Carcinoma in situ and invasive

Carcinoma Breast
 Introduction
► One of the commonest human cancers
► Incidence: US-25% of the malignancies among females
► Reduced incidence due to diligent screening
► Male breast carcinomas: rare
► Usually presents as solitary, palpable non painful mass
► More common in upper outer quadrant
► Bilaterality in 4%; common in lobular
► The tumor arises in TDLU’s (90%)
► Early diagnosis by triple method approach
- Palpation (Self breast examination)
- FNAC
- Sono-mammography
Breast carcinoma: Histologic classification

Tumors of the nipple: Pagets disease

of the nipple
Metastatic tumours
Breast carcinoma: molecular
classification
Introduction: Risk factors
► Geographical and racial factors: Incidence 4-6 time higher in
developed countries
► Family history: first degree relatives have 2-6 fold higher risk
(number of blood relatives with disease/younger age at time of
presentation/bilateral cancers/ other malignancies)
► Menstrual and obstetric history: Early menarche/ nulliparity/
late age of first child birth/ late menopause
► Fibrocystic change: Proliferative breast disease with/without
atypia
► Miscellaneous
❖ Consumption of increase fat/ cigarette smoking/ alcohol/ breast
augmentation surgery/ high breast density/ exposure to ionizing
radiation
Introduction: Etiology and
Pathogenesis
► Hormonal and genetic factors are the two major etiological
factors implicated in the pathogenesis of the breast malignancy
► Hormonal Factors: # High risk
❖ Early menarche and late menopausal female
❖ Unmarried nulliparous females
❖ Late child birth (>30Yrs)
❖ Functioning estrogen secreting tumor (granulosa cell tumor)
❖ HRT in post menopausal females
❖ Males treated with estrogen for prostatic cancer
# Low Risk- Breast feeding/ bilateral oophorectomy/ Long term
use of OC’s
Introduction: Etiology and pathogenesis

► Genetic Factors
Introduction: Etiology and
Pathogenesis
► Genetic factors: 10 % of the breast cancer have found to have
genetic inheritance of mutations, mainly the BRCA gene (BRCA1
and BRCA 2) and p53 mutation (sporadic cases)
► BRCA1:
- Located on chromosome 17
- DNA repair gene; cell cycle regulated protein
- Implicated both in breast and ovarian malignancies
- 2/3rd of the patients have strong family history
- Can be detected by IHC
Introduction: Etiology and
Pathogenesis
► BRCA-2
- Located at chromosome 13
- DNA repair gene
- About 1/3rd of breast cancer patients have positive family
history

► P53 gene mutation

- The gene is located in chromosome 17
- Responsible for almost 40% of sporadic cases
- Is also associated with Li-Fraumeni syndrome (Tumors of
brain/sarcomas/adreno-cortical tumors)
Ductal carcinoma in situ (DCIS)
► Confined within mammary TDLU’s
► The number of cases of DCIS has increased from <5% to 15-30%
in the past two decades
► Presents as palpable mass in more than half of the cases, an
nipple discharge in some (30%)
► The lesion begins as atypical hyperplasia of the ductal
epithelium followed by complete occlusion of ducts with the
tumor cells
Ductal Carcinomas In Situ
► Consists of malignant population of cells that lack the capacity
to invade through the basement membrane and are incapable
of distant metastasis
► Approximately 25% of these patients develop invasive
malignancy during a follow up of 10years
► High grade and large size of the in situ carcinoma predicts
multifocality and propensity for invasion
DCIS: Histologic types
DCIS: Histological types
Lobular Carcinoma In Situ (LCIS)

► Neoplastic transformation of epithelial cells lining terminal ducts

and acini of small size
► Typically multifocal and bilateral; usually non-palpable
► 6 - 9 fold increased risk for development of invasive cancer
 Paget’s Disease of the Breast
► In situ carcinoma of lactiferous ducts with extension to
epidermis
► Involving the nipple and areola
► May present with nipple discharge, crusting, or excoriation of
nipple surface
► Results from an intra-ductal spread of malignant cells to involve
the nipple
► 1-2% of the breast cancer patients present with this disease
► 50-60% have palpable mass
► Over 90% have underlying infiltrating duct carcinoma
► Prognosis depends upon the behavior of underlying disorder
Pagets Disease
Pagets Disease (Epidermal invasion)
Invasive breast carcinoma
IDC-NST
Lobular
Mucinous
Medullary
Tubular
Invasive Ductal Carcinoma-NST

