Assessing the support needs of women with early breast cancer in Australia

The purpose of the current study was to access the degree to which the support needs of women with a newly diagnosed, early invasive, primary breast cancer and their families are being met. A random sample of 544 women diagnosed with early breast cancer was recruited to participate in a telephone survey via state and territory cancer registries. Sixteen percent of women reported not receiving enough support during their diagnosis and treatment, and only 65% of these women reported that their families received enough support. The primary sources of support for women and their families were medical practitioners (eg, surgeons, oncologists, and general practitioner) with very few women or family members utilizing mental health professionals. Given the importance of adequate support when being diagnosed and treated for breast cancer, urgent attention needs to be paid to training medical professionals in providing appropriate support and referrals for their patients.

Characterisation of human kallikrein 6 protease M expression in ovarian cancer

Kallikrein 6 (hK6, also known as protease M/zyme/neurosin) is a member of the human kallikrein gene family. We have previously cloned the cDNA for this gene by differential display and shown the overexpression of the mRNA in breast and ovarian primary tumour tissues and cell lines. To thoroughly characterise the expression of this kallikrein in ovarian cancer, we have developed a novel monoclonal antibody specific to hK6 and employed it in immunohistochemistry with a wide range of ovarian tumour samples. The expression was found elevated in 67 of 80 cases of ovarian tumour samples and there was a significant difference in the expression levels between normal and benign ovarian tissues and the borderline and invasive tumours (P<0.001). There was no difference of expression level between different subtypes of tumours. More significantly, high level of kallikrein 6 expression was found in many early-stage and low-grade tumours, and elevated hK6 proteins were found in benign epithelia coexisting with borderline and invasive tissues, suggesting that overexpression of hK6 is an early phenomenon in the development of ovarian cancer. Quantitative real-time reverse transcription-polymerase chain reactions also showed elevated kallikrein 6 mRNA expression in ovarian tumours. Genomic Southern analysis of 19 ovarian tumour samples suggested that gene amplification is one mechanism for the overexpression of hK6 in ovarian cancer.

Symptoms and diagnosis of borderline, early and advanced epithelial ovarian cancer

Objective. To document symptoms associated with borderline, early and advanced ovarian cancer and identify personal characteristics associated with early versus late diagnosis. Methods. Information concerning symptoms and diagnosis history was available from 811 women with ovarian cancer who took part in an Australian case–control study in the early 1990s. Women were classified into three groups for comparison based on their diagnosis: borderline, early (stage I–II) and advanced (stage III–IV) invasive cancer. Results. Sixteen percent of women with borderline tumors, 7% with early cancer and 4% with advanced cancer experienced no symptoms before diagnosis (P < 0.0001). Among women with symptoms, abdominal pain (44%) or swelling (39%) were most frequently reported; an abdominal mass (12%) and gynecological symptoms (12%) were less common. Compared to advanced stage cancer, women with early stage cancer were more likely to report an abdominal mass or urinary symptoms but less likely to report gastrointestinal problems or general malaise. General malaise and ‘other’ symptoms were least common in borderline disease. Older women, and those with higher parity or a family history of breast or ovarian cancer, were more likely to be diagnosed at an advanced stage of disease. Conclusions. Women who experience persistent or recurrent abdominal symptoms, particularly swelling and/or pain should be encouraged to seek medical attention and physicians should be alert to the possibility of ovarian cancer even in the absence of an abdominal mass. Further information about the prevalence of these symptoms in the general population is essential to assist physicians in patient management.

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.

Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

The molecular genetics of breast cancer: The contribution of comparative genomic hybridization

Comparative genomic hybridization (CGH) has been the technique of choice over the last 10 years for mapping DNA copy number changes in human tumors. Here we review the literature to demonstrate how CGH has contributed to the comprehension of molecular aspects of breast tumorigenesis. At least two distinct molecular pathways of breast cancer have been characterized that show a strong correlation with histological grade. It seems that grade I invasive ductal carcinomas (IDCs) arise from well-differentiated ductal carcinoma in situ (DCIS), whereas grade III IDCs come from poorly differentiated DCIS. In addition, dedifferentiation from a low- to a high-grade breast cancer has proven an unlikely phenomenon. CGH has been instrumental in dissecting distinct molecular pathways toward breast malignancy and in establishing a direct relationship between genotype and clinical pathological features. (C) 2005 Elsevier GrnbH. All rights reserved.

