Axillary Surgery Following Neoadjuvant Chemotherapy - Multidisciplinary Guidance From the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology.

AIMS: These multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer. MATERIALS & METHODS: Following a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines. KEY RECOMMENDATIONS: In patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.

Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers.

BACKGROUND: The clinical effectiveness of treating ipsilateral multifocal (MF) and multicentric (MC) breast cancers using breast-conserving surgery (BCS) compared with the standard of mastectomy is uncertain. Inconsistencies relate to definitions, incidence, staging and intertumoral heterogeneity. The primary aim of this systematic review was to compare clinical outcomes after BCS versus mastectomy for MF and MC cancers, collectively defined as multiple ipsilateral breast cancers (MIBC). METHODS: Comprehensive electronic searches were undertaken to identify complete papers published in English between May 1988 and July 2015, primarily comparing clinical outcomes of BCS and mastectomy for MIBC. All study designs were included, and studies were appraised critically using the Newcastle-Ottawa Scale. The characteristics and results of identified studies were summarized. RESULTS: Twenty-four retrospective studies were included in the review: 17 comparative studies and seven case series. They included 3537 women with MIBC undergoing BCS; breast cancers were defined as MF in 2677 women, MC in 292, and reported as MIBC in 568. Six studies evaluated MIBC treated by BCS or mastectomy, with locoregional recurrence (LRR) rates of 2-23 per cent after BCS at median follow-up of 59·5 (i.q.r. 56-81) months. BCS and mastectomy showed apparently equivalent rates of LRR (risk ratio 0·94, 95 per cent c.i. 0·65 to 1·36). Thirteen studies compared BCS in women with MIBC versus those with unifocal cancers, reporting LRR rates of 2-40 per cent after BCS at a median follow-up of 64 (i.q.r. 57-73) months. One high-quality study reported 10-year actuarial LRR rates of 5·5 per cent for BCS in 300 women versus 6·5 per cent for mastectomy among 887 women. CONCLUSION: The available studies were mainly of moderate quality, historical and underpowered, with limited follow-up and biased case selection favouring BCS rather than mastectomy for low-risk patients. The evidence was inconclusive, weakening support for the St Gallen consensus and supporting a future randomized trial.

False-negative MRI breast screening in high-risk women.

AIM: To determine the frequency of and reasons for false-negative breast magnetic resonance imaging (MRI) examinations in high-risk women undergoing annual screening. MATERIALS AND METHODS: The family history clinic database was interrogated and women at high risk of breast cancer who had undergone screening MRI and been diagnosed with breast cancer within 2 years of the MRI examination were identified. All available MRI examinations were reviewed and classified by two radiologists. RESULTS: Of 32 women diagnosed with breast cancer, 23 had MRI images available for review. Fourteen were diagnosed at MRI, four at interim mammography, two symptomatically, one incidentally on ultrasound, and two at risk-reducing mastectomy. Ten women (43%) had potentially avoidable delays in diagnosis. The preceding MRIs were classified as false-negative screens in five women (one prevalent, four incident), false-negative assessment in seven and minimal signs in three (three women were assigned dual classifications). Common reasons for diagnostic delay included small enhancing masses that were overlooked, areas of non-mass enhancement that showed little or no change between screens, false reassurance from normal conventional imaging at assessment, and overreliance on short-interval repeat MRI. CONCLUSION: Small enhancing foci, masses, and areas of segmental non-mass enhancement are common MRI features of early breast cancer. Lack of change of non-mass enhancement on serial examinations does not exclude malignancy. Double reading of both screening and assessment examinations is recommended. Ready access to MRI biopsy is essential. Short-interval repeat MRI should be limited to reassessing low suspicion areas likely to be benign glandular enhancement. Annual mammography remains important in these women.

A randomised pilot study comparing 13 G vacuum-assisted biopsy and conventional 14 G core needle biopsy of axillary lymph nodes in women with breast cancer.