► Most common
► Accounts for 70% cases of breast cancer
► Most of these cancers exhibit marked increase in dense, fibrous
tissue stroma giving tumour a hard consistency
► May have an infiltrative attachment to surrounding structures
with fixation of the tumour to underlying chest wall, retraction
of the nipple and dimpling of the skin
Infiltrating Duct Carcinoma: Gross
Lymphatic spread – Peu-de Orange..
Invasive lobular carcinoma
► Accounts for 5-10% of all breast cancers
► Tend to be bilateral (20%) far more frequently than other
subtypes
► Multicentric within same breast
► Have diffusely invasive pattern which make both primary and
metastasis difficult to detect either by physical examination or
by radiologic studies
► More frequently metastasize to CSF, serosal surfaces, ovary,
uterus and bone marrow than other subtypes
Targetoid pattern

Indian file pattern

Lobular Carcinoma
 Tumour Grade (Histological)

► Modified Bloom-Richardson system:

 Carcinoma Breast: TNM Staging
► Stage 1 - Tumour less than 2cm in diameter with no LN involvement
► Stage 2 - Tumour 2-5cm with or without LN involvement
► Stage 3 - Tumour cells spread to axillary LN’s but not to other parts of
the body
► Stage 4 - The cancer cells spread to other parts of the body
 Carcinoma Breast: Prognosis

St 5-year 7-year
Definition
ag Surv (%) Surv (%)
I Tumor 2 cm or less without spread 96 92

Tumor 2-5cm with regional lymph node

involvement but without distant
II 81 71
metastases, OR > 5 cm in diameter
without spread
Any size with skin/chest wall fixation, &
axillary or internal mammary nodal
III 52 39
involvement, without distant
metastases
Tumor of any size with or without
IV regional spread but with evidence of 18 11
distant metastases
 Carcinoma Breast: Spread
► Direct: skin, pec major, seratus anterior, chest wall
► Lymphatic: skin (Peau d’orange), axillary, internal thoracic. Later
to supraclavicular, abdominal, mediastinal, groin, contralateral
nodes.
► Blood stream: lungs, liver, bones (sites of red bone marrow)
brain, ovaries, adrenal glands.
► Trans-coelomic: pleural (effusion) and peritoneal (ascites) in
advanced disease
 Carcinoma breast: Diagnosis
► Mammography
► Ultrasound
► Fine Needle Aspiration Biopsy
► Core Biopsy
► Excision Biopsy
► Frozen section
► Immunohistochemistry ( ER,PR, Her2neu)
► Molecular techniques – Gene detection ( BRCA1,2, p53 loss).
 Carcinoma Breast: Prognostic factors
► Size of primary tumor
► Lymph node involvement and extent
► Grade
► Histologic and molecular type ( based on estrogen/progesterone
and Her-2 neu receptors and Ki-67)
 ER/PR
► Expression of oestrogen and progesterone receptors is a very
powerful and useful predictor.
► The response rate to hormonal treatment in breast cancer is
associated with the presence of oestrogen and progesterone
receptors
► Assessment of the receptor expression profile allows for
prediction of breast cancer response to hormonal treatment.
► The higher the content of ER and PR in breast cancer, the
greater the likelihood of response to hormonal therapy
 Her 2-neu
► HER2 gene amplification and protein overexpression drive
cancer progression
► HER2 status is an important prognostic and predictive biomarker
in breast cancer
► HER2 signaling activates multiple major signaling pathways (Ras
/ Raf / MEK / MAPK and PI3K / AKT) that promote cellular
proliferation and antiapoptosis
► Overexpressed in ~15% of invasive breast tumors and in ~30%
of ductal carcinoma in situ (DCIS)
► Her-2 neu: scoring
Microphotograph showing IHC in invasive ductal carcinoma (IDC)

Luminal A Luminal B Her 2-neu enriched Triple neg

Triple
negative
 Carcinoma Breast: Treatment
► Modern treatment based on multimodal approach combining
surgery, chemo, RT and HT
► Chemotherapy (CMF) / Radiotherapy
► Tamoxifen (if ER +ve)
► Arimidex (if ER +ve, postmenopasual and contraindication to
Tamoxifen)
► Herceptin (if HER2 positive)
 Carcinoma Breast: Treatment
► Breast conserving surgery (BCS)
- Wide local excision (WLE)
- +/- axillary sampling (at least four nodes) or axillary clearance

Contra-indications to BCS
► Pregnancy
► Previous irradiation to breast
► Multifocal/diffuse disease (including carcinoma in situ)
► Positive margins/residual disease after BCS
► Tumours >5cm
 Carcinoma Breast: Screening
► Prior breast cancer or atypia
▪ Annual mammography
▪ 6 monthly CBE
► Family Hx
▪ 10 yrs younger than relative’s diagnosis
▪ 6 mo CBE
► BRCA
▪ 25 yr – annual mammography
▪ 6 mo CBE