20th June 2023

Breast Cancer and Head and Neck Cancer

Breast Cancer

Overview of Breast Cancer

Breast cancer is the most common cancer in the UK, accounting for 15% of all new cancer cases. 1 in 7 UK females will be diagnosed with breast cancer in their lifetime. It is the 4th most common cause of cancer death in the UK, accounting for 7% of all cancer deaths. In the UK, breast screening is offered routinely to all women from the age of 50 to 70, every 3 years. Male breast cancer accounts for 1% of all breast cancers and 0.1% of male cancer deaths.

Risk Factors

Genetic, hormonal, and environmental factors play a role in the pathogenesis of breast cancer. ~5-10% of breast cancers are due to mutation in BRCA1, BRCA2, AT or TP53 genes. BRCA1 and BRCA2 genes are located in chromosomes 17q and 13q respectively, and both genes function as tumour suppressor genes. Human epidermal growth factor receptor 2 (HER2) is a membrane tyrosine kinase and proto-oncogene that is overexpressed in about 25-30% of breast cancers. It is located in the long arm of chromosome 17 (17q12). Hormonal factors, particularly oestrogen exposure, are also one of the significant risk factors for breast cancer. Reported risk factors include nulliparity, first pregnancy >30 years old, early menarche, late menopause, long term use of HRT in postmenopausal women. Short-term use of HRT may not be associated with a high risk of breast cancer. Alcohol intake, physical inactivity and obesity are also related to an increased risk of breast cancer. Prior radiotherapy to the breast or chest wall also increases the risk.

Precursor lesions and Malignant lesions

Breast cancer arises from the epithelial cells lining the terminal duct lobular unit. The development of invasive breast cancer is thought to be due to a multistep process. Lobular carcinoma in situ, atypical ductal hyperplasia, ductal carcinoma in situ (DCIS) and microinvasive carcinoma are described as precursor lesions by the modified WHO classification of breast cancer. DCIS accounts for 3-5% of palpable breast cancer and is seen as widespread or unifocal microcalcification on mammography. DCIS has variable potential for development into an invasive disease and is defined as the proliferation of malignant-appearing mammary ductal epithelial cells without evidence of invasion beyond the basement membrane. Broadly, there are five subtypes of DCIS: comedo, solid, cribriform, micropapillary and papillary. Treatment of DCIS is aimed at preventing local recurrence, particularly of invasive cancer. Treatment options include surgery alone, or surgery followed by radiotherapy and hormonal therapy. With mammographic follow-up, breast-cancer disease-free survival in DCIS approaches 100%.

Invasive ductal carcinoma accounts for 70-80% of all invasive carcinoma whereas invasive lobular carcinoma represents 10-15%. Medullary cancers tend to affect younger patients while colloid/mucoid tend to affect the elderly. 60-70% of breast cancers are oestrogen receptor positive conveying better prognosis. Overexpression of HER2 (growth factor receptor gene) is associated with aggressive disease and poor prognosis. 15% of breast cancers lack the expression of oestrogen, progesterone and HER2 receptors (often referred to as triple-negative breast cancer) and are associated with a high rate of local and systemic recurrence.

Diagnosis and Prognosis

Usual presentations are a painless breast lump, distortion of breast, or nipple discharge. All breast lumps should undergo triple assessment which consists of clinical examination in combination with imaging and histological assessment. Breast examination may reveal a non-tender, well- or ill-defined lump with or without fixity to the skin or chest wall and changes in overlying skin. Lymph nodes in the axilla and supraclavicular fossa may be involved. Clinical examination may contribute to tumour and nodal staging. Ultrasound is more accurate in detecting invasive breast cancer, though mammography remains most accurate at detecting ductal carcinoma in situ (DCIS). MRI is used in the assessment of multifocal/bilateral disease and patients with cosmetic implants who are identified as high risk. Pathological diagnosis can be obtained by FNA or core biopsy or open surgical biopsy. TNM staging is used for staging the disease and planning for management. Immunohistochemistry (IHC) evaluation is mandatory nowadays for treatment decision making.
Less than 10% of patients initially present with metastatic disease. The most common sites of distant disease include bones (70%), lungs (60%), liver (55%), pleura (40%), adrenals (35%), skin (30%) and brain (10-20%). Staging investigations should include CXR, bone scan, liver USS, CT/MRI or PET-CT, LFT and calcium.
Overall prognosis depends on tumour size, grade, lymph node status, oestrogen (ER) and progesterone receptors (PR) status, and presence, or absence of vascular invasion.

