Interleukin-3 production by basal-like breast cancer cells is associated with poor prognosis.

Breast cancer represents a collection of pathologies with different molecular subtypes, histopathology, risk factors, clinical behavior, and responses to treatment. "Basal-like" breast cancers predominantly lack the receptors for estrogen and progesterone (ER/PR), lack amplification of human epidermal growth factor receptor 2 (HER2) but account for 10-15% of all breast cancers, are largely insensitive to targeted treatment and represent a disproportionate number of metastatic cases and deaths. Analysis of interleukin (IL)-3 and the IL-3 receptor subunits (IL-3RA + CSF2RB) reveals elevated expression in predominantly the basal-like group. Further analysis suggests that IL-3 itself, but not the IL-3 receptor subunits, associates with poor patient outcome. Histology on patient-derived xenografts supports the notion that breast cancer cells are a significant source of IL-3 that may promote disease progression. Taken together, these observations suggest that IL-3 may be a useful marker in solid tumors, particularly triple negative breast cancer, and warrants further investigation into its contribution to disease pathogenesis.

Looking beyond workforce parity: addressing gender inequity in pathology.

While women pathologists have made up over one-third of pathologists in the Australian workforce for over 15 years and at least 50% since 2019, they are under-represented in senior leadership roles, scientific publications, grant recipients, editorial boards, key presentations, and professional awards. This is not unique to pathology and is seen in the broader medical and academic community. Barriers to gender equity and equality in pathology, medicine and academia include gender stereotypes, gender-based discrimination, structural and organisational barriers as well as broader social and cultural barriers. A diverse leadership reflective of the whole professional body and the broader community is important for optimal health outcomes. It is the responsibility and moral duty of individuals and organisations to address any gender disparities, inequities, and inequalities by monitoring, identifying, and acting on gender biases and systemic barriers that hinder appropriate levels of representation by women.

10-Year axillary recurrence in the RACS SNAC1 randomised trial of sentinel lymph node-based management versus routine axillary lymph node dissection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Silver In Situ Hybridization for the Rapid Assessment of MDM2 Amplification in Soft Tissue and Bone Tumors. Validation Based on an Audit of 192 Consecutive Cases Evaluated by Silver In Situ Hybridization and Fluorescence In Situ Hybridization.

The discovery of almost invariable mouse double minute 2 (MDM2) amplification among atypical lipomatous tumors (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma is incorporated into the contemporary diagnostic workup of fatty lesions. MDM2 amplifications are also found frequently in intimal sarcomas and in low-grade osteogenic sarcoma. At present, fluorescence in situ hybridization (FISH) is the reference test for MDM2 assessment. We are interested in evaluating silver in situ hybridization (SISH) for this purpose. Between October 2016 and May 2020, in 192 consecutive cases requiring MDM2 FISH, SISH was also performed concurrently, including 77 (40.1%) core biopsies and 115 (58.9%) surgical specimens. The mean patient age was 61.0 years. SISH results were available overnight or within 48 hours if repeat testing was required. FISH results were available within 2 to 5 weeks. The cost of SISH was one third of FISH. FISH demonstrated MDM2 amplification in 44 cases (23.6%), was negative in 144 cases (74.4%) and nondiagnostic in 4 decalcified cases (2.0%). SISH showed MDM2 amplification in 33 cases (17.2%), no amplification in 119 cases (62.0%), and indeterminate results because of poor signal in 40 (20.8%) cases. All 33 (100%) SISH-amplified tumors and 113 of 119 (95.0%) nonamplified results were confirmed by FISH. There were no clear differences in the performance of SISH on NCB versus surgical specimens. The overall performance indices of SISH are sensitivity 75%, specificity 78.5%, positive predictive value 100%, and negative predictive value 95.8%. FISH is not required when SISH is clearly amplified. This is clinically useful and improves efficiency. Nonamplified SISH results provide early indications of the likely FISH findings, but there is a 4.2% chance of FISH being positive. At present, the main drawback of SISH is the high rate of nondiagnostic tests. Optimization of SISH signal detection to reduce the proportion of indeterminate results is our current focus.

Reporting of Surgically Removed Lymph Nodes for Breast Tumors: Recommendations From the International Collaboration on Cancer Reporting.

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 metastasis is one of the most important prognostic factors in breast cancer. OBJECTIVE.­: To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. DATA SOURCES.­: Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. CONCLUSIONS.­: The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.

Three cases of BRAF-mutant melanoma with divergent differentiation masquerading as sarcoma.

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 of melanoma, including BRAF gene mutations. Gene mutation analysis of tumour DNA, now standard practice for all melanomas of stage III or above, may establish the diagnosis of melanoma in some advanced malignancies of unknown lineage. A prior history of melanoma or risk factors for melanoma may be the first clue that an advanced malignancy represents metastatic melanoma. Recognition of this presentation of melanoma can allow a patient to access well-tolerated life-prolonging therapies such as targeted therapy, inhibiting the BRAF/MEK pathway, and immune checkpoint inhibitor therapy.

Investigating the breast cancer screening-treatment-mortality pathway of women diagnosed with invasive breast cancer: Results from linked health data.

