Breast Cancer

# Cancer Breast Patients at KAUH:

< 60 YO  85.1 %

< 50 YO  64.5 %

< 40 YO  30.6 %

# Incidence:

12% life time risk

# Introduction:

 Monoclonal
 Average doubling time = 100 days
 One cell  1 cm lump in 8 – 10 years
 At 2nd or 3rd year  Hematogenous & lymphatic invasion by cancer cells
 Women die from breast cancer because of metastasis
 Local surgical treatment to control local disease & may prevent further metastasis
 Systemic treatment should be considered in all

# Risk factors:

Major:

 Age (elderly)
 female (100 x male risk)
 Family Hx (especially: young, bilateral, more than 1 relative)
 Cancer breast in other side (more common in < 50 YO, lobular)  1 - 3%
synchronous contralateral cancer , 5 – 8 % metachronous bilateral breast CA
 Carcinoma in situ
 Prior lumpectomy [of breast]
 Atypical epithelial hyperplasia  4 x risk
 Hyperplasia (moderate/florid)  2 x risk
 DCIS , LCIS
 Mutation of the major breast cancer susceptibility inherited genes (BRCA I & II) 
very IMPortant (easy: BR = Breat Cancer, CA = cancer)

Minor:

 Nulliparous
 1st pregnancy after age of 30 - 35
 Early menarche < 12 – 13 YO
 late menopause > 51 - 55 YO
 OCP, HRT for 10 years  1 – 1.5 relative risk
 Diet (↑ fat & alcohol)
 Endometrial Ca
 Obese
  Radiation
 No breast feeding

NOTE: fibrocystic disease is NOT a risk factor for breast cancer

# Common signs & symptoms:

1. No symptoms 
2. Palpable mass
3. most are painless
4. Nipple discharge (Intraductal papilloma is the most common cause of bloody nipple
discharge in young woman)
5. Nipple rash\retraction
6. Skin changes (dimples)  skin retraction occurs due to tumor involvement of
Cooper's ligaments and subsequent traction on ligaments pull skin inward
7. Local edema
8. Palpable axillary/supraclavicular lymph nodes

# Clinical Presentation:

 Most common site: UOQ (50%), Lt Breast

 Ill defined, hard, fixed, lump in the breast

# Hx of metastasis in Breast Ca:

 Brain  projectile vomiting WITHOUT nausea, headache, seizures

 Lung  cough (early), hemoptysis
 Liver  RUQ pain, Jaundice
 Bone  Pain
 Wt loss

NOTE:

Lymph nodes are the most common site of metastasis, & Bone is the most common site for
"distant" metastasis

# TNM staging:

(T)

0  no primary tumor

IS  in situ (DCIS, LCIS), Paget's sisease WITHOUT tumor

1  less than 1 cm

2  2 – 5 cm

3  more than 5

4  Peau D'Orange (orange peel)  the appearance of the edema of dermis in

inflammatory carcinoma of the breast
(N)

0  no LN metastasis

1  ipsilateral axillary LN  movable

2  ipsilateral axillary LN  fixed

3  ipsilateral intramummary LN

4  ipsilateral supraclavicular  which is distant metastasis

(M)

0  no distant metastasis

1  distant metastasis [skeletal (most common) especially lumbar, liver, lung, brain, others]

# Staging:

T
Stage Total TNM N Survival rate
M
TIS
0 N0 95%
M0
T1
I 1 N0 85%
M0
T1 T2
A 2 N1 N0 70%
M0 M0
II
T3 T2
B 3 N0 N1 60%
M0 M0
T any
A (Total N = 2) N2 55%
M0
T any
III (Total N = 3) N3
M0
B 30%
T4
7 (Total T = 4) N any
M0

IV Whenever there is metastasis (M = 1) 5 – 10 %

# Screening:

a. Breast Self Exam (BSE)  At 20 YO, monthly , best time: 7 – 8 days (1 week) after
menstrual period
 b. Physical examination (by physician) 

 20 – 40 YO: Q 2 – 3 years
 >40 YO: annually

c. Mammography 

 40 - 50 YO: Q 1 – 2 years (every year, or every other year)

 > 50 YO: annually (maximum benefit from age 50 – 69 YO)

# Diagnosis (work up for a breast mass):

[1] Clinical breast Exam

[2] breast Ultrasound / Mammogram:

 Younger age (less than 35 YO)  do US, as they have more fibrous tissue, which
makes mammograms harder to interpret.
 Those over 35 YO  mammogram, as breast tissue undergoes fatty replacement
with age, making masses more visible.

