Download Invasive Breast Carcinoma

Monica Enamandram, HMS III
Gillian Lieberman, MD
Oct-Nov 2011
Invasive Breast Carcinoma
Monica Enamandram
Harvard Medical School, Year III
Gillian Lieberman, MD
Monica Enamandram, HMS III
Gillian Lieberman, MD
Outline
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Breast Cancer: an overview of epidemiology
Screening guidelines for breast cancer
Patient #1: initial evaluation and diagnostic work-up
Role of diagnostic mammogram, ultrasound and MRI
in evaluation of a palpable breast mass
Overview of image-guided biopsy procedures
Patient #2: initial evaluation and diagnostic work-up
Facts on invasive breast carcinoma
Summary and learning objectives
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Breast Cancer: Incidence
ƒ Worldwide, most common cancer
diagnosed in women.
ƒ Main cause of death in women
aged 40-59 in the U.S.
ƒ 210,000 new cases of invasive
breast cancer diagnosed in 2010
in the United States.
ƒ 40,000 die from the disease
yearly in the U.S.
ƒ The average lifetime probability
of developing invasive disease is
1 in 8.
Figure: Warner, E. N Engl J Med 2011.
Jemal, et al. CA Cancer J Clin 2010.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Breast Cancer: Mortality
ƒ Mortality rates have declined since 1975: due to use of screening
mammography, greater use and improvements in adjuvant therapies.
ƒ In a 2002 study, Duffy et al reported a 39% reduction in breast
cancer mortality when comparing the periods pre- and post-advent of
population-based screening.
ƒ 75% of reduction estimated to be due to mammographic screening.
ƒTumor stage is the most important determinant of disease outcome
ƒ Mortality decline has been greater in women younger than age 50
(3.8%), compared to older women (2.2%) per year.
Duffy, et al. Cancer 2002.
Warner, E. N Engl J Med 2011.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Screening Guidelines
The decision to screen a particular population is based on
weighing benefits vs. costs of screening.
ƒBenefits: reduction in the risk of death
as well as number of life-years gained.
ƒCosts: financial costs, costs associated
with screening regimen itself (radiation
risk, pain, inconvenience, and anxiety),
ensuing diagnostic workup for false
positive results, over-diagnosis. Cost
Image: ACS (www.cancer.org)
benefit ratio also varies widely with age.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Screening Guidelines (continued)
ACR guidelines
ƒ Average risk: annual screening beginning at age 40
ƒ High risk:
ƒBRCA1 or BRCA2 mutation carrier
ƒLifetime risk of breast cancer ≥ 20% based on family history
Yearly screening at age 30 but not before age 25
OR
10 years earlier than age of diagnosis of index relative.
ƒ Other high risk groups: includes women that have a history
of chest irradiation between the ages 10-30, history of personal
breast cancer or with dense breast tissue. These groups also
warrant modified screening recommendations.
Lee, et al. JACR 2010
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Meet Patient #1: clinical presentation
ƒ 47-year-old healthy female who presents to her PCP
due to concern about a left breast cyst that had been
followed for many years.
ƒ Recently, the area containing the cyst had become
indurated and tender.
ƒ On physical exam, her PCP noted dimpling of the left
breast above the areola, along with a 3-cm firm area.
ƒ What study did she recommend?
DIAGNOSTIC MAMMOGRAM AND BREAST
ULTRASOUND
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Differential Diagnosis: Breast Mass
Fibrocystic Disease or Cyst
Fibroadenoma
Breast carcinoma
Intraductal papilloma
Lipoma
Breast abscess/mastitis
Fat necrosis
Phyllodes Tumor
Appropriate Intervention:
For a palpable breast mass in
a patient 30 years or older,
mammography should be
done first. Additionally,
ultrasound following the
initial radiography is
recommended for further
concordance with clinical
findings.
American College of Radiology. ACR Appropriateness Criteria: Palpable Breast Mass 2009.
Ziegfeld, CR. Lippincott’s Primary Care Practice 1998.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Mammography: Normal findings
Image: Chen MY, et al. Basic Radiology, 2011.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Diagnostic Mammogram
• Begins with the two-view standard mammogram,
supervised by radiologist.
• Additional projections, magnification, and spot
compression may be used to provide better detail
and disperse overlapping breast tissue to
visualize suspicious findings.
• Abnormalities include spiculation, irregularity,
soft tissue masses, architectural distortion, and
clustered microcalcifications.
Chen MY, et al. Basic Radiology 2011.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
What is the role of ultrasound?
ƒ Screening: used primarily as a complementary tool, to
discern solid masses from cysts and increase specificity of
findings.
