Hugh Carmalt

Phyllodes tumours of the breast : a clinicopathological analysis of 65 cases from a single institution

The aim of this study was to document the clinical and pathological features of a large single institutional series of ethnically diverse patients with phyllodes tumours (PTs), and to determine which characteristics were predictive of outcome. Sixty five PTs were analysed; 34 were benign, 23 borderline and eight malignant (34 low grade and 31 high grade PTs on a two tiered grading system). Nine patients (15%) had local recurrences. A greater percentage of higher grade tumours recurred and women of Asian origin had a higher recurrence rate compared to the non-Asian patients. The 5 year disease-free survival was 81% and time to recurrence was significantly lower in the high grade group. No metastases or deaths from disease were recorded. The mean age at diagnosis significantly increased with tumour grade. The mean tumour volume also significantly increased with grade. Tumour grade was the only parameter related significantly to outcome.

Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome.

Triple‐negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non‐small‐cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC.

SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in breast cancer and redefine lymphatic drainage from the breast to the axilla

BACKGROUND Historical studies of lymphatic drainage of the breast have suggested that the lymphatic drainage of the breast was to lymph nodes lying in the antero-pectoral group of nodes in the axilla just lateral to the pectoral muscles. The purpose of this study was to confirm this is not correct. METHODS The hybrid imaging method of SPECT/CT allows the exact anatomical position of the sentinel lymph node (SLN) in the axilla to be documented during pre-operative lymphoscintigraphy (LS) in patients with breast cancer. We have done this in a series of 741 patients. The Level I axillary nodes were defined as anterior, mid or posterior. This was related to the anatomical location of the primary cancer in the breast. RESULTS A SLN was found in the axilla in 97.8% of our patients. Just under 50% of SLNs located in the axilla were not in the anterior group and lay in the mid or posterior group of Level I axillary nodes. There was a SLN in a single node field in 460 patients (63%), two node fields in 261(36%), three node fields in 6 and four node fields in 1 patient. CONCLUSION Axillary lymphatic drainage from the breast is not exclusively to the anterior (or antero-pectoral) group of Level I nodes. SYNOPSIS SPECT/CT lymphoscintigraphy shows that the breast does not always drain to the anterior group of Level I lymph nodes in the axilla but may drain to the mid axilla and/or posterior group in about 50% of patients with breast cancer regardless of the location of the cancer in the breast. These data redefine lymph drainage from the breast to axillary lymph nodes.

BREAST CANCER IN YOUNG WOMEN

BACKGROUND It is believed that cancer of the breast is more difficult to diagnose in young women and it has long been disputed whether breast cancer occurring in women aged < or = 40 years is more aggressive than that occurring later in life. A number of reports in the literature suggest that the disease is of similar aggressiveness in the young patients and older age groups, while other reports suggest that it is more aggressive and carries a higher mortality in young women. METHODS To address these aspects of breast cancer we have undertaken a review of the cases treated at The Strathfield Breast Centre between 1989 and 1996 and compared the disease in the young and old groups with particular reference to the modes of diagnosis, the pathological staging and types of tumour and the outcomes of treatment. RESULTS The accuracy of ultrasound and fine needle aspiration biopsy were similar in both groups, but the false negative rate of mammography in the young patients was 15% or 50% greater than that which was observed in the older patients. The incidence of histopathological type, bilaterality, size of lesion and receptor positivity were the same in both groups. In the young group, 40% had Grade 3 tumours compared with 27% in the older group. Nineteen per cent of young patients had 4 or more lymph nodes involved while only 10% of the older patients had similar lymph node involvement. Overall 5-year survival was 79% in the older patients compared with 90% in the young patients. CONCLUSIONS The spectrum of disease is similar in both the young and older patient and the prognosis is no worse for the young group but mammography is less effective in the diagnosis of the young patient.

p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours

Karim R Z, Gerega S K, Yang Y H, Spillane A, Carmalt H, Scolyer R A & Lee C S
(2010) Histopathology 56, 868–875
p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours

Proteins from the Wnt pathway are involved in the pathogenesis and progression of mammary phyllodes tumours

Background: The Wnt pathway is important in cell signalling transduction and is involved in the pathogenesis of multiple tumour types. A comprehensive analysis of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours (PTs) has not been previously performed. Aims: To evaluate the immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome. Methods: 65 PTs (34 benign, 23 borderline and 8 malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemical stains were performed on tissue microarrays for β-catenin, Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately. Results: Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant progressive increases in expression with increasing grade (p = 0.002 and p = 0.02 respectively). Epithelial membranous and stromal nuclear β-catenin, epithelial cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression with increasing tumour grade, however, the differences were not significant. Disease-free survival was significantly decreased (p = 0.0017) with positive epithelial E-cadherin staining. Conclusions: Results suggest that alterations in the Wnt pathway are important in the progression and in the epithelial and stromal interactions in PTs. They have important implications for understanding the pathogenesis of these uncommon but clinically important tumours.

