Lobular Neoplasia of Breast

Susanna Tam Wai Yin

Kwong Wah Hospital

Joint Hospital Surgical Grand Round 21st April, 2012

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

Outline

1. Pathology & cytogenetics

2. Clinical Features– Upstaging – Marker of increased risk

3. Management

PATHOLOGY

Lobular Carcinoma in-situ (LCIS)

♣ 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

• Frances P O’Malley. Lobular neoplasia: morphology, biological potential and management in core biopsies. Modern Pathology (2010) 23, S14–S25

Atypical Lobular Neoplasia (ALH)

♣ 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

ALH

LCIS

• Frances P O’Malley. Lobular neoplasia: morphology, biological potential and management in core biopsies. Modern Pathology (2010) 23, S14–S25

MOLECULAR PATHOLOGY & CYTOGENETICS

•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.

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

Am J Surg Pathol 2007;31:417–426

CLINICAL FEATURES

Presentation

♣ Clinically occult♣ Often not detectable by MMG♣ Multicentric & bilateral

♣ Incidentally found on core bx

Upstaging on ExcisionPatients & MethodsPatients & Methods ALHALH LCISLCIS

Hussain M et al. Management of lobular carcionma in-stu and atypical hyperplasia of the breast – a review. Eur J Surg Oncol. 2011; 37:279-89

•1229 LN, 789 (64%) excision

•Outcomes of patients without excision rarely reported

19% 32%

Luedtke C et al. Outcomes of prospective excision for classic LCIS and ALH on percutaneous breast core biopsy. Abstract no. 209. US and Canadian Acad of Pathology Annual Meeting; 2011.

•Retrospective review at Memorial Sloan-Kettering Cancer Center (MSKCC)

•82 LN, routine excision

•11 were excluded for synchronous lesions requiring excision or radiologic-pathologic discordance

3%one low grade DCIS & one tubular cancer

0%

Translational Breast Cancer Research Consortium. TBCRC 020

•Prospective study started Nov 2004

•Expected to complete by 2014

In progresshttp://pub.emmes.com/study/bcrc/

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.

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.

MANAGEMENT

LN Diagnosed by Core Bx

♣ Routine local excision♣ Or only if:

1. Presence of another lesion indicating excision2. Radio-pathological discordance3. Associated mass/distortion4. Indeterminate between ductal and lobular lesion5. 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.

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

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.

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

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

End