AIM: To compare the acceptability, safety, and feasibility of vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) of axillary lymph nodes in women with breast cancer. MATERIALS AND METHODS: This parallel, non-blinded, randomised study was approved by the National Research Ethics Service. Following written informed consent, women with abnormal appearing axillary lymph nodes and radiologically malignant breast masses were randomised 1:1 to lymph node sampling under local anaesthetic with either 14 G CNB or 13 G VAB in a single UK centre. Primary outcomes were study uptake rate and patient willingness to undergo a repeat procedure if necessary. Procedure duration, immediate and post-procedure pain scores, diagnostic yield, complications, and surgical histopathology were recorded. RESULTS: Ninety-five women were approached; 81 (85.3%) consented and were randomised. Forty underwent CNB; 40 underwent VAB; one was excluded. Median age was 57 years. The median procedure time was 2 minutes for both techniques. The median number of samples obtained was three for CNB and four for VAB. Median pain scores for the procedure and first 3 days were 1/10 and 1/10 for CNB and 1/10 and 2/10 for VAB (p=0.11 and 0.04). More women were prepared to undergo repeat CNB compared to VAB, but the difference was not significant (38/39 versus 33/39; p=0.11). Two patients developed a haematoma after VAB. One CNB and six VABs failed to yield adequate tissue (p=0.11), but the sensitivity was similar at 79% and 78%. CONCLUSION: Study uptake was high. Acceptability of the two procedures was similar, but VAB was associated with more post-procedure pain. The sensitivity appears to be similar.

Intensive breast screening in BRCA2 mutation carriers is associated with reduced breast cancer specific and all cause mortality.

BACKGROUND: The addition of annual MRI screening to mammography has heightened optimism that intensive screening along with improved treatments may substantially improve life expectancy of women at high risk of breast cancer. However, survival data from BRCA2 mutation carriers undergoing intensive combined breast screening are scarce. METHODS: We have collated the results of screening with either annual mammography or mammography with MRI in female BRCA2 mutation carriers in Manchester and Oslo and use a Manchester control group of BRCA2 mutation carriers who had their first breast cancer diagnosed without intensive screening. RESULTS: Eighty-seven BRCA2 mutation carriers had undergone combined (n = 34) or mammography (n = 53) screening compared to 274 without such intensive screening. Ten year breast cancer specific survival was 100 % in the combined group (95 % CI 82.5-100 %) and 85.5 % (95 % CI 72.6-98.4 %) in the mammography group compared to 74.6 % (95 % CI 66.6-82.6 %) in the control group. Better survival was driven by lymph node status (negative in 67 % of screened vs 39 % of unscreened women; p < 0.001) and a significantly greater proportion of intensively screened women had invasive breast cancers <2 cm at diagnosis (74.6 % vs 50.4 %; p = 0.002). CONCLUSION: Intensive combined breast cancer screening with annual MRI and mammography appears to improve survival from breast cancer in BRCA2 mutation carriers. Data from larger groups are required to confirm the effectiveness of combined screening in BRCA2 carriers.

Rosai-Dorfman disease of the breast.

A 56-year-old female was recalled for assessment following screening mammography that demonstrated a new 9-mm indeterminate density in the left breast. Clinical breast examination was normal. Ultrasound confirmed a 9-mm predominantly well-defined hypoechoic breast mass. Core biopsy demonstrated large histiocytes with emperipolesis and positive staining for S100, which is consistent with Rosai-Dorfman disease (RDD). Multidisciplinary team discussion concluded case concordance. The patient was discharged back to the screening programme. RDD is a rare, benign condition that may mimic breast cancer. This case demonstrates that identification of RDD on core needle biopsy may help avoid unnecessary surgery.

Outcomes of patients with lobular in situ neoplasia of the breast: the role of vacuum-assisted biopsy.

OBJECTIVES: To audit the outcomes of patients with non-pleomorphic lobular in situ neoplasia (LISN) of the breast and clarify the role of vacuum-assisted biopsy (VAB), surgical biopsy and conservative management for this condition. MATERIALS AND METHOD: A single-centre retrospective review of hospital databases covering a 14-year period was performed. Patients with LISN as the most pertinent diagnosis on core needle biopsy (CNB), vacuum-assisted biopsy (VABs) or surgical biopsy were identified. The radiological features, histopathological findings and outcome of subsequent annual mammography were recorded. RESULTS: Between 1998 and 2012 there were 70 patients with LISN as the most pertinent diagnosis at CNB, VAB or surgery. 52 underwent VAB, typically 18 11-gauge samples. The pathology was upgraded from the preceding 14-gauge CNB in 7 cases. Of 11 patients who underwent surgery after VAB, one (who had undergone a low tissue yield VAB) was upgraded. There were no new breast cancers during a mean annual mammographic follow-up period of 53 months in 40 patients who had VAB with complete radiological-histopathological concordance. CONCLUSION: Provided there is adequate tissue sampling and radiological-pathological concordance, VAB is a safe alternative to open biopsy in the management of non-pleomorphic LISN.