Treatment

Surgical management of breast cancer includes breast conservative surgery which is the removal of the tumour by wide local excision (WLE). Patients who are not suitable for conservative surgery undergo mastectomy with or without reconstruction. Breast cancer during pregnancy, prior radiotherapy to the breast or chest wall, tumour >5 cm, women <35 years or pre-menopausal with BRCA 1, BRCA 2 mutation, inflammatory breast disease, and multifocal disease are contraindications to breast conservation surgery.
Sentinel node biopsy is widely used in clinically node-negative breast cancer. However, patients with clinically positive nodes will undergo axillary dissection during primary breast surgery.
Radiotherapy is recommended for all patients with invasive cancer who received breast conservative surgery. Axillary radiotherapy is used if lymph node positive on sampling and surgical clearance is not performed.
Adjuvant systemic treatments such as chemotherapy, hormonal therapy and trastuzumab provide survival benefit in suitable patients. Anthracycline based chemotherapies (e.g., AC regime – Doxorubicin and Cyclophosphamide) were some of the widely used regimes for adjuvant therapy. However, cardiac-related toxicity can be a limitation to using anthracyclines, particularly in patients with underlying heart disease. The addition of taxanes (paclitaxel and docetaxel) has provided additional benefits to adjuvant treatment regimes. Taxanes act by inhibiting microtubular depolymerisation causing cancer cells to stop dividing and slowing the growth of cancer or killing the cells.
Patients with hormone receptor positive tumours should be considered for adjuvant hormonal therapy to block the oestrogen stimulus. In pre-menopausal women, tamoxifen (with or without ovarian suppression) is the standard choice. Tamoxifen is a selective oestrogen receptor modulator (SERM) and inhibits breast cancer cells by acting as a competitive antagonist at the oestrogen receptor. Side effects include an increased risk of uterine cancer and thromboembolic events. Aromatase inhibitors which block the conversion of androgens to oestrogen are used in post-menopausal women. The adjuvant use of trastuzumab, a monoclonal antibody targeted towards HER2 receptor, in selected HER2 positive breast cancer patients showed a reduction in recurrence and mortality. However, cardiac toxicity is the most concerning side effect associated with this medication.
Patients with metastatic breast cancer can present to A&E with acute oncology problems. Patients with bone metastasis can present with malignant hypercalcaemia which needs urgent medical treatment. Some patients with spinal metastasis can present with metastatic cord compression which needs urgent referral to acute oncology team and MRI whole spine. The treatment approach for metastatic breast cancer is generally considered non-curative in nature and is aimed at palliation, improving quality of life and prolonging survival. Bisphosphonate therapy together with adequate calcium and vitamin D supplementation is helpful in reducing skeletal related events in patients with bony metastasis.

Head and Neck Cancers

Overview

Head and neck cancers are typically squamous cell tumours that arise in the oral cavity, pharynx, larynx, paranasal sinuses, and nasal cavity.

Risk Factors

The main risk factor for head and neck tumours is smoking. Alcohol has also been implicated as a causative factor; the effects of alcohol and tobacco may be synergistic. Cancers of oral cavity are associated with smoking, alcohol, betel chewing practice, dietary habits, poor dental hygiene, and certain infections. Some head and neck cancers are related to occupational risk factors. Cancers in the larynx may be associated with asbestos and solvents. Nasal cavity and ethmoid sinus adenocarcinomas have been linked to occupations associated with wood dust, such as the furniture industry, sawmill work, and carpentry. Human papillomavirus infection (HPV), most commonly HPV-16, plays a role in the development of certain head and neck cancers, particularly those in the oropharynx. HPV positive tumours appear to have a better prognosis than HPV negative tumours.

Diagnosis and Management

Presentation depends on the location of the primary tumour and the extent of the disease. Common presenting features by location in head and neck cancers are listed below.

