected by tissue density and could become a way to determine response to therapy, according to Rush. Also, it&apos;s attractive to women because it doesn&apos;t require compression: like CBBCT, the woman lies prone on a table with her breast hanging through an opening.
  • Molecular breast imaging and are not affected by dense breasts or implants. The imaging units are similar to mammography devices, and positioning requires an experienced technologist to produce the best results.
    Molecular breast imaging uses a single gamma camera, and literature indicates that the presence of tumours smaller than 3 mm and/or located farther from the camera decreases the technology&apos;s sensitivity,
  • Diagnostic Procedures
    Fine needle aspiration: Fine needle aspiration (FNA) is no longer the criterion standard for initial evaluation of all palpable breast masses. However, it is particularly useful in the evaluation of cystic lesions detected by ultrasonography. FNA results are reported as benign, suggestive of malignancy, or nondiagnostic. Aspiration of a benign cystic lesion should result in collapse of the cavity. Documentation of complete collapse by follow-up ultrasonography may be helpful in decreasing the incidence of recurrence. Persistence of a palpable mass and recurrence following aspiration are general indications for further workup. Importantly, note that the cytopathologist cannot distinguish invasive carcinoma from DCIS. To rule out DCIS, histologic confirmation of invasion with core needle biopsy or excisional biopsy is obtained prior to axillary staging.
    Core needle biopsy: Core needle biopsy (CNB) is a more useful alternative than FNA for initial diagnosis of breast cancer. One advantage is that a surgical pathologist can distinguish between invasive cancer and DCIS based on architectural information provided by the larger tissue sample in CNB. Another advantage to CNB is that a well-trained surgical pathologist can examine the specimen; with FNA, a highly-skilled cytopathologist is required for accurate results. The adoption of image-guided needle biopsy of nonpalpable lesions has defrayed cost and improved patient care by eliminating cosmetic deformity associated with excisional biopsy. Since CNB removes only part of the lesion, one must ensure that the results are concordant with radiographic findings and that proper follow-up is initiated with the patient. With the use of large bore needles and vacuum-assisted devices, adequate sampling of the lesion is much more likely.
    Image-guided breast biopsy: This is an alternative useful for workup of nonpalpable lesions. Ultrasonography, mammography, and MRI may all be used to perform image-guided core needle biopsies. Advantages of this modality include the ability to perform localization and excision in a single procedure. Limitations include cost, availability, and inability to perform biopsy on lesions located close to the chest wall or in patients with small breast volume.
    Excisional biopsy: Complete surgical removal of a palpable breast lesion is referred to as an excisional biopsy. This technique is indicated if (1) neither FNA nor CNB is technically feasible, (2) attempts have produced nondiagnostic results, or (3) pathology is discordant with radiographic imaging. The specimen should always be carefully oriented by the surgeon to aid the pathologist in assessing margins.
  • After induction of anesthesia, 5 cc of 1% methylene blue for injection is infiltrated into the subareolar tissue (yields higher identification rate with blue dye than other sites [36-38]), except when there is a transverse biopsy scar across the upper outer quadrant or axillary tail of the breast, in which case the dye is injected into the parenchyma superolateral to the scar (the presence of such a scar reduces SLN identification rate after subareolar injection [36,37]). In either case, special care must be taken to avoid injection into the skin or submammary connective tissue and muscle. The breast is then massaged for 5 minutes.
    The surgical site is prepared and the surgeon goes directly for the SLN via an axillary incision if breast conserving surgery is the definitive procedure. If mastectomy is the definitive procedure, the surgeon goes for the sentinel node after creating the superior flap. All blue nodes and any node receiving a blue lymphatic channel are sentinel nodes. After removal of sentinel nodes, adjacent tissue is palpated and any additional hard or large nodes are also removed. Total number of nodes removed should usually not exceed three, otherwise the benefits of the limited dissection required for SLNB could be compromised. The following variables are then recorded unto a pre-coded form: surgeons (surgeon and first assistant), mastectomy versus breast conserving surgery, site of injection, SLN identified or not, number of SLNs, Berg&apos;s level at which SLN found, and number of any non-SLN removed. The unfixed nodes are sent to the pathologist. The operation is then completed, including ALND (in the first 13 cases and if indicated in the others).
  • injected into breast (7:00 lesion) draining into right axilla nodes (A) and internal mammary nodes (B)blue dye stain identifies the sentinel node
  • Lumpect+che+rad
    Breast-conservation therapy is recommended as the standard of care for patients of all ages with early breast cancer. Studies of elderly women have found that they also prefer BCT over mastectomy, and BCT is often associated with better quality of life
  • The NSABP-P1 trial has demonstrated the efficacy of tamoxifen, a SERM, in the prevention of invasive breast cancer.7 Treatment with tamoxifen reduced the risk of invasive breast cancer by 49%. Moreover, a 50% reduction in the risk of noninvasive cancers was demonstrated.
    In terms of prevention, tamoxifen is approved by the US Food and Drug Administration (FDA) for use in healthy women at high risk for the development of invasive breast cancer and in patients with early invasive lesions at risk of secondary contralateral cancer. Dosing should be 20 mg/d for 5 years. Significant relative toxicity from tamoxifen use includes increased risk of endometrial cancer and pulmonary embolism in women older than 50 years. Results have been reported from the NSABP P-2 trial (Study of Tamoxifen and Raloxifene [STAR] trial) to compare the efficacy of tamoxifen with raloxifene, which is a SERM used for treatment of osteoporosis.8 Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but has a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs.9 aromatase inhibitors (AI), is being explored for efficacy in the chemoprevention of breast cancer. Three third-generation aromatase inhibitors (anastrozole, letrozole, exemestane) have already been approved by the FDA for use in adjuvant therapy for postmenopausal women with hormone receptor–positive breast cancer.
