Lobular carcinoma of breast

1. LOBULAR CARCINOMA OF
BREAST
DR. PRAMESH PRASAD SHRESTHA
FCPS RESIDENT
DEPARTMENT OF GI SURGERY AND DIGESTIVE DISEASES
NEPAL MEDICITI

2. INTRODUCTION
• Breast cancer that begins in the lobules of breast
• Two type:
• Lobular Carcinoma in situ (LCIS) or Lobular neoplasia
• Invasive lobular carcinoma (ILB) or infiltrating lobular Carcinoma
• 2nd most common histologic form of Breast cancer, representing 5%
to 15% of all invasive breast cancers.
Rakha EA, Patel A, Powe DG, Benhasouna A, Green AR, Lambros MB, Reis-Filho JS, Ellis IO.
Clinical and biological significance of E-cadherin protein expression in invasive lobular
carcinoma of the breast. Am. J. Surg. Pathol. 2010 Oct;34(10):1472-9

3. Lobular Carcinoma in Situ
• LCIS is technically not a cancer, but is thought to be an pre malignant
condition.
• The dysplastic cells, rarely spreads to other parts of the breasts or
body
• Are occasionally bilateral

4. LCIS
• Even though, metastases is rare, 20 % may develop Invasive lobular
breast carcinoma in the next 15 years
• Most of the time, these later cancers begin in the ducts rather than
the lobules.

5. Diagnosis
• Usually LCIS is asymptomatic and diagnosed during screening or
incidentally.
• They may not even be seen in routine Mammograms.
• Are usually found, when breast biopsies are done for other
conditions.

6. Treatment
• Women with low risk does not need immediate surgery or medicines
• However requires regular follow ups and screening.
• If strong family history is present,
• Medical therapy is recommended with
• ANASTROZOLE
• EXEMESTANE
• RALOXIFENE
• TAMOXIFENE
• Goal of therapy is to lower the risk of development of invasive breast
carcinoma

7. TREATMENT (Contd.)
• Some females may need surgery to remove tissues in the LCIS
• If patient is a high risk patient, Prophylactic mastectomy (unilateral or
bilateral) may be suggested.

8. INVASIVE LOBULAR CARCINOMA OF BREAST
• Usually associated with LCIS
• Biologically distinct from Invasive Ductal Carcinoma (which is more
common than ILC)

9. Etiology
• Inactivation of E-cadherin
• Presence of LCIS and atypical lobular hyperplasia are precursors for
development of ILC
• Mutations of genes of phosphatidylinositol 3-kinase pathway
(viz PIK3CA)
Harrison BT, Nakhlis F, Dillon DA, Soong TR, Garcia EP, Schnitt SJ, King TA. Genomic profiling of
pleomorphic and florid lobular carcinoma in situ reveals highly recurrent ERBB2 and ERRB3 alterations.
Mod. Pathol. 2020 Jan 13;
Schipper K, Seinstra D, Paulien Drenth A, van der Burg E, Ramovs V, Sonnenberg A, van Rheenen J, Nethe
M, Jonkers J. Rebalancing of actomyosin contractility enables mammary tumor formation upon loss of E-
cadherin. Nat Commun. 2019 Aug 23;10(1):3800

10. Epidemiology
• Incidence of all breast cancers
• World : 46.3 per 100,000 population
• Death rate: 12.7 per 100,000 patients
• Second leading cause for death from cancers after lung cancer
• ILC represents 5%-15% of all breast cancers
• Average age of diagnosis 3 years greater than invasive ductal
carcinoma.
GLOBOCAN 2018
McCart Reed AE, Kutasovic JR, Lakhani SR, Simpson PT. Invasive lobular
carcinoma of the breast: morphology, biomarkers and 'omics. Breast Cancer
Res. 2015 Jan 30;17:12.

