CARCINOMA BREAST

MODERATOR: DR MOHAN LN

PRESENTER : [Link] NIRANJAN.G

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INTRODUCTION

● Breast cancer is the most frequent cancer among women

● 2nd leading cause of cancer deaths
● Incidence of breast Ca in India – 23.2/ lakh population
● Mean age: India – 42 yrs
Western countries – 53 yrs

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INCIDENCE
● 30% of all female cancers
● 20% of cancer related deaths
● 2-4% bilateral
● 2-5% hereditary
● Lump in the breast – Most common presentation(75%)
● 10% presents with pain
● 35-45% with mutation of BRCA-I gene
● 70% blood spread occurs to bones

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RISK FACTORS :

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RISK FACTORS:

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RISK FACTORS:

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Genetics:
1) BRCA-1
❏ Chr. 17
❏ AD
❏ It constitutes 45% of inherited breast cancer/ 80% of inherited ovarian cancer
❏ Increase risk of Breast Ca,ovarian Ca, Colon ca, Prostate Ca
❏ Breast Ca:
❏ Youngr Age
❏ Invasive ductal Ca
❏ High grade
❏ ER/PR -ve
❏ Her-2-neu -ve

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2) BRCA 2
● Chr. 13
● AD
● 35-40% of inherited Breast Ca
● 20-80% lifetime risk of Breast Ca
● 20% lifetime risk of ovarian Ca
● Increased risk of Breast Ca, Ovarian Ca, Colon Ca , Prostate Ca , Pancreas Ca , Stomach
Ca , Gallbladder Ca , Melanoma
● Breast Ca:
Young age
ER/PR +ve
Better than BRCA1

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Other genes/Syndromes
1) Li-Fraumeni Syndrome

● P53 Gene
● chr. 17
● 50-90% lifetime Risk of breast Ca

2) Cowden Syndrome

● PTEN Gene
● Chr.10
● 25-50%. lifetime risk of breast ca

3) Hereditary diffuse Gastric ca syndrome

● CDH-1 Gene
● chr. 16
● 60% Lifetime risk of breast ca
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Other Genes/Syndromes

4) Peutz Jegher Syndrome

● STK-11 Gene
● chr. 19
● 30-50% lifetime risk of breast ca
5) Ataxia Telangiectasia
● ATM Gene
● chr. 11
● 15-20%. Lifetime risk of breast ca

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Pathology
● Breast carcinoma arises from the milk ducts in 90% (ductal
carcinoma) or from the lobule in 10% (lobular carcinoma).
● The disease may remain confined to the epithelium of the duct or
lobule with no breach in the basement membrane; this is called in
situ disease.
● Infiltration of the surrounding tissue through a breach in the
basement membrane leads to invasive or infiltrative' ductal or
lobular carcinoma

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Pathology

● The tumour cells may overexpress oestrogen receptors (ER positive),

progesterone receptors (PR positive), human epidermal growth factor
receptor 2/neu (HER2/neu positive) and androgen receptors (AR positive).
The degree of mitosis can be detected by the Ki-67 mitotic index

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 Classification of Breast Ca

In situ Invasive
(15-30%) (70-85%)

Ductal Ca in situ Lobular Ca in situ

(DCIS) – 80% 20%

Paget’s disease of Invasive Invasive Lobular Ca Rare cancers

nipple Ductal Ca 10%
80%
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Invasive ductal carcinoma

● Invasive Ductal Ca -No special type (NST) - 80%

● Medullary Ca -4%
● Mucinous (colloid) Ca - 2%
● Papillary Ca - 2%
● Tubular Ca - 2%

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Clinical manifestation of Carcinoma Breast
● Lump: Hard , painless, fixed to breast tissue
● Nipple discharge: spontaneous, single duct ,
bloody/serosanguinous
● A change in the size or shape of the breast
● The skin of the breast, areola, or nipple may be
scaly,red, or swollen.
● Nipple retraction
● Skin irritation or dimpling
● Breast pain
● Nipple pain or tenderness
● Skin ulceration
● Enlarged axillary or supraclavicular lymph nodes
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Clinical manifestation
● Peau’d orange is a sign of locally advanced disease due
to obstruction of cutaneous lymphatic drainage of the
breast
● Cancer en cuirasse is due to excessive tumor infiltration
of the skin of the breast,chest(in case of post
mastectomy recurrence), upper limb and abdomen

