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 plausible alternative to surgery.
Design
We performed a systematic review of the Pubmed, Cochrane and Embase databases, focusing on the following eligibility criteria: full papers, published after 1998, in English, included at least 5 RS, provided information on needle biopsy gauge and upgrade rates based on the excised lesion. For the meta-analysis, studies were grouped by the presence of histologic atypia and the core needle gauge. Study-specific and pooled upgrade rates were calculated for each subgroup.
Results
49 studies that included 3163 RS with surgical outcomes are included. There were 217 upgrades to malignancies, 71 (32.7%) invasive and 144 (66.4%) DCIS. The random-effects pooled estimate was 7% (95% CI 5, 9%). Among the pre-planned subgroups, in RS assessed by 14G NCB the upgrade rates were: without atypia − 5% (95% CI 3, 8%), mixed or presence of atypia not specified − 15% (95% CI 10, 20%), with atypia − 29% (95% CI 20, 38%). For RS assessed by a mix of 8-16G cores the respective upgrade rates were 2% (95% CI 1, 4%), 12% (95% CI 6, 18%) and 11% (95% CI 3, 23%) and for RS assessed by 8–11 vacuum assisted biopsies 1% (95% CI 0, 4%), 5% (95% CI 0, 11%) and 18% for the one study of RS with atypia assessed by VAB. Surgery after VAB excision showed no upgrades. The difference across all subgroups was statistically significant.
Conclusion
When stratified by atypia and biopsy gauge, upgrade rates in RS are consistent and predictable. RS assessed by VABs and lacking atypia have a 1% (95% CI 0, 4%) upgrade rate to DCIS. Other groups have upgrade rates of 2–28%. This risk may be reduced by VAB excision. The results of this meta-analysis provide a decision aid and evidence-based selection criteria for surgery after a needle biopsy diagnosis of RS.
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. We wished to address these issues through the study of a large series of SDBC, with other presentations serving as controls.
Design
Deidentified cases of female invasive cancer, diagnosed in Australia and New Zealand during 2005–2015, were retrieved from the BreastSurgANZ Quality Audit (BQA). Method of detection and selected patient, tumour and treatment data were assessed. Immunohistochemical surrogates for molecular subtypes were defined as Luminal A (ER+ and/or PR+, HER2−), Luminal B (ER+ and/or PR+, HER2+), HER2-enriched (ER−, PR− and HER2+) and basal-like (triple negative). Results were compared with the findings of controls and previous studies.
Result
100983 invasive cancers were diagnosed, including 32493 (32.7%) SDBC and 66907 (67.3%) with other presentations. The biomarker profile for SDBC versus other presentations in the same population was ER 89.3 versus 80.3%, PR 78.8 versus 69.8% and for HER2 11 versus 15.6%. The distribution of molecular subtypes was Luminal A 81.9 versus 70.74%, Luminal B 7.39 versus 9.52%, HER2-enriched 3.63 versus 6.06% and Basal-like 7.08 versus 13.68%. These differences were significant (
p
< 0.0001).
Conclusion
Molecular profiles of SDBC are significantly different from those of symptomatic cancers, with over-representation of the Luminal A and proportionately lower rates of all other subtypes. We have shown, for the first time, significantly lower rates of HER2 positivity in SDBC. These differences may contribute to the better survival of SDBC and have implications for prognostication, targeted therapy decisions and for laboratory quality assurance programs in setting target ranges for proportions of ER-positive and HER2 results in heavily screened populations.
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 evaluated with IHC and ISH for HER2. The sample tested was the breast primary or axillary nodes in all but 57 (2.7%) distant metastases. For 1824 cases with both dual-probe ISH and IHC results, the ISH subgroup was 1: 299 (16.4%), 2: 19 (1.0%), 1.0%, 3: 6 (0.3%), 4: 48 (2.6%) and 5: 1452 (79.6%). Ultimately 21% of group 2 and 4 cases and 80% of group 4 cases were positive. The change in HER2 status between the 2018 vs 2013 was: amplified in 323 (15.2%) vs 15.5%; not amplified in 1804 (84.6%) vs 82.2%; equivocal in 0 vs 2.3% previously. In 22 of 2127 cases (1.03%) the 2013 and 2018 results were discordant, all in groups 2-4. The discrepant cases included 15 of 331 (4.5%) of 2013 amplified cancers, now negative (all in groups 2 or 3) and 7 of 1796 (0.4%) 2013 nonamplified cases, now positive (all in group 4). Because of routine testing with both IHC and ISH, we found 6 of 1147 (0.52%) IHC negative (0 or 1+) cases were amplified by ISH. Further, 19 of 289 (6.6%) of IHC 3+ cases were nonamplified by ISH, circumstances not covered by these guidelines. In summary at the population level, the 2018 ASCO-CAP guidelines have a 99% agreement with the 2013 results. A major advantage is the abolishment of the clinically problematic equivocal category. Routine performance of both IHC and ISH uncovers a small proportion of cancers whose HER2 status is not addressed by these guidelines.
