Carcinoma of the breast

• Incidence:
- Generalized enlargement of the thyroid gland
- Breast cancer is the most commonly diagnosed cancer in women worldwide (23% of total cancers)
- Most cases develop after the age of 50 with a peak at 70 years.
- It’s rare under the age of 30

• Risk factors:
1. Age: most important factor, most cases develop after the age of 50 with a peak at 70 years
extremely rare below the age of 20 years,
2. Gender: 99% of breast cancer is in women
3. Genetics: BRCA1, BRCA2 and p53 → familial (run in family)
o BRCA1 associated with breast, ovarian and colorectal cancers, BRCA2 is associated with
male breast cancer.
4. Diet: high alcohol intake increases the risk while caffeine decreases the risk. Smoking hasn’t been
proven to be a risk factor.
5. Endogenous estrogen exposure:
▪ Early menarche or Late menopause
▪ Nulliparity
▪ Age of first pregnancy after 35 years
▪ Postmenonpausal obesity BMI >28, due to increased conversion of steroid to estradiol
▪ Chronic liver disease
▪ Breastfeeding history (breastfeeding is a protective factor)
6. Exogenous estrogen exposure:
▪ Contraceptives: increased risk during use, lowers to baseline at 10 yrs after discontinuation)
▪ Hormonal replacement therapy for >5 years >age 50 years
7. History of previous breast cancer, invasive or in situ carcinoma
8. Precancerous conditions: Ductal papilloma, fibrocystic disease

• Features suggesting familial breast cancer:

1. Very young at presentation
2. Family history of male with breast cancer
3. Bilateral breast cancer: a patient treated in one breast and then after a while develops breast
cancer in the other breast
 Next step is to screen the family members for breast cancer (MRI)

• Types of primary breast cancer:

A. In situ breast cancers (the basement membrane is not breached):
▪ Ductal carcinoma in situ (DCIS): More common, associated with micro-calcification
▪ Lobular carcinoma in situ (LCIS): Less common tend to be multifocal and bilateral
B. Invasive breast cancer:
▪ Ductal carcinoma, the most common (78%). Classical firm lump
▪ Lobular carcinoma (5-10%), may be bilateral and multicentral
▪ Mixed: both ductal & lobular features

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 ▪ Medullary carcinoma (5-7%): intense infiltration by lymphocytes and plasma cells.
▪ Mucinous (colloid) carcinoma (3%), its cells produce abundant mucin
▪ Tubular carcinoma (2%)
▪ Papillary carcinoma (1-2%)
▪ Inflammatory carcinoma, a rare, highly aggressive cancer
▪ Paget’s disease of the breast, it’s an intraductal carcinoma that reaches the skin of the nipple.

• Spread of breast cancer:

A. Local spread:
▪ To the skin, pectoral muscles and even the chest wall if diagnosed late.
B. Lymphatic spread:
▪ Primarily to the axillary lymph nodes
▪ Tumors in the posterior one-third of the breast are more likely to drain to the internal
mammary nodes.
▪ Involvement of supraclavicular LN or any contralateral LN represents advanced disease.
C. Blood stream spread:
▪ to the lungs, bones (in order of frequency: lumbar vertebrae, femur, thoracic vertebrae, ribs,
skull), brain and liver.

• Hormone receptors:
1. Estrogen receptors (ER +ve): in 60% of breast cancers
2. They may also exhibit progesterone receptors (PR +ve)
3. About 20% exhibit HER2/neu receptors (human epidermal growth factor receptors)
4. About 30% of patients are don’t have any of the receptors (Triple negative)
 Overexpression of HER2/neu or triple negative indicates a worse prognosis.

• Presentation:
A. Symptoms:
▪ Painless breast lump: The majority of breast cancers (50%) are located in the upper outer
quadrant.
▪ Nipple changes: Bloddy discharge, circumferential retraction.
▪ Constitutional symptoms: wight loss, anorexia, fever
B. Signs:
▪ Breast: asymmetry, enlargement
▪ Nipple changes: Discharge, Dimpling of skin, Deviation, Displacement, Destruction, Retraction.
▪ Skin change: Ulceration, erythema, dimpling, Tethering of the skin, Péau dé orange, ,
▪ Mass (lump): hard, irregular, ill defined, mobile, Fixed with skin, and underlying tissue.
▪ LN: Axillary and supraclavicular lymph nodes: number and mobility of palpable lymph nodes
C. Symtpms and sign of distant mets:
▪ Bone: Spinal cord compression (most common), Bone pain, pathological fractures
▪ Lung: Pleurisy, dyspnea, cough, hypercalcemia
▪ CNS: Behavioral changes, fits & convulsions,
▪ Liver: Hepatomegaly, jaundice, ascites

 Skin tethering due to invasion and shortening of ligament of cooper

 Skin fixation: direct infiltration of skin by the tumor

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• Staging:
- The management and prognosis of breast cancer depends on the stage of the disease.
- Axillary lymph nodes are the most important prognostic factor.
- There are 2 common systems of staging: the international TNM staging system and the union for
international cancer control staging (UICC)