 US:

When you do an US  It will tell if it's cystic or solid:

If it's cystic  do FNA (fine needle aspiration)  see:

o If the mass disappears after aspiration  That's fine (fibrocystic disease) 

Follow Up (F/U)
o If it's bloody (increased vasularity: indicate CA) do biopsy
o Cytology is done for nipple discharge, but not routinely done for breast
cystic fluid; bloody fluid should be sent for cytology

If it's solid  excise

 Mammography:

Radiological Classification [Breast Imaging Reporting & Data System (BI-RADS) Catergory]:

0  need additional imaging evaluation

1  negative

2  benign finding

3  probably benign finding  6 months follow up

4  suspicious abnormality  consider biopsy

5  highly suggestive of malignancy  appropriate action should be taken

6  known (biopsy proven) malignancy  treat

Signs in mammogram suggestive of malignancy?

1) Irregular / Spiculated mass (classic picture of breast cancer on mammogram)

2) Distortion of breast architecture
3) Asymmetrical fibrosis
4) Microcalcephications
5) Increased vascularity
6) Skin thickening / skin edema

NOTEs:

 The mammogram is obtained 1st before biopsy, as tissue extraction (core or open)
may alter the mammographic findings.
 FNA may be done prior to the mammogram b'coz the FN usually will not affect the
mammographic findings.

[3] Biopsy:

Indications of Biopsy:

- Persistent mass after aspiration

- Solid mass
- Blood in cyst aspirate
- Suspicious lesion by mammography/US/MRI
- Bloody nipple discharge
- Ulcer or dermatitis of nipple
- Patient's concern of persistent breast anomaly

Types of Biopsy:

1) Open incisional biopsy

2) True cut (open excisional) biopsy  most reliable
3) Core needle biopsy
4) Mammographic localization needle biopsy
5) Mammotome biopsy (computerized stereotactic imaging-guided needle biopsy)

Proceed to open biopsy of breast cyst in case of:

- Second cyst recurrence

- Bloody fluid in the cyst
- Palpable mass after aspiration

What you need to Do?

 Hormone receptor assay (immune-histo-chemistry):

Check for estrogen (ER) & progesterone (PR) & HER-2 (human epidermal growth
factor 2) receptors in the biopsy specimen
  Pathological Classification (Grading):

1) Non-invasive:  Carcinoma In Situ

o DCIS (Ductal Carcinoma In Situ), aka Intraductal Carcinoma  cancer cells
in the ducts without invasion .. (Age: same as invasive CA)
o LCIS (Lobular Carcinoma In Situ)  carcinoma cells in the lobules of the
breast without invasion .. (Age: > 50 % premenopausal)

Incidence: 2 -3 % of all breast Ca

Axillary LNs are rare (less than 2%, usually when microinvasion is seen with DCIS), so LN
dissection is not required

Multi- Transformation to Beast CA

Diagnosis Treatment
centricity incidence Type Which breast
(NSABP B-17, B- 40 – 60 % Ductal Ipsilateral
24)
Cluster of
- breast
microcalcifications
conservation
on mammogram
- lumpectomy +/-
(80%) , nonpalpable
RT if ≥ 1 cm clear
mass.
margin  considered premalignant lesion, if
Core or open
- if close or +ve untreated  potentially fatal invasive
biopsy  histologic
margin  skin cancer:
, cytological factors,
DCIS 35 %. sparing
nuclear geade,
mastectomy or Subsequent development of infiltrating
presence or
simple ductal carcinoma (30%) in the same breast
absence of
mastectomy +/- (Cancer arises Directly in the ipsilateral
necrosis.
reconstruction + breast)
The most
tamoxifen
aggressive
- axillary LN
histologic type is
dissection &
Comedo (necrosis).
systemic therapy
is NOT indicated.
- close 20 % Ductal Bilateral
observation
(physical exam
every 6 – 12
months & annual  considered a marker for ↑ risk of
mammograms, invasive CA:
monthly BSE)
- consider Equal risk of invasive carcinoma in both
Found incidentally prophylactic breasts (LCIS is a risk marker for future
on biopsy, no tamoxifen 10 mg development of cancer in either breast).
& bilateral
LCIS mammographic BID for 5 years
(60 – 80 %)
findings (occult), no OR About 30% of women with LCIS develop
lump (never) - bilateral, invasive breast CA in the 20 years after
prophylactic diagnosis.
simple
mastectomy w/ Most common type, infiltrating ductal
or w/out carcinoma, with equal distribution in the
reconstruction as contralateral & ipsilateral breasts.
the marker lesion
in itself may not
be dangerous.
 2) Invasive: [atypical hyperplasia on mammotome biopsy]
1. Ductal  5 subtypes:
 Medullary
 Colloid
 Tubular
 Papillary
 Scirrhous
2. Lobular
3. Paget's:
Scaling Rash / Dermatitis (Itching or burning) of the nipple (caused by
invasion of skin by cells from a ductal carcinoma), superficial erosions or
ulceration of the skin +/- mass  underlying invasive ductal CA in X %
Treatment: mastectomy or excision of nipple-areolar complex if limited to
retroareolar area
4. Inflammatory:
The most malignant form of breast CA. metastasis is common at time of
diagnosis.
C/P: rapidly growing, diffusely enlarged breast. Skin is erythematous,
edematous & warm. NO mass.
Dx: redness of 1/3 of breast skin + biopsy shows invasion of subdermal
lymphatics.
Suspect it if: "MASTITIS" doesn't clear up in 1 – 2 weeks with antibiotics 
do biopsy.
Treatment: Chemotherapy 1st..!! Then often followed by radiation,
mastectomy, or both.