Epithelial to mesenchymal transition (EMT) facilitates tissue remodelling during embryonic development and is viewed as an essential early step in tumour metastasis. We found that all five members of ...the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez. Enforced expression of the miR-200 family alone was sufficient to prevent TGF-β-induced EMT. Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. Inhibition of the microRNAs was sufficient to induce EMT in a process requiring upregulation of ZEB1 and/or SIP1. Conversely, ectopic expression of these microRNAs in mesenchymal cells initiated mesenchymal to epithelial transition (MET). Consistent with their role in regulating EMT, expression of these microRNAs was found to be lost in invasive breast cancer cell lines with mesenchymal phenotype. Expression of the miR-200 family was also lost in regions of metaplastic breast cancer specimens lacking E-cadherin. These data suggest that downregulation of the microRNAs may be an important step in tumour progression.
•Incidence of soft tissue sarcoma in Australia has increased between 1982 and 2009, especially in people ≥70 years old.•A small but statistically significant increase in overall survival during the ...study period was observed.•With the growing ageing population the health care of older people with soft tissue sarcoma will need increased attention.
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.
A retrospective population-based observational study was conducted between 1982 and 2009 of all patients with a diagnosis of STS using the Australian Institute of Health and Welfare (AIHW) Australian Cancer Database. Incidence rates per 100,000; incidence rate ratios, age-standardized incidence rates, prevalence and incidence rates of subtypes of STS, median, one-year and 5-year survival rates were examined.
A total of 26,970 patients were identified. Between 1982 and 2009 STS incidence rates significantly increased from 3.99 95% CI 3.68–4.32 to 6.12 95% CI 5.80–6.46 per 100,000 Australian population, with a peak incident rate ratio (IRR) of 1.59 95% CI 1.51–1.69 (p < 0.0001) in 2001. Median age at diagnosis increased from 58 to 63 years. Incidence rates were stable across all 10-year age cohorts, except for people aged over 70 where it increased. Overall, age-standardized incidence rates increased from 4.70 95% CI 4.42–5.00 in 1982 to 5.87 95% CI 5.63–6.11 per 100 000 Australians in 2009. Leiomyosarcoma (20.43%), malignant fibrous histiocytoma (16.14%), and soft tissue tumors/sarcomas, not otherwise specified (10.18%) were the most common STS subtypes. Median survival from diagnosis increased from 5.80 years 95% CI 5.06–6.54 in 1985–1989 cohort to 8.18 years 95% CI 7.54–8.81 in the 2000–2004 cohort (log-rank test p < 0.0001).
The incidence of STS is increasing in Australia, most noticeably in those aged over 70 years, with a small but statistically significant increase in overall survival rates.
Purpose
This 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 estimation of hot spot areas. For hot spot cell counting, positive and negative cell numbers were recorded for total cell counts of 300–500, 500–800 and 800–1000 cells. Visual estimation involved allocation of a score from 1 to 5 using a visual scale to estimate percentage positivity. Interobserver agreement for hot spot counting was calculated using a two-way fixed effects intraclass correlation model, and by using Cohen’s kappa measure for visual assessment. Prognostic concordance between the two methods was also calculated using Cohen’s kappa.
Results
Samples from 96 patients were included in this analysis. Interobserver agreement for hot spot cell counting was excellent (> 0.75) across all three cell count ranges, with correlation coefficients of 0.88 (95% CI 0.84–0.92), 0.87 (95% CI 0.82–0.91) and 0.89 (95% CI 0.85–0.92), respectively. Interobserver agreement with visual estimation was greatest for hot spots compared with areas of intermediate or low proliferation, with kappa scores of 0.49, 0.42 and 0.40, respectively. Both assessment methods demonstrated excellent prognostic agreement.
Conclusions
Interobserver and prognostic concordance in Ki67 immunohistochemistry assessments was high using either hot spot cell counting or visual estimation, further supporting the utility and reproducibility of these cost-efficient methods to assess proliferation.
Sentinel node-based management (SNBM) is the international standard of care for early breast cancer that is clinically node-negative based on randomised trials comparing it with axillary lymph node ...dissection (ALND) and reporting similar rates of axillary recurrence (AR) without distant disease. We report all ARs, overall survival, and breast cancer-specific survival at 10-years in SNAC1.