Screen‐detected breast cancer compared to symptomatic presentation: An analysis of surgical treatment and end‐points of effective mammographic screening

Background: Mammographic screening has been shown to reduce mortality from breast cancer and to offer more opportunity for breast conservation surgery (BCS). The minimum standards (or surrogate end‐points) that need to be achieved by a screening programme if it is to reduce mortality have been derived from the Two County Study. Three surrogate end‐points that can be used to gauge the quality of the screening service are that 50% of the identified infiltrating cancers should be < 15 mm; at least 30% of grade 3 cancers should be < 15 mm; and 70% of screen‐detected cancers should have a negative axillary dissection. The present study assesses these end‐points of effective screening in an urban population referred to The Strathfield Breast Centre (TSBC). The screening end‐points and surgical treatment of one group of women referred with a BreastScreen New South Wales (NSW)‐detected breast cancer (screen group) were compared to all the other, mostly symptomatic, breast cancer referrals (symptom group). The problems with the current pattern of acceptance of mammographic screening in TSBC’s referral area are discussed.

Primary squamous cell carcinoma of the breast

A 69-year-old woman presented with a large fungating mass, filling the lateral half of her right breast and a large clinically involved right axillary lymph node. She also presented with mid-thoracic back pain. Computed tomography (CT) scans confirmed the large soft tissue mass in the right axilla but also revealed a right-sided pleural effusion and extensive vertebral body destruction. Bone scans confirmed widespread metastatic carcinoma, and a core biopsy of the breast confirmed squamous cell carcinoma. The patient died of her distant metastatic disease while receiving palliative radiotherapy.

Recent insights into the molecular pathogenesis of mammary phyllodes tumours

Phyllodes tumours (PTs) of the breast are true biphasic neoplasms within which interactions between the epithelium and stroma are critical for tumour development and progression. Despite numerous studies reporting the results of ancillary marker investigations in PTs, the current histological grading systems remain unreliable at predicting clinical outcome even when supplemented by these markers. As a consequence, there has been much interest in the prospect of using molecular/genetic techniques to develop a more robust “grading” system. This review focuses on recent cytogenetic and molecular studies investigating the pathogenesis of PTs and those correlating molecular findings with clinicopathological features of the tumours. Recent data highlight that intratumoural genetic heterogeneity is common in PTs and may account for the reported lack of correlation between histological grading and clinical behaviour. The entire spectrum of molecular aberrations in PTs are yet to be fully defined, however recent array-based studies using comparative genomic hybridisation have reported that copy number changes increase with the progression from benign PT to malignancy. Tumour recurrence and progression is likely to reflect the presence of under-recognised subclones. p16INK4a (CDKN2A) inactivation also appears to be important in PT pathogenesis. Further additional studies will be required to identify and validate new prognostic markers and therapeutic targets in order to improve the diagnosis, classification, prediction of outcome and management of patients with this rare neoplasm. Data generated from modern sequencing technologies are likely to provide new insights into the disease and assist in this endeavour.

Preservation or division of the intercostobrachial nerve in axillary dissection for breast cancer: Meta-analysis of Randomised Controlled Trials

PURPOSE Management of the ICBN during axillary dissection is controversial and the division of ICBN is often trivialised. The effect of dividing the ICBN, and its association with sensory disturbance, is unclear. A systematic review and meta-analysis was performed to evaluate the effect of preserving the ICBN during axillary dissection. METHODS A systematic literature review and meta-analysis is performed according to the PRISMA and Cochrane Collaboration guidelines. RESULTS Three RCTs and four non-RCTs were reviewed. A meta-analysis demonstrated that the incidence of sensory disturbance was significantly lower with preservation of ICBN compared to division of the ICBN with Mantel-Haenzel combined odds ratio 0.31 (0.17-0.57, 95% CI). There was relatively low level of heterogeneity (I(2) = 19%, χ(2) = 2.48, df = 2). The sensory disturbance was more likely to be hyposensitivity when compared to hypersensitivity (p < 0.0001). No difference on number of lymph nodes dissected or operating time was noted. CONCLUSION This meta-analysis demonstrates that division of the ICBN is associated with higher risk of sensory disturbance, and that the nature of this sensory disturbance is more likely to be hyposensitivity, attributable to reduced nerve function.