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Invasive Breast Carcinoma Monica Enamandram Harvard Medical School, Year III Gillian Lieberman, MD Oct-Nov 2011 Monica Enamandram, HMS III Gillian Lieberman, MD

Invasive Breast Carcinoma - Lieberman's eRadiology Learning Sites

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Page 1: Invasive Breast Carcinoma - Lieberman's eRadiology Learning Sites

Invasive Breast Carcinoma

Monica EnamandramHarvard Medical School, Year III

Gillian Lieberman, MD

Oct-Nov 2011Monica Enamandram, HMS IIIGillian Lieberman, MD

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Outline1. Breast Cancer: an overview of epidemiology2. Screening guidelines for breast cancer3. Patient #1: initial evaluation and diagnostic work-up4. Role of diagnostic mammogram, ultrasound and MRI

in evaluation of a palpable breast mass5. Overview of image-guided biopsy procedures6. Patient #2: initial evaluation and diagnostic work-up7. Facts on invasive breast carcinoma8. Summary and learning objectives

Monica Enamandram, HMS IIIGillian Lieberman, MD

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Breast Cancer: IncidenceWorldwide, 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.

Monica Enamandram, HMS IIIGillian Lieberman, MD

Figure: Warner, E. N Engl J Med 2011. Jemal, et al. CA Cancer J Clin 2010.

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Breast Cancer: MortalityMortality 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 breastcancer 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 outcomeMortality 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.

Monica Enamandram, HMS IIIGillian Lieberman, MD

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Screening GuidelinesThe decision to screen a particular population is based on

weighing benefits vs. costs of screening.

Monica Enamandram, HMS IIIGillian Lieberman, MD

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 benefit ratio also varies widely with age.

Image: ACS (www.cancer.org)

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Screening Guidelines (continued)Monica Enamandram, HMS IIIGillian Lieberman, MD

ACR guidelines

Average risk: annual screening beginning at age 40High risk:

BRCA1 or BRCA2 mutation carrierLifetime 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

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Meet Patient #1: clinical presentation47-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?

Monica Enamandram, HMS IIIGillian Lieberman, MD

DIAGNOSTIC MAMMOGRAM AND BREAST ULTRASOUND

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Differential Diagnosis: Breast MassFibrocystic Disease or Cyst

FibroadenomaBreast carcinoma

Intraductal papillomaLipoma

Breast abscess/mastitisFat necrosisPhyllodes Tumor

Monica Enamandram, HMS IIIGillian Lieberman, MD

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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Mammography: Normal findingsMonica Enamandram, HMS IIIGillian Lieberman, MD

Image: Chen MY, et al. Basic Radiology, 2011.

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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 IIIGillian Lieberman, MD

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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 IIIGillian Lieberman, MD

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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 IIIGillian Lieberman, MD

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Characteristic Findings: Ultrasound

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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

Monica Enamandram, HMS IIIGillian Lieberman, MD

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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 IIIGillian Lieberman, MD

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Our patient’s diagnostic mammogram

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Images: Views of L breast CC (left) and MLO with magnification (right) shown. From BIDMC PACS

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Dense Breast Tissue: ImplicationsMore 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 ductalhyperplasia.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Mandelson, et al. J Natl Cancer Inst 2000.Santen RJ and Mansel R. N Engl J Med 2007.

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Dense Breast Tissue: Implications

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Compared to women with less than 10% of their mammogram, women with density 75% or more are at increased risk of breast cancer.

The increase in relative risk is by a factor of 5.Image: Stanten RJ and Mansel R. N Engl J Med 2005

Boyd et al. N Engl J Med 2007

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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.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Images: BIDMC PACS

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Our patient’s ultrasound findings

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Images: BIDMC PACS

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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 IIIGillian Lieberman, MD

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BI-RADS ClassificationTool designed to standardize mammography reporting, reduce confusion in imaging interpretations and facilitate outcome monitoring.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Eberl, et al. JABFM 2006.

Category Assessment Recommended Management0 Assessment incomplete Review prior films, obtain additional studies1 Negative Continue routine screening2 Benign finding Continue routine screening3 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 biopsy5 Highly suspicious of

malignancyBiopsy and treatment as necessary.

6 Known biopsy-proven malignancy

Assure that the treatment is completed.

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Image-Guided Biopsy

22Image: Miller, E. MGH Radiology Rounds Newsletter 2006.

Monica Enamandram, HMS IIIGillian Lieberman, MD

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Image-Guided Biopsy

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Biopsy Method Advantages DisadvantagesUltrasound- guided

1. Real-time visualization of biopsy 2. Accessibility of breast and axilla3. Multidirectional sampling possible4. Low cost, short duration, well- tolerated

1. Can only be performed if lesion is evident on US2. Difficulty in confirming lesion retrieval

Stereotactic 1. Can be used for nearly all lesions visualized on mammograms2. X-ray of biopsy specimen can confirm that the targeted lesion was sampled

1. No real-time visualization2. Breast compression required3. Must have arms raised4. Compressed breast thickness (approx. 4 cm) required for biopsy

MRI-guided Can be performed when lesions are visible on MRI but not other modalities

1. Transient contrast enhancement may limit ability to see lesion2. Difficult to confirm lesion retrieval3. Time consuming, expensive4. Weight, claustrophobia may also be limiting factors

Vandromme MJ, et al. J Surg Oncol 2011.

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Our patient’s biopsy resultsPathology 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

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Monica Enamandram, HMS IIIGillian Lieberman, MD

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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.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

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Diagnostic MammogramAt 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.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Images: R breast MLO (left) and CC (right) views shown. From BIDMC PACS

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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.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Images: BIDMC PACS

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Core Needle Biopsy: resultsClips were placed at biopsied sites

corresponding to the 12:00 and 2:00 lesions.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

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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Invasive Breast Carcinoma

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Monica Enamandram, HMS IIIGillian Lieberman, MD

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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Invasive Breast Carcinoma

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Invasive ductal carcinoma with productive fibrosis accounts for 80% of breast cancers. Presents with macroscopic or microscopic axillary lymph node metastases in 60% of patientsAlmost 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.

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Back to our patientPatient #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.

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Monica Enamandram, HMS IIIGillian Lieberman, MD

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Summary: Breast Imaging Abnormalities

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Monica Enamandram, HMS IIIGillian Lieberman, MD

Mammography UltrasoundMasses

SpiculationIrregular margins

Calcifications Fine, linear, branchingPleomorphic/heterogeneous

AsymmetryArchitectural Distortion

MassIll-defined margins Micro-lobulationHeight greater than widthInternal echogenicity Spiculation/angulation Hypervascularity at edges

CalcificationsNipple retractionSkin 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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Summary: Learning ObjectivesBecome 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

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Monica Enamandram, HMS IIIGillian Lieberman, MD

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References1. 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 IIIGillian Lieberman, MD

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References11. 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 (BI-

RADS). 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 Mar-

Apr;2(2):121-8.35

Monica Enamandram, HMS IIIGillian Lieberman, MD

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AcknowledgmentsI would like to extend a special thank you to the following

people for their help with preparing this presentation:

Dr. Gillian LiebermanDr. Krithica Kaliannan

Dr. Iva PetkovskaDr. Ranjna Sharma

Emily HansenClaire Odom

My fellow medical students

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Monica Enamandram, HMS IIIGillian Lieberman, MD