11. Epidemiology (Contd.)
• Lobular carcinoma are likely to be Luminal A between 45%-51%,
• less frequent in young (<50 years) and African-American women
• In Nepal, overall incidence of breast cancer is low. However, the
incidence of breast cancer among young women (<40 Years) is
relatively high.
• More than 1/4th patient diagnosed with Breast Carcinoma are young women
and are usually HER2-Enriched.
Williams LA, Hoadley KA, Nichols HB, Geradts J, Perou CM, Love MI, Olshan AF, Troester
MA. Differences in race, molecular and tumor characteristics among women diagnosed with
invasive ductal and lobular breast carcinomas. Cancer Causes Control. 2019 Jan;30(1):31-39.
Bibhusal T, Yogendra S. Prakash S. Uttam K. S. , Ranjan S. Gita S. Breast Cencer in Young
Women from a Low Risk Population in Nepal, Asian Pac J Cancer, 2013, 14 (9), 5095-5099,
DOI:http://dx.doi.org/10.7314/APJCP.2013.14.9.5095

12. Pathophysiology
• Invasive lobular breast cancer has low rate (0-11%) of complete
pathological response after neoadjuvant chemotherapy.
• Positive resection margins after BCS are frequent
• 17-65% require re-resection.
• Detection of mutation rates in CDH1/E-cadherins – 12-83%
• Other modecular factors linked to ILC:
TP53, PIK3CA, FOXA1, ZNF703, FGFR1 AND BCAR4
Christgen M, Steinemann D, Kühnle E, Länger F, Gluz O, Harbeck N, Kreipe H. Lobular breast cancer: Clinical,
molecular and morphological characteristics. Pathol. Res. Pract. 2016 Jul;212(7):583-9
Tabagua TT, Semiglazov VV, Bus'ko EA, Semiglazova TIu, Voroshnikov VV. [Clinical and morphological features
and treatment for lobular breast cancer]. Vopr Onkol. 2013;59(3):386-9

13. History and Physical Exam
• Usually asymptomatic and may be missed in mammogram and
physical exam until at advanced stages
• Mass, usually vague/diffuse nodularity
• At advanced stages,
• Palpable mass
• Thickening of nipples
• Exudative scab, flushing, swelling of the skin
• Axillary or Supraclavicular LNs
• Gastric symptoms in a patient with breast Ca should undergo OGD to
detect gastric metastasis
Owen WA, Brazeal HA, Shaw HL, Lee MV, Appleton CM, Holley SO. Focal breast
pain: imaging evaluation and outcomes. Clin Imaging. 2019 May - Jun;55:148-155
Ushida Y, Yoshimizu S, et al. Clinicopathological Features of Metastatic Gastric Tumors
Originating From Breast Cancer: Analysis of Eleven Cases. World J Oncol. 2018 Aug;9(4):104-109

14. Screening
• Asymptomatic women
• Average risk (without genetic predisposition, family history)
• Women aged 40-44: no screening
• Women aged 45-49: screening every 2-3 years
• Women aged 50-69: Screening every 2 years
• Women aged 70-74: Screening every 3 years

15. Risk estimation
• Gail model- most commonly used

16. Evaluation
• Triple assessment
• Challenging – difficult to detect clinically, radiologically and with
biopsies.
• Mammography: High false negative rates
• Mass with irregular margins
• Architectural distortion and asymmetric focal density
• Microcalcifications are uncommon (0-24%)
• Normal or benign mammographic findings in 8 – 16%
Krecke KN, Gisvold JJ. Invasive lobular carcinoma of the breast: mammographic
findings and extent of disease at diagnosis in 184 patients. AJR Am J
Roentgenol. 1993 Nov;161(5):957-60

17. • The use of screening mammography in women <50 years of age is
more controversial for several reasons:
(a) breast density is greater, and screening mammography is less likely to
detect early breast cancer (i.e., reduced sensitivity);
(b) screening mammography results in more false-positive test findings (i.e.,
reduced specificity), which results in unnecessary biopsy specimens; and
(c) Generally, worldwide, younger women are less likely to have breast cancer
(i.e., lower incidence), so fewer young women will benefit from screening.

19. • Ultrasonography:
• Hypoechoic mass with irregular or indistinct margins and posterior acoustic
shadowing (60%)
• Shadowing with no appearance of mass (15-18%)
• Well circumscribed mass lesion (9-13%)
• Invisible (~10%)
Phalak KA, Milton DR, Yang WT, Bevers TB, Dogan BE. Supplemental ultrasound screening in patients with a history of lobular
neoplasia. Breast J. 2019 Mar;25(2):250-256

20. • Magnetic Resonance Imaging:
• More accurate than USG and mammography
• Useful in estimating extent of tumor
• Seen as enhancing solitary nodule
with spiculated or ill defined margins
Yeh ED, Slanetz PJ, Edmister WB, Talele A, Monticciolo D, Kopans DB. Invasive lobular carcinoma: spectrum of enhancement and
morphology on magnetic resonance imaging. Breast J. 2003 Jan-Feb;9(1):13-8.

