R.D. Macmillan

Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial

BACKGROUND The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features. METHODS Patients with primary invasive breast cancer <2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both. FINDINGS The actuarial breast cancer specific survival in 1135 randomised patients at 10 years was 96%. Analysis by intention to treat showed that LR after WLE was reduced in patients randomised to radiotherapy (RT) (HR 0.37, CI 0.22-0.61 p<0.001) and to tamoxifen (HR 0.33, CI 0.15 - 0.70 p<0.004). Actuarial analysis of patients entered into the four-way randomisation showed that LR after WLE alone was 1.9% per annum (PA) versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomised to both adjuvant treatments developed LR. Analysis by treatment received showed LR at 2.2%PA for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments. CONCLUSIONS Even in these patients with tumours of excellent prognosis, LR after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments.

Sentinel node biopsy for breast cancer may have little to offer four-node-samplers: results of a prospective comparison study

The aims of the study were to determine how often four node axillary sampling (4NAS) encompasses the sentinel node (SN) and to compare the relative sensitivity of 4NAS with sentinel node biopsy (SNB) for axillary node staging. 200 patients with breast cancer were preoperatively injected with 27 MBq 99m-Tc-labelled colloid adjacent to the tumour. At operation, standard 4NAS was performed. Each node was counted ex vivo using a probe. A search was then made to find a node with higher counts in vivo directed by the probe. If found, it was excised. Each node was submitted separately to pathology. A SN was identified in 191 patients (96%). The SN was contained in the 4NAS in 153 patients (80%) and identified separately in 38 patients (20%). Of 60 node-positive patients, 49 were positive by 4NAS and SNB, the SN was not identified in 2 and in 8 the SN was falsely negative compared with 4NAS. For 1 patient, the SN was positive and the 4NAS negative. SNB performed using radiolabelled colloid has no advantage over 4NAS when nodes are assessed by standard histological technique.

Germ line mutations associated with breast cancer susceptibility

Laboratory-based research in germ line mutations associated with breast cancer susceptibility is rapidly being integrated into clinical practice with profound implications. A Medline search was performed for all relevant articles published since 1990. Where appropriate, historical articles referenced in those identified were also reviewed. The results suggested that while mutations in the BRCA1 and BRCA2 genes are the most clinically relevant, much of the data on which clinical decisions are based must be interpreted with wide confidence intervals. Between 1 in 152 and 1 in 833 individuals carry such mutations. They account for less than 5% of all breast cancer, but up to 10% of cancers in those under the age of 40 years. Founder mutations are responsible for a larger proportion of breast cancer cases within certain inbred communities. Phenotypic expression and penetrance of different mutations is not currently predictable and estimates of penetrance are largely based on highly selected populations. BRCA1 mutations are more commonly associated with ovarian cancer than BRCA2 mutations. BRCA1 cancers tend to have more distinct pathological features and are usually oestrogen receptor (ER)-negative. To conclude, the evidence in this review suggests that caution should be exercised when translating scientific progress in breast cancer germ line genetics into clinical practice. Most of the available data are derived from studies on highly selected populations. The importance of other less penetrant, but more prevalent, germ line mutations may be realised in the future.

Size of invasive breast cancer and risk of local recurrence after breast-conservation therapy

Risk of local recurrence is one important factor that determines a womans suitability for breast-conservation therapy. With the evolution of oncoplastic surgery, tumours of a size that traditionally require mastectomy may be treated by breast conservation and partial breast reconstruction. This article reviews the evidence relating to tumour size as a risk factor for local recurrence to assess whether this change in practice is appropriate. A literature review through Medline and Pubmed was performed. All pathological studies analysing tumour size as a predictor of multifocality and all randomised trials and large case series of breast conservation including tumours larger than 2 cm were reviewed and critically interpreted. Pathological studies report consistent evidence that tumour size is not predictive of multifocality. Randomised trials and clinical series of breast conservation report conflicting evidence relating to tumour size as a risk factor for local recurrence, although most studies report no association. Evidence relating to cancers over 3 cm is limited. There is little evidence to justify the use of tumour size alone as an exclusion criterion for breast-conservation therapy. A registration study of patients with cancers larger than 3 cm treated by breast conservation with or without partial breast reconstruction is proposed.

Incidence of clinically significant lymphoedema as a complication following surgery for primary operable breast cancer

There has recently been considerable interest for the need for specialist lymphoedema nurses to be appointed in the NHS. However, we had noticed in our cancer follow-up clinics that the incidence of lymphoedema appeared to be very low. Treatment for primary breast cancer (>5 cm) has been surgery and low axillary sampling (ANS). Radiotherapy (RT) or axillary clearance is subsequently performed in patients found to be node positive. The patients are followed-up in the primary breast cancer (PBC) clinic weekly. Follow-up is initially at 3-month intervals up to 2 years and then 1 yearly indefinitely. We conducted a two phased study in patients being followed up in our post cancer clinic in order to identify the incidence of LE in these patients. Phase 1 involved symptomatic patients identified at routine follow up in a 15-week period and the number of patients reporting arm swelling was recorded. The aim of this was to provide an estimate to power a phase 2 study (prospective questionnaire based). Phase 2 was conducted over a 13-week period. All patients attending the clinic were administered modified FACT B4, EQ-50 and Speilberger questionnaires. A total of 1242 patients were examined and lymphoedema found in 5 (0.04%). Of these 5, 3 had undergone axillary clearance, 1 ANS plus radiotherapy and only 1 had ANS alone. A policy of ANS, with prophylactic treatment for lymph node positivity either by surgery or RT alone, gives a very low rate of lymphoedema.

Transverse Upper Gracilis (TUG) flap for volume replacement in breast conserving surgery for medial breast tumours in small to medium sized breasts

Excision of medial sited breast tumours in small breasted patients can result in poor cosmetic outcomes, making this a difficult group of patients to manage. Traditional oncoplastic volume replacement techniques available to treat this area of the breast are limited and usually require disruption of the remaining breast to allow access for pedicled flaps. The alternative is mastectomy and total breast reconstruction. The use of a small volume free Transverse upper Gracilis (TUG) flap allows like for like replacement for these defects. Excellent cosmetic results are achievable with minimal breast and donor site morbidity. This initial experience of small volume TUG flaps used in four patients is presented to support the feasibility and assess early outcomes of this technique in the management of this niche group of patients.