Height, age at menarche, and risk of epithelial ovarian cancer

Objective: We hypothesized that the hormonal changes of adolescence influence ovarian cancer risk particularly in younger women. We investigated this possibility by examining the relationship between ovarian cancer and adult height and age at menarche as both factors reflect pubertal hormonal levels. Methods: Participants were a population-based sample of women with incident ovarian cancer (n = 794) and control women randomly selected from the Australian Electoral Roll (n = 855). The women provided comprehensive reproductive and lifestyle data during a standard interview. Results: Although neither height nor age at menarche was significantly related to the risk of ovarian cancer overall, increasing height was associated with increasing risk of the subgroup of mucinous borderline ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for women 175 cm compared with women < 160 cm, P-trend = 0.02). Similarly, later age at menarche was associated with increasing risk of mucinous borderline cancers (odds ratio, 3.8; 95% confidence interval, 1.3-11.4 for those with age at menarche >= 44 years compared with those < 12 years, P-trend = 0.003). Women with mucinous borderline cancers were significantly younger than the women diagnosed with invasive cancers (mean 44 versus 57 years; P < 0.0001). Conclusions: Development of mucinous borderline ovarian cancers, predominantly diagnosed in women ages under 50 years, seems to be associated with age at menarche and attained adult height. These results are consistent with our original hypothesis that pubertal levels of reproductive hormones and insulin-like growth factor-I influence ovarian cancer risk in younger women.

RAD52 Y415X truncation polymorphism and epithelial ovarian cancer risk in Australian women

The RAD52 gene is involved in the homologous recombination repair pathway and is a plausible candidate ovarian cancer predisposition gene. We undertook a case-control comparison of 508 epithelial ovarian cancer cases (91 low malignant potential and 417 invasive) and 298 healthy controls to assess the RAD52 Y415X polymorphism as a risk factor for epithelial ovarian cancer in Australian women. Heterozygote frequencies of 2.6 and 4% were observed among cases and controls, respectively. The risk estimate was 0.55 (95%CI 0.24-1.24), suggesting that the RAD52 Y415X polymorphism is not associated with epithelial ovarian cancer in Australian women. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast

Aims: Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC. Methods and results: A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002). Conclusions: Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.

Dimensions of quality of life and psychosocial variables most salient to colorectal cancer patients

Colorectal cancer is one of the most common invasive cancers, and is responsible for considerable physical and psychosocial morbidity. Understanding the quality of life experienced by colorectal cancer patients is essential for evaluating the full impact of the disease on individuals, their families and their communities. Patient perspective is essential in establishing a proper understanding of the quality of life of colorectal cancer patients. Despite this, few studies have employed a qualitative methodology to explore quality of life issues for colorectal cancer patients. A review of the literature identified only seven qualitative studies pertaining to quality of life issues for colorectal cancer patients, a surprising finding given the prevalence of this cancer. Accordingly, this study sought to build on the findings of previous qualitative research by providing descriptive data on the quality of life and psychosocial variables most salient to colorectal cancer patients. Six core themes emerged from interview and focus group data: Satisfaction with diagnosis and treatment; support (including information provision); quality of life; benefits of diagnosis; making sense of the cancer experience; and coping strategies. The information derived from this study will help inform the development of supportive care services to address the needs of the increasing number of people diagnosed with colorectal cancer. Copyright (c) 2005 John Wiley & Sons, Ltd.

Benign epithelial ovarian tumours - cancer precursors or markers for ovarian cancer risk?

The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.

Minimally invasive esophagectomy

Background: We aimed to assess the outcomes including the effect on quality of life (QoL) of a group of patients having a minimally invasive esophagectomy (MIE). Methods: Patients with esophageal cancer were offered MIE over a 22-month period. Data on outcomes were collected prospectively, including formal quality-of-assessments. Results: There were 25 patients offered MIE. Two patients were converted to a laparotomy to improve the lymphadenectomy. There were no deaths. Respiratory problems (pneumonia, 28%) were the most common in the 64% of patients who had a complication. The median blood loss was 300 ml, time of surgery 330 min, and time to discharge 11 days. There was a decrease in the measured QoL both in general and specifically for the esophageal patients, taking 18-24 months to return to baseline. Conclusion: MIE was performed with morbidity similar to other approaches. There were no clear benefits shown in this group of patients with respect to postoperative recovery or short- to medium-term QoL.