    However, tamoxifen remains the standard of care for adjuvant endocrine therapy for premenopausal women. In select patients with small tumors and no nodal metastases, tamoxifen may provide a means for systemic treatment without the use of systemic chemotherapy. Conversely, ER(-) tumors are predictive of improved response to chemotherapy and minimal benefit from tamoxifen.
    Trastuzumab is a relatively new chimerized mouse/human monoclonal antibody that targets the extracellular portion of the Her-2/neu membrane protein
    Neoadjuvant therapy for locally advanced breast cancer should involve anthracycline or taxane-based regimens
    Various chemotherapeutic regimens used following surgical treatment include anthracyclines, taxanes, and cyclophosphamide. Choice of the optimal adjuvant chemotherapeutic regimen should be made based on multiple factors including patient age, menopausal status, hormone receptor and Her-2/neu expression, lymph node involvement, and size of the primary lesion.
    .
  • Ductal excision: Ductal excision may be indicated for suggestive nipple discharge without an associated palpable or radiographic lesion. Bloody discharge and spontaneous clear discharge from a single duct are findings with an increased risk of malignancy. Ductal excision can be performed using a small (4.0) lacrimal duct probe to localize the draining duct. A cone-shaped sample of tissue then should be excised around the probe. The most common histologic findings in this setting are intraductal papilloma or ductal ectasia (approximately 80%). Most of the remaining lesions demonstrate intraductal or infiltrating carcinoma.
    Excisional biopsy or lumpectomy: This should be performed for palpable lesions with suggestive or malignant findings on needle biopsy. Benign or inconclusive findings on needle biopsy also may prompt excisional biopsy in the presence of high clinical suspicion (eg, large mass fixed to the chest wall, atypical epithelial hyperplasia). In general, circumareolar incisions should be made for lesions close to the nipple and radial incisions for lower outer quadrant lesions. All incisions should be made with consideration of potential need for incorporation into subsequent mastectomy incisions. The surgeon should carefully orient specimens with suture for histologic assessment of individual margins. The procedure may be performed safely with local anesthesia and/or monitored intravenous sedation. The need for open biopsy can usually be obviated by the use of CNB as described in Diagnostic Procedures.
    Lumpectomy or wide local excision: Most often performed along with some form of lymph node dissection as part of a breast conservation procedure, lumpectomy involves excision of a palpable malignant breast lesion with adequate margins. In the case of nonpalpable lesions, a needle-localization procedure may precede lumpectomy. This is performed with ultrasonographic or mammographic assistance for nonpalpable, radiographically identified lesions. Following placement of a fine J wire under radiographic guidance, the lesion can be excised surgically. Care must be taken to obtain a solid core of breast tissue around the tip of the wire with margins of at least 1 cm. The specimen should be reevaluated radiographically to confirm excision of the intended lesion prior to completion of the operation.
    Quadrantectomy: This is removal of an entire quadrant of the breast, which is less cosmetically satisfactory than lumpectomy.
    Sentinel lymph node biopsy (SLNB): The sentinel lymph nodes (SLN) are the first nodes that receive drainage from tumors. The technique involves injecting radiocolloid, blue dye, or both in the tissues of the breast. Several techniques of injection are available, including subareolar, peritumoral, intradermal, or intraparenchymal. After injection, an incision is made with consideration of the potential need for subsequent completion lymph node dissection (see next paragraph). Therefore, the incision can be elongated easily if the SLN is positive for metastasis.
    Completion Lymph Node Dissection (CLND): If an SLN is found to be positive on histologic evaluation, a CLND is indicated to assess the degree of lymph node involvement. This can have a significant impact on staging as well as adjuvant treatment.
    Axillary Lymph Node Dissection (AxLND): This procedure is equivalent to SLNB combined with CLND. Axillary lymph node staging provides prognostic information to both the patient and the treating physicians. A formal level I and II axillary lymph node dissection has historically been the standard of care in surgical therapy for the axilla. However, AxLND can result in significant morbidity. Complications of AxLND include pain, paresthesia, seroma, infection, limitation of shoulder motion, and lymphedema.
    Breast conservation therapy: This term is used to describe lumpectomy, quadrantectomy, or segmental mastectomy with or without axillary dissection and adjuvant radiation therapy.
    Total or simple mastectomy: This describes removal of breast parenchyma, including nipple-areolar complex, with no node dissection. It may be performed as a therapeutic or a prophylactic procedure in select patients at high risk.
    Modified radical mastectomy (MRM): This procedure involves resection of the breast parenchyma and axillary nodes lateral to and behind the medial border of the pectoralis minor (levels I and II).
    Subcutaneous/skin-sparing mastectomy: This procedure involves subcutaneous removal of breast parenchymal tissue and the nipple-areolar complex and may be accompanied by level I and II axillary dissection; it also is referred to as prophylactic mastectomy when performed in healthy patients with strong risk factors such as LCIS or multiple affected family members.
    Patey modified radical mastectomy: Primarily of historical significance, this involves modified radical mastectomy (MRM) with additional removal of level III nodes requiring division or resection of the pectoralis minor; compared to MRM, this procedure increases lymphedema from 3-10% in the arm.
    Radical (Halsted) mastectomy: This procedure entails removal of all breast, axillary nodes through level III, and both the pectoralis minor and pectoralis major muscles; historically, this was the most commonly performed procedure for breast cancer.