1. TNM staging system

T: tumor size Tis: in situ

T0: no tumor
T1: <2 cm
T2: 2 - 5 cm
T3: >5 cm
T4: regardless of size:
A: invade the chest wall
B: invade the skin: ulceration, satellite nodules, peau d’orange
C: invade both
D: inflammatory CA & fungating

N: Node N0; no LN invasion

N1: mobile ipsilateral axillary
N2: fixed ipsilateral axillary
N3: contralateral side/ edema

M: met M0: no mets

• M1: mets / supraclavicular LN

2. UICC staging

Stage UICC Description Category

Stage 1 T1, N0, M0 Early breast cancer
Stage 2 2a T2, N1, M0 Early breast cancer
2b T3, N0, M0 Locally advanced breast cancer
Stage 3 3a T1-3, N1-3, M0 Locally advanced breast cancer
3b T4, any N, M0 Locally advanced breast cancer
Stage 4 Any T, any N, M1 Metastatic

• Investigations:
A. Aim: Diagnosis carcinoma, staging, general condition of the pt.
B. Triple assessment:
1. Hx & clinical examination
2. Imaging: US or mammography
3. Tissue pathology: FNAC or true cut biopsy
C. For staging: CXR, US abdomen, ALP, MRI brain, MRI spine, bone scan , pelvic X-ray

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• Treatment of Breast Cancer:
1. Early Breast CA:
- curative treatment, for Stage 1 or 2a
- Either breast conservative surgery, or modified radical mastectomy.

• Breast conservative surgery (BCS):

 Method:
1. Wide local excision with 2cm Safety margin
2. Sentinel LN Biopsy; if +ve → Axillary LN clearance
3. Post op radiotherapy for 4 weeks
4. Hormonal therapy:
▪ Estrogen receptor +ve: Tamoxifen (ER blocker), Anastrazole (aromatase inhibitor)
▪ HER2/Neu +ve: monoclonal Antibody: Herceptin, Trastuzumab
5. Chemotherapy: +ve axillary nodes, <70 yrs, more than 1 cm, HER2/Neu +ve /ER -ve

 Indications:
a. Small tumor ≤ 4cm
b. Solitary or multifocal lesions (lesions present in one quadrant)
c. Peripheral lesion
d. large lesions in large breasts

 Contra indications:
a. Central lesion
b. Multi-centeric lesions
c. extensive micro-calcifications
d. Pregnancy, in situ

• Modified radical mastectomy (Patey’s operation):

 Method:
a. Simple mastectomy + axillary clearance + breast reconstruction (skin flap using
latissimus dorsi muscle or transverse rectus abdominis muscle Flap)
b. Adjuvant radiotherapy

 indications: (BCS Contra indications)

a. Central tumors
b. Multi-centeric tumor (tumors in more than one quadrant)
c. Pregnancy (do simple mastectomy in which axillary LN are not dissected)
d. Large tumors in smaller breasts.
e. Local recurrence
f. Patient preference

• Follow up: every 6 months for 5 years, then annually for 10 years by mammography.

2. Locally advanced (stage 3):

• Neoadjuvant chemotherapy → downstage cancer
• If responded → BCS (breast reconstruction surgery)
• if not → modified radical mastectomy + palliative chemotherapy

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 3. Advanced breast CA: (stage 4)
- The aim is palliation and improving the quality of life
- Palliative measure:
• Radiotherapy, for palliation of pain or ulceration
• Chemotherapy, the basic treatment of metastatic disease, response rate is 60 – 70%.
• Hormone therapy: for receptor +ve patients. Tamoxifen is not given for more than 5 years
to avoid the risk of endometrial cancer or thrombogenesis. If no response use aromatse
inhibitors.
• Surgery is indicated for the following case
a. Toilet mastectomy for unpleasant malodorous fungating tumor (only improve
appearance and quality of life and not done to cure the cancer)
b. Pathological fractures: Internal fixation
c. Spinal cord compression: Urgent decompression and stabilization of the spine
• Cerebral metastases: corticosteroids + radiotherapy
• Pleural effusion: systemic therapy and chest tube drainage. If not, give cytotoxic bleomycin
• Liver metastases: chemotherapy.

4. Chemotherapy:
• Indications of chemotherapy:
a. LN +ve
b. Triple negative tumors
c. HER2/neu +ve
d. Large tumors
e. Stage III & IV
f. Metastases
g. Lymphovascular invasion
• Agents used in chemotherapy:
a. First-generation regimen: Cyclophosphamide, methotrexate and 5-fluorouracil
b. Modern regimens (2nd & 3rd generations): Anthracycline (doxorubicin or epirubicin) +
Taxanes.

• NB.:
- Axillary clearance 5% risk for lymphedema (useless arm)
- Axillary radiotherapy 5% risk
- If Both 30% risk, so: don't do both
- Complications of modified mastectomy:
1. Nerve injury: Medial pectoral or Lateral pectoral N, Intercostobrachial N, N. to serratus ant.
(Long thoracic N.), N. to latissimus dorsi.
2. Frozen shoulder
3. Lymphedema
4. Psychological