Gelareh Farshid

Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has b...

Context.— The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastas...

Melanoma is an important cause of skin cancer related death throughout the world, particularly in Europe, the United States, and Australia. Rarely melanoma undergoes divergent differentiation to simulate the full morphologic and immunohistochemical features of other malignancies, notably sarcoma. However, such cases retain the molecular signatures...

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed dea...

Objective To examine the screening–treatment–mortality pathway among women with invasive breast cancer in 2006–2014 using linked data. Methods BreastScreen histories of South Australian women diagnosed with breast cancer (n = 8453) were investigated. Treatments recorded within 12 months from diagnosis were obtained from linked registry and adminis...

Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both ind...

PurposeThis study aimed to determine the interobserver concordance of two methods for proliferation assessment in breast cancer using Ki67 immunohistochemistry.Methods Ki67 was independently assessed in randomly selected tumour samples from patients with lymph node-negative breast cancer using two different methods: either cell counting or visual e...

Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Bot...

Objective We investigated treatment and survival by clinical and sociodemographic characteristics for service evaluation using linked data. Method Data on invasive female breast cancers (n = 13,494) from the South Australian Cancer Registry (2000–2014 diagnoses) were linked to hospital inpatient, radiotherapy and universal health insurance data. T...

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of Euro...

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of Euro...

Background: We investigated treatment and survival by clinical and sociodemographic characteristics in South Australia for service evaluation using linked data. Method: Data on invasive female breast cancers (n=13494) from the South Australian Cancer Registry (2000-2014 diagnoses) were linked to hospital inpatient, radiotherapy, and universal healt...

Objective Using linked cancer registry and administrative data to monitor, tumour, node and metastases (TNM) stage and survival from female breast cancer in Australia. Method Analysis of 2000–2014 diagnoses with linked population-based data to investigate: (1) sociodemographic predictors of advanced stage (stages III and IV), using unadjusted and...

The 2018 iteration of the ASCO-CAP HER2 testing guidelines proposes significant changes with an emphasis on the integration of concurrent immunohistochemistry (IHC) and in situ hybridization (ISH). We wished to evaluate the impact of these changes on clinical practice. Between Jan 2012 to Feb 2017, 2132 consecutive invasive breast carcinomas were e...

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management frame...

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible caus...

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utilit...

Background: Sarcomas comprise a heterogenous group of malignant tumours of mesenchymal origin and can arise in the skin. Definitive management of skin sarcoma usually entails surgical resection with wide margins, often requiring reconstruction. The incidence and demographics of these neoplasms in Australia are poorly understood. Method: Incidence,...

Background: Soft tissue sarcomas (STS) are rare, often fatal tumors, but little is known of the epidemiology and survival in the Australian population. This study aims to provide the first epidemiological analysis of incidence and survival rates of STS in the Australian population. Methods: A retrospective population-based observational study wa...

Background Australia’s Aboriginal and Torres Strait Islander women have poorer survival and twice the disease burden from breast cancer compared to other Australian women. These disparities are influenced, but not fully explained, by more diagnoses at later stages. Incorporating breast screening, hospital and out of hospital treatment and cancer re...

The latest update to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing in breast cancer guidelines was published in 2018. A multidisciplinary expert committee, convened under the auspices of the Royal College of Pathologists of Australasia (RCPA) Structured Pathology Reporting framework, evaluated th...

Background Since concurrent malignancy may be associated with radial scars (RS) in up to 45% of RS diagnosed on core biopsy, surgical excision is usually advised. Recent very low upgrade rates have caused a re-evaluation of the need for routine surgery. We aimed to find subsets of RS at such low risk of upgrade, as to render imaging surveillance a...

Background Detection of breast cancers by mammographic screening confers a survival advantage of 20–50% compared to symptomatic presentations. The improved prognosis is only partly explained by stage migration. The distribution of the molecular subtypes of screen-detected breast cancer (SDBC) or their HER2 status has not been studied extensively. W...

Background: Sentinel lymph-node biopsy has reduced the need for extensive axillary surgery for staging. It still exposes women to associated morbidity. Risk models that use clinical and pathology information of the primary tumour to predict sentinel lymph-node metastasis may allow further improvements in care. This study assessed the performance o...

The interplay between inflammation and cancer is the subject of intense interest. The recent approval of a number of checkpoint inhibitors has opened novel therapeutic pathways for several cancers. Conversely, biologic suppressors of inflammation, such as Tumor Necrosis Factor (TNF) inhibitors, have been utilized over the past two decades for the m...