  • Terminal duct excision (single duct). ( a ) A periareolar incision is made. ( b ) The involved duct is identified by means of blunt dissection. ( c ) The duct is removed along with a core of breast tissue. ( d ) The entire subareolar ductal complex is excised from immediately beneath the nipple dermis to a depth of 4 to 5 cm within breast tissue
    Ductal excision: Ductal excision may be indicated for suggestive nipple discharge without an associated palpable or radiographic lesion. Bloody discharge and spontaneous clear discharge from a single duct are findings with an increased risk of malignancy. Ductal excision can be performed using a small (4.0) lacrimal duct probe to localize the draining duct. A cone-shaped sample of tissue then should be excised around the probe. The most common histologic findings in this setting are intraductal papilloma or ductal ectasia (approximately 80%). Most of the remaining lesions demonstrate intraductal or infiltrating carcinoma.
  • Lumpectomy or wide local excision: Most often performed along with some form of lymph node dissection as part of a breast conservation procedure, lumpectomy involves excision of a palpable malignant breast lesion with adequate margins. In the case of nonpalpable lesions, a needle-localization procedure may precede lumpectomy. This is performed with ultrasonographic or mammographic assistance for nonpalpable, radiographically identified lesions. Following placement of a fine J wire under radiographic guidance, the lesion can be excised surgically. Care must be taken to obtain a solid core of breast tissue around the tip of the wire with margins of at least 1 cm. The specimen should be reevaluated radiographically to confirm excision of the intended lesion prior to completion of the operation.
  • Quadrantectomy: This is removal of an entire quadrant of the breast, which is less cosmetically satisfactory than lumpectomy.
    Sentinel lymph node biopsy (SLNB): The sentinel lymph nodes (SLN) are the first nodes that receive drainage from tumors. The technique involves injecting radiocolloid, blue dye, or both in the tissues of the breast. Several techniques of injection are available, including subareolar, peritumoral, intradermal, or intraparenchymal. After injection, an incision is made with consideration of the potential need for subsequent completion lymph node dissection (see next paragraph). Therefore, the incision can be elongated easily if the SLN is positive for metastasis.
  • Cant give radiation
  • Completion Lymph Node Dissection (CLND): If an SLN is found to be positive on histologic evaluation, a CLND is indicated to assess the degree of lymph node involvement. This can have a significant impact on staging as well as adjuvant treatment.
    Axillary Lymph Node Dissection (AxLND): This procedure is equivalent to SLNB combined with CLND. Axillary lymph node staging provides prognostic information to both the patient and the treating physicians. A formal level I and II axillary lymph node dissection has historically been the standard of care in surgical therapy for the axilla. However, AxLND can result in significant morbidity. Complications of AxLND include pain, paresthesia, seroma, infection, limitation of shoulder motion, and lymphedema.
  • Total or simple mastectomy: This describes removal of breast parenchyma, including nipple-areolar complex, with no node dissection. It may be performed as a therapeutic or a prophylactic procedure in select patients at high risk.
  • Modified radical mastectomy (MRM): This procedure involves resection of the breast parenchyma and axillary nodes lateral to and behind the medial border of the pectoralis minor (levels I and II).
  • Patey modified radical mastectomy: Primarily of historical significance, this involves modified radical mastectomy (MRM) with additional removal of level III nodes requiring division or resection of the pectoralis minor; compared to MRM, this procedure increases lymphedema from 3-10% in the arm.
  • Radical (Halsted) mastectomy: This procedure entails removal of all breast, axillary nodes through level III, and both the pectoralis minor and pectoralis major muscles; historically, this was the most commonly performed procedure for breast cancer.
  • Seromas beneath the skin flaps or in the axilla represent the most frequent complication of mastectomy and axillary lymph node dissection, reportedly occurring in as many as 30% of cases. The use of closed-system suction drainage reduces the incidence of this complication. Catheters are retained in the wound until drainage diminishes to &lt;30 mL per day. Wound infections occur infrequently after a mastectomy and the majority are a result of skin-flap necrosis. Cultures of specimens taken from the infected wound for aerobic and anaerobic organisms, débridement, and antibiotic therapy are effective management. Moderate or severe hemorrhage in the postoperative period is rare and is best managed with early wound exploration for control of hemorrhage and re-establishment of closed-system suction drainage. The incidence of functionally significant lymphedema after a modified radical mastectomy is 10 to 20%. Extensive axillary lymph node dissection, the delivery of radiation therapy, the presence of pathologic lymph nodes, and obesity are predisposing factors. The use of individually fitted compressive sleeves and intermittent compression devices may be necessary.
  • Because LCIS is considered a marker for increased risk rather than an inevitable precursor of invasive disease, the current treatment options for LCIS include observation, chemoprevention with tamoxifen, and bilateral total mastectomy. The goal of treatment is to prevent or detect at an early stage the invasive cancer that subsequently develops in 25 to 35% of these women. There is no benefit to excising LCIS, because the disease diffusely involves both breasts in many cases and the risk of invasive cancer is equal for both breasts. The use of tamoxifen as a risk reduction strategy should be considered in women with a diagnosis of LCIS.
  • Women with DCIS and evidence of extensive disease (&gt;4 cm of disease or disease in more than one quadrant) usually require mastectomy. For women with limited disease, lumpectomy and radiation therapy are recommended. Low-grade DCIS of the solid, cribriform, or papillary subtype that is &lt;0.5 cm in diameter may be managed by lumpectomy alone without radiation if the margins of resection are widely free of disease. For nonpalpable DCIS, needle localization techniques are used to guide the surgical resection. Specimen mammography is performed to ensure that all visible evidence of cancer is excised. Adjuvant tamoxifen therapy is considered for DCIS patients. The gold standard against which breast conservation therapy for DCIS is evaluated is mastectomy. Women treated with mastectomy have local recurrence and mortality rates of &lt;2%. Women treated with lumpectomy and adjuvant radiation therapy have a similar mortality rate, but the local recurrence rate increases to 9%. Forty-five percent of these recurrences will be invasive cancer when radiation therapy is not used. The use of radiation therapy markedly decreases the risk of in-breast recurrence and significantly reduces the risk that any recurrence will be invasive disease. Both Lagios and Gump noted that recurrence of DCIS was greatest when the cancers were &gt;2.5 cm in size, the criteria for histologic confirmation of clear margins were not rigorously applied, and the DCIS was of the comedo type. They noted that recurrences frequently occurred within the original surgery site, which indicates that inadequate clearance of DCIS, rather than the biology of the cancer, was responsible.