21. Histopathology
• Macroscopic Findings:
• Irregular and poorly delimited tumors, difficult to define macroscopically
• Microscopic Findings:
• Proliferation of small cells, lacking cohesion, dispersed individually
• Mitoses are typically infrequent
• Histological Variants
• Solid Type
• Pleomorphic Lobular Carcinoma
• Tubulo-lobular variant
• Alveolar variant
• Mixed type
Thomas M, Kelly ED, Abraham J, Kruse M. Invasive lobular breast cancer:
A review of pathogenesis, diagnosis, management, and future directions of
early stage disease. Semin. Oncol. 2019 Apr;46(2):121-132

22. • Immunoprofile:
• 80-95% are ER Positive v/s 70-80% in Invasive Ca of NOS
• 60-70% PR positive in both types
• HER2 overexpression and amplification are rare in ILB (may be
present in some pleomorphic lobular carcinoma)
• p53, basal markers and myoepithelial markers expression is rare
• Proliferation rate (Ki67. MIB1) is generally low
Arpino G, Bardou VJ, Clark GM, Elledge RM. Infiltrating lobular carcinoma of the breast: tumor
characteristics and clinical outcome. Breast Cancer Res. 2008;6(3):R149-56.

23. Histological Grading
Nottingham histologic score
(Elston-Ellis modification of
Scarff-Bloom-Richardson
grading System)
Grade 1 – Score: 3-5,
Grade 2 – Score: 6-7
Grade 3 – Score: 8-9,

24. Treatment and Management
• Depends on bilaterality and multifocality
• Determination of extent of tumor
• Slow growing tumor, therefore provides enough time to treat with the
help of different modalities
• Hormonal therapy
• Chemotherapy
• Surgery
• Radiation therapy

25. • Mastectomy/Lumpectomy is the treatment of Choice bilateral or
multifocal disease.
• If multifocal and contralateral disease is not present, then
conservative treatment is most appropriate

26. • Wider negative margins are not necessary in ILC
• Markedly decreased amount of fibrotic reaction makes it difficult for
estimating the expansion of the disease during surgery and get tumor
free margins
• Late recurrence in 10 years follow up have been reported in BCS
requiring completion mastectomy in 50% of patients

27. • Operable cancers may be approached with upfront surgery or
undergo surgery after preoperative neoadjuvant therapy
• Surgical excision may be followed by Radiation therapy for early stage
disease
• Adjuvant hormone therapy is also indicated, in view of High
percentages of ER/PR Positive cases.

28. • ECIBC guidelines suggests
• Administration of adjuvant endocrine therapy if 1% or greater of tumor cells
show estrogen receptor /progesterone receptor positivity.
• Not using 70 gene signature test when women are at low clinical risk but
recommends when women are at high clinical risk
• Using 21 gene recurrence score

29. • Chemotherapy is of limited benefit, owing to low proliferation rates

30. Staging • AJCC TNM Classification

35. Differential Diagnosis
• Invasive ductal carcinoma with lobular findings
• Gastric signet ring carcinoma metastatic to the breast
• Sclerosing epithelioid fibrosarcoma
• Leukemic and lymphomatous involvement of the breast
• Granular cell tumor

36. Prognosis
• Different studies show different prognosis compared to invasive ductal
carcinoma
• ILC metastasizes more frequently to ovary, GI tract, uterus, serosal cavities,
meninges or bone v/s Invasive Ca NOS which metastasize to Lungs
• Older age (>60 Y), larger tumor size and metastasis has poor prognostic
factors
• Pleomorphic variant is aggressive with frequent recurrent and poor
prognosis

37. Postopeprative and Rehabilitation care
• Drain and wound care
• Usually use absorbable sutures, (removal of sutures not needed)
• Shower two days after surgery
• Avoid tugging on to the drain and keep the drain site clean
• Measurement of drain
• Negative pressure
• Remove drain 1-2 weeks after surgery
• Arm exercise program
• Arm and hand care:
avoid physical injuries to the arm, watch for swellings
• Physical appearance