31st December 2024

Management of breast cancer

Management of early breast cancer

Patients with early breast cancer (stages I-II) have a disease which can, by definition, be fully excised; they should be offered surgery if fit. This may be either mastectomy or breast-conserving surgery (wide local excision, WLE, or ‘lumpectomy’), depending on factors including size and position of the lesion and overall breast size. Patients simultaneously undergo axillary surgery:

• For those with established nodal disease at diagnosis, axillary lymph node clearance is recommended. This carries the risk of lymphoedema and shoulder stiffness.
• Patients who are node negative at diagnosis may undergo sentinel lymph node biopsy, in which the excised sentinel nodes are used to complete pathological staging and determine the need for node clearance.

Surgery for early breast cancer is usually followed by the offer of adjuvant therapy to reduce the risk of recurrence. Adjuvant radiotherapy may be offered to reduce the risk of locoregional recurrence, whilst adjuvant systemic therapies may be offered to reduce the risk of distal recurrence from occult micrometastases.

Adjuvant systemic therapies include chemotherapy, hormonal therapy and targeted therapy:

• Hormonal therapy is offered to patients with ER-positive breast cancer. Tamoxifen is first line in pre- and peri-menopausal women; aromatase inhibitors such as letrozole are first line in post-menopausal women. Tamoxifen increases the risk of venous thromboembolism and endometrial cancer, whilst arthralgia syndrome (isolated joint pain and swelling) is the most common reason for discontinuation of aromatase inhibitors. This is secondary to reduced oestrogen levels causing reduced bone mineral density.
• Targeted anti-HER2 therapy is offered to patients with HER2-positive breast cancer and is usually in the form of recombinant monoclonal antibodies trastuzumab (Herceptin) and/or pertuzumab. The main associated adverse effect is of cardiotoxicity and patients are surveyed with regular echocardiograms.
• Targeted therapy with abemaciclib (a CDK4/6 inhibitor) is authorised for use alongside aromatase inhibitors in cases of hormone receptor-positive, HER2-negative, node-positive early breast cancer where there is estimated to be a high risk of recurrence. Abemaciclib can cause diarrhoea, which can be explosive.

Neoadjuvant systemic therapy (given prior to surgery) aims to reduce tumour size and, therefore, make breast-conserving surgery more feasible, as well as reduce the risk of recurrence. Neoadjuvant therapy is indicated in a number of settings, one example being HER2-positive early breast cancer where there is a high risk of recurrence, in which case neoadjuvant therapy combining taxane-containing chemotherapy with targeted anti-HER2 therapy (pertuzumab plus trastuzumab) is usually offered.

Management of advanced breast cancer

Patients with advanced breast cancer may have locally advanced disease and/or distal metastases, meaning their disease is not, at least initially, completely resectable. In patients with locally advanced disease, achieving local control to prevent tumour fungation is a priority. Patients are usually treated with a combination of radiotherapy and systemic therapies. If there is a good response, surgery may become feasible. Metastatic breast cancer is incurable and any treatment is with palliative intent. A full description of treatment options is beyond the scope of this chapter. However, it is important to appreciate that, as with early breast cancer, decisions are guided by performance status, hormone receptor status and, increasingly, immune-related biomarkers. Several examples follow.

ER-positive, HER2-negative advanced breast cancer: first-line management is usually endocrine therapy, which, as in the adjuvant setting, may be combined with targeted therapy (e.g. letrozole ± a CDK4/6 inhibitor such as abemaciclib). Chemotherapy is usually reserved for hormone-refractory disease further down the line.

PD-L1-positive advanced triple negative breast cancer: patients whose tumours express specific immune-related biomarkers may be offered targeted treatment with immune checkpoint inhibitors. These work to ‘activate’ the immune system against tumour cells by preventing tumour cells from binding to and de-activating T-cells. First-line treatment options for advanced triple-negative breast cancers include:

• Pembrolizumab (anti-PD-1) + nab-paclitaxel (paclitaxel bound by albumin nanoparticles, also known as Abraxane)
• Atezolizumab (anti-PD-L1) + nab-paclitaxel

Management of carcinoma in situ

Patients with DCIS are offered resection (usually wide local excision, unless very large), and adjuvant radiotherapy should be considered. LCIS may be observed unless features are non-classical (usually pleomorphic LCIS), in which case patients may be offered resection.