  • Currently, mastectomy with assessment of axillary lymph node status and breast conserving surgery with assessment of axillary lymph node status and radiation therapy are considered equivalent treatments for patients with stage I and II breast cancer. Axillary lymphadenopathy confirmed to be metastatic disease or metastatic disease in a sentinel lymph node (see later) necessitates an axillary lymph node dissection. Breast conservation is considered for all patients because of the important cosmetic advantages.
  • Women with stage IIIA and IIIB breast cancer have advanced local-regional breast cancer but have no clinically detected distant metastases.145 In an effort to provide optimal local-regional disease-free survival as well as distant disease-free survival for these women, surgery is integrated with radiation therapy and chemotherapy (Fig. 17-30). Neoadjuvant chemotherapy should be considered in the initial management of all patients with locally advanced stage III breast cancer. Surgical therapy for women with stage III disease is usually a modified radical mastectomy, followed by adjuvant radiation therapy. Chemotherapy is used to maximize distant disease-free survival, whereas radiation therapy is used to maximize local-regional disease-free survival. In selected patients with stage IIIA cancer, neoadjuvant (preoperative) chemotherapy can reduce the size of the primary cancer and permit breast-conserving surgery. Investigators from the M. D. Anderson Cancer Center reported that low local-regional failure rates could be achieved in selected patients with stage III disease treated with neoadjuvant chemotherapy followed by breast-conserving surgery and radiation.146 The 5-year actuarial ipsilateral breast tumor recurrence–free survival rates in this study were 95%. They noted that the ipsilateral breast tumor recurrence rates increased when patients had clinical N2 or N3 disease, &gt;2 cm of residual disease in the breast at surgery, a pattern of multifocal residual disease in the breast at surgery, and lymphovascular space invasion in the primary tumor. This study and others demonstrate that breast-conserving surgery can be used for appropriately selected patients with locally advanced breast cancer who achieve a good response with neoadjuvant chemotherapy. For patients with stage IIIA disease who experience minimal response to chemotherapy and for patients with stage IIIB breast cancer, neoadjuvant chemotherapy can decrease the local-regional cancer burden enough to permit subsequent modified radical mastectomy to establish local-regional control. In both stage IIIA and IIIB disease, surgery is followed by adjuvant radiation therapy.
  • Treatment for stage IV breast cancer is not curative but may prolong survival and enhance a woman&apos;s quality of life.147 Hormonal therapies that are associated with minimal toxicity are preferred to cytotoxic chemotherapy. Appropriate candidates for initial hormonal therapy include women with hormone receptor–positive cancers; women with bone or soft tissue metastases only; and women with limited and asymptomatic visceral metastases. Systemic chemotherapy is indicated for women with hormone receptor–negative cancers, symptomatic visceral metastases, and hormone-refractory metastases. Women with stage IV breast cancer may develop anatomically localized problems that will benefit from individualized surgical treatment, such as brain metastases, pleural effusion, pericardial effusion, biliary obstruction, ureteral obstruction, impending or existing pathologic fracture of a long bone, spinal cord compression, and painful bone or soft tissue metastases. Bisphosphonates, which may be given in addition to chemotherapy or hormone therapy, should be considered in women with bone metastases. Whether to perform surgical resection of the local-regional disease in women with stage IV breast cancer has recently been debated after several reports have suggested that women who undergo resection of the primary disease have improved survival over those who do not. Khan and associates used the National Cancer Data Base to identify patterns of treatment in women with metastatic breast cancer and found that those who had surgical resection with negative margins had a better prognosis than those women who did not have surgical therapy.148 Gnerlich and colleagues reported similar findings using the SEER database, and there have been several reports subsequent to this study from single institutions that have confirmed these findings.149 Some have suggested that the findings of improved survival are due to selection bias and that local therapy should be reserved for palliation of symptoms. A proposal has recently gone forward to study this question in a randomized fashion through the Breast Cancer Intergroup of North America. In the meantime, surgical management of patients with stage IV disease should be addressed by obtaining multidisciplinary input and by considering the treatment goals of each individual patient and the patient&apos;s treating physicians.
  • Local-Regional Recurrence
    Women with local-regional recurrence of breast cancer may be separated into two groups: those who have had mastectomy and those who have had lumpectomy. Women treated previously with mastectomy undergo surgical resection of the local-regional recurrence and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered, and adjuvant radiation therapy is given if the chest wall has not previously received radiation therapy. Women treated previously with a breast conservation procedure undergo a mastectomy and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered.
