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.
