Challenging Lobular Lesions of the Breast What to Do?

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1 Challenging Lobular Lesions of the Breast What to Do? Dennis R. Holmes, M.D. Breast Cancer Surgeon Medical Director Los Angeles Center for Women s Health

2 Is Lobular Neoplasia a Risk Factor? Precursor Lesion? or Both?

3 Is Lobular Neoplasia a Risk Factor? Precursor Lesion? or Both? YES*

4 Confused?

5 " Anyone who isn't confused really doesn't understand the situation." - Edward R. Murrow

6 Why The Confusion? Lack of clear definition Unclear outcomes Variable management

7 Lobular Lesions 1941 (Foote and Stewart): ( LCIS ) Malignant and warranted complete mastectomy 1919 (Ewing) Precancerous changes 1978 (Haagensen): ( Lobular Neoplasia ) Benign proliferation that increased risk of subsequent CA, req. monitoring and close follow-up Where are we Now?

8 Overview Discuss Definition of Lobular Neoplasia Discuss Risk Factor, Precursor, and Both? Discuss Management Options

9 Lobe with Lobules Ductal Anatomy

10 Terminal Ductal Lobular Unit (where most breast cancers arise) TDLU Ascinus TDLU Lobule

11 Definition Lobular Intraepithelial Neoplasia (LIN) Spectrum of lesions from atypical lobular hyperplasia and lobular carcinoma in situ Monotonous cell population filling ductules Lobular units Lobular neoplasia Normal Duct Ascinus

12 Definition Lobular Intraepithelial Neoplasia (LIN) LIN1 = Atypical Lobular Hyperplasia LIN2 = Lobular carcinoma in situ (LCIS) LIN3 = Pleomorphic Lobular carcinoma in situ

13 LIN 1 Atypical Lobular Hyperplasia Less than one half of a lobular unit involved Lobule not enlarged Lumen present

14 LIN 1 Atypical Lobular Hyperplasia 3 to 5-fold increase risk of invasive breast cancer Nashville Cohort Study and Nurses Health Study 9.6 X increase risk if premenopausal Risk is ipsilateral

15 More than 50% of a lobular unit involved Marked Lobular unit enlargement LIN2 Lobular carcinoma in situ Lumen absent But, Mitosis and necrosis are usually absent

16 LIN 2 Lobular carcinoma in situ True incidence is unknown Lacks clinical and mammographic signs 0.5%-3.6% of benign biopsies 9-12 X increased risk of Inv BC Subsequent IDC or ILC More likely to be lobular (25-88%) DCIS E-cadherin + Molecular studies support LCIS is a direct precursor to ILC. Frequently seen with ILC Multicentric and bilateral LCIS E-cadherin -

17 One or multiple distended lobules Large discohesive cells with irregularly shaped nuclei Single of multiple nuclei Abundant cytoplasm Mitosis and necrosis usually present Similar to DCIS LIN3 Pleomorphic LCIS

18 Pleomorphic LCIS (LIN3) Uncommon Frequently associated with invasive cancer Associated with radiographic abnormalities Molecular studies show LIN3 is a precursor to ipsilateral invasive carcinoma

19 Is Lobular Neoplasia a Risk Factor? Precursor Lesion? or Both?

20 Is Lobular Neoplasia a Risk Factor? Precursor Lesion? or Both? Depends

21 Definition Lobular Intraepithelial Neoplasia (LIN) LIN1 = Atypical Lobular Hyperplasia» UNILATERAL RISK FACTOR LIN2 = Lobular carcinoma in situ (LCIS)» BILATERAL RISK FACTOR and PRECURSOR LIN3 = Pleomorphic LCIS» BILATERAL RISK FACTOR and PRECURSOR

22 Management Implications Depends on if diagnosis was made with excision or core needle biopsy

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24 Diagnosis by Excision Lobular Intraepithelial Neoplasia (LIN) LIN1 = Atypical Lobular Hyperplasia» NO FURTHER SURGERY, unless CA is found LIN2 = Lobular carcinoma in situ (LCIS)» NO FURTHER SURGERY, unless CA is found LIN3 = Pleomorphic LCIS» NO FURTHER SURGERY, unless CA is found

25 Diagnosis by Core Needle Bx Lobular Intraepithelial Neoplasia (LIN) LIN1 = Atypical Lobular Hyperplasia» NO SURGERY LIN2 = Lobular carcinoma in situ (LCIS)» EXCISIONAL BIOPSY (without margins) LIN3 = Pleomorphic LCIS» EXCISIONAL BIOPSY (with margins, if possible)

26 EXCISIONAL BIOPSY FINDINGS after Core Needle Biopsy of LIN Series LIN Malignancy % Mulheron B Sohn VY Lavoue V Hwang H Nagi CS Menon S Arpino G Zuiani C Margenthaler JA Brem RF Mahoney MC Londero V Elsheikh TM Georgian- Smith D, Lawton TJ. Radiol Clin N Am

27 Removal of Entire Imaging Abnormality

28 Follow-up Determination of Risk (e.g., Gail Model) Risk-Based Screening Semiannual clinical breast examination Annual Screening Mammography Annual Bilateral Screening MRI (if lifetime risk >20%) Chemoprevention Tamoxifen, Raloxifene, Exemestane Bilateral Prophylactic Surgery (LIN2 or LIN3)

29 Follow-up Determination of Risk (e.g., Gail Model)

30 Follow-up Determination of Risk (e.g., Gail Model)

31 Indications for Annual Breast MRI From American Cancer Society n BRCA 1 or BRCA 2 Mutation n 1st Degree Relative with BRCA 1 or 2 Mutation n Lifetime Risk of Breast Cancer >20% n Radiation to chest between ages n Personal history of hereditary breast cancer (or 1st Degree Relative) n Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome

32 Does LIN at the Margin of An Lumpectomy For Cancer Require Re-excision? Presence of Lobular Carcinoma in Situ Does Not Increase Local Recurrence in Patients Treated with Breast-Conserving Therapy. Ciocca R et al. Annals of Surgical Oncology 2008;15: (Northwestern U) LCIS at margin (n=84) LCIS present but not at margin (n=206) LCIS not present (n=2604) Local Recurrence Rate 5 yr 10 yr p 6% 6% 1% 15% 2% 6% NS

33 Surgical Recommendations LCIS At Margins The presence of LCIS at the margins of lumpectomy specimens does not impact Local Recurrence Rate Do Not Recommend margin re-excision, except for PLEOMORPHIC LCIS if associated with an imaging abnormality

34 Summary The type of LN lesion matters Management depends on type LIN1 is a unilateral risk factor LIN2 & LIN3 are precursors and bilateral risk factors LIN2 & LIN3 dx d by CNB should be excised Follow-up should include CBE, MMG, +/- MRI Discuss Chemoprevention and Prophylactic Surgery

35 Clearer?

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