ƒ Adjunct: dense breast tissue assessment, evaluation of
high-risk women who cannot tolerate MRI.
ƒ For a palpable breast mass: immediate US is recommended
following diagnostic mammography. Can also guide ensuing
intervention.
ƒ Ensures that palpable clinical finding corresponds with
that on mammogram.
ACR Appropriateness Criteria: Palpable Breast Mass 2009.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
What is the role of ultrasound?
• Sonographic evaluation of masses:
– Features to characterize include shape, orientation,
margin, lesion boundary, echo pattern, posterior acoustic
features and surrounding tissues.
• Analysis of surrounding tissues: evaluation of adjacent
ducts, Cooper’s ligaments, tissue edema, architectural
distortion, skin thickening, skin retraction and irregularity.
• Calcifications often diagnosed more frequently on
mammogram, however vascularity pattern can be better
assessed with US using Doppler.
Stavros, et al. Radiology, 1995.
Sedgwick E. Sem in Roent, 2011.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Characteristic Findings: Ultrasound
A
B
C
Patient A: oval, anechoic cyst with enhanced posterior acoustic
features and well-circumscribed margins.
Patient B: Irregular mass with angular margins and internal
calcifications, proven to be invasive breast carcinoma
Patient C: Isoechoic, oval mass found to be a fibroadenoma.
Images and text: Sedgwick, E. Sem in Roent. 2011
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Monica Enamandram, HMS III
Gillian Lieberman, MD
What about breast MRI?
• Higher sensitivity when screening for women > 20% lifetime
risk of breast cancer.
• Evaluation of ipsilateral breast for synchronous lesions, if
newly-diagnosed breast cancer is believed to be more
extensive than seen on standard imaging.
• Detection of clinically and mammographically occult breast
cancer in the contralateral breast after a new cancer diagnosis
• Women with mammographically occult primary disease, in
whom an adenocarcinoma of unknown primary site is
identified in the axillary lymph nodes.
Schell, et al. AJR, 2008.
Del Frate, et al. Breast, 2007
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Our patient’s diagnostic mammogram
Images: Views of L breast CC (left) and MLO with
magnification (right) shown. From BIDMC PACS
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Dense Breast Tissue: Implications
ƒ More complicated detection of mammographic abnormalities,
and known risk factor for interval cancer after a previously
benign screening exam.
ƒ Mammographic sensitivity 80% among women with fatty
breasts, but down to 30% in women with extremely dense
breasts.
ƒ Higher proportion of stromal and glandular tissue, and
increased number of lesions classified as atypical ductal
hyperplasia.
Mandelson, et al. J Natl Cancer Inst 2000.
Santen RJ and Mansel R. N Engl J Med 2007.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Dense Breast Tissue: Implications
Compared to
women with less
than 10% of their
mammogram,
women with
density 75% or
more are at
increased risk of
breast cancer.
Image: Stanten RJ and Mansel R. N Engl J Med 2005
Boyd et al. N Engl J Med 2007
The increase in
relative risk is by
a factor of 5.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Our patient’s ultrasound findings
Left breast showing 2.6 x 1.8 x 2.6 cm hypoechoic, irregular, lobulated,
spiculated mass in the subareolar location corresponding to the palpable
lesions. Abnormal vascularity noted on Doppler.
Images: BIDMC PACS
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Our patient’s ultrasound findings
Images: BIDMC PACS
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Monica Enamandram, HMS III
Gillian Lieberman, MD
What is the next step?
Based on these findings, Patient #1’s imaging was
classified as BI-RADS 5:
“Abnormal Finding Highly Suspicious for
Malignancy. Appropriate action should be
taken. Findings discussed by phone with PCP
prior to proceeding with biopsy.”
From BIDMC, OMR
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Monica Enamandram, HMS III
Gillian Lieberman, MD
BI-RADS Classification
Tool designed to standardize mammography reporting, reduce confusion
in imaging interpretations and facilitate outcome monitoring.
Category Assessment
Recommended Management
0
Assessment incomplete
Review prior films, obtain additional studies
1
Negative
Continue routine screening
2
Benign finding
Continue routine screening
3
Probably benign finding
Short-term follow-up mammogram at 6 months,
then every 6-12 months for 1 to 2 years
4
Suspicious abnormality
Perform biopsy, preferably needle biopsy
5
Highly suspicious of
malignancy
Biopsy and treatment as necessary.
6
Known biopsy-proven
malignancy
Assure that the treatment is completed.