 Histological Grading:  NOTE: It's old & not used currently

Grade 1: well differentiated breast cells; cells generally appear normal

Grade 2: moderately differentiated breast cells have characteristics between grade 1 and
grade 3 tumor
Grade 3: poorly differentiated breast cells

# Investigations:

a. All patients must be tested for:

1. LFT especially ALP
2. CXR
b. Symptomatic / previously test +ve :
1. Brain CT (headache, vomiting)
2. Chest CT (nodule on CXR)
3. Abdomen CT (↑ ALP, jaundice)
4. Bone scan (bone pain, ↑ ALP)

# Management:

 Pre-operative evaluation of patients with primary operable breast CA:

 Complete Hx & physical Ex

  Bilateral mammography (cancer in one breast is a risk factor for cancer in the
contralateral breast).
 Chest radiograph (CXR) to check for lung metastasis
 LFTs to check for liver metastasis
 Further studies only when indicated by symptoms.

 Prognostic factors:

May be at higher risk to develop metastasis

High risk group (many +ve factors) may benefit from systemic therapy

Proven factors:

 Tumor size
 Axillary lymph node status
 Estrogen & progesterone receptor status (ER & PR)
 Human epidermal growth factor receptor (HER-2 / neu)

Questionable value:

 Breast mucin marker (CA 15-3, CA 549, CAM 26, CAM 29)
 CEA
 Mutation of tumor suppressor gene TP 53 (P53)
 S-phase fraction
 Ki-67 antibody
 Thymidine labeling indix (mitotic indix)

 Choice of management depend on:

1. Stage (more mportant than grade)

2. Histologic grade
3. Hormone receptor assay

 General Guidelines:

 Hormonal therapy:
Check estrogen, progesterone (ER & PR) & HER-2 receptor status of the biopsy in all
patients using immune-histochemistry  affects the response to hormonal therapy

+ve -ve
ER 60 % response < 5%
PR 80 % response

+ve ER may carry a better prognosis.

Available treatments:

1. Tamoxifen: in pre- & post- menopausal. 10 mg twice daily for at least 2 years.
 SFx :
- Endometrial CA (2.5 relative indix)
- DVT, pulmonary embolism
- Cataract
- Hot flushes
- Mood swings

NOTE: if chemotherapy is used, Tamoxifen is started AFTER the completion of chemo.

2. Aromatase inhibitors (e.g. Letrozole) : used as second line treatment in

postmenopausal patients (only) failing hormonal treatment.

If HER-2 is strongly +ve (score +3), Herceptin (trastuzumab) [monoclonal antibody IV] can be
given.
25% of CA breast over express HER-2. These tumors grow faster & recurs more than HER-2
–ve.
SFx:
- Fever +/- chills
- Weakness, nausea, vomiting, …
- Cardiac & respiratory failure

 Types of Breast Surgery (Mastectomy):

 Subcutaneous: removal of breast tissue, spares nipple-areolar complex, skin &
nodes. NOT a CA operation.
 Partial: Removal of part of the breast; e.g. lumpectomy
 Total (Simple): removal of the whole breast
 Radical: removal of the breast tissue + axillary LNs + underlying pectoralis
muscle. (rare to be done)
 Modified Radical Mastectomy (MRM): removal of the entire breast + axillary LNs
but not muscle