1.088 women with clinically node-negative, unifocal breast cancers 3 cm or less in diameter were randomly assigned to either SNBM with ALND if the sentinel node (SN) was positive, or to SN biopsy followed by ALND regardless of SN involvement.
First ARs were more frequent in those assigned SNBM rather than ALND (11 events, cumulative risk at 10-years 1·85%, 95% CI 0·95–3.27% versus 2 events, 0·37%, 95% CI 0·08–1·26%; HR 5·47, 95% CI 1·21–24·63; p = 0·013). Disease-free survival, breast cancer-specific survival, and overall survival were similar in those assigned SNBM versus ALND. Lymphovascular invasion was an independent predictor of AR (HR 6·6, 95% CI 2·25–19·36, p < 0·001).
First ARs were more frequent with SNBM than ALND in women with small, unifocal breast cancers when all first axillary events were considered. We recommend that studies of axillary treatment should report all ARs to give an accurate indication of treatment effects. The absolute frequency of AR was low in women meeting our eligibility criteria, and SNBM should remain the treatment of choice in this group. However, for those with higher-risk breast cancers, further study is needed because the estimated risk of AR might alter their choice of axillary surgery.
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 registry records into a person-linked data system can improve our understanding of breast cancer outcomes. We focussed one such system on a population-based cohort of Aboriginal women in South Australia diagnosed with breast cancer and a matched cohort of non-Aboriginal women with breast cancer. We quantify Aboriginal and non-Aboriginal women's contact with publicly funded screening mammograms; quantify exposure to a selection of cancer treatment modalities; then assess the relationship between screening, treatment and the subsequent risk of breast cancer death.
Breast cancers registered among Aboriginal women in South Australia in 1990-2010 (N = 77) were matched with a random selection of non-Aboriginal women by birth and diagnostic year, then linked to screening records, and treatment 2 months before and 13 months after diagnosis. Competing risk regression summarised associations of Aboriginality, breast screening, cancer stage and treatment with risk of breast cancer death.
Aboriginal women were less likely to have breast screening (OR = 0.37, 95%CIs 0.19-0.73); systemic therapies (OR = 0.49, 95%CIs 0.24-0.97); and, surgical intervention (OR = 0.35, 95%CIs 0.15-0.83). Where surgery occurred, mastectomy was more common among Aboriginal women (OR = 2.58, 1.22-5.46). Each of these factors influenced the risk of cancer death, reported as sub-hazard ratios (SHR). Regional spread disease (SHR = 34.23 95%CIs 6.76-13.40) and distant spread (SHR = 49.67 95%CIs 6.79-363.51) carried more risk than localised disease (Reference SHR = 1). Breast screening reduced the risk (SHR = 0.07 95%CIs 0.01-0.83). So too did receipt of systemic therapy (SHR = 0.06 95%CIs 0.01-0.41) and surgical treatments (SHR = 0.17 95%CIs 0.04-0.74). In the presence of adjustment for these factors, Aboriginality did not further explain the risk of breast cancer death.
Under-exposure to screening and treatment of Aboriginal women with breast cancers in South Australia contributed to excess cancer deaths. Improved access, utilisation and quality of effective treatments is needed to improve survival after breast cancer diagnosis.
Background
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.
Methods
Women undergoing core biopsy between January 1997 and December 2007 for <10‐mm lesions are included. Patient demographics, imaging features and final histology were tabulated. Performance indices were evaluated.
Results
This audit includes 803 lesions <10 mm. Based on core histology, 345 women (43.0%) were immediately cleared of malignancy and 300 (37.4%) were referred for definitive cancer treatment. A further 157 women (19.6%) required diagnostic surgical biopsy because of indefinite or inadequate core results or radiological‐pathological discordance, and one woman (0.1%) needed further imaging in 12 months. The open biopsies were malignant in 46 (29.3%) cases. The positive predictive value of malignant core biopsy was 100%. The negative predictive value for benign core results was 97.7%, and the false‐negative rate was 2.6%. The lesion could not be visualized after core biopsy in 5.1% of women and in 4.0% of women with malignant core biopsies excision specimens did not contain residual malignancy. Excessive delays in surgery because of complications of core biopsy were not reported.
Conclusion
Even at this small size range, core biopsy evaluation of screen‐detected breast lesions is highly effective and accurate. A lesion miss rate of 3.1% and under‐representation of lesions on core samples highlight the continued need for multidisciplinary collaboration and selective use of diagnostic surgical biopsy.
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