Eberl, et al. JABFM 2006.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Image-Guided Biopsy
Image: Miller, E. MGH Radiology Rounds Newsletter 2006.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Image-Guided Biopsy
Biopsy Method
Advantages
Disadvantages
Ultrasoundguided
1. Real-time visualization of biopsy
2. Accessibility of breast and axilla
3. Multidirectional sampling possible
4. Low cost, short duration, welltolerated
1. Can only be performed if lesion is
evident on US
2. Difficulty in confirming lesion
retrieval
Stereotactic
1. Can be used for nearly all lesions
visualized on mammograms
2. X-ray of biopsy specimen can
confirm that the targeted lesion was
sampled
Can be performed when lesions are
visible on MRI but not other modalities
1. No real-time visualization
2. Breast compression required
3. Must have arms raised
4. Compressed breast thickness
(approx. 4 cm) required for biopsy
1. Transient contrast enhancement may
limit ability to see lesion
2. Difficult to confirm lesion retrieval
3. Time consuming, expensive
4. Weight, claustrophobia may also be
limiting factors
MRI-guided
Vandromme MJ, et al. J Surg Oncol 2011.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Our patient’s biopsy results
ƒ Pathology showed invasive ductal carcinoma, grade 2,
ER/PR positive, HER-2 negative, with DCIS present.
ƒ Microcalcifications were noted in the left breast upper
outer region
ƒ Stereotactic biopsy would therefore be recommended
if the patient chooses breast conservation therapy
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Companion Patient #2: clinical presentation
ƒ 63-year-old female who presented to her PCP for routine
yearly examination, in her usual state of health.
ƒ Her physical exam was notable for a 2-cm palpable mass
in the 12:00 position of her right breast.
ƒ There were no recent known skin changes, nipple
retraction or discharge noted on history or during her
physical examination.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Diagnostic Mammogram
At the site of palpable concern in
the R breast, a 2.3 cm solid
mass with poorly defined
margins is noted.
A 9 mm poorly defined mass is
also noted in the upper inner
quadrant, 2.5 cm from the
larger tumor.
Images: R breast MLO (left) and CC
(right) views shown. From BIDMC PACS
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Breast ultrasound
On the R breast, at the 12 o'clock position, 2 cm superior to the nipple, a large irregular
hypoechoic mass measuring 2.1 x 1.5 x 2.3 cm in size was noted. At the 2 o'clock
position, 4 cm from the nipple, a second irregular hypoechoic mass was noted, likely
a satellite lesion. The R axilla revealed normal-appearing lymph nodes.
Based on these findings, Patient #2 underwent ultrasound-guided core needle biopsy.
Images: BIDMC PACS
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Core Needle Biopsy: results
Clips were placed at biopsied sites
corresponding to the 12:00 and 2:00 lesions.
Pathology from the 12:00 position lesion
was invasive carcinoma with mucinous
features, grade 2, ER positive, PR negative,
HER-2/neu pending.
Pathology from the 2:00 position lesion was
invasive carcinoma with prominent
mucinous features, grade 2, ER/PR positive,
HER-2/neu pending.
Images: R breast MLO view shown.
From BIDMC PACS
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Invasive Breast Carcinoma
Lobular or ductal in origin. To qualify as a special-type cancer, at least 90% of
the cancerous cells must contain the defining histologic features.
Image: Kumar V, et al. Robbins & Cotran Pathologic Basis of Disease, 2009.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Invasive Breast Carcinoma
ƒ Invasive ductal carcinoma with productive fibrosis accounts for 80%
of breast cancers. Presents with macroscopic or microscopic axillary
lymph node metastases in 60% of patients
ƒ Almost always features a palpable mass. Nipple retraction present if
central breast region involved. Lymphatic obstruction may lead to
lymphedema and dermal thickening, characteristic peau d’orange
quality.
ƒ Multimodality of treatment employed: surgery, chemotherapy,
radiation therapy and endocrine therapy are typically utilized.
ƒ Size, histology and hormone receptor status guide treatment chosen.
Therapy also influenced by disease status in the axilla, lymph nodes
and/or distant sites of metastasis.
Brunicardi FC, et al. Schwartz’s Principles of Surgery, 2011.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Back to our patient
ƒ Patient #1 underwent genetic testing, given her young age and
family history, to determine if she is a BRCA1 or BRCA2
carrier.
ƒ She is contemplating between mastectomy and breast
conservation for her surgical therapy.
ƒ She is to undergo pre-operative breast MRI to further evaluate
the L breast tissue, given the possibly diffuse nature of her
disease.