 Chemotherapy:
 Types:
- CMF: cyclophosphamide, methotrexate (MTX), 5-fluorouracil (5FU) 
used to be 1st line
- CAM: cyclophosphamide, Adriamycin, 5-fluorouracil (5FU)
- Taxotere (Taxol)  1st line now
 Indications:
A. Neoadjuvant chemotherapy (before Sx):
Taxane (paclitaxel / Docetaxel) + Doxorubicin given preoperatively to down
stage the cancer.
B. Adjuvant chemotherapy (after Sx):
Given postopearatively to kill residual tumor & eliminate microscopic mets.
C. Rx of metastasis to liver, lung, brain

 Management of breast cancer according to stage:

In all stages, if receptor +ve  give hormonal therapy

[1] stage I & II:

We have 2 options (MRM or BCT) + chemo if LN +ve, high grade (poorly differentiated), or
invasion of lymphatics:

a) Modified radical mastectomy (MRM):

Remove everything with sparing of pectoralis major muscle.
b) Breast conservative therapy (BCT):
Lumpectomy with negative margins + axillary LN dissection or sentinel LN(s) (SNL)
biopsy + irradiation to breast

 in the OR  we do lumpectomy. Then ask the pathologist for frozen section to see if the
margins of breast are diseased or not. If it's –ve [no disease]  map out the sentinel LN (1st
regional set of LNs to receive the tumor cells; primary draining LNs) by injecting the breast
with a dye (methylene blue or technetium-labeled sulfur colloid). If the dye was taken by 1st
LN in the breast, it means that the LNs are diseased  remove them all (dissection). Then, 2
weeks later start Radiotherapy.

 SNL –ve:
- No further axillary dissection 
- False –ve is negligible
- Little risk of axillary failure in SNL-ve patients with no axillary dissection
 SNL +ve:
- Complete axillary dissection or NOT..!!  Ongoing observation vs axillary
dissection.
- Axillary dissection is necessary if:
1. Significant probability of additional tumor bearing nodes (+ve
nodes).
2. Axillary dissection has therapeutic value.

 BCT in Saudi Arabia is done in 15.7% patients, WHY? (USA = 45.7%)

- Late Presentation
- No standard Protocols for treatment
- Neoadjuvant chemotherapy is stage III is not widely used

 Relative contraindications of BCT:

- Large mass in small sized breast
- Subareolar tumor
- Multifocal tumor

 How do you choose: MRM or BCT?

1. Factors favoring BCT:
- Patient preference
- Tumor location & size are favorable for anesthetic result
- Unifocal tumor
- High risk for general anesthesia
 2. Factors favoring MRM:
- Patient preference
- Multifocal tumor
- Difficulty with follow-up anticipated
- Inability to achieve –ve margin at lumpectomy
- Large mass in small sized breast (no cosmetic advantage)
- Contraindication to radiotherapy:
o Pregnancy  major contraindication
o Previous radiation to the chest
o Collagen vascular disease; like scleroderma

 Potential complications after MRM:

- Ipsilateral arm lymphedema
- Infection
- Injury to nerves
- Skin falp necrosis
- Hematoma / seroma
- Phantom breast syndrome

[2] stage III:

Down staging using neoadjuvant chemotherapy then treat as stage I & II.

[3] stage 4:

Palliative treatment (10 – 20 %). Mainly hormonal +/- chemo, radio, mastectomy.

 Breast reconstruction:

It doesn't prevent the diagnosis of recurrence. (see Mont Reid)

1. Prosthetic Implant between pectoralis minor & major. Usually, saline filled.
Also, silicon.
2. TRAM flap  Transverse Rectus Abdominis Myocutaneous flap (see Surgical
Recall page 379, 4th Edition)
3. Latissimus dorsi flap
4. Other flaps

# Follow-Up:

Metastasis occurs most frequently within the 1st 3 years, & risk ↑ with +ve LN involvement:

A. Physical Ex: Q6 months for 3 years, Q 6 – 12 months for 2 years, Q 12 months

forever.
B. BSE: monthly
C. Mammogram: annual
# Recurrence:

Factors associated with high risk of recurrence:

1. Young age ( < 35 YO)

2. Tumor > 2 cm (stage II)
3. Poor histologic grade
4. –ve ER & PR
5. Over expression of HER-2

Best of Luck… 

angelic_doc
Sources:

(Dr. Hassan Moria) Kia Ora's summary sheet 2008 – DiDi's sheet (Current & Browse Text
Books) – Surgical Recall – Prof. Adnan Merdad's Lecture 2006 – Dr. Mohammed Gogandy's
"IMPORTANT POINTS in The Surgical Clinical Exam" 2007-2008.