Breast Cancer : Features, Diagnosis and Management
Breast cancer is an abnormal proliferation of cells in the breast tissue. It is the commonest cause of cancer death in women after cancer of the lungs accounting for 6% of all female death.
The diagnosis of breast cancer is by Triple Assessment.
A)Clinical Evaluation – Lump and regional nodes.
B)Imaging (ultrasound <35 years old or mammography >35 years old).
C) Cytology or Histology.
Clinical Manifestations of breast cancer
- Most women will present with complaints of a painless breast lump in more than 70% cases.
- Some present with painful breast lumps due to the following reasons
- Ischaemic changes and necrosis
- Inflammatory carcinoma of the breast
- Lymphedema of the breast
- Local invasion into intercostals spaces and muscles plus nerves
- Superimposed infection
- Mass rapid growth -Duration of the mass-Changes with menses
- Nipple discharge
- Ulceration and other skin changes-irritation and eczematous skin change
- Rarely, patients show signs of metastatic disease without a palpable mass in either breast back pain, cough with hemoptysis.
Advanced disease symptoms
Chronic cough-lung metastasis
Weight loss, anorexia, and generalized fatigue
Upper limb swelling-axillary lymph nodes involvement with lymphedema
Back pain-metastasis to the back , Yellowness of eyes
History of predisposing factors to breast cancer
1) Breast cancer in the contralateral breast.
2) Benign breast disease with hyperplasia and atypia, Benign breast disease with multiple papillomas.
3) Advancing age>50 years. (Most cancers occur between 35-45 years).
4) Family history of breast cancer, GIT or ovarian cancer.
6) Early menarche in younger than 13 years and late menopause that comes after 50 years.
7) Age at first delivery. If aged 30 years or older, relative risk is 2 times that of patients who gave birth when younger than 20 years.
8) Oral contraceptive.
9) Hormonal replacement therapy.
10) Whether breastfed and Length of breastfeeding.
11) Irradiation to chest-therapeutic or occupational.
13) Cigarette smoking and alcohol consumption.
14) Diet-Fatty diet.
On general examination you as the doctor you shall look at:
Explain to the patient the examination and her consent.
Exposure by removing the clothes up to the waist.
With the patient seated facing the examiner check:
- The symmetry of the breasts noting the sizes and Levels of the nipples.
- Nature of the nipples whether they are everted or inverted and any discharges.
- Any masses obvious on inspection if any note its location and extent, skin changes over it, any ulcers or discharged from it.
- Any other skin changes-ulcers, hyperpigmentation, peau d’ orange, discharges
NB. Obvious size discrepancy, nipple inversion, skin dimpling, scaling, and edema (peau d’orange) are suggestive carcinoma
- It is started on the normal side.
- Palpate in quadrants-lower outer quadrant, then lower inner , upper inner, upper outer quadrant and the axillary’s tail then peri-areolar region.
- If there are any masses fully described then taking note of the site, size, shape, temperature, skin changes, tenderness, margins, mobility and attachments, consistency, any thrills or bruits.
- Ask the patient to squeeze the nipple for any discharge.
Lymph nodes Exam
Examine the tail and the axillary lymph nodes-apical, lateral, posterior and anterior
Supraclavicular, infraclavicular, and axillary lymphadenopathy can be suggestive of advanced disease.
Note that Benign lesions are more frequently smaller, rubbery, well-circumscribed, and mobile.
Characteristics suggestive of malignancy include skin involvement, fixation to the chest wall, irregular border, firmness, and enlargement.
Unilateral nipple discharge, nonmilky fluid, and origin from a single duct. Intraductal papilloma, a benign finding, is the most common cause of unilateral bloody nipple discharge.
Other benign pathology associated with nipple discharge includes subareolar duct ectasia and fibrocystic changes.
Usually, malignant pathology presenting with nipple discharge also is associated with a palpable mass and/or suggestive mammographic findings.
1.Axillary lymph nodes and supraclavicular nodes.
Differential diagnosis of breast cancer
1.Giant fibroadenoma, Fibrosarcoma.
2.Deep breast mycosis.
3.Chronic breast abscess eg tuberculosis.
4.Secondary malignancies to the breast melanoma-lungs, melanoma
Mammography is the most useful technique for the detection of early breast cancer. The two methods of mammography in common use are ordinary film screen radiography and xeroradiography.