A needle core biopsy diagnosis of atypical ductal hyperplasia is an indication for open biopsy. The launch of randomized clinical trials of active surveillance for low-risk ductal carcinoma in situ leads to the paradoxical situation of women with low-grade ductal carcinoma in situ being observed, whereas those with atypical ductal hyperplasia have...

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementa...

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitor...

This Australian human epidermal growth factor receptor 2 (HER2) testing program aimed to analyse >800 cases tested in a coordinated setting to further evaluate the criteria to establish HER2 status in advanced gastric and gastro-oesophageal junction (GOJ) cancer. Heterogeneity, and minimum number of biopsy fragments for reliable HER2 assessment wer...

Background/aim: This study tested the utility of retrospectively staging cancer registry data for comparing stage and stage-specific survivals of Aboriginal and non-Aboriginal people. Differences by area level factors were also explored. Methods: This test dataset comprised 950 Aboriginal cases and all other cases recorded on the South Australia...

Background: Sarcomas affecting the head and neck often require complex management due to the combination of anatomic, aesthetic and oncological considerations. The incidence and patterns of presentation are poorly understood and have not been reviewed in the Australian population. Method: This study sourced incidence and demographic data from th...

Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post-diagnostic survivals through lead-time and related effects, as well as mortality reductions. Linked c...

Purpose: In contemporary practice, 5% of women with non-malignant needle biopsies of screen-detected lesions still require diagnostic open biopsy (OBx). Our aims are to (i) capture a snapshot of the contemporary indications for OBx in screen-detected lesions; (ii) determine upgrade rates to malignancy (DCIS or invasive cancer); (iii) identify indi...

Rationale: Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more com...

Appropriate and accurate determination of HER2 status in women with breast cancer is critical for stratifying anti-HER2 therapies, and for access to subsidised treatment in the Australian setting. We conducted a regulated, nationwide program providing HER2 in situ hybridisation (ISH) testing for patients with newly diagnosed breast cancer. Cases wi...

Rationale, aims and objectives: Stratification of women with screen-detected ductal carcinoma in situ (DCIS) by risk of subsequent invasive breast cancer (IBC) could assist treatment planning and selection of surveillance protocols that accord with risk. We assessed the utility of routinely collected administrative data for stratifying by IBC risk...

Despite aggressive multi-modal treatment strategies, limited improvement in overall survival rates for patients diagnosed with Ewing sarcoma, the second most prevalent solid bone tumor observed in children and young adolescents, has been achieved over the past thirty years. As such, new targeted therapies are urgently required particularly for thos...

Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours fr...

There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of...

Axillary ultrasound (AUS) and biopsy are now part of the preoperative assessment of breast cancer based on the assumption that any nodal disease is an indication for axillary clearance (AC). The Z0011 trial erodes this assumption. We applied Z0011 eligibility criteria to patients with screen detected cancers and positive axillary assessment to dete...

To estimate over-diagnosis due to population-based mammography screening using a lead time adjustment approach, with lead time measures based on symptomatic cancers only. Women aged 40-84 in 1989-2009 in South Australia eligible for mammography screening. Numbers of observed and expected breast cancer cases were compared, after adjustment for lead...

In screening, the distinction between phyllodes tumour (PT) and fibroadenoma (FA) is imprecise, often needing surgery. In this retrospective cohort study and literature review, we wished to (i) present our experience with PT diagnosed among screening participants; (ii) identify discriminating features between FA and PT; (iii) assess the efficacy of...

Technical advances have improved the detection of small mammographic lesions. In the context of mammographic screening, accurate sampling of these lesions by percutaneous biopsy is crucial in limiting diagnostic surgical biopsies, many of which show benign results. Women undergoing core biopsy between January 1997 and December 2007 for <10-mm lesio...

Factors secreted by tumor cells shape the local microenvironment to promote invasion and metastasis, as well as condition the premetastatic niche to enable secondary-site colonization and growth. In addition to this secretome, tumor cells have increased abundance of growth-promoting receptors at the cell surface. We found that the tyrosine phosphat...

Background: Few population-based data are available indicating the breast cancer risk following detection of atypia within a breast screening program. Methods: Prospectively collected data from the South Australian screening program were linked with the state cancer registry. Absolute and relative breast cancer risk estimates were calculated for...