  • Transcript of "Breast Cancer"

    1. 1. Breast Cancer Seyed Morteza Mahmoodi
    2. 2. Contents Breast Cancer OVERVIEW WORK UP TREATMENT PROGNOSIS
    3. 3. Contents Breast Cancer OVERVIEW WORK UP TREATMENT PROGNOSIS
    4. 4. OVERVIEW  Anatomy  Histology  Physiology  Pathology  Presentation
    5. 5. Lymphatics of the Mammary Gland Superficial lymphatics From the skin except nipple and areola a. Upper marginal >>apical nodes after piercing CP fascia. >>infraclavicular nodes. b. Upper lateral with axillary tail>>pectoral group c. Lower lateral >> pectoral + ant. Abdominal wall d. Medial >>sternal group of same and opposite side. a b d c Sternum
    6. 6. Deep lymphatics From the parenchyma and glandular tissue + Skin of nipple and areola •75% to axillary nodes- anterior or pectoral group. •20% to internal mammary nodes •5% to posterior to posterior intercostal nodes •Some pass to abdominal cavity from lower medial quadrant.
    7. 7. a b&c Sternum From retromammary space a. Upper part >>Apical group d b. Upper lateral parts>>pectoral c. Lower lateral>>pectoral + ant abdominal wall d. Upper medial>>sternal group of same and opposite side. e. Dangerous area >> plexus on rectus sheath; along falciform ligament to hepatic nodes and into peritoneal cavity c e Rectus sheath Peritoneal cavity
    8. 8. Hormones  Estrogen ►  Progesterone ►  Development of the breast and lactiferous ducts Secretory acinar tissue – lobules Prolactin ► Synergizes the effect of estrogen and progesterone
    9. 9. The female breast: Normal breast anatomy & anatomical location of common breast lesions
    10. 10. Breast – Neoplastic diseases:  Benign:  Fibroadenoma.  Phyllodes tumor.  Papilloma. Stromal tumors  Malignant:  Carcinoma in situ:  Ductal carcinoma in situ (DCIS).  Lobular carcinoma in situ (LCIS).  Invasive carcinoma:  No special type carcinoma (NST “ductal”).  Lobular.  Tubular / cribriform.  Mucinous (colloid) carcinoma.  Medullary carcinoma.  Papillary carcinoma.  Metaplastic carcinoma.
    11. 11. In situ (noninvasive ) carcinoma – Morphology: C
    12. 12. In situ (noninvasive) carcinoma – Morphology:
    13. 13. In situ (noninvasive) carcinoma – Morphology:
    14. 14. In situ (noninvasive) carcinoma – Morphology:
    15. 15. Invasive (infiltrating) carcinoma – Morphology: Invasive ductal carcinoma
    16. 16. Invasive (infiltrating) carcinoma – Morphology: Invasive lobular carcinoma.Parallel arrays of single files of small, poorly cohesive cells are embedded within a dense fibrous stroma
    17. 17. Invasive (infiltrating) carcinoma – Morphology: Colloid carcinoma.
    18. 18. Invasive (infiltrating) carcinoma – Morphology: Medullary carcinoma with lymphoid infiltrates,
    19. 19. Invasive (infiltrating) carcinoma – Morphology: Tubular carcinoma.
    20. 20. Syndrome Breast/ovarian Gene BRCA1 Inheritance Cancers Other Features AD* Breast, ovarian Cancer syndrome BRCA2 AD Li-Fraumeni syndrome TP53 AD Breast, ovarian, Fanconi anemia in prostate, homozygotes pancreatic Breast, brain, soft tissue sarcomas, leukemia, adrenocortical, others Cowden disease PTEN AD Breast, ovary, follicular thyroid, colon Adenomas of thyroid, fibroids, GI polyps Peutz-Jegher syndrome STKII/LKB1 AD GI, breast Ataxiatelangiectasia ATM AD Breast Site-specific CHEK2 AD Breast Hamartomas of bowel, pigmentation of buccal mucosa Homozygotes: leukemia, lymphoma, cerebella ataxia, immune deficiency, telangiectasias Low penetrance
    21. 21. Li-Fraumeni Syndrome ► Mutation  of p53 gene Tumor suppressor ► Premenopausal     breast CA Childhood sarcoma Brain tumors Leukemia Adrenocortical CA ► Accounts for 1% of breast CA
    22. 22. Cowden Syndrome ► Major criteria       ► Thyroid CA (follicular) Marcocephaly Cerebellar tumors Endometrial CA Breast CA – 25%-50% risk Skin and mucosal lesions Minor criteria      Thyroid lesions GU tumors GI hamartomas Fibrocystic breast Mental retardation
    23. 23. Tumor Grade  Histologic grade  Well differentiated, >75% tubule  Moderately differentiated, 10-75% tubule formation  Poorly differentiated, < 10% tubule formation, worse prognosis Intermediate grade Low grade – Small nuclei, no necrosis Grading of breast carcinomas • Most classification systems rely primarily on nuclear morphology and have 3 grades
    24. 24. Presentation & Assessment  Symptoms Lump 80% Painful lump or lumpiness Pain Nipple discharge Nipple change Miscellaneous  Triple Assessment  Clinical examination 99% accurate
    25. 25. Symptoms & possible diagnosis 1.Lump Fibroadenoma Juvenile Fibroadenoma Giant fibroadenoma Phyllodes tumours Cysts Galactocele 2.Pain Mastalgia : Cyclical & Non cyclical 3.Nipple Physiological Bloodstained in pregnancy Intraductal papillomas and associated conditions Duct Ectasia Galactorrhoea discharge 4.Nipple change Developmental inversion of nipple Acquired nipple retraction : duct ectasia, periductal mastitis etc Eczema Paget’s disease etc. Infections : Lactational & Non lactational 5.Cosmetic Comon cosmetic problems : size, shape & symmetry of breast & other mound problems Uncommon cosmetic problems : developmental & acquired Trauma Rare problems
    26. 26. Charecterestics of nipple discharges
    27. 27. Contents Breast Cancer OVERVIEW WORK UP TREATMENT PROGNOSIS
    28. 28. Laboratory Studies Genetic and molecular testing  Oncotype DX  Serum markers 
    29. 29. BRCA BRCA (breast cancer) tumor suppressor gene,  breast cancer type susceptibility protein  Chromosome 17,  Chromosome 13 
    30. 30. BRCA ► Account to 25% of early-onset breast Ca ► 36%-85% lifetime risk of breast CA ► 16-60% lifetime risk of ovarian CA ► BRCA 1 gene  Ovarian CA ► BRCA    2 gene Male breast CA Prostate CA Pancreatic CA
    31. 31. BRCA is it a Screening tool or a Prognostic tool?