A general medical evaluation should be performed, including a thorough head and neck examination and clearly document the location and extent of the primary tumour and any clinically positive lymph nodes. Almost all patients should undergo contrast-enhanced computed tomography (CT) and/or MRI to further define the extent of local–regional disease. CXR, CT Chest and PET-CT are considered for distant metastasis.
Most head and neck malignant neoplasms (90%) arise from the surface epithelium and are squamous cell carcinoma (SCC) or one of its variants, including lymphoepithelioma, spindle cell carcinoma, verrucous carcinoma, and undifferentiated carcinoma and the remaining cases include lymphomas and a wide variety of other malignant and benign neoplasms. Generally, the management of head and neck tumours depends largely on the stage of the tumour which is determined by TNM staging. In the head and neck regions, lymph nodes are organised into levels. Level I includes the submental and submandibular areas; levels II to IV include the internal jugular vein lymph nodes; level V includes the posterior triangle. Generally, which lymph node levels are involved is predictive of the primary site. For example, lip, oral cavity, and facial skin tumours typically spread to levels I and II initially; larynx and pharynx cancers have a predilection for spreading to levels II and III.
Generally, early head and neck cancer is managed with single-modality therapy, surgery, or radiotherapy. The determinants of choice between the two are complex and multifactorial. The mainstay of treatment for locoregionally advanced head and neck squamous cell carcinoma is either surgery followed by adjuvant radiation therapy or definitive concurrent chemoradiation, reserving surgery as salvage therapy, referred to as the organ-preservation approach. Head and neck cancer treatment requires a multidisciplinary approach with medical, surgical, and radiation oncology, pathology, radiology, and supportive services including physical and occupational therapy, speech and swallow therapy, and nutrition.

Nasopharynx

Nasopharyngeal carcinomas (NPC) are common in South-East Asia and male to female ratio is 3:1. The most common site of origin for NPC is the lateral wall of the nasopharynx, especially the fossa of Rosenmüller, followed by the superior posterior wall. Viral infection (e.g. Epstein-Barr virus), genetic predisposition and environmental factors are associated with the incidence of NPC. Unilateral deafness is the most common local symptom, followed by epistaxis and nasal obstruction. Cranial nerve involvement is common in NPC and 5th nerve involvement is frequent owing to the tumour in or around the foramen ovale. Tumour in the cavernous sinus can lead to diplopia secondary to compression of the III, IV, or VI nerves. The posterior cranial nerves (IX to XII) can be involved by direct parapharyngeal spread or compression by retropharyngeal lymph nodes. The majority of patients have a metastatic neck node at presentation (70%). Radiation therapy is the treatment of choice. Neck dissection is usually only indicated for radiotherapy failures. Concurrent chemoradiotherapy with induction or subsequent chemotherapy improved survival. Stage of the disease is the most important prognostic factor in terms of survival and other prognostic features include cranial nerve palsies, involvement of skull base, advanced age, male sex, and involvement of the lymph nodes in the supraclavicular fossa.

Oropharynx

The commonest sites for malignancies within the oropharynx are the tonsil and tongue base. Initial presenting symptoms of oropharyngeal cancers are often vague and non-specific; consequently, the majority of patients who present often have locally advanced disease at the time of diagnosis. Human papillomavirus (HPV) is a prognostic marker and tumour HPV positivity is associated with substantially higher cure rates and improved survival. As with all head and neck tumours, management decisions should be made in a multidisciplinary meeting depending on the stage of the disease and the patient’s factors. Surgery and radiotherapy produce similar cure rates. As excision of the base of the tongue generally causes greater disability and because of the high risk for bilateral lymphatic involvement, radiotherapy, or chemoradiotherapy, is usually the treatment of choice.

Larynx

Male and female ratio for cancers of the larynx is 5:1. Hoarseness is the most common presenting symptom and other symptoms include dysphagia, irritation, and coughing. Airway compromise in the form of stridor, which can result from circumferential extension of subglottic carcinomas, needs urgent referral to an ENT team. Early-stage disease is generally managed with surgery or radiotherapy depending on the site of the tumour and morbidity. Induction chemotherapy may select patients with advanced carcinoma suitable for full-course radiotherapy to save the larynx. Voice rehabilitation and psychosocial support are essential for the patient who was treated surgically, particularly total laryngectomy and permanent tracheostomy.