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Lobular Neoplasia of Breast

Joint Hospital Surgical Grand Round 21st April, 2012. Lobular Neoplasia of Breast. Susanna Tam Wai Yin Kwong Wah Hospital. Lobular Neoplasia. Comprises LCIS & ALH Rare breast lesion 3.19 per 100000 women; 0.5-4% in all biopsy

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Lobular Neoplasia of Breast

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  1. Joint Hospital Surgical Grand Round 21st April, 2012 Lobular Neoplasia of Breast Susanna Tam Wai Yin Kwong Wah Hospital

  2. Lobular Neoplasia • Comprises LCIS & ALH • Rare breast lesion • 3.19 per 100000 women; 0.5-4% in all biopsy • Ellis OI et al. Invasive breast carinoma. In: Tavassoli FA et al. Tumours of the Breast and Female Genital Organs. Lyon: IARC Press;; 2003:60-62. • More than doubled in the past 25 yrs • Elsheikh TM et al. Follow-up surgical excision is indicated when breast core needle biopsyies show atypical lobular hyperplasia or lobular carcinoma in situ: a correlative study of 33 patients with review of the literature. Am J Surg Pathol. 2005;29:534-543. • Clinically important: • risk marker, possible precursor of CA breast • Challenges & controversies in: • Diagnosis & classification • Understanding of its biological behaviour • Appropriate management

  3. Outline • Pathology & cytogenetics • Clinical Features • Upstaging • Marker of increased risk • Management

  4. pathology

  5. Lobular Carcinoma in-situ (LCIS) • Frances P O’Malley. Lobular neoplasia: morphology, biological potential and management in core biopsies. Modern Pathology (2010) 23, S14–S25 • A monomorphic population of dyshesive cells expanding the terminal duct lobular unit • Acini are completely filled with cells and causing distension of at least 50% of the acini • Foote FW Jr, Stewart FW (1941) Lobular carcinoma in situ. A rare form of mammary cancer. Am J Pathol 17:491–496

  6. Atypical Lobular Neoplasia (ALH) LCIS ALH • Frances P O’Malley. Lobular neoplasia: morphology, biological potential and management in core biopsies. Modern Pathology (2010) 23, S14–S25 • A less well developed form of LCIS • Acini only partially filled by loosely cohesive cells; <50% of acini involved if distension present • Page DL, Dupont WD, Rogers LW, et al. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985;55:2698–2708. • Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985;312:146–151

  7. Hanby AM et al. In situ and invasive lobular neoplasia of the breast. Histopathology 2008; 52: 58-66 O’Malley FP. Lobular neoplasia: morphology, biological potentil and management in core biopsies. Modern Pathology 2010. 23:S14-25. Molecular Pathology & Cytogenetics

  8. E-Cadherin • An adhesion molecule localized at zonula adherens which enchances cellular cohesion • Biallelic loss or down-regulation of E-cadherin gene (CDH1;16q21.1) in LN & ILC • differentiates vs. ductal neoplasms • a/w inherited ILC and diffuse gastric CA

  9. Am J Surg Pathol 2007;31:417–426 Non-obligate precursor

  10. CLINICAL FEATURES

  11. Presentation • Clinically occult • Often not detectable by MMG • Multicentric & bilateral • Incidentally found on core bx

  12. Upstaging on Excision

  13. Marker of Increased CA Risk • Subsequent CA develops away from original core bx site • Ipsilateral breast slightly > contralateral • Renshaw AA et al. Lobular neoplasia in breast core needle biopsy specimens is associated with a low risk of ductal carcionma in sit u or invasive carcinoma on subsequent excision. Am J Clin Pathol 2006; 126:310-313.

  14. Relative Risk • ALH: 4-5x; LCIS: 8-10x • Page DL etal. Lobular neoplasia of the breast: higher risk for subsequent invasiver cancer predicted by more extensive disease. Hum Pathol. 1991;22:1232-9. • Lifetime risk ~1% per year after dx of LCIS • 13% in first 10yrs, 26% after 20yrs, 35% by 35yrs • Bodian CA et al. Lobular neoplasia. Long term risk of breast cancer and relation to other factors. Cancer. 1996;78:1024-34.

  15. Management

  16. LN Diagnosed by Core Bx • Routine local excision • Or only if: • Presence of another lesion indicating excision • Radio-pathological discordance • Associated mass/distortion • Indeterminate between ductal and lobular lesion • Pleomorphic LCIS or other variants • 1-3% missing rate • Renshaw AA et al. Lobular neoplasia in breast core needle biopsy specimens is associated with a low risk of ductal carcionma in sit u or invasive carcinoma on subsequent excision. Am J Clin Pathol 2006; 126:310-313.

  17. Surveillence • Yearly MMG, P/E Q6-12mth • NCCN Breat Cancer Screening and Diagnois Clinical Practice Guidelines • Routine MRI screening not supported • No difference in cancer detection rate or trend towards earlier stage at dx • American Cancer Society guidelines • Oppong BA et al. Recommendations for women with lobular carcinoma in situ (LCIS). Oncology. Oct 2011: 1051-1058

  18. Chemoprevention • Premenopausal: 5yrs of tamoxifen • NSABP Breast Cancer Prevention Trial (BCPT, P-1) 1998 • Postmenopausal: raloxifene • Multiple Outcomes of Raloxifene Evaluation (MORE) study 1999 • NSABP Study of Tamoxifen and Raloxifene (STAR, P-2) 2006 • Aromatase inhibitors - not recommended • American Society of Clinical Oncology (ASCO) • Highly effective with significant risk • LCIS: 56% ↓; atypical hyperplasia 86% ↓ • 3x PE, 2.5x endometrial CA, 1.8x stroke • Fisher B et al. Tamoxifen for prevention of beast cancer: report of the National Sugical Adjunct Breast and Bowel Project P-1 study. J Natl Cancer Inst. 1998;90:1371-1388. • Not widely embraced `.` risk • Port et al. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol. 2001;8:580-5.

  19. Bilateral Prophylactic Mastectomy • For a subset of high risk patients (e.g. Strong FHx) • Careful counselling & ample time for consideration needed • risk, benefit, QoL, cosmetic outcome • +/- nipple preservation and/or reconstruction • Oppong BA et al. Recommendations for women with lobular carcinoma in situ (LCIS). Oncology. Oct 2011: 1051-1058

  20. Conclusion • Understanding of LN is evolving • “carcinoma in-situ”  marker of increased CA risk  + non-obligate precursor • Avoid over-treatment • Surveillence is mandatory • If dx by core bx  excision only in selected cases • If dx by mammotome / surgical excision  re-excision not needed • Further prospective follow-up & cytogenetic study is warranted

  21. End

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