    32. 32. Screening (Significant FH) 2 or more first-degree relatives  2 or more second-degree relatives (on the same side of the family) who meet the following:  Breast cancer age less than 50 years  Breast and ovarian cancer in the same bloodline or in the same individual  Male relative breast cancer age less than 50 years  Family members bilateral breast cancer 
    33. 33. BRCAPRO is a statistical model, with associated software, for assessing the probability that an individual carries a germline deleterious mutation of the BRCA1 and BRCA2 genes, based on family history of breast and ovarian cancer, including male breast cancer and bilateral synchronous and asynchronous diagnoses
    34. 34. BRCA + ► Management    Monthly BSE beginning18yo 6 mo CBE & annual mammo beginning 25yo Discuss risk reducing options Prophylactic mastectomies ► Salpingo-oophorectomy – upon completion of child bearing ►  6 mo transvaginal US & CA125 – 35 yo
    35. 35. Prognostic Breast cancer age less than 40 years  Males with breast cancer  Two or more cancers 
    36. 36. BRCA1 Has a medullary histology  "triple negative"  high nuclear grade  Has a higher rate of proliferation  Overexpresses p53 
    37. 37. Hormone Receptor (HR) status  ER + Indicator of growth not metastatic potential  More likely to be well differentiated lower fraction of dividing cells  Less likely to be associated with mutations, loss of breast cancer related genes such as p53, HER-2/neu, or EGFR  In early stage 5-10% lower likelihood of recurrence  More likely to metastasize to bone, soft tissues or genital sites   ER More likely to metastasize to brain, liver associated with shorter survival
    38. 38. Breast, adenocarcinoma, immunohistochemical stain for estrogen receptor - Low and medium power Antibodies used to stain a section from the biopsy specimen show that virtually all of the tumor cells express estrogen receptor protein (brown stain). 1.Staining for estrogen and progesterone receptors Positive for both receptors
    39. 39. Does ER- patients benefit from tamoxifen?
    40. 40. Since tamoxifen can potentially affect cellular functions by binding to calmodulin or inhibiting protein kinase C , it has been used for its ability to inhibit cell growth and induce apoptosis independently of the presence of ER
    41. 41. New prognostic factors  HER-2/neu receptor status     + relatively resistant to adjuvant endocrine therapy + tumors may benefit from anthracyclinebased chemotherapy Trastuzumab (Herceptin) Bevacizumab (Avastin)
    42. 42. Breast cancer, immunohistochemical stain for HER2/neu High power Immunohistochemical detection of HER2 protein expression in a section of tissue containing the tumor shows an intense cell-surface staining pattern.
    43. 43. Molecular changes associated with breast cancer progression  Increased expression of oncogenes   c-erb-B2, her2/neu, c-ras, c-myc Decreased expression of tumor suppressor genes  P53, RB, E-cadherins, Strong (3+) membrane immunoreactivity for HER2/neu in highgrade breast carcinoma. The HER2 proto-oncogene encodes a cell surface receptor that is over-expressed in approximately 25%-30% of breast cancers. • Trastuzumab (Herceptin®) is the first monoclonal antibody that targets the extracelluar domain of the HER2 protein, and inhibits growth of breast cancer cells that over express this protein. •
    44. 44. Oncotype DX recurrence score  21 gene expression used to predict recurrence in early stage invasive breast cancer    High risk females derived a significant benefit from chemotherapy Low risk females with tumors derived minimal benefit from chemotherapy Guides the type of chemotherapy use
    45. 45. Hybridization signals are detected using a confocal laser scanner and downloaded to a computer for analysis (red squares, expression of the gene is higher in tumor; green square, expression of the gene is higher in normal tissue; black squares, no difference in the expression of the gene between tumor and normal tissue). In the display, the horizontal rows correspond to each gene contained in the array; each ventrical row corresponds to single samples.
