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 1. 2. 3. 4. 5. 6. 7. 8.
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 2
Monica Enamandram, HMS III Gillian Lieberman, MD
Breast Cancer: Incidence Worldwide, most common cancer diagnosed in women. Main cause of death in women aged 40-59 in the U.S. 210,000 new cases of invasive breast cancer diagnosed in 2010 in the United States. 40,000 die from the disease yearly in the U.S. 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. 3
Monica Enamandram, HMS III Gillian Lieberman, MD
Breast Cancer: Mortality Mortality rates have declined since 1975: due to use of screening mammography, greater use and improvements in adjuvant therapies. 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. 75% of reduction estimated to be due to mammographic screening. Tumor stage is the most important determinant of disease outcome 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.
4
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. Benefits: reduction in the risk of death as well as number of life-years gained. Costs: 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. 5
Monica Enamandram, HMS III Gillian Lieberman, MD
Screening Guidelines (continued) ACR guidelines Average risk: annual screening beginning at age 40 High risk: BRCA1 or BRCA2 mutation carrier Lifetime 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. 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 6
Monica Enamandram, HMS III Gillian Lieberman, MD
Meet Patient #1: clinical presentation 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. Recently, the area containing the cyst had become indurated and tender. On physical exam, her PCP noted dimpling of the left breast above the areola, along with a 3-cm firm area. What study did she recommend? DIAGNOSTIC MAMMOGRAM AND BREAST ULTRASOUND
7
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. 8
Monica Enamandram, HMS III Gillian Lieberman, MD
Mammography: Normal findings
Image: Chen MY, et al. Basic Radiology, 2011. 9
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.
10
Monica Enamandram, HMS III Gillian Lieberman, MD
What is the role of ultrasound? Screening: used primarily as a complementary tool, to discern solid masses from cysts and increase specificity of findings. Adjunct: dense breast tissue assessment, evaluation of high-risk women who cannot tolerate MRI. For a palpable breast mass: immediate US is recommended following diagnostic mammography. Can also guide ensuing intervention. Ensures that palpable clinical finding corresponds with that on mammogram. ACR Appropriateness Criteria: Palpable Breast Mass 2009. 11
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. 12
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
13
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 14
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 15
Monica Enamandram, HMS III Gillian Lieberman, MD
Dense Breast Tissue: Implications More complicated detection of mammographic abnormalities, and known risk factor for interval cancer after a previously benign screening exam. Mammographic sensitivity 80% among women with fatty breasts, but down to 30% in women with extremely dense breasts. 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. 16
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. 17
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
18
Monica Enamandram, HMS III Gillian Lieberman, MD
Our patient’s ultrasound findings
Images: BIDMC PACS
19
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 20
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.
21
Monica Enamandram, HMS III Gillian Lieberman, MD
Image-Guided Biopsy
Image: Miller, E. MGH Radiology Rounds Newsletter 2006.
22
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.
23
Monica Enamandram, HMS III Gillian Lieberman, MD
Our patient’s biopsy results Pathology showed invasive ductal carcinoma, grade 2, ER/PR positive, HER-2 negative, with DCIS present. Microcalcifications were noted in the left breast upper outer region Stereotactic biopsy would therefore be recommended if the patient chooses breast conservation therapy
24
Monica Enamandram, HMS III Gillian Lieberman, MD
Companion Patient #2: clinical presentation 63-year-old female who presented to her PCP for routine yearly examination, in her usual state of health. Her physical exam was notable for a 2-cm palpable mass in the 12:00 position of her right breast. There were no recent known skin changes, nipple retraction or discharge noted on history or during her physical examination.
25
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 26
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 27
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 28
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.
29
Monica Enamandram, HMS III Gillian Lieberman, MD
Invasive Breast Carcinoma 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 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. Multimodality of treatment employed: surgery, chemotherapy, radiation therapy and endocrine therapy are typically utilized. 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.
30
Monica Enamandram, HMS III Gillian Lieberman, MD
Back to our patient Patient #1 underwent genetic testing, given her young age and family history, to determine if she is a BRCA1 or BRCA2 carrier. She is contemplating between mastectomy and breast conservation for her surgical therapy. She is to undergo pre-operative breast MRI to further evaluate the L breast tissue, given the possibly diffuse nature of her disease. She will have a sentinel node biopsy to evaluate her left axillary lymph nodes for surgical planning. 31
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.
32
Monica Enamandram, HMS III Gillian Lieberman, MD
Summary: Learning Objectives Become familiar with the epidemiology and role of screening for breast cancer Understand the role of ultrasound and MRI as adjuncts to both screening and diagnostic mammography Be able to characterize concerning breast lesions identified on mammography and ultrasound Learn the role of various imaging modalities in the diagnostic evaluation of a suspicious palpable breast mass 33
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. 34
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. 35
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 36
