Malignant disease - Breast Cancer

Aetiology and pathology
The majority of breast cancer arise from the epithelial cells of the milk ducts and reproduce their histological feature in a variety of patterns, of which the most common is an infiltrating ductal carcinoma. Approximately 10% of women have familial breast cancer and 3% have detectable mutations in BRCA1/2 genes and TP53.

Breast cancer - Symptoms and treatment by MedNotez
Symptoms and signs
Most women with symptomatic rather than screen-detected breast cancer present with a painless increasing mass which may also be associated with nipple discharge, skin tethering, ulceration and in inflammatory cancers, oedema and erythema.

Investigations
The triple assessment of any symptomatic breast mass by palpation, radiology and fine needle aspiration cytology is the most reliable way to differentiate breast cancer from the 15 times more common benign breast masses. Staging is both surgical with respect to tumour size and axillary lymphnode status and in advanced disease by investigation of common sites of metastasis by chest X-ray and CT scan of lungs and liver and bone scan.

Prognostic factors
The following are all significant independent predictors of risk of recurrence:

• Size of the primary tumor
• Histological subtype
• Histological grade/differentiation
• Oestrogen and progesterone receptor status
• Patient age
• Menopausal status

Local treatment
Surgery may vary from wide local excision or segmental mastectomy and breast conservation for masses <3cm in diameter, to simple mastectomy with or without reconstruction. Radiotherapy is given to the conserved breast after wide local recurrence and to the chest wall after mastectomy if there are risk factors for local recurrence to complete the local control measures. The indications for adjuvant radiotherapy are:

• Breast conserving surgery
• Large high-grade primary tumour
• Proximity to surgical margins
• >2 lymph node metastases

Endocrine treatment
Premenopausal women
In premenopausal women a reduction in estrogens can be achieved by oophorectomy (removal of ovaries) or pituitary down regulation using a gonadotrophin-releasing hormone (GnRH) analogue.

• Selective oestrogen receptor modulators (SERM); tamoxifen, fulvestrant
• Synthetic progestogens

Postmenopausal women
In postmenopausal women, androgens are synthesized by the adrenal glands and converted in subcutaneous fat to estrone by the enzyme aromatase. The aromatase inhibitors, anastrozole, letrozole and exemesthane, reduce circulating oestrogen levels and oestrogen synthesis in tumour cells and have shown greater efficacy than tamoxifen in the treatment of metastatic breast cancer and equivalence in the adjuvant setting.

Anti-HER2 Mechanisms of Approved HER2 Inhibitors by MedNotez
Her2/c-erbB2 targeted therapy
Patients in whom the breast cancer overexpresses Her2 additional therapy with trastzumab and taxane reduces the mortality rate by 33%. Trastuzumab has a direct toxic effect upon the myocardium that is additive to pre-existing myocardial damage, especially that caused by anthracyclines, and should not be given concurrently. An alternative regimen with docetaxel, carboplatin and trastuzumab is equally as effective and can avoid much of the myocardial toxicity.
Alternative approaches which block the Her2 signaling with a different monoclonal antibody pertuzumab holds promise for preventing the development of resistance to these targeted therapies.