Benign papilloma diagnosed on image-guided 14 G core biopsy of the breast: effect of lesion type on likelihood of malignancy at excision.

AIM: To ascertain the negative predictive value (NPV) for atypia and malignancy of 14 G core biopsy of papillomas and to determine whether lesion type influences the likelihood of malignancy at lesion excision. MATERIALS AND METHODS: Ninety-six lesions with a 14 G core biopsy diagnosis of benign papilloma without atypia in 95 women were included. The imaging features (mass or microcalcification), biopsy mode, and number of core samples taken were documented. All patients subsequently underwent lesion excision with either extensive vacuum-assisted biopsy (VAB; 72 lesions) or surgery (24 lesions). Mammographic follow-up of at least 2 years was available for 32 lesions that were benign at VAB. RESULTS: Atypia or malignancy was found more commonly in association with microcalcification (six of 29 lesions: 21%; median number of nine 14 G cores) than a mass (five of 67 lesions: 7%; median number of three 14 G cores), although the difference does not reach statistical significance (p = 0.088). The NPV of a 14 G core biopsy diagnosis of papilloma for atypia or malignancy is 89% (85/96). Disease underestimation may be more common in microcalcification lesions despite the greater number of cores obtained. CONCLUSION: Excision (using VAB or surgically) of all papillomas diagnosed as benign on 14 G needle core biopsy is recommended. Surgery may be more appropriate than VAB for some microcalcification lesions unless they are small and can be confidently removed in their entirety using VAB.

A survey of current UK practice regarding the biopsy of clinically and radiologically benign breast masses in young women.

AIM: To determine current practice in the UK of needle sampling of clinically and radiologically benign breast masses in young women. METHOD: A questionnaire regarding needle sampling practice in young women with clinically and radiologically benign breast masses was sent to 481 members of the Royal College of Radiologists Breast Group. This included questions on whether a written protocol is in place to allow avoidance of biopsy, and if so, the clinical and radiological criteria used. RESULTS: Responses were available for analysis from 80 units. Forty-two (53%) units had no written policy in place, whilst 38 (47%) adhered to a written policy. Of those with a policy, an age criterion for safe avoidance of biopsy was present in 36 out of the 38 units (95%). The age limit used ranged from <25 years to <35 years. Twenty-seven (71%) written policies included clinical criteria but only four (10%) policies included a size criterion. Radiological criteria were present in all policies and the majority (74%) adhered to full Stavros criteria. Seven units (18%) used a revised form of the Stavros criteria and three units used their own criteria. CONCLUSION: There is little concordance between symptomatic breast clinics regarding the criteria for avoidance of breast biopsy in this young patient group. Given the very low incidence of breast carcinoma in women less than 25 years old it is considered safe and feasible to adopt a standardized protocol across the UK and avoid the often-unnecessary benign biopsies in these patients.

Criteria for the safe avoidance of needle sampling in young women with solid breast masses.

AIM: To establish clinical and ultrasonic criteria by which needle sampling can be safely avoided in young women with solid breast masses. MATERIALS AND METHODS: The databases of a large hospital were searched for breast cancers, phyllodes tumours, and papillomas diagnosed in women below the age of 30 years. In addition, the clinical and sonographic findings in female patients less than 25 years of age presenting with a solid breast mass over a 1-year period were reviewed. RESULTS: Nine women with breast cancer, seven with phyllodes, and six with papillomas were found. No delayed diagnoses in those who had ultrasound would have been made if the following criteria had been applied to avoid needle sampling: age less than 25 years; no known risk factors for breast malignancy; mass not rapidly enlarging; smooth discrete mobile mass on clinical examination, or lesion impalpable; well-defined homogeneously isoechoic or mildly hypoechoic solid mass; less than 3 cm in greatest dimension; ovoid shape, aligned parallel to the skin surface; smooth or gently lobulated contour (two or three lobulations only; no microlobulation); thin echogenic pseudocapsule; no calcification; no acoustic shadowing. Needle sampling could have been safely avoided in approximately two-thirds of the women reviewed below the age of 25 with a solid breast mass. CONCLUSION: Application of the proposed criteria would spare a significant number of young women unnecessary needle sampling.

Ultrasound-guided vacuum-assisted excision of breast papillomas: review of 6-years experience.

