Breast cancer

Notes
  • It is the top cancer in women globally
  • In developing countries, limited resources for surveillance, treatment, research, public awareness campaigns for early detection and treatment affect the rate of cancer diagnosis and treatment adversely.
  • Statistics: global mortality rate in women - 508,000; global mortality rate in men - 400 (with the annual incidence of 2600 globally); breast cancer survival rates - 40% in low-income countries to 80% in developed countries;  age of most  breast cancers female patients - > 50 years; percentage of women with breast  cancer and breast cancer 1 or 2 gene (BRCA1 or BRCA2 gene) - 5%; percentage increase of risk of breast cancer from the use of oral contraceptives – 0.008% (practically negligible); women diagnosed with breast cancer globally who have HER2-positive breast cancer (that is aggressive form of the disease) - 20%; proportion of breast cancer that will metastasize in life time - 20 to 40%;  mortality rate of breast cancer patients due to metastasis - 90%; new breast cancer cases that are initially Stage IV or metastatic (“de novo” metastatic disease) - 6 to 10%;

the five-year survival rate after diagnosis for stage 4 breast cancer patients in developed countries: 22%; the five-year relative survival rate in developed countries: 72%; the five-year relative survival rate for stage 2 breast cancer patients in developed countries: 90%.

Symptoms
  • Palpable painless mass of tissue
  • Nipple retraction
  • Enlargement of the breast (without the mass)
  • A firmer thickening in one breast.
  • Satellite nodules
  • Breast pain (late sign)
  • Erythema (especially in PDN and IBC)
  • Crusting and scaling (especially in PDN)
  • Ulcers
  • Discharge (especially in PDN)
  • Pathologic fracture (in case of metastasis)
  • Pulmonary dysfunction (in case of metastasis).
  • Matted axillary lymph nodes, supraclavicular lymphadenopathy and infraclavicular lymphadenopathy (in case of metastasis)
  • Peau d'orange breast (skin with ridges or pitted like the skin of an orange) – common in IBC
Diagnosis
  • Mammography;

It is a low-dose of X-ray radiation imaging of breasts.

It aims at detection of calcified lesions in breasts that are less than 1cm in size.

Screening begins at age 40 yrs and is repeated every 2 year(s) upto the age of 75 years).

It is known to have a sensitivity of 67.8% and specificity 75%. However, when it is combined with clinical breast examination, sensitivity rises to 77.4% and specificity reduces to 72%.

  • Clinical breast examination (CBE);

Comprehensive clinical review must be done.

All breast quadrants are examined for lumps, changes of skin colour or swelling and nipples for blood or any other discharge.

Sensitivity and specificity of CBE have been found by some studies to be 51.7% and 94.3% respectively.

  • Breast ultrasonography;

It is not mainly used for screening of breast cancer alone though its use advised in males, lactating women, small-breasted women and in premenstrual women.

It is also used as guidance in taking of image-directed biopsies 

  • MRI is recommended for the high-risk subjects (e.g. in BRCA1 and BRCA2 gene positive cases) and when the mammogram / ultrasound results are indeterminate.
  • Monthly breast self-examination (BSE)

It should be done on the same day each month at day 10 of menstrual cycle).

  • Biopsy;

A core needle biopsy (manually or ultrasound / stereotactic guided)

Fine needle aspiration is not recommended for diagnostic use.

Histopathological reporting of biopsy  should include the following:

_Specification of the histological type of breast cancer

_Grade of cancer

_Lymphovascular invasion

_Tumour dimensions

_Number of nodes sampled

_Number of nodes involved

_Presence of necrosis

  • Analysis for estrogen and progesterone receptors
  • Immunohistochemistry for detection of HER2 protein
  • To confirm HER2 overexpression Fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) is done.
  • Cells extracted from blood or saliva samples to be tested for BRCA1 and BRCA2 genes (after clinical evaluation).
  • Ruling out metastatic disease by Chest x-ray, liver function tests, complete blood count and serum calcium.
Differential
  • Breast abscess and masses
  • Fibroadenomas and cysts
  • Fat necrosis
  • Fibrocystic breast
  • Galactocele (cyst or milk cyst)
  • Hydid cyst
  • Antibioma (a chronic and sterile abscess that is formed as a result of incomplete treatment of an infection with antibiotics without incision and drainage).
  • Tuberculosis (affecting breast and lymph node)
Management
  • Surgery
  • Radiation therapy
  • Systemic therapy: Hormone therapy, chemotherapy, or both
  • Generally combination chemotherapy regimens tend to be more effective than a single drug.
  • Premenopausal women who are hormone receptor negative, HER2 positive, and lymph node positive (high-risk disease) benefit greatly from DDC in breast cancer treatment.
  • Some of the popular adjuvant chemotherapy regimens in treatment of breast cancer are:

The standard treatment in a Low-Resource setting (LRS) is doxorubicin + cyclophosphamide or;

_The alternative regime in the LRS is cyclophophomide + methotrexate + 5FU or;

_Doxorubicin + cyclophosphamide and paclitaxel or other taxanes concurrently or sequentially

_Cisplatin or carboplatin can also be used in the above combination.

This regime  is administered with Growth factors that stimulate bone marrow such as filgrastim and pegfilgrastim.

If tumors overexpress HER2, add trastuzumab at least a year.

In case the presence of estrogen and progesterone receptor expression administer hormone therapy that include: tamoxifen, raloxifene, aromatase inhibitors such as anastrozole, letrozole and exemestane

  • Treatment of metastatic breast tumour

In premenopausal women

_Tamoxifen or

_Surgical removal of ovary (ovarian ablation by surgery) or

_Radiation therapy or

_Luteinizing-releasing hormone (LRH) agonist such as buserelin, goserelin, leuprolide or

_Ovarian ablation + Tamoxifen or an aromatase inhibitor such as anastrozole, letrozole and exemestane.

In postmenopausal women;

_An aromatase inhibitor such as anastrozole, letrozole and exemestane.

 aromatase inhibitors are being increasingly used as primary hormone therapy. _Chemotherapeutics: capecitabine, doxorubicin, gemcitabine, paclitaxel and docetaxel, and vinorelbine.

_For tumors that overexpress HER2: trastuzumab alone or with hormone therapy or chemotherapy.

_Radiation therapy alone may be used to treat isolated, symptomatic lesions

_Palliative mastectomy

_Bisphosphonates such as zoledronate reduce pain in the bone pain as well as reducing loss of bone. They are also useful in the treatment of hypercalcemia.

  • Summary of management of breast cancer:

Stage of

Cancer

Management

Stage 0 (lobular carcinoma in situ, LCIS)

Since 10-20% of LCIS cases are also DCIS positive wide excision is recommended before therapy  to rule out DCIS

Monitor  or

Monitor  + estrogen antagonist  such as Raloxifene (for postmenopausal women) or Tamoxifen (for pre or postmenopausal women)

Prophylactic mastectomy (bilateral) in patient with high risk of  breast cancer

Stage 0 (ductal carcinoma in situ, DCIS)

Lumpectomy  (breast-conserving surgery) with the following;

_No  radiation therapy + No lymph node surgery (in case of lower-level evidence) or

_No axillary dissection + whole-breast radiation therapy

_with Tamoxifen for 5 years in patient  with estrogen receptor (ER) -to reduce the risk

 or

Total mastectomy with or without sentinel node biopsy

Stage I, IIA, IIB, or IIIA

Surgery;

_Excision or mastectomy + axillary dissection  or sentinel node biopsy

_Radiotherapy + chemotherapy

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