    46. 46. Serum Markers  CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 Screening?  Diagnosing?  Prognostic CA 15-3  Follow-up  Monitoring therapy   Indications have not been standardized American Society of Oncology
    47. 47. Mammography
    48. 48. Mammography Symmetry  Size  General density  Glandular distribution  Masses, densities, calcifications, architectural distortions,  Masses: shape, margins, density  BI-RADS category 
    49. 49. BI-RADS BI-RADS Classification Features 0 1 2 3 4 Need additional imaging Negative – routine in 1 yr Benign finding – routine in 1 yr Probably benign, 6mo follow-up Suspicious abnormality, biopsy recommended 5 Highly suggestive of malignancy; appropriate action should be taken
    50. 50. Screening ► American Cancer Society recommends annual mammography and examination by a physician beginning at age 40 years with no maximum upper age limit ► Family Hx  10 yrs younger than relative’s diagnosis ► BRCA  25 yo – annual mammography
    51. 51. Calcification               Malignant Greater density Irregular and (usually) spiculated margins small (<0.5 mm) Shapes pleomorphic or heterogeneous or fine granular, fine linear, or branching Benign Low density smooth margins Large specific shapes: eggshell: cyst walls, tramlike: arterial walls, popcorn type: fibroadenomas, large and rodlike with possible branching: ectatic ducts
    52. 52. Ultrasound ► ► ► ► ► ► ► ► ► Not a screening tool Palpable vs cystic Mammographic detected lesion Mammography has limitations, Dense breasts Extremely peripherally located masses Evaluation of axillary node status Examining breasts recently operated or acutely inflamed During pregnancy
    53. 53. Ultrasound ► Malignant     Hypoechoic, spiculated Taller than wide Duct extension microlobulation ► Benign     Intensely hyperechoic Elliptical shape (wider than tall) Lobulated Complete tiny capsule
    54. 54. MRI ► ► ► ► High risk patients  Personal history of breast ca  LCIS, atypia  1st degree relative with breast cancer  Very dense breast Axillary lymphadenopathy undetectable primary tumor Palpable lesions not visualized by diagnostic mammography or ultrasonography High sensitivity (95-100%)  10-20% will have a biopsy
    55. 55. Digital Breast Tomosynthesis
    56. 56. Scintimammography
    57. 57. CT laser mammography (CTLM)
    58. 58. Positron Emission Mammography
    59. 59. Thermography
    60. 60. Diagnosis ► Fine  Cytology ► Core   needle aspiration biopsy Image guided Stereotactic ► Excisional  biopsy Needle localization
    61. 61. Excisional Biopsy ► Atypical lesions ► LCIS ► Atypical papillary lesions ► Radiologic-pathologic discordance ► Inadequate tissue harvesting
    62. 62. Vacuum Assisted Biopsy
    63. 63. Sentinel Lymph Node Biopsy How to assess axillary LN metastasis?  Reports suggest that the sentinel lymph node has a high predictive value in determining the presence of axillary metastases. Identification of a sentinel lymph node that is free of metastatic tumor cells may eliminate the necessity of performing a standard axillary lymph node dissection with its attendant morbidity   The sensitivity of SLNB ranged from 67 to 100 per cent, with a pooled estimate of 88 (95 per cent confidence interval 85 to 90) percent
    64. 64. lymphoscintography
    65. 65. Staging AJCC  Primary tumor = T         Tx - Primary tumor cannot be assessed T0 - No evidence of primary tumor Tis - Carcinoma in situ T1 - Tumor ≤2 cm in greatest dimension T2 - Tumor > 2 cm but ≤5 cm T3 - Tumor > 5 cm T4 - Tumor of any size with direct extension to chest wall or skin (including inflammatory carcinoma)
    66. 66. Staging Regional lymph nodes N  Nx - cannot be assessed  N0 - No regional lymph node metastases  N1 - Metastases to ipsilateral axillary lymph nodes without fixation  N2 - Metastases to ipsilateral axillary lymph nodes with fixation to each other (matted), with fixation to other structures N3 - Infraclavicular nodes have metastases with or without axillary lymph node involvement, 
    67. 67. Staging Distant metastases = M  Mx - Cannot be assessed  M0 - No metastases  M1 - Distant metastases, including ipsilateral supraclavicular lymph nodes 
    68. 68. Stage Primary tumor size (T) Lymph node involvement (N) Metastatic disease (M) 0 Tis N0 M0 1 T1 N0 M0 2a T0 N1 M0 2a T1 N1 M0 2a T2 N0 M0 2b T2 N1 M0 2b T3 N0 M0 3a T0 N2 M0 3a T1 N2 M0 3a T2 N2 M0 3a T3 N1 M0 3a T3 N2 M0 3b T4 N0 M0 3b T4 N1 M0 3b T4 N2 M0 3c Any N3 M0 4 Any Any M1
    69. 69. Stage 1 Tumor size less than 2 cm
    70. 70. Stage 2 2-5 cm with N1 or N0 More than 5cm but N0 Less than 2 cm or T0 but no more than N3
    71. 71. Stage 3 Larger than 5 cm with any N Less than 5 cm with nodal matting Less than 5 cm with supraclavicular LN involvement
    72. 72. Stage 3 Inflammatory breast
    73. 73. Stage 4 Metastatic breast cancer
    74. 74. Contents Breast Cancer OVERVIEW WORK UP TREATMENT PROGNOSIS
    75. 75. Case 1  An annual screening mammogram in a 55year-old nurse administrator revealed suspicious microcalcifications. The patient is postmenopausal with no family history of breast cancer. Lobular carcinoma in situ was identified by biopsy; the lesion was not completely excised.
    76. 76. What are reasonable options to reduce this patient's risk of developing invasive breast cancer?  Re-excise the lesion until there are clear margins  Bilateral salpingo-oophorectomy  Treatment with raloxifene  Unilateral prophylactic mastectomy
    77. 77. Case 2     RG, a 77-year-old, white, former schoolteacher, presents with a palpable mass in the right breast and 1 palpable axillary lymph node. The breast mass measures 2.1 x 2.7 cm on mammography, and ultrasonography shows a prominent axillary lymph node. The biopsy reveals poorly differentiated invasive ductal carcinoma with the "triple-negative" phenotype The patient is classified as having stage IIb disease (T2N1M0). RG has several comorbid conditions for which she is prescribed numerous medications. She has hypertension, mitral and tricuspid regurgitation, atrial fibrillation, and a pacemaker. She takes atenolol, warfarin, and atorvastatin. The patient walks with a cane due to complications from osteoarthritis. RG also has early-stage dementia.
