242 Breast lump
Salient features
History
• History of a palpable mass in breast and/or axilla
• Breast pain (present in 10% of breast cancer patients) and unrelated to menstrual cycle
• Nipple discharge, erosion, enlargement or itching of the nipple
• Back or bone pain, jaundice or weight loss (indicate systemic metastases)
• Family history (20% of breast cancer have family history)
• Some forms of mammary dysplasia
• History of cancer in the other breast
Examination
• Breast lump that is non-tender and has poorly delineated margins. Asymmetry of the breasts and retraction or dimpling of the skin can often be accentuated by having the patient raise her arms overhead or press her hands on her hips to contract the pectoralis muscle.
• Examine axillary and supraclavicular lymph nodes
• Look for oedema of the ipsilateral arm (as a result of metastatic infiltration of regional lymphatics)
• Examine the chest (metastases, lymphangitis carcinomatosa)
• Examine for hepatomegaly (metastases); breast cancer spreads to the bones, lungs, brain and liver.
Questions
How would you investigate such a patient?
• FBC and ESR (ESR is consistently raised)
• Urea and electrolytes, liver function tests (hypercalcaemia, raised alkaline phosphatase level indicates bone or liver metastases)
• Biopsy: large needle-core biopsy, fine-needle aspiration or open biopsy under local anaesthesia
• Carcinoembyronic antigen (CEA) could be a marker for recurrence
Advanced-level questions
How would you investigate a patient with a suspicious mammogram but no clinical evidence of mass?
Although a mass cannot be palpated, the patient should undergo a mammographic localization biopsy.
What are the histological types of breast cancer?
They are of two main types, which may be invasive or in situ.
• Ductal: arising from the epithelial lining of large or intermediate-sized ducts. Most arise from intermediate ducts and are invasive (e.g. invasive ductal, infiltrating ductal). When ductal carcinoma has not invaded extraductal tissue, it is intraductal or in situ ductal.
• Lobular: arising from the epithelium of the terminal ducts of the lobules.
How are patients with breast cancer managed?
Surgery
• Breast-conserving surgery (lumpectomy, axillary dissection and radiation therapy) is usually offered to patients with single tumours <4 cm in diameter because the cosmetic outcome of excising larger tumours is poor. However, in 80% of patients with large tumours and in 25% of those with locally advanced breast cancers, breast conservation is possible if the size of the tumour is reduced by a course of primary systemic treatment (such as combination chemotherapy and hormonal therapy).
• Modified radical mastectomy (total mastectomy, removal of the overlying skin, nipple as well as the underlying pectoralis fascia with axillary lymph node dissection). The major advantage is that radiation is not necessary, but many patients suffer from the psychological trauma of breast loss.
Adjuvant therapy
• CMF regimen (cyclophosphamide, methotrexate and fluorouracil)
• MMM regimen (mitozantrone, methotrexate and mitomycin C)
• Doxorubicin and cyclophosphamide
• Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor type 2 (HER2), is associated with an improvement of approximately 50% in disease-free survival among the 15–20% of women with HER2-positive disease
• Weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with axillary lymph node-positive or high-risk, lymph node-negative breast cancer.
Palliative therapy
• Radiotherapy is indicated for most patients who undergo breast-conserving surgery for invasive disease. The one subgroup of patients for whom breast-conserving surgery without radiation can be considered an appropriate option is women who are at least 70 years of age who are treated with surgery and hormonal therapy for oestrogen receptor-positive stage I breast cancer. In this cohort, the risk of local recurrence without radiation therapy is <10%. Accelerated, hypofractionated, whole-breast irradiation is useful in selected women with node-negative breast cancer after breast-conserving surgery. Accelerated partial-breast irradiation is delivered with double-plane or balloon-based radioactive implants and through conformational three-dimensional external-beam treatment. Radiation may be complicated by brachial plexus neuropathy.
• Hormonal treatment (tamoxifen, diethylstilbestrol, megestrol acetate, aminoglutethimide), chemotherapy (doxorubicin, paclitaxel, docetaxel, trastuzamab or hereceptin).
What are the prognostic factors in ‘node-negative’ breast cancer?
• Oestrogen and progesterone receptor status
• Percentage of cells in the S phase (i.e. synthesizing DNA)
• The HER-2/neu (c-erbB2) oncogene. The HER-2/neu (c-erbB2) oncogene is expressed by 25% of breast cancers and is associated with a poorer prognosis but a better response to doxorubicin and herceptin therapy.
What is the role of gene-expression profiling?
Basal-like breast cancers. These mostly correspond to tumours that are negative for ER, progesterone receptor (PR) and HER2 mutations (hence, ‘triple-negative’ tumours). Although these are biologically aggressive, they can still have an excellent outcome with breast-conserving surgery and whole-breast irradiation. These cancers are BRCA1-related cancers and are difficult to detect by mammography. Therefore, screening for these cancers with MRI is warranted. The risk of contralateral breast cancer among carriers of BRCA1 and BRCA2 is significant (~3% per year), requiring more vigorous breast surveillance with MRI or even prophylactic mastectomies.
Luminal-A cancers. These are mostly ER positive and histologically low grade. (The one subgroup of patients who can be offered breast-conserving therapy without irradiation as the standard of care are those who are at least 70 years of age who have stage I, ER-positive disease treated with adjuvant hormonal therapy.)
Luminal-B cancers. These are also mostly ER positive but may express low levels of hormone receptors and are often high grade.
HER2-positive cancers. These show amplification and high expression of ErbB2 and several other genes of the ErbB2 amplicon.
What are the theories of cancer spread?
• The ‘Halstedian’ theory proposed that breast cancer begins as a strictly local disease and that tumour cells spread over time in a contiguous manner away from the primary site through lymphatics; consequently, even distant metastases are the result of direct extensions of local involvement (affecting the breast, the chest wall, axillary and supraclavicular lymph nodes, or any combination of the sites). This concept therefore required aggressive local therapy for control of disease in the breast, chest wall and regional lymph nodes as this should have a substantial effect on survival. These ideas also provided basis for evermore radical breast cancer surgery.
• The ‘systemic’ theory proposed by Bernard Fisher and others considers breast cancer as a systemic disease that can be divided into two distinct groups: tumours that have the ability to metastasize to distant sites and those that lack this ability (Cancer Res 1980;40:3863–74). According to this concept, if distant metastases were destined to develop, they would already exist at the time of diagnosis of the breast tumour. As the length of a patient’s overall survival is a function of distant disease, this theory hypothesized that therapies that improve local control would have little or no effect on patient’s survival. Therefore, the emphasis was on the importance of effective systemic therapy in breast cancer therapy.