AIM: To review the outcome of vacuum-assisted removal of breast papillomas performed in the Bolton Breast Unit. MATERIALS AND METHODS: Twenty-six benign breast papillomas were excised using an ultrasound-guided, vacuum-assisted technique under local anaesthetic over a 6-year period. An 8G Mammotome was used for 12 lesions, an 11G Mammotome for 13 lesions and a 7G EnCor for one lesion. The mean lesion size was 9 mm (range 3-17 mm). The mean number of cores taken per case was nine. RESULTS: One patient developed a post-procedure haematoma, which did not require treatment. There were no other short-term complications. None of the papillomas were associated with atypia or malignancy. Subsequent breast imaging (mostly routine screening mammography) was reviewed and evidence of recurrence recorded. To date, 16 patients have received at least one subsequent routine screening mammogram, with a mean follow-up to latest mammogram of 30 months. Mammographic evidence of papilloma regrowth has been observed in two patents, with a third patient presenting with recurrence of the original symptom of a palpable lump. All three recurrent lesions were surgically excised and confirmed to be benign papillomas. These lesions measured 6, 12, and 15 mm prior to the original vacuum-assisted excision. CONCLUSION: The findings suggests that vacuum-assisted removal is a satisfactory alternative to surgery for the majority of patients, but that particular attention should be paid to ensuring complete lesion removal in view of the relatively high recurrence rate in this series.

The Royal College of Radiologists Breast Group breast imaging classification.

Standardisation of the classification of breast imaging reports will improve communication between the referrer and the radiologist and avoid ambiguity, which may otherwise lead to mismanagement of patients. Following wide consultation, the Royal College of Radiologists Breast Group has produced a scoring system for the classification of breast imaging. This will facilitate audit and the development of nationally agreed standards for the investigation of women with breast disease. This five-point system is as follows: 1, normal; 2, benign findings; 3, indeterminate/probably benign findings; 4, findings suspicious of malignancy; 5, findings highly suspicious of malignancy. It is recommended that this be used in the reporting of all breast imaging examinations in the UK.

Follow-up for screen-detected ductal carcinoma in situ: results of a survey of UK centres participating in the Sloane project.

AIMS: To investigate the variations in follow-up practice for screen-detected ductal carcinoma in situ (DCIS) in the UK. METHODS: A questionnaire enquiring about follow-up practice and the perceived value of clinical follow-up after surgery for screen-detected DCIS was sent to the 74 UK screening centres participating in the Sloane Project. RESULTS: Responses were received from 66 hospitals serving 54 screening centres. These demonstrate wide variations in practice. Clinical follow-up duration ranges from 1 year to indefinite, with the frequency of visits from three-monthly to annually. Formal mammographic follow-up duration ranges from none to indefinite. Mammographic frequency ranges from 1 to 2 years. Follow-up varies according to factors such as size and grade of disease and margin status in 23 units and according to whether adjuvant therapy is given in 23. Seven hospitals perform mammography of reconstructed breasts. Thirty-one centres consider clinical follow-up of DCIS to be of value or limited value whereas 28 consider it to be of little or no value. CONCLUSIONS: There is no consensus with regard to the duration and frequency of follow-up for screen-detected DCIS, the contribution of predictive and treatment factors, the use of mammography of the reconstructed breast or the perceived value of clinical follow-up. Published guidelines show no consensus. Multidisciplinary teams involved in the care of women with screen-detected non-invasive cancer should contribute to audits such as the Sloane Project in order to determine the most effective and efficient ways to treat and follow up these patients.

Molecular identification of bacteria on the tongue dorsum of subjects with and without halitosis.

AIM: Compare the microbial profiles on the tongue dorsum in patients with halitosis and control subjects in a UK population using culture-independent techniques. MATERIALS AND METHODS: Halitosis patients were screened according to our recently developed recruitment protocol. Scrapings from the tongue dorsum were obtained for 12 control subjects and 20 halitosis patients. Bacteria were identified by PCR amplification, cloning and sequencing of 16S rRNA genes. RESULTS: The predominant species found in the control samples were Lysobacter-type species, Streptococcus salivarius, Veillonella dispar, unidentified oral bacterium, Actinomyces odontolyticus, Atopobium parvulum and Veillonella atypica. In the halitosis samples, Lysobacter-type species, S. salivarius, Prevotella melaninogenica, unidentified oral bacterium, Prevotella veroralis and Prevotella pallens were the most commonly found species. For the control samples, 13-16 (4.7-5.8%) of 276 clones represented uncultured species, whereas in the halitosis samples, this proportion increased to 6.5-9.6% (36-53 of 553 clones). In the control samples, 22 (8.0%) of 276 clones represented potentially novel phylotypes, and in the halitosis samples, this figure was 39 (7.1%) of 553 clones. CONCLUSIONS: The microflora associated with the tongue dorsum is complex in both the control and halitosis groups, but several key species predominate in both groups.

