Breast Cancer Pathology

The histological features of breast cancer depend upon the underlying diagnosis. The invasive component is usually
comprised of ductal cells (unless it is an invasive lobular cancer). In situ lesions may co-exist (such as DCIS).
Typical changes seen in conjunction with invasive breast cancer include:
1. Nuclear pleomorphism
2. Coarse chromatin
3. Angiogenesis
4. Invasion of the basement membrane
5. Dystrophic calcification (may be seen on mammography)
6. Abnormal mitoses
7. Vascular invasion
8. Lymph node metastasis
The primary tumour is graded on a scale of 1-3 where 1 is the most benign lesion and 3 the most poorly differentiated.

Immunohistochemistry for oestrogen receptor and herceptin status is routinely performed.

The grade, lymph node stage and size are combined to provide the Nottingham prognostic index

Breast Cancer Management

TNM definitions
Primary tumor (T):
Tis : CIS; Intraductal ca, Lobular ca in situ or Paget's dis. ē no associated tumor.
T1 : ≤ 2 cm
T2 : 2 -5 cm
T3 : > 5 cm
T4 : Any size involving chest wall or skin

Lymph nodes (N):

NX : Regional lymph nodes cannot be assessed (e.g., previously removed)
N0 : No lymph node metastasis
N1 : Palpable, mobile involved ipsilateral axillary lymph node(s) (usually 1-3 nodes)
N2 : Fixed involved ipsilateral axillary lymph node(s) (usually 4-9 nodes)
N3 : Ipsilateral internal mammary lymph node(s) (usually >10 nodes)

Nodal status is important because it serves as a marker of tumor metastatic potential

Distant metastasis (M):
MX : Presence of distant metastasis cannot be assessed
M0 : No distant metastasis
M1 : Distant metastasis present (includes supraclavicular LN)

AJCC stage groupings

0 : Tis, N0, M0
I : T1, N0, M0
II : T1/2 , N0/1 , M0
III : T4 , N0-3 , M0
IV : Any T, Any N, M1
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Nottingham Prognostic Index (NPI)
NPI can be used to give an indication of survival. In this system the tumour size is weighted less heavily than other
major prognostic parameters.

Calculation of NPI : Tumour Size x 0.2 + Lymph node score(From table below)+Grade score(From table below).

Lymph nodes involved Grade

Score

1 0 1

2 1-3 2

3 >3 3

Prognosis

Score Percentage 5 year survival

2.0 to 2.4 93%

2.5 to 3.4 85%

3.5 to 5.4 70%

>5.4 50%

● Triple Assessment should be done in all lumps of breast

Clinical examination
Imaging (US or Mammo)
Cytology/ histology (FNAC, core / truecut / open biopsy)

● Surgery is performed in most patients suffering from breast cancer.

● Chemotherapy used to downstage tumours & allow breast conserving surgery. Hormone therapy may be used for the
same purposes.

● Radiotherapy is given to all patients who have undergone breast conserving surgery.

● Patients who have undergone mastectomy may be offered a reconstructive procedure either in conjunction with their
primary resection or as a staged procedure at a later date.

● Surgical options: Mastectomy vs Wide local excision

Mastectomy Wide Local Excision

Multifocal tumour Solitary lesion

Central tumour Peripheral tumour

Large lesion in small breast Small lesion in large breast

DCIS >4cm DCIS <4cm

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 Patient Choice Patient choice

Central lesions may be managed using breast conserving surgery, where an acceptable cosmetic result may be
obtained, this is rarely the case in small breasts

● Axillary disease
• As a minimum, all patients with invasive breast cancer should have their axilla staged. In those who do not
have overt evidence of axillary nodal involvement this can be undertaken using sentinel lymph node biopsy.
• Patients with a positive sentinel lymph node biopsy or who have imaging and cytological or histological
evidence of axillary nodal metastasis should undergo axillary node clearance.
• Axillary node clearance is associated with the development of lymphoedema, increased risk of cellulitis and
frozen shoulder.
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● USG is the 1 line imaging of breast <35 yrs
st
Mammo is the 1 line imaging of breast >35 yrs, (USG is also done )

● FNAC provides cells for cytology, not tissue for histology. FNAC inconclusive then Core/ Truecut biopsy

indicated
● CORE/ TRUECUT BIOPSY provides tissue for histology.

● If feature – shows carcinoma; (e.g. hard mass, skin tethering present)in those cases only appropriate Invx is core/
truecut biopsy

● (+)ve core biopsy is mandatory b4 proceeding to a cancer operation

● OPEN BIOPSY is done when diagnosis was not possible in triple assessment (no more than 20gm tissue is removed.)
● STEREOTYPE CONE BIOPSY used where there’s no abnormality in palpation but mammo suspicious (e.g.
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diffuse calcific )

● BRCA-1; long arm chromosome-17 : cancers of breast, ovary, prostate, colon

BRCA-2; long arm chromosome-13 : cancers of breast(male, female), ovary

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● Surgery is 1 line RX for breast ca.,Although, breast conserving surgery WLE(Wide Local Excision) is done where
its possible.
● INDICATION OF WLE
• stage I or II disease
• single primary lesion
• < 4 cm (poor cosmetic results in WLE for tumors > 4cm; however >4 cm may b treated ē WLE if big breast

● If vascular invasion, an axillary clearance is needed. Following surgery, then chemotherapy. Note: the practice of
sentinel node biopsy is alternative & recommended in every woman with breast ca (RCS guidelines). Using a dye
technique, if the sentinel node is found to be cancer-free, women can be spared axillary surgery.