    78. 78. Case Cont.      What would you recommend as the initial management approach for this patient? Neoadjuvant chemotherapy followed by modified radical mastectomy and radiotherapy (RT) Lumpectomy followed by adjuvant chemotherapy and RT Lumpectomy with sentinel lymph node sampling followed by adjuvant RT Modified radical mastectomy followed by adjuvant endocrine therapy
    79. 79. Medical Therapy       Chemoprevention Selective estrogen receptor modulators (SERM) (tamoxifen) Aromatase inhibitors (AI) (anastrozole, letrozole, exemestane) Trastuzumab Neoadjuvant therapy (anthracycline or taxanebased) Adjuvant (anthracyclines, taxanes, and cyclophosphamide)
    80. 80. Chemoprevention     Tamoxifen use for 5 years reduces risk for at least 10 years in premenopausal women, particularly estrogen receptor (ER) positive invasive tumors Tamoxifen and raloxifene are equally effective in reducing risk of ER positive breast cancer in postmenopausal women. Recommendations  For women with increased risk for breast cancer, offer tamoxifen (20 mg/d for 5 y) to reduce risk of invasive breast cancer.  In postmenopausal women, raloxifene (60 mg/d for 5 y) may also be considered.  Aromatase inhibitors (eg, anastrozole, exemestane, letrozole), fenretinide, or other SERMs are not recommended outside of a clinical trial. American Society of Clinical Oncology (ACOG)
    81. 81. Adjuvant Rx ► All tumors > 1cm ► All postmenopausal women with positive LN ► Postmenopausal women with lesion greater than 2 cm (T2 lesion)
    82. 82. Adjuvant Hormonal Rx ► All premenopausal women with tumor > 1cm ► All postmenopausal unless a contraindication
    83. 83. Adjuvant Radiation Rx ► All pts. With conservative Rx ► When > 4 LN, radiation to axilla
    84. 84. Surgical Therapy          Ductal excision Lumpectomy or wide local excision Quadrantectomy Completion Lymph Node Dissection (CLND) Axillary Lymph Node Dissection (AxLND) Total or simple mastectomy Modified radical mastectomy (MRM) Patey modified radical mastectomy Radical (Halsted) mastectomy
    85. 85. Needle localization
    86. 86. Contraindications to Breast Conservation ► Tumour >5cm ► Larger tumor to breast ratio ► Two large tumours in two separate quadrants ► Previous breast radiation ► Collagen Vascular disease (scleroderma & Lupus) ► Diffuse calcifications or subareolar tumor
    87. 87. Lymph Node Dissection
    88. 88. Patey modified radical mastectomy
    89. 89. Complications Seromas most frequent complication 30%  Closed-system suction drainage <30 mL per day  Wound infections skin-flap necrosis  Hemorrhage  lymphedema 10 to 20% 
    90. 90. LCIS LCIS chemoprevention with tamoxifen,  Bilateral total mastectomy  No benefit to excise LCIS 
    91. 91. DCIS DCIS and evidence of extensive disease (>4 cm of disease or disease in more than one quadrant) mastectomy  Limited disease, lumpectomy and radiation therapy  Low-grade DCIS of the solid, cribriform, or papillary subtype that is <0.5 cm in diameter, lumpectomy alone if the margins of resection are widely free of disease 
    92. 92. Early Invasive Breast Cancer (I, II) Mastectomy with axillary lymph node status and  Breast conserving surgery with axillary lymph node status and radiation therapy equivalent treatments  Axillary lymph node dissection  Breast conservation is considered for all patients because of the important cosmetic advantages  Adjuvant chemotherapy 
    93. 93. Advanced Local-Regional Breast Cancer (III) Neoadjuvant chemotherapy for all  Modified radical mastectomy,  Adjuvant radiation therapy  Adjuvant chemmotherapy 
    94. 94. Distant Metastases (IV) Hormonal therapies are preferred  Systemic chemotherapy  Role of Surgery is under investigation 
    95. 95. Local-Regional Recurrence Mastectomy vs. Lumpectomy  Surgical resection of the local-regional recurrence  Chemotherapy and  Antiestrogen therapy  Adjuvant radiation 
    96. 96. BSO BSO has been used to reduce the risk for breast cancer, as well as to decrease the risk for ovarian cancers in women with known BRCA mutations. In premenopausal women, BSO is estimated to decrease the risk for breast cancer by 50%
    97. 97. Prophylactic Mastectomy    To date, PM as well as the use of CPM in breast cancer patients have yet to show a decisive impact on survival In very high-risk patients with concerns about hereditary cancer, the use of CPM addresses and substantially reduces risk for CBC. Aggressive screening vs surgery in mutation carriers, PM and CPM are the most cost-effective strategies
    98. 98. Contents Breast Cancer OVERVIEW WORK UP TREATMENT PROGNOSIS
    99. 99. Prognosis Biological, and independent patient factors  Genetic predisposition  Tumor size  receptor status  Axillary node involvement  Choice of treatment modality 
    100. 100. Prognosis 5-year survival rates for women in the United States have improved to 98% for disease localized to the breast  With nodal involvement, this decreases to 81%,  With distant metastases, the 5-year survival is only 26%. 
    101. 101. Male Breast Cancer Rare disease, accounting for ∼1% of all breast cancer cases  Similar to breast cancer in females in its etiology, family history, prognosis, and treatment  30% FH  Personal history of prostate cancer  liver cirrhosis  Testicular Disorders  Gynecomastia 
    102. 102. Breast Cancer Awareness Month October 2010 THANK YOU
    103. 103. Contents Acute Lymphoblastic Leukemia INTRODUCTION CLASSIFICATION EITIOLOGY CLINICAL PRESENTATION DIAGNOSIS TREATMENT
    104. 104. Contents Acute Lymphoblastic Leukemia INTRODUCTION CLASSIFICATION EITIOLOGY CLINICAL PRESENTATION DIAGNOSIS TREATMENT
    105. 105. Awareness Ribbons 
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