Its sensitivity is decreased significantly in young patients with dense breast tissue and possibly with augmentation prosthesis. Useful in evaluating the breast for calcifications, architectural distortion, skin thickening, nipple changes, and axillary adenopathy.
Enlargement, stellate shape, irregular or spiculated margins, and the presence of pleomorphic calcifications less than 0.5 mm in a given lesion all are suggestive of malignancy.
As an adjunct to mammography, it can be particularly useful in younger patients or women with fibrocystic change. Its main use remains in distinguishing solid from cystic lesions.
In the workup of nonpalpable lesions, ultrasound can be used to guide a needle biopsy or to place a localizing wire to direct an excisional biopsy
Other imaging modalities include CT and MRI are used n the evaluation of metastasis
Fine-needle aspiration (FNA)
Fine needle aspiration is one of the first-line diagnostic procedures in the evaluation of a palpable breast mass.
It is particularly useful in the evaluation of cystic lesions.
Persistence of a palpable mass and recurrence following a repeat aspiration are general indications for open biopsy.
Bloody cyst fluid should be examined by pathology and warrants an open biopsy.
Clearly malignant and suggestive lesions warrant an open biopsy.
However, performing a biopsy of benign or indeterminate lesions depends on the assessment of individual patient risk and correlation with physical examination findings.
True-cut (core) needle biopsy
Gives architectural information and determine the invasiveness of a lesion.
This is a distinct advantage over FNA, particularly in patients with large palpable masses suggestive of cancer. In this instance, definitive diagnosis of malignancy by true-cut biopsy may eliminate the need for an open biopsy prior to definitive surgical treatment (eg, modified radical mastectomy, conservation).
Tissue examination for Estrogen and Progesterone receptors
Benefit for treatment with Tamoxifen-Selective Estrogen Receptor Modifier
Also BRCA and 2
Other Lab investigations
Histology types of breast cancer
WHO classifies breast cancer to be:
- Ductal carcinoma in situ (DCIS)
- Lobular carcinoma in situ (LCIS)
- Ductal (85%)
- Lobular (1%)
- Mucinous (5%)
- Papillary (<5%)
- Medullary (<5%)
B)Mixed Connective tissue and Epithelial
Staging of breast cancer
Tx - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis - Carcinoma in situ
T1 - Tumor less than 2 cm in greatest dimension
T2 - Tumor > 2 cm but less than or equal to 5 cm
T3 - Tumor > 5 cm
T4 - Tumor of any size with direct extension to chest wall or skin (including inflammatory carcinoma)
Nx - Regional lymph nodes cannot be assessed
N0 - No regional lymph node metastases
N1 - Metastases to ipsilateral axillary lymph nodes without fixation
N2 - Metastases to ipsilateral axillary lymph nodes with fixation
N3 - Metastasis to ipsilateral supraclavicular or internal mammary lymph node
Mx - Cannot be assessed
M0 - No metastases
M1 - Distant metastases including ipsilateral supraclavicular lymph nodes
Manchester staging system of breast cancer
Tumour confined to the breast. Any skin involvement covers an area less than the size of the tumor. No lymph node involvement.
Tumour confined to the breast. Palpable, mobile axillary nodes.
Tumour extends beyond the breast tissue because of skin fixation in an area greater than the size of the tumor or because of ulceration. Tumour fixity underlying fascia.
Management of breast cancer
Breast cancer management modalities are divided into three:-
Specific management and
Supportive management entails:
2.Hematinics or blood transfusion.
4.Nutritional build up.
5.Antibiotics if superimposed infection.
Specific management on the other hand includes:
The aim of breast cancer surgery is:-
To achieve cure if excised before metastatic spread has occurred and or
-To prevent unpleasant sequelae of local recurrence.