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Paget’s Disease of Breast
● It is ductal carcinoma insitu which spread within the duct , reaches the nipple
and infiltrates the epidermis of the nipple , areola and surrounding skin with
resulting inflamatory reaction , crusting and scaling
● It is rare, accounting for 0.7-4.9% of breast malignancies
● Clinical presentation: Itching , ulceration, eczema like , bleeding, destruction of
NAC
● IOC: Biopsy: Large,pale, vacuolated cells
● IHC: Her 2 Positive, CEA +ve
● Treatment:

Breast conservation with post-operative radiotherapy

Modified Radical mastectomy 18

Spread of Breast cancer
● Local spread
It may involve the skin, leading to ulceration and satellite nodules,
and/or involve pectoralis major, serratus anterior and even the chest
wall
● Lymphatic metastasis
This occurs mainly to axillary lymph nodes. Tumours from the inner
half of the breast may also spread to the internal mammary nodes.
Involvement of the contralateral lymph nodes in the absence of a
contralateral primary represents metastatic disease

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Haematogenous spread
● Haematogenous metastasis occurs to the skeletal
system (in order of frequency: lumbar vertebrae, neck
of femur, thoracic vertebrae, rib and skull).
● Haematogenous metastasis may also occur to the
liver, lungs and brain and, occasionally, the adrenal
glands and ovaries

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Diagnostic evaluation

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Screening and early detection
● Yearly mammograms are recommended starting at age 40 and continuing
for as long as a women is in good health.
● Clinical breast exam (CBE) about every 3 years for women in their 20s and
30s and every year for women 40 and over.
● During clinical breast examination to look for differences in size or shape
between breasts. The skin of breasts is checked for a rash, dimpling, or
other abnormal signs. Look for nipple discharge

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TNM
CLASSIFICATION
OF BREAST
CARCINOMA

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STAGING OF BREAST CARCINOMA

l A : T1 N0 M0
ll A : T2 N0, T1, N1 Early breast Carcinoma
ll B : T3 N0 , T2 N1
lll A : T3N1, T2N2 , T3N2 ……
lll B : T4N0 ,T4N1, T4N2 Locally advanced Breast Ca (LABC)
lll C : T(Any) N3
lV : T(Any) N (Any) M1 Metastatic Breast Ca
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Treatment of Breast carcinoma
● The treatment of breast cancer is multimodal (includes surgery, systemic
treatment [chemotherapy, targeted therapy, hormonal therapy] and
radiotherapy); hence, specialist breast centres employ a multidisciplinary team
(MDT) that should include the surgeon, radiologist, pathologist, radiation
oncologist, medical oncologist, plastic surgeon and allied health professionals,
such as a breast care nurse, psychological counsellor and preferably a genetic
counsellor
● While some patients with low disease burden and low biological aggressiveness
can be treated with surgery followed by adjuvant therapy, others require
downsizing of disease with neoadjuvant systemic therapy or primary systemic
therapy 26
Treatment of Breast Carcinoma

● Neoadjuvant systemic therapy

● Surgery
● Chemotherapy
● Radiotherapy
● Hormonal Therapy
● Targeted Therapy

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Treatment of Breast Cancer
● The two basic principles of treatment are to reduce the chance of local
recurrence and the risk of metastatic spread.
● Treatment of early breast cancer will usually involve surgery with or
without radiotherapy.
● Systemic therapy such as chemotherapy or hormone therapy is added if
there are adverse prognostic factors such as lymph node involvement,
indicating a high likelihood of metastatic relapse.
● At the other end of the spectrum, locally advanced or metastatic disease is
usually treated by systemic therapy to palliate symptoms, with surgery
playing a much smaller role.
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Neoadjuvant systemic therapy
Neoadjuvant systemic therapy (NAST) consists of neoadjuvant chemotherapy (NACT),
targeted therapy or hormonal therapy prior to surgery. It aims to downsize the disease and
enable clinicians to know the in vivo response of the tumour to therapy.

The indications for NACT are as follows:

1)Locally advanced breast cancer T3, T4/N2, N3 disease: to downsize the tumour.

2)Select cases of early breast cancer:

● to downsize the tumour to facilitate breast conservation surgery (BCS);

● HER2/neu-positive tumours;
● triple-negative breast cancer (TNBC); in
● premenopausal women (age <50 years);
● patients with axillary node metastasis.
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Neoadjuvant targeted therapy

Neoadjuvant targeted therapy (trastuzumab, pertuzumab) is administered for

HER2/neu-positive tumours >5 mm in diameter

Neoadjuvant Hormonal therapy

• Neoadjuvant hormonal therapy is offered to elderly or frail women (with ER and/or,
PR-positive advanced tumours) who are deemed unfit to receive systemic
chemotherapy. Neoadjuvant hormonal treatment takes longer (around 3-6 months)
for the response to become clinically evident.

