Adrian Harnett
Case history
A 36-year-old Russian security guard at Sizewell nuclear power station presented to her GP with a lump in her left breast. There was no nipple discharge or distortion. She had not had any lumps in the past. She had two children aged 5 and 3 who had been breastfed for about 11 months. She was seen with her English husband, also a security guard at the power station. Mammography followed by core biopsy confirmed malignancy.
Question
1. What is unusual about this case?
Answer
1. What is unusual about this case?
The patient is young, under 40, and so it is important to enquire about a family history of breast cancer.
Her grandmother on her father’s side had breast cancer in her 60s and she is now 85. Her grandfather’s sister had breast cancer in her 50s and died at the age of 85.
She has worked at Sizewell for 8 years as a security officer on the main gate. She has no relevant past medical history, is not on any medication, and is a non-smoker.
Question
2. What does this information indicate?
Answer
2. What does this information indicate?
Although two of her relatives had breast cancer, they were not close relatives and developed cancer after the menopause so it is unlikely that she has a BRCA1 or -2 mutation. It is interesting to note that both lived on to old age so did not have particularly aggressive breast cancers. Her employment at Sizewell is extremely unlikely to have had any role in the aetiology, because if she had had any increased radiation exposure it would have been at a very low level and it would be most unusual for it to cause a breast cancer within the short timescale of 8 years. However, records monitoring her radiation exposure should be checked and confirmation sought that she had not been exposed to any radiation incidents.
A mastectomy and axillary clearance were performed. Histopathology revealed a 51mm grade II invasive ductal carcinoma with associated intermediate ductal carcinoma in situ (DCIS) (see Fig. 7.1A). There was intermediate-grade DCIS and a background of in situ lobular neoplasia and also pseudo-angiomatoid stromal hyperplasia (PASH) (Fig. 7.1B). This latter feature is not uncommon in breast specimens but tends to be seen in younger patients. Ibrahim et al. (1989) found microscopic foci of PASH in 23% of 200 consecutive breast specimens obtained for benign and malignant conditions, 89% of which were from patients younger than 50 years.
Lymphovascular invasion was present. Margins were clear but 3/14 lymph nodes were involved and extracapsular invasion was seen. The tumour was strongly ER receptor positive and HER-2 negative.
Fig. 7.1 (images courtesy of dr Joseph Murphy) (See also colour plate section)
Questions
3. Is this result surprising?
4. What course of action would you recommend?
Answers
3. Is this result surprising?
Breast cancer in patients aged under 40 is more likely to be high grade and HER-2 positive (particularly if BRCA negative). Fewer cancers are hormone receptor positive in the under 40s than the over 40s. The nodal involvement is not surprising, but it is unusual to have such a large grade II ductal carcinoma. Lobular carcinomas tend to be more diffuse. The histopathology should be reviewed.
In summary, this was a conventional mammary carcinoma with no particular features to suspect it was radiation induced.
4. What course of action would you recommend?
In view of the young age of the patient and the large tumour, staging investigations including CT and bone scans should be performed.
Staging investigations did not reveal any evidence of distant metastatic disease.
Question
5. Is there any other line of enquiry that should be pursued?
Answer
5. Is there any other line of enquiry that should be pursued?
It should be noted that the patient is Russian. Enquiry should be made into her upbringing and when she came to the UK. More details about her family should be sought.
She lived 200 to 300km south of Chernobyl and left the area when she finished school in 1989. She was 14 when the nuclear accident occurred there. Neither she nor her family were evacuated at the time; in fact they learnt of the accident 15 months later. Her younger sister, who was also exposed to radiation from Chernobyl, died of a brain tumour at the age of 3.
Question
6. What further management would you recommend?
Answer
6. What further management would you recommend?
Firstly you would have to explain that the radiation incident at Chernobyl is highly likely to have caused her breast cancer, as well as the brain tumour in her younger sister. This could also explain the slightly unusual pathology as discussed in the answer to Question 2.
Reassurance should be given about her treatment to date and that the surgery she has completed has been a large component of that treatment. It has removed most if not all of the cancer and the scans give reassurance in that there is no evidence of distant spread. However, she is at risk of developing recurrence later due to the presence of undectable microscropic disease, and the risk of this can be significantly reduced by giving adjuvant treatment.
