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Case History

Image not available. A 50-year-old woman had a left-sided modified mastectomy and axillary lymph node clearance for a 2 cm grade II invasive ductal carcinoma. Lymphovascular invasion was present and two out of 15 lymph nodes were positive for metastatic carcinoma. The deep margin was closest at 2 mm. The tumour was oestrogen receptor (ER) and progesterone receptor (PR) negative and HER-2/neu 2+ on immunohistochemistry. Her medical history included a myocardial infarction 5 years ago and subsequent endovascular coronary artery stenting. She has a 20 pack-year smoking history and drinks 30 units of alcohol per week. She is taking aspirin, carvedilol, ramipril and atorvastatin. She is asymptomatic and routine bloods are all normal.

Before considering adjuvant therapy in this patient what further work-up is required?

What is the current thinking on immunohistochemistry and fluorescence in-situ hybridization (FISH) analysis for HER-2/neu status?

If this patient's cancer is deemed definitely HER2-positive, what is the evidence for adjuvant trastuzumab?

What are the safety issues with trastuzumab and how should you monitor for trastuzumab toxicity?

Background

Before considering adjuvant therapy in this patient what further work up is required?

Image not available. Anthracycline-containing chemotherapy is the standard of care for lymph node negative breast cancer with any risk of recurrence. Lymph node positive patients may be given doxorubicin/cyclophosphamide followed by a taxane.1 Before this patient starts such a regimen, her baseline left ventricular ejection fraction (LVEF) needs to be assessed with echocardiography or multiple-gated acquisition scanning (MUGA). Her medical history and smoking history have particular relevance in view of the effect of anthracyclines on the heart. The sample should be sent for FISH analysis of HER-2/neu status (see below).

A radiation oncology opinion should be sought in view of the close deep margins and lymph node spread. This referral could be made during chemotherapy, as the final decision on radiotherapy does not change the plan for chemotherapy. As always (see Chapter 39) a detailed family history of malignancy is important. A liver ultrasound is often done but there are scant data to support its usefulness in this setting. There is no documented role for full body computed tomography (CT) scanning or isotope bone scanning in this scenario.

Discussion

What is the current thinking on immunohistochemistry and FISH analysis for HER-2/neu status?

Image not available. It is important to evaluate accurately the HER-2/neu status of invasive breast cancer. There can be significant inter-observer variability in immunohistochemistry analyses. However, when an automated cellular imaging system (ACIS), which is not routine, is used with immunohistochemistry it has been shown that when the score is Image not available.1.5 and >2.6 the correlation between FISH and immunohistochemistry is good (Figure 37.1 - see inside front cover). Current thinking suggests that all immunohistochemistry reported as 2+ should be sent for FISH. When the ACIS is used FISH may not be required with scores of ...

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