Cystic cavitation of the lymph nodes associated with hyposplenism is a rare and under-recognised complication of coeliac disease. This report encompasses the clinical, radiological and pathological features of this condition, while demonstrating the pivotal role radiological imaging plays in achieving a clinical diagnosis.

This article covers three areas. In recognition of the central importance of an appreciation of the normal structure and function of the breast, as underpinning the pathogenesis and consequences of breast cancer, the first part of the article discusses the histology, microanatomy, and physiological changes in the normal breast. Starting with lactat...

We report a case of synchronous, multicentric low-grade myofibroblastic sarcoma presenting in a 62-year-old man. He initially presented with inflammatory symmetric polyarthritis and adhesive capsulitis of his shoulder and hips bilaterally and did not respond to a trial of disease modifying antirheumatic drugs. Over a period of several years he deve...

The purpose of this course will be to provide pathologists with an update on breast core needle biopsy procedures using examples of such cases to address areas of recurrent diagnostic difficulty. The educational needs we will be targeting are primarily medical knowledge. We will select cases that constitute recurrent diagnostic problems and discuss...

Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consult...

Debate about the extent of breast cancer over-diagnosis due to mammography screening has continued for over a decade, without consensus. Estimates range from 0-54%, but many studies have been criticized for having flawed methodology. In this study we used a novel study design to estimate over-diagnosis due to organised mammography screening in Sout...

Background: Data from BreastScreen Australia Screening and Assessment Services (SAS) for 2002-2010 were analysed to determine whether some SAS characteristics were more conducive that others to high screening performance, as indicated by high priority performance indicators and standards. Materials and methods: Indicators investigated related to...

Purpose: To examine breast cancer (BC) incidence trends in relation to mammographic screening and risk factor prevalence in South Australia (SA). Materials and methods: Trends in annual BC incidence rates were calculated using direct standardisation and compared with projected incidence derived from Poisson regression analysis of pre-screening r...

We wished to analyse patterns of use of needle biopsy procedures by BreastScreen Australia (BSA) accredited programs to identify areas for improvement. BSA services provided anonymous data regarding percutaneous needle biopsy of screen detected lesions assessed between 2005-2009. 12 services, from 5 of 7 Australian states and territories provided d...

Nutlin-3a is a small molecule antagonist of p53/MDM2 that is being explored as a treatment for sarcoma. In this study, we examined the molecular mechanisms underlying the sensitivity of sarcomas to Nutlin-3a. In an ex vivo tissue explant system, we found that TP53 pathway alterations (TP53 status, MDM2/MDM4 genomic amplification/mRNA overexpression...

The natural history of lobular carcinoma in-situ (LCIS) suggests that women are at increased risk of subsequent invasive breast cancer. Questions of effective management for women with this lesion have led to the need for evidence-based guidance and, in particular, guidance regarding management after LCIS is found at core needle biopsy (CNB). A sys...

There is considerable interest in whether mammography screening leads to over-diagnosis of breast cancer. However self-selection into screening programmes may lead to risk differences that affect estimates of over-diagnosis. This study compares the breast cancer risk profiles of participants and non-participants of population-based mammography scre...

Purpose: This study aims to measure the impact of HRT use at the time of screening on rates of screen-detected invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS), interval cancers and investigative procedures, within a well-established population-based mammography screening program. Methods: Using South Australian BreastScreen data...

Background: Sentinel node biopsy is an accurate method for staging the axilla in early (small) breast cancers. However, data for the role of this technique for large breast cancers remain limited. Method: From the Royal Adelaide Hospital Sentinel Node database and the SNAC trial database, 100 subjects were identified with clinically node negativ...

Introduction: Lymphatic mapping and sentinel node biopsy (LM/ SNB) techniques for melanoma and breast cancer management potentially expose staff, including operating theatre personnel, radiologists, pathologists and others, to ionising radiation. Aims: To ascertain exposure levels in a practical setting and to establish safe work practices for staf...

In August 2006, the Australian government approved subsidized trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, and it was mandated that HER2 testing should be performed using in situ hybridization (ISH) rather than immunohistochemistry (IHC). Here we review results of the first regulated, nationw...

Trastuzumab provides a survival benefit in patients with human epidermal growth factor receptor 2 (HER2)-amplified/overexpressed advanced gastric and gastroesophageal junction cancers (GC/GJCs). However, the optimal method for testing is unclear. The aim of this study was to assess interlaboratory agreement on HER2 scoring in GC/GJC to aid the deve...