Surgical options for breast cancer are:
i)Breast-Conserving Surgery (BCS)
Breast-conserving surgery is regarded as either wide local excision (lumpectomy),quadrantectomy or segmentectomy.
ii) Simple/Total mastectomy
iii)Radical mastectomy - obsolete
Mastectomy + reconstruction (immediate or delayed)
Indications for breast-conserving surgery are:
1) Small (<5cm)single tumors in a large breast
2) Peripheral location
3) No local advancement or extensive nodal involvement
For tumors that are suitable for breast conservation, there is no difference in local recurrence or overall survival when BCS + radiotherapy is compared to mastectomy
Contraindications for breast-conserving surgery.
b)Widespread multifocal disease
c)Central tumors beneath or involving the nipple
d)Poor tumor differentiation
Wide local excision
Remove tumor + a ream of at least 1cm of normal breast
In advanced diseases
For local-regional control -remove the primary tumor For surgical toilet if fungating and ulcerative
Indications for mastectomy
1.Congenital supranumerary breasts
2.Extensive destruction of breast architecture due to;
Chronic infections (TB, Fungi), Sarcoidosis, Severe trauma
a) Early breast cancer (Carcinoma in-situ)
b) Large tumors (in relation to the size of the breast)
c) Central tumors beneath or involving the nipple
d) Multifocal disease
e) Local recurrence
f) Palliative (Toilet Mastectomy)
g) Prophylaxis where there is a strong family history
h) Patient preference
The landmarks for mastectomy are: (Remember surgery is medial to lateral);
Upper - Clavicle
Lower - 6th Rib
Medially - Lateral sternal border
Laterally - Anterior Axillary Fold
Types of mastectomy surgery.
1.Total or simple mastectomy:
This describes the removal of breast parenchyma, including the nipple-areolar complex, with no node dissection. Commonly done.
Any form of radical surgery is rarely done.
2.Modified radical mastectomy:
This procedure involves resection of the breast parenchyma and axillary nodes lateral and behind the medial border of the pectoralis minor (levels I and II).
3. Patey modified radical mastectomy:
This describes modified radical mastectomy (MRM) with additional removal of level III nodes requiring division or resection of the pectoralis minor; compared to MRM, this procedure increases lymphedema from 3-10% in the arm.
4.Radical (Halsted) mastectomy:
This procedure entails the removal of all breast, axillary nodes through level III, and both the pectoralis minor and major muscles.
Rarely done because of associated morbidity following surgery.
Aims of axillary surgery
About 30-40% of patients with early breast cancer have nodal involvement. Therefore axillary surgery aims to:
- Eradicate local disease.
- Determine prognosis to guide adjuvant therapy.
Clinical evaluation of the axilla is unreliable (30% false positive, 30% false negative).
No reliable imaging techniques available.
Surgical evaluation important and should be considered for all patients with invasive cancer.
Levels of axillary clearance
Levels of axillary clearance are assessed relative to pectoralis minor.
Level 1 - below pectoralis minor.
Level 2 - up to the upper border of the pectoralis minor.
Level 3 - to the outer border of the first rib.
Axillary samplings remove more than 4 nodes
Sentinel node biopsy
Sentinel node biopsy aims to accurately stage the axilla without the morbidity of axillary clearance.
The technique is used to identify the first nodes that tumor drains to.
They can be located following the injection of either;
- Combination of isotope and blue dye
It can be injected in peritumoral, subdermal or subareolar sites, therefore, allowing a more detailed examination of nodes removed.
Another modality of breast cancer treatment is radiotherapy. It requires a minimum of weeks after surgery.
The technique is usually used to clear the breast bed of any residual tumor thus used for local-regional treatment.
Up to a total of 600 grays fractionated.
Indications for radiotherapy
1.Extensive local disease with infiltration of the chest wall-local regional control.
2.Heavy node-positive disease & Extensive lymphovascular invasion.
4.Secondary to breast conservation surgery (Local radiotherapy) or simple mastectomy (Axillary radiotherapy).
5. Can be used in metastasis to the spine and bone for pain control
3.Chemotherapy in breast cancer
The third treatment modality is chemotherapy. It can be given as:
Primary systemic therapy prior to locoregional treatment or adjuvant therapy following locoregional treatment
Post-operative adjuvant chemotherapy depends primarily on: Age / menopausal status, Nodal status and Tumour grade.
Combination chemotherapy more effective than a single drug
The most commonly used regimen = CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil).
These chemotherapeutic drugs are given as six cycles at monthly intervals because of so far no evidence that more than 6 months of treatment is of benefit to the patient.
The greatest benefit is seen in pre-menopausal women.
High -dose chemotherapy with stem cell rescue produces no overall survival benefit.
Primary (neoadjuvant) chemotherapy
Neoadjuvant is a treatment given as a first step to shrink a tumor before the main treatment and in this case, is surgery. Therefore primary chemotherapy is chemotherapy prior to surgery for large or locally advanced tumors.
