Globally, the incidence of breast cancer is second only to that of lung cancer, and the disease represents the leading cause of cancer-related deaths among women. Invasive ductal carcinoma with or without ductal carcinoma in situ (DCIS) is the most common histology, accounting for 70%, whilst invasive lobular carcinoma accounts for most of the remaining cases. DCIS constitutes 20% of breast cancers detected by mammography screening. It is multifocal in one-third of women and has a high risk of becoming invasive (10% at 5 years following excision only). Pure DCIS does not cause lymph node metastases, although these are found in 2% of cases where nodes are examined, owing to undetected invasive cancer. Lobular carcinoma in situ (LCIS) is a predisposing risk factor for developing cancer in either breast (7% at 10 years). The survival for breast cancer by stage is outlined in Box 1.

Box1. Five-year survival rates for breast cancer by stage

Pathogenesis

 Both genetic and hormonal factors play a role: about 5%–10% of breast cancers are hereditary and occur in patients with mutations of BRCA1, BRCA2, AT or TP53 genes. Prolonged oestrogen exposure associated with early menarche, late menopause and use of hormone replacement therapy (HRT) has been associated with an increased risk. Other risk factors include obesity, alcohol intake, nulliparity and late first pregnancy. There is no definite evidence linking use of the contraceptive pill to breast cancer.

Clinical features

 Breast cancer usually presents as a result of mammographic screening or as a palpable mass with nipple discharge in 10% and pain in 7% of patients. Less common presentations include inflammatory carcinoma with diffuse induration of the skin of the breast, and this confers an adverse prognosis. Around 40% of patients will have axillary nodal disease, with likelihood correlating with increasing size of the primary tumour. Distant metastases are infrequently present at diagnosis and the most common sites of spread are bone (70%), lung (60%), liver (55%), pleura (40%), adrenals (35%), skin (30%) and brain (10%–20%).

Investigations

 Following clinical examination, patients should undergo imaging with mammography or ultrasound evaluation, and a biopsy using fine needle aspiration for cytology or core biopsy for histology. Histological assessment should be carried out to assess tumour type and to determine oestrogen and progesterone receptor (ER/PR) status and HER2 status. If distant spread is suspected, CT of the thorax and abdomen and an isotope bone scan are required. Molecular subtyping is being used to classify tumours into four major subtypes: luminal A, luminal B, HER2 type and basal-like (often called ‘triple negative’, as these tumours are ER-, PR- and HER2 negative). This may allow more targeted selection of therapies in future.

 Management

 Surgery is the mainstay of curative treatment. This can range from a lumpectomy, where only the tumour is removed, to mastectomy, where the whole breast is removed. Breast-conserving surgery is as effective as mastectomy if complete excision with negative margins can be achieved. Lymph node sampling is performed at the time of surgery.

There is significant evidence to support the use of additional therapies to reduce the risk of breast cancer recurrence. Adjuvant radiotherapy is given to reduce the risk of local recurrence. In those patients considered at high risk of recurrence (i.e. tumour of >1 cm, ER-negative disease or the presence of involved axillary lymph nodes) cytotoxic chemotherapy may be offered. In patients with HER2-positive breast cancer adjuvant trastuzumab, a humanised monoclonal antibody to HER2, may be used alongside standard cytotoxic chemotherapy. These treatments are increasingly being used in the neoadjuvant setting, with the aim of achieving a complete pathological response when the cancer is resected, often with a more organ-preserving surgical procedure. In patients with ER-positive tumours adjuvant hormonal therapy may gain additional disease-free and overall survival benefits. Patients at low risk of recurrence (i.e. small, ER-positive disease) may require only adjuvant hormonal therapy. In post-menopausal women adjuvant bisphosphonate therapy may also be used.

The treatment of metastatic breast cancer is complex. Radiotherapy may be used to palliate painful bone metastases. SACT decisions are made with consideration of ER status, HER2 status, the distribution of metastatic disease and previous neo/adjuvant treatment, alongside assessments of performance status (PS) and comorbidities. For example, in a post-menopausal patient with ER-positive, HER2-negative bone-only metastatic disease who is PS 0, hormonal therapy (i.e. an aromatase inhibitor) in combination with a CDK4/6 targeted therapy (i.e. palbociclib, abemaciclib or ribociclib) may be used as first-line treatment. In a similar patient with additional symptomatic liver metastases, cytotoxic chemotherapy may be more appropriate.

مواضيع ذات صلة

Hepatocellular carcinoma (liver cell cancer)

تدبير سرطانات الدرق المتمايزة بعد الجراحة

السرطان الحليمي Papillary carcinoma

العقدة الدرقية الوحيدة

السلعة السمية متعددة العقد Toxic multinodular goiter

Colorectal carcinoma

Colorectal polyps

أورام الغدد اللعابية

الكيسات الغلصمية Branchial cleft cysts

الكيسة الدرقية اللسانية

الجينات المثبطة للورم Tumor suppressor genes

Cytotoxic chemotherapy