ƒ She will have a sentinel node biopsy to evaluate her left
axillary lymph nodes for surgical planning.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Summary: Breast Imaging Abnormalities
Mammography
Ultrasound
Masses
Spiculation
Irregular margins
Calcifications
Fine, linear, branching
Pleomorphic/heterogeneous
Asymmetry
Architectural Distortion
Mass
Ill-defined margins
Micro-lobulation
Height greater than width
Internal echogenicity
Spiculation/angulation
Hypervascularity at edges
Calcifications
Nipple retraction
Skin dimpling
Once such findings are identified, core needle biopsy is recommended.
Ultrasound-guided biopsy most frequently is the chosen modality.
Bast RC, et al. Holland Frei Cancer Medicine, 2000.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Summary: Learning Objectives
ƒ Become familiar with the epidemiology and role of
screening for breast cancer
ƒ Understand the role of ultrasound and MRI as adjuncts to
both screening and diagnostic mammography
ƒ Be able to characterize concerning breast lesions
identified on mammography and ultrasound
ƒ Learn the role of various imaging modalities in the
diagnostic evaluation of a suspicious palpable breast mass
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Monica Enamandram, HMS III
Gillian Lieberman, MD
References
1. American Cancer Society. Mammograms and Other Breast Imaging Procedure. Accessed Nov 11,
2011. http://www.cancer.org.
2. American College of Radiology. ACR Appropriateness Criteria: Palpable Breast Mass. Accessed
Nov 10, 2011. http://www.acr.org/ac.
3. Bast RC, et al. Holland Frei Cancer Medicine. 5th ed. Hamilton (ON): BC Decker; 2000.
4. Boyd NF, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med.
2007 Jan 18;356(3):227-236.
5. Del Frate C, et al. Role of pre-surgical breast MRI in the management of invasive breast
carcinoma. Breast. 2007 Oct;16(5):469-481.
6. Eberl MM, et al. BI-RADS classification for management of abnormal mammograms. J Am
Board Fam Med. 2006 Mar-Apr;19(2):161-4.
7. Esserman LJ, Wolverton D, Hylton N. Integration of breast imaging into cancer management.
Curr Oncol Rep. 200 Nov;2(6):572-81.
8. Freimanis RI, Ayoub JS. Chapter 5 Radiology of the Breast. In: Chen MY, Pope TL, Ott DJ, eds.
Basic Radiology. 2nd ed. New York: McGraw-Hill; 2011.
9. Hunt KK, et al. Chapter 17. The Breast. In: Brunicardi FC, et al. Schwartz's Principles of Surgery.
9th ed. New York: McGraw-Hill; 2011.
10. Jemal A, et al. Cancer statistics 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
References
11. Kumar V, et al. Robbins & Cotran Pathologic Basis of Disease. 8th ed. Philadelphia, PA:
Saunders Elsevier; 2009.
12. Mandelson MT, et al. Breast density as a predictor of mammographic detection: comparison
of interval- and screen-detected cancers. J Natl Cancer Inst. 2000 Jul 5;92(13): 1081-7.
13. Miller JC. Percutaneous Image-Guided Breast Biopsy. Radiology Rounds: Massachusetts
General Hospital Department of Radiology. 2006 Sept;4(9):1-4.
14. Santen RJ, Mansel R. Benign breast disorders. N Engl J Med. 2005 Jul 21;353(3):275-285.
15. Schell AM, Rosenkranz K, Lewis PJ. Role of breast MRI in the preoperative evaluation of
patients with newly diagnosed breast cancer. Am J Roentgenol. 2009 May;192(5):1438-44.
16. Sedgwick E. The breast ultrasound lexicon: breast imaging reporting and data system (BIRADS). Sem in Roentgenol. 2011 Oct;46(4): 245-51.
17. Stavros AT, et al. Solid breast nodules: use of sonography to distinguish between benign and
malignant lesions. Radiology 1995 Jul; 196(1):123-134.
18. Vandromme MJ, Umphrey H, Krontiras H. Image-guided methods for biopsy of suspicious
breast lesions. J Surg Oncol. 2011 Mar 15;103(4):299-305.
19. Warner E. Breast-cancer screening. N Engl J Med. 2011 Sep 15;365(11):1025-32.
20. Zeigfeld CR. Differential diagnosis of a breast mass. Lippincotts Prim Care Prac. 1998 MarApr;2(2):121-8.
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Monica Enamandram, HMS III
Gillian Lieberman, MD
Acknowledgments
I would like to extend a special thank you to the following
people for their help with preparing this presentation:
Dr. Gillian Lieberman
Dr. Krithica Kaliannan
Dr. Iva Petkovska
Dr. Ranjna Sharma
Emily Hansen
Claire Odom
My fellow medical students
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