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Response assessment and timing of surgery
The patient is examined 3 weeks after admission of the second cycle of NACT
Response evaluation criteria in solid tumours (RECIST) are used for reporting the response to
NACT.
The four RECIST categories are:
● complete response (CR) (lesion not detectable on clinical palpation and imaging);
● partial response (PR) (≥30% reduction in the maximal diameter);
● stable disease (SD) (<30% reduction in maximal diameter);
● progressive disease (PD) (≥20% increase in the maximal diameter).
For patients with CR and PR, the entire chemotherapy regimen may be delivered prior to surgery
For patients showing stable or progressive disease, after the initial two cycles of chemotherapy,
the patient should undergo surgery and be given second-line chemotherapy after surgery.
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Treatment

DCIS:
BCS+SLNB+/- Radiotherapy (or)
Simple mastectomy(NAC sparing/skin sparing)
LCIS:
Close surveillance
Chemoprevention
Prophylactic B/l Mastectomy

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Treatment

Early Breast Carcinoma(EBC):

Adjuvant chemotherapy—-> Surgery—--->Chemotherapy
Locally advanced breast carcinoma(LABC) :
lll A : Surgery (MRM)-----> Adjuvant chemotherapy (or)
Neoadjuvant chemotherapy—----->BCT
lll B,lll C: NACT—--> Surgery (MRM/BCT)

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Surgical management
● Surgery plays a central role in the management of breast cancer. There
has been a general deescalation towards more conservative
techniques.
● The aim of surgery is to remove all disease in the breast and axilla with
negative margins. The pathologist reports the distance of the tumour
to the nearest excision margin in the breast specimen. Indelible India
ink is applied on the specimen surfaces. There should be no tumour
cells on the cut edge or 'inked margins' of the tumour for invasive
cancer. However, in patients with DCIS a minimum of 2 mm is
considered a safe margin.
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EARLY BREAST CANCER (stages 0, l,II)

● The surgical options for the primary tumour include mastectomy or

BCS.
● Mastectomy is indicated for large tumours (in relation to the size of the
breast), multicentric disease, diffuse microcalcification on a
mammogram indicative of DCIS, BRCA-positive cancers, local
recurrence following BCS or the patient's preference. It entails
removal of the entire breast tissue, including the skin over the tumour,
the nipple-areola complex and the axillary tail.
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Early breast cancer (stages 0, 1,II)

● Skin and nipple-sparing mastectomy is an option in DCIS and early breast

cancers where a mastectomy is indicated and the tumour is >1 cm away
from the skin and >2 cm away from the nipple. The breast may then be
reconstructed using autologous tissue flaps/fat or a silicone breast implant

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Breast conservation surgery (BCS)
● Breast conservation surgery (BCS) is aimed at removing the tumour along with a 1-cm
margin of normal breast tissue.
● This is important if one or more margins is positive on histological examination.
Patients with involved margins should have a revision of margins called a 'cavity
shave'.
● All patients with BCS receive radiotherapy. BCS together with radiotherapy is called
breast conservation therapy (BCT): BCS + RT = BCT.
● Contraindications of BCS: Patients with a multicentric tumour, diffuse
microcalcifications on a mammogram, a large tumour-to-breast ratio, two times
positive surgical margins after re-excision, a history of previous breast or chest wall
radiation, systemic lupus erythematosus or other collagen vascular disease, or
ankylosing spondylitis
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Wide local excision (WLE)
● Wide local excision (WLE) of up to 20% of the breast volume can be
achieved by excision of the tumour with adequate margins and closure
of the defect by approximation of the breast tissue with absorbable
sutures.
● Volume loss greater than 20% or an unfavourable breast-to-tumour
ratio requires an oncoplastic procedure to fill the defect so created by
mobilising the breast tissue.
● Oncoplasty is defined as tumour excision with wide margins followed
by repair of the defect by local rearrangement/ replacement of the
breast tissue and the nipple-areola complex to maintain shape and
symmetry 39
Surgical techniques

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Sentinel lymphnode surgery

● In sentinel node surgery, radiolabeled colloid, blue dye, or both are

injected into breast tissue at the site of the primary tumor; the material
passes through the lymphatics to the first draining node(s), where it
accumulates.
● The sentinel node is identified as a blue, radioactive, fluorescent, or
magnetic node or a combination of these.
● If the pathologic analysis of the sentinel node is negative for evidence of
metastasis, the likelihood that other nodes are involved is sufficiently low
that ALND is not required.