● Treatment with radiotherapy is mandatory in the case of a young woman who has undergone breast conservation
surgery

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● breast-conserving surgery a course of ipsilateral chest wall radio to prevent local

recurrence. radio can also be used to treat the chest wall, post mastectomy, for those pt. ē high risk of

local recurrence:
- Grade III multifocal or near to skin or muscle
- ≥ 4cm
- Presence of lymphovascular invasion
- >3 LN(+)ve in axilla

● MASTECTOMY is usually required if ca is : >4cm; multi focal; centrally situated.

Simple : Breast tissue + some skin + nipple
Subcutaneous : Only breast tissue removed. Skin + nipple intact
Radical : Breast tissue + some skin + nipple + Pectoralis’ + axillary contents
Radical(modified) : Radical mainly (but pectoralis not removed)
Radical(Patey modified) : Modified Radical mainly (Here pectoralis minor division not done)

● Breast conserving surgery, WLE( Wide Local Excision) is usually in UK : high rate of recurrence

● H/O WLE, now presenting with hard mass just below previous scar; mammo & USG inconclusive,-These types cases
requires MRI to differentiate scar from recurrent ca --- pls consider, recurrence

● Complications of breast surgery

• Long thoracic nerve injury: This may occur during the axillary dissection and result in winging of the scapula.
• Intercostobrachial nerve injury: These nerves traverse the axilla. When they are divided (which they often
are) the patient will notice an area of parasthesia in the armpit.
• Injury to the thoracodorsal trunk: This nerve and vessels supply latissimus dorsi. If they are damaged the
functional effects are not too serious, the greatest setback is that a latissimus dorsi flap cannot be used for
reconstruction purposes.
• Infections: Cellulitis of the chest wall and arm may be a major problem if axillary nodal clearance is
undertaken. Infections may run a protracted course and require polytherapy for treatment.
• Lymphoedema: Usually complicates axillary node clearance or irradiation. Treatment is with manual lymphatic
drainage and compression sleeves.
• Seroma: This is an accumulation of fluid at the site of surgery. The fluid is usually straw coloured and may re-
accumulate despite drainage. Most will resolve with time.

● Axillary LN clearance
Level 1 : LN upto lat.border of PM (removes nodes around Ax.V. superficial to PM & Ax tail)
Level 2 : All LN upto med.border of P.minor (nodes deep to PM)
Level 3 : All LN of axilla (requires division of P.minor) (upto apex of axilla)

● Axillary LN Stations
Level 1 : Inferior to P.minor
Level 2 : Behind the P.minor
Level 3 : Above the P.minor

● Hormonal Thearapy is Used:

- To ↓ risk of local, regional & distal recurrence
- To ↓ risk of development of contralateral breast Ca.

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● Usually ER & PR (+)ve pt. cases :- hormonal therapy used

● Hormonal Therapy – 3 types drug used- SERM(Selective Estrogen Receptor Modulator) , Aromatase inhibitor,
LHRH agonist
- Tamoxifen – SERM . It binds with estrogen receptor and blocks estrogen action
TM
- Anastrozole(Arimidex ); Letrozole; Aminoglutethemide; Exemestane:- Aromatase inhibitor. They
block peripheral convertion of androgen to estrogen and also block intra-tumoral synthesis of estrogen
TM
- Goserelin(Zoladex ): - LHRH agonist. Used incase of pre-menopausal ER(+) ve women

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● Elderly & unsuitable for GA ē ER (+)ve ca:– usually Tamoxifen/ Arimidex used to control disease Progres .
Arimidex – most popular

● One of the main problem of Tamoxifen : Cant be used with the H/O thrombosis

● Post menopausal ē ER(+)ve invasive ca:Who cant use Tamoxifen, they are suggested to take Anastrozole.

● ER(-)ve suggests poor response to hormonal therapy ē tamoxifen. In these cases (+)ve C-erb B2 (HER2/neu)
suggests TRASTUZUMAB (Herceptin) may be effective

● Chemotherapy used usually - FEC (5-FU,Epirubicin, Cyclophosphamide) or CMF(Cyclophosphamide , MTx,5-FU)

- Young / pre-menopausal
- LN (+)ve & lymphoreticular invasion
- ER (-)ve
- Grade III pt.
- Large tumor

● NEO-ADJUVANT CHEMO
- Young pt. with high grade ca specially if >3cm
- To down-stage the tumors with an aim to provide breast conserving surgery

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● RX LOCALLY ADVANCED CA (ulcerating; hard,fixed2skin/muscle of chest, back, neck; nipple retract ; orange;
edematous; large palpable LN; ca en cuirasse)
- Toilet mastectomy(non-curative attempt)
- Radiotherapy(↓bleeding from ulecerated tumor)
- Hormone therapy if ER(+)ve
- Chemotherapy

● INFLAMMATORY CA : warm, oedematous, erythematous breast, may be get confused with cellulites. Jaundice may
present. Often occurs during pregnancy and lactation. It is classified in Stage – III, straight-forward. Rx is:
- Primary chemotherapy
- Then mastectomy and axillary clearance

● Metastatic ca RX : hormonal & chemo therapy

● Cause of periductal mastitis in smoker postmenopausal women is anaerobic bacteria. Rx would be metronidazole.

● ANDI (Aberration of Normal Development & Involution) group

- Cyclical mastalgia
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- Cyst
- Sclerosing adenitis
- Duct actasia
- Fibroadenoma
- Pappiloma