Trends for in situ and invasive melanoma in Queensland, Australia, 1982-2002

Objectives Queensland, the north-eastern state of Australia, has the highest incidence of melanoma in the world. Control measures started earlier here than probably anywhere else in the world; early detection programmes started in the 1960s and primary prevention in the 1980s. Data from the population-based Queensland Cancer Registry therefore provide an internationally unique data source with which to assess trends for in situ and invasive melanomas and to consider the implications for early detection and primary prevention. Methods We used Poisson regression to estimate the annual percentage change in rates across 21 years of incidence data for in situ and invasive lesions, stratified by age and sex. Joinpoint analyses were used to assess whether there had been a statistically significant change in the trends. Results In situ melanomas increased by 10.4% (95% CI: 10.1%, 11.1%) per year among males and 8.4% (7.9%, 8.9%) per year among females. The incidence of invasive lesions also increased, but not as quickly; males 2.6% (2.4%, 2.8%), females 1.2% (0.9%, 1.5%). Valid data on thickness was only available for 1991 to 2002 and for this period thin-invasive lesions were increasing faster than thick-invasive lesions (for example, among males: thin 3.8%, thick 2.0%). We found some suggestive evidence of lower proportionate increase for the most recent years for both in-situ and invasive lesions, but this did not achieve statistical significance. Among people younger than 35 years, the incidence of invasive melanoma was stable and there was a suggestion of a birth cohort effect from about 1958. Mortality rates were stable across all ages, and there was a suggestion of decreasing rates among young women, although this did not achieve statistical significance. Conclusion Age-standardised incidence is continuing to increase and this, in combination with a shift to proportionately more in situ lesions, suggests that the stabilisation of mortality rates is due, in large part, to earlier detection. For primary prevention, after a substantial period of sustained effort in Queensland, there is some suggestive, but not definitive, evidence that progress is being made. Incidence rates are stabilising in those younger than 35 years and the proportionate increase for both in situ and invasive lesions appears to be lower for the most recent period compared with previous periods. However, even taking the most favourable view of these trends, primary prevention is unlikely to lead to decreases in the overall incidence rate of melanoma for at least another 20 years. Consequently, the challenge for primary prevention programmes will be to maintain momentum over the long term. If this can be achieved, the eventual public-health benefits are likely to be substantial.

The Role of Aquaporin 3 (AQP3) in Breast Cancer

The increasing prevalence of breast cancer (BC) in different parts of the world, particularly in the UK, highlights the importance of research into the aetiology and pathology of the disease. BC is the most common malignancy affecting women worldwide. Aquaporins (AQPs) are membrane protein channels that regulate cellular water flow. Recently, studies have demonstrated that expression of AQP3 is up-regulated in cancerous breast tissue. The present study examines the role of AQP3 in BC cell biology. Examination of clinical cases of BC showed higher AQP3 gene and protein expression in cancer tissues compared to healthy border tissues. In distinct clinicopathological groups however there were no differences observed with regards to AQP3 expression, suggesting that AQP3 expression may not be a predictor of lymph node infiltration or tumour grade. shRNA technology was used to knockdown gene expression of AQP3 in the invasive MDA-MB-231 BC cellular model. Cellular proliferation, migration, invasion, adhesion and response to the 5- fluorouracil (5-FU) based chemotherapy treatment were investigated in parental and knockdown cell line. AQP3 knockdown cells showed reduction in cellular proliferation, migration, invasion and increase in cell sensitivity to 5-FU compared with wild type (WT) or scrambled control (SC) cells. The effects of AQP3 knockdown on cellular glycolytic ability and ATP cellular content were quantified. Indirect glucose uptake was also measured by quantifying reconditioned media. AQP3 knockdown cells showed significantly lower levels of glucose uptake as compared to WT or SC. However there was no difference in the glycolytic ability and ATP content of the cells suggesting AQP3 has no role in cancer cell energetics. These data collectively suggest AQP3 expression is associated with the BC disease clinically and plays a role in multiple important aspects of BC pathophysiology, thus AQP3 represents a novel target for therapeutic intervention.

BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells

Cancer stem cells (CSCs) are initiating cells in colorectal cancer (CRC). Colorectal tumours undergo epithelial to mesenchymal transition (EMT)-like processes at the invasive front, enabling invasion and metastasis, and recent studies have linked this process to the acquisition of stem cell-like properties. It is of fundamental importance to understand the molecular events leading to the establishment of cancer initiating cells and how these mechanisms relate to cellular transitions during tumourigenesis. We use an in vitro system to recapitulate changes in CRC cells at the invasive front (mesenchymal-like cells) and central mass (epithelial-like cells) of tumours. We show that the mesoderm inducer BRACHYURY is expressed in a subpopulation of CRC cells that resemble invasive front mesenchymal-like cells, where it acts to impose characteristics of CSCs in a fully reversible manner, suggesting reversible formation and modulation of such cells. BRACHYURY, itself regulated by the oncogene β-catenin, influences NANOG and other 'stemness' markers including a panel of markers defining CRC-CSC whose presence has been linked to poor patient prognosis. Similar regulation of NANOG through BRACHYURY was observed in other cells lines, suggesting this might be a pathway common to cancer cells undergoing mesenchymal transition. We suggest that BRACHYURY may regulate NANOG in mesenchymal-like CRC cells to impose a 'plastic-state', allowing competence of cells to respond to signals prompting invasion or metastasis. Copyright © 2011 UICC.