Crude open biopsy rates for benign screen detected lesions no longer reflect breast screening quality--time to change the standard.

OBJECTIVES: To investigate the changing nature of the benign screen detected breast abnormalities removed at open biopsy over a seven year period and to compare this with the improving cancer detection rate and non-operative diagnosis rate. SETTING: The Bolton, Bury, and Rochdale Breast Screening Programme. METHODS: The histopathology reports of the benign lesions removed from patients undergoing open biopsy for screen detected abnormalities between 1 April 1994 and 31 March 2001 were reviewed and the lesions classified on the B1 to B5 scale. Cancer detection rates and non-operative cancer diagnosis rates were ascertained from the breast screening computer system. RESULTS: 148 benign surgical biopsies were performed in the seven year period. There was a moderate increase in the overall benign biopsy rate over the period (from 1.26 open biopsies per 1000 women screened for the three years 1994-97 to 1.63 open biopsies per 1000 women screened for the three years 1998-2001). The biopsy rate for B2 (benign) lesions decreased slightly over the study period but the biopsy rate for B3 lesions (that is, of uncertain malignant potential) more than doubled. The majority (84%) of the B3 lesions were radial scars. There was a steady improvement in the cancer detection rate and the non-operative cancer diagnosis rate over the period, similar to that seen nationally. CONCLUSIONS: Improvements in screening technique and detection ability result in an increase in the number of subtle radiologically indeterminate or suspicious lesions detected. Many of these are radial scars, which require excision. Crude benign open biopsy rates for screening programmes are no longer meaningful, and should now be refined with separate rates for B2 lesions and B3 lesions. High quality programmes can expect to have low B2 open biopsy rates and high B3 open biopsy rates. It is inappropriate to have an upper limit for the B3 open biopsy rate.

Uric acid is closely linked to vascular nitric oxide activity. Evidence for mechanism of association with cardiovascular disease.

OBJECTIVES: The study was undertaken to determine whether the mechanism of association of elevated serum uric acid level (SUA) with cardiovascular disease (CVD) is secondary to a common link with vascular nitric oxide (NO) activity. BACKGROUND: Epidemiologic studies demonstrate an association of elevated SUA with CVD. The mechanism of this association is unknown, but both may be linked via an impairment in vascular NO activity. To examine this, we determined the relationship of SUA to vascular NO activity and to CVD risk. We then determined the effect of enhancing vascular NO activity on SUA. METHODS: In part 1, individuals with various degrees of CVD (n = 458) were surveyed and underwent measurement of flow-mediated brachial artery vasodilation (FMV), a measure of vascular NO activity. In part 2, we performed an analysis of data pooled from six separate clinical trials of a medical food designed to enhance vascular NO activity in individuals with CVD (n = 217 subjects representing 253 treatment periods) to determine the effect on SUA. RESULTS: In part 1, of all risk factors tested, SUA was second only to age in correlation with FMV, accounting for 7% (p < 0.0001) of the variability in FMV. Both SUA and FMV were related to the degree of disease risk (p < 0.0001 and p = 0.00025 by analysis of variance, respectively). By multivariate analysis, SUA did not continue to contribute significantly to the determination of FMV. In part 2, enhancement of FMV (5.8 +/- 4 to 8.6 +/- 5, p < 0.0001) was associated with a decrease in SUA (5.5 +/- 1.5 to 5.0 +/- 1.5, p < 0.0001). There was no placebo effect on FMV or SUA. CONCLUSIONS: These results suggest that the association of elevated SUA with CVD may be a consequence of an impairment of vascular NO activity. This may be owing to an ability of NO to modulate uric acid production through its influence on xanthine oxidase activity.

Primary and metastatic lobular carcinoma of the breast.

Invasive lobular carcinoma of the breast is the second most common type of primary breast cancer, accounting for 8-14% of cases, but is often difficult to diagnose early. It typically shows a diffuse pattern of infiltration within the breast, resulting in a variety of often subtle radiological appearances. A similar infiltrative pattern is seen in its metastatic form, with involvement of the gastrointestinal tract, peritoneum, retroperitoneum, bone marrow, meninges and uterus occurring more frequently than with the more common infiltrating ductal carcinoma of the breast. This pictorial essay illustrates the spectrum of radiological appearances which may be encountered with both primary and secondary lobular carcinoma.