This shrinks tumor often allowing breast-conserving surgery rather than mastectomy.
70% of tumors show a clinical response. In 20–30% this is response is complete.
Surgery is required even in those with a complete clinical response because in about 80% of these patients still have histological evidence of tumor.
Primary systemic therapy has not to date been shown to improve survival.
4.Systemic Hormonal therapy
Systemic hormonal therapy is directed at putative micrometastases to delay relapse and prolong survival;
1) To palliate symptoms in locally advanced or metastatic disease.
2) Lymph node-positive.
3) Poor prognostic node-negative women.
4) For women with estrogen or progesterone receptor-positive tumors; mostly postmenopausal women.
This therapy is effective in 8% of receptor-negative patients.
Selective Estrogen Receptor Modulators (SERM), Oestrogen receptor antagonists e.g. Tamoxifen is administered at a dose of 20 mg once daily for 5 years.
It is started immediately diagnosis is made. It is also beneficial in reducing tumors in the contralateral breast
With this therapy the risk of contralateral breast cancer reduced by 40%.
The greater benefit was seen in estrogen receptor rich tumors.
Benefit still was seen in estrogen receptor-negative tumors.
The benefit observed in both pre and postmenopausal women.
1. Endometrial changes - Hyperplasia, polyps, cancer & uterine sarcoma
3. Occasional cystic ovarian swellings in premenopausal women
4. Occasional hypercalcemia if bony metastases
Other hormonal drugs
1. Oral aromatase inhibitors e.g. anastrozole.
These block conversion of androgens to estrogens in the peripheral tissues.
For post-menopausal women who are unable to take tamoxifen therapy because of high-risk thromboembolism or endometrial abnormalities.
2.Gonadorelin (LHRH) analogs e.g. Goserelin.
They induce a reversible ovarian suppression.
Ovarian ablation in pre-menopausal receptor +ve patients.
They are used for the management of advanced breast cancer in pre-menopausal women
3.Monoclonal antibody –Tras-tuzu-mab
Tumors +ve for the HER2 protein may respond
Symptomatic & Terminal care
DXT to painful bony lesions
Prevention of breast cancer
1. Breast self-examination, performed monthly, is recommended for women beginning at 18 years.
2. Annual evaluation -With mammography is advised for those older than 40 years.
3. Same done annually irrespective of age after removal of contralateral breast for breast cancer.
4.Removal of breast lumps.
5. Tamoxifen is approved use in healthy women at high risk for the development of invasive breast cancer and for patients with early invasive lesions at risk of secondary contralateral cancer.
6. Lifestyle modification-diet, cigarette and alcohol smoking should be stopped
7.Prophylactic mastectomy-patients with strong family history and ask for it themselves
Inflammatory Breast Cancer
Inflammatory breast cancer is the appearance of inflamed breasts (red and warm) with dimples and/or ridges caused by the infiltration of tumor cells into the lymphatics. Inflammatory breast cancer can sometimes be difficult to distinguish between benign (non-cancerous) conditions (such as mastitis) and inflammatory malignancy (cancerous conditions). Though rare, inflammatory breast cancer may spread quickly to other parts of the body.
Treatment of inflammatory breast cancer treatment is generally quite similar to the treatment of Stage IIIB or IV breast cancer. In addition, patients usually undergo chemotherapy, hormonal therapy and/or radiation treatment.
Patients who respond positively to systemic treatment may be candidates for mastectomy.
Paget’s Disease of the Nipple
Paget’s disease of the nipple is a rare form of breast cancer that begins in the milk ducts and spreads to the skin of the nipple and areola.
The skin may appear crusted, red, or oozing.
Prognosis is better if nipple changes are the only sign of breast disease and no lump is felt.
Recurrence of Breast Cancer
Women who experience a recurrence of breast cancer after a lumpectomy is often treated simply by mastectomy (with or without breast reconstruction).
If cancer reoccurs after mastectomy, additional surgery may be necessary to remove tumors near the mastectomy site, followed by radiation therapy. Chemotherapy and/or hormonal therapy may also be administered.
Alternative treatment options for recurrent breast cancer include:
• Hormone therapy
• Surgery and/or radiation therapy if cancer is confined to one area and is operable
• Entry into a clinical trial testing new chemotherapy or hormonal drugs, or biological therapy