Adjuvant chemotherapy using a combination regime was given. She received eight courses of FEC chemotherapy (5-FU, epirubicin, and cyclophosphamide) and on completion was commenced on tamoxifen. She was given post-operative radiotherapy to the left chest wall and supraclavicular fossa (40Gy in 15 fractions over 3 weeks) to reduce the risk of loco-regional relapse because she had a large, node-positive tumour with lymphovascular invasion in the primary tumour and extracapsular invasion in the nodes.
Questions
7. In retrospect does she fulfil the criteria for neoadjuvant chemotherapy?
8. Discuss the advantages and disadvantages of neoadjuvant chemotherapy.
Answers
7. In retrospect does she fulfil the criteria for neoadjuvant chemotherapy?
The tumour was more diffuse and larger histologically than the pre-operative examination and imaging had suggested. Neoadjuvant chemotherapy would have been a very reasonable alternative management option if the extent of disease had been appreciated before surgery. Neoadjuvant chemotherapy is indicated for:
♦ locally advanced and inflammatory breast cancer—where it should be the standard of care;
♦ T2 and T3 tumours where it is acceptable and preferable to routine post-operative adjuvant chemotherapy.
It is reasonable to give neoadjuvant chemotherapy to any patient who needs adjuvant chemotherapy.
8. Discuss the advantages and disadvantages of neoadjuvant chemotherapy.
The advantages of neoadjuvant chemotherapy outweigh the disadvantages: some are obvious and some are theoretical but we shall discuss them together.
Advantages:
♦ It increases the breast conservation rate due to tumour regression.
♦ It can make inoperable tumours suitable for mastectomy.
♦ It can measure marker lesions to monitor the response to chemotherapy, unlike with adjuvant treatment.
♦ Systemic treatment makes sense, treating any nodal or microscopic disease early when the breast primary is still in situ.
♦ The tumour is less viable and tumour shedding at surgery is reduced if neoadjuvant therapy is employed.
♦ Recent studies have confirmed an overall survival benefit for neoadjuvant therapy.
♦ Forty per cent of positive axillary nodes convert to negative nodes after neoadjuvant therapy.
Disadvantages:
♦ Histology is only available from a core biopsy, so from a limited amount of tissue, but more importantly it does not take account of tumour heterogeneity.
♦ There is no surgical staging.
♦ You may not know where the tumour is! It is important to be prepared for success, to know where the tumour is, and how to image it.
♦ You can get a response that leaves residual multifocal disease spread over the same area that was involved prior to chemotherapy.
One year after completion of treatment she is well and clinical examination is unremarkable. She wishes to have a breast reconstruction.
Questions
9. How would you advise her?
10. What other factors should be discussed with the patient?
Answers
9. How would you advise her?
It is entirely reasonable and understandable that she wishes to have breast reconstruction. She has coped with all her treatment well and has no evidence of recurrent disease. If the breast cancer does relapse this is most likely to occur in a few years’ time as the tumour was hormone receptor positive. It is probably unreasonable to expect her to wait some years before considering reconstruction. The surgical options are reduced as she has had post-operative radiotherapy. A tissue expander technique is contraindicated as the elasticity of the irradiated skin and tissues will have been considerably compromised.
10. What other factors should be discussed with the patient?
It is important the patient is as fit as possible, not overweight, and a non-smoker. The usual recommendation is a body mass index of less 30 (kg/m2) and ideally less than 27. Failure of the reconstruction is far more likely to happen in smokers because of compromised vasculature. Several consultations are often necessary in preparation for breast reconstruction, involving not only specialist nurses and physiotherapists but also dieticians and, when appropriate, smoking cessation clinics.
Progress and follow-up
The patient was referred for breast reconstruction, which was carried out after weight reduction and without complication (Fig. 7.2). She has been very pleased with the result and continues to remain well on follow-up 4½ years after the original diagnosis.
Fig. 7.2
Further reading
Hortobagyi G. William L. McGuire Memorial Lecture: neoadjuvant systemic therapy: promising experimental model, or improved standard of care? Cancer Research 2012; 72(24 Suppl): abstract ML-1.
Ibrahim RE, Sciotto CG, Weidner N. Pseudoangiomatous hyperplasia of mammary stroma. Some observations regarding its clinicopathologic spectrum. Cancer 1989; 63: 1154–1160.