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Adjuvant treatment
Radiotherapy :Radiotherapy is shown to decrease the risk of locoregional and
systemic recurrence and improve survival.

The indications include the following:

● patients with locally advanced breast cancers T3, T4, N1, N2, N3 disease;
● following BCS;
● after mastectomy if: tumour size ≥5 cm; skin or chest wall involvement;
lymphovascular invasion (LVI), axillary lymph node positive for metastasis.

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Radiotherapy

● In pathologically lymph node negative tumours, radiotherapy after

BCS is given to the breast only as a dose of 45-50.4 Gy delivered in
25 fractions or of 40-42.5 Gy delivered in 15 or 16 fractions .
● In patients after mastectomy (T3N0M0), chest wall radiotherapy is
given if the sentinel lymph nodes are negative.
● In patients with lymph node-positive disease locoregional
-radiotherapy is given covering the chest wall, supraclavicular region,
internal mammary nodes and the axilla.

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 Chemotherapy
This is the most common systemic treatment for breast cancer. The following regimens are
used:

● cyclophosphamide (C), methotrexate (M) and 5-fluorouracil (F) (CMF);

● Anthracycline-based regimens: CAF (A, Adriamycin [doxorubicin]), CEF (E,
epirubicin);
● taxane (docetaxel, paclitaxel)-based regimens.

Adjuvant chemotherapy is indicated for all invasive carcinomas >1 cm in diameter, tumours
>0.5 cm with poor prognostic factors (presence of lymphovascular invasion , high grade,
HER2/neu positive, TNBC) and node-positive tumours.
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Chemotherapy
In patients with endocrine-responsive breast cancer, those with luminal A tumours may avoid
chemotherapy if they have a low-risk i.e. ER-positive, HER2/ neu-negative and node-negative
tumours

Patients with a high clinical and genomic risk should be considered for chemotherapy with an
anthracycline (epirubicin) or taxane-based therapy

Patients with luminal B tumours should receive an anthracycline and/or taxane-based therapy
because of the greater risk of relapse.

Those with HER2/neu-positive tumours should receive trastuzumab+pertuzumab along with

chemotherapy (taxane + anthracycline), while those with triple negative tumours should receive
chemotherapy (taxane + anthracycline).

Carboplatin-based regimens may be beneficial for tumours with aggressive biology

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Targeted therapy.

The monoclonal antibody trastuzumab (Herceptin) is effective against the HER2/neu

receptor.

It is used along with pertuzumab to treat HER2/neu-positive tumours along with

chemotherapy.

The cytotoxic agent T-DM1 is used in HER2/neu-positive disease

A chemotherapy agent, emtansine, is conjugated to trastuzumab to allow targeted delivery

of the chemotherapy to HER2-positive cells.

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Hormone therapy.
● The selective oestrogen receptor modulator tamoxifen and aromatase inhibitors (anastrozole,
letrozole, exemestane) are used for hormonal therapy in breast cancer.
● In premenopausal patients only tamoxifen is used for 5 years in low-risk patients and for 10 years
in patients with a high risk of relapse (node positive, tumour >5 cm, LVI).
● Aromatase inhibitors are used in postmenopausal women; in an adjuvant setting they have shown
beneficial effect compared with tamoxifen in terms of relapse-free survival and overall survival.
● They are more expensive than tamoxifen and their use is associated with bone density loss and risk
of fracture.
● A bone density scan is advised prior to commencement of treatment with aromatase inhibitors.
Bisphosphonates with vitamin D and calcium are used to restore bone loss and may also reduce the
risk of recurrence.

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Breast reconstruction - after MRM
1) Immediate
2) Delayed - if patient needs postoperative radiotherapy
● IMPLANTS: Saline

Silicone

At the time of MRM - tissue expander is placed either Subcutaneous/sub-pectoral

● Autologous flaps : Latissimus dorsi Flap

TRAM flap(Transverse rectus abdominis myocutaneous flap)

Pedicled

Free
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Prognosis
Stage is most important.
Single most imp: Axillary LN status.
Single most imp. factor in metastatic breast Ca: ER/PR status
- Nottingham prognostic index (NPI):
NPI = (0.2xsize) + LN Group + Grade(1,2,3)
if NPI : <2.4 = I (Excellent prognosis)
2.4-3.4- II (Good)
3.4-5.4 - lll (modenate)
>5.4 - lV (poor prognosis) 50
Thank you.

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