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 administrative data. Associations of screening history with treatment were investigated using logistic regression and with cancer mortality outcomes using competing risk analyses, adjusting for socio-demographic, cancer and comorbidity characteristics. RESULTS AND CONCLUSION: For screening ages of 50-69 years, 70% had participated in BreastScreen SA ≤ 5 years and 53% ≤ 2 years of diagnosis. Five-year disease-specific survival post-diagnosis was 90%. Compared with those not screened ≤5 years, women screened ≤2 years had higher odds, adjusted for socio-demographic, cancer and comorbidity characteristics, and diagnostic period, of breast-conserving surgery (aOR 2.5, 95% CI 1.9-3.2) and radiotherapy (aOR 1.2, 95% CI 1.1-1.3). These women had a lower unadjusted risk of post-diagnostic cancer mortality (SHR 0.33, 95% CI 0.27-0.41), partly mediated by stage (aSHR 0.65, 95% CI 0.51-0.81), and less breast surgery (aSHR 0.78, 95% CI 0.62-0.99). Screening ≤2 years and conserving surgery appeared to have a greater than additive association with lower post-diagnostic mortality (interaction term SHR 0.42, 95% CI 0.23-0.78). The screening-treatment-mortality pathway was investigated using linked data.

Female breast cancer treatment and survival in South Australia: Results from linked health data.

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. Treatments ≤12 months from diagnosis and survival were analysed, using adjusted odds ratios (aORs) from logistic regression, and adjusted sub-hazard ratios (aSHRs) from competing risk regression. RESULTS AND CONCLUSION: Five-year disease-specific survival increased to 91% for 2010-2014. Most women had breast surgery (90%), systemic therapy (72%) and radiotherapy (60%). Less treatment applied for ages 80+ vs <50 years (aOR 0.10, 95% CI 0.05-0.20) and TNM stage IV vs stage I (aOR 0.13, 95% CI 0.08-0.22). Surgical treatment increased during the study period and strongly predicted higher survival. Compared with no surgery, aSHRs were 0.31 (95% CI 0.26-0.36) for women having breast-conserving surgery, 0.49 (95% CI 0.41-0.57) for mastectomy and 0.42 (95% CI 0.33-0.52) when both surgery types were received. Patients aged 80+ years had lower survival and less treatment. More trial evidence is needed to optimise trade-offs between benefits and harms in these older women. Survival differences were not found by residential remoteness and were marginal by socioeconomic status.

Interobserver concordance in visual assessment of Ki67 immunohistochemistry in surgical excision specimens from patients with lymph node-negative breast cancer.

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.

Monitoring TNM stage of female breast cancer and survival across the South Australian population, with national and international TNM benchmarking: A population-based cohort study.

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 adjusted logistic regression; and (2) sociodemographic factors and stage as predictors of breast cancer survival using competing risk regression. DESIGN: Population-based registry cohort. SETTING AND PARTICIPANTS: 14 759 South Australian women diagnosed in 2000-2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Stage and survival. RESULTS: At diagnosis, 46% of women were classified as stage I, 39% as stage II, 12% as stage III and 4% as stage IV. After adjusting for sociodemographic factors, advanced stage was more common: (1) for ages <50 years; and although not statistically significant, for ages 80+ years; and (2) in women from socioeconomically disadvantaged areas. Compared with 2000-2004 diagnoses, stage and sociodemographic adjusted risks (sub-HRs (SHRs)) of breast cancer death were lower in 2005-2009 (SHR 0.75, 95% CI 0.67 to 0.83) and 2010-2015 (SHR 0.57, 95% CI 0.48 to 0.67). Compared with stage I, the SHR was 3.87 (95% CI 3.32 to 4.53) for stage II, 10.87 (95% CI 9.22 to 12.81) for stage III, and 41.97 (95% CI 34.78 to 50.65) for stage IV. Women aged 70+ years at diagnosis and those living in the most socioeconomically disadvantaged areas were at elevated risk of breast cancer death, independent of stage and sociodemographic factors. CONCLUSIONS: Stage varied by age, diagnostic period and socioeconomic status, and was a stronger predictor of survival than other statistically significant sociodemographic predictors. Achieving earlier diagnosis outside the original BreastScreen target of 50-69 years (as applying <2014) and in residents of socioeconomically disadvantaged areas likely would increase cancer survival at a population level.

The impact of 2018 ASCO-CAP HER2 testing guidelines on breast cancer HER2 results. An audit of 2132 consecutive cases evaluated by immunohistochemistry and in situ hybridization.

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.

A population-based study of soft tissue sarcoma incidence and survival in Australia: An analysis of 26,970 cases.

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 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. RESULTS: 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). CONCLUSION: 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.

Disparities in breast screening, stage at diagnosis, cancer treatment and the subsequent risk of cancer death: a retrospective, matched cohort of aboriginal and non-aboriginal women with breast cancer.

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 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

ASCO/CAP 2018 breast cancer HER2 testing guidelines: summary of pertinent recommendations for practice in Australia.

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 the implications of these guidelines for clinical practice in Australia. Following feedback from professional bodies, including the RCPA and CanSAC, peer review was invited. The final document prepared by the authors, endorsed by the Expert Committee RCPA Structured Pathology Reporting of Breast Cancer and by CanSAC, is published herein.

Meta-analysis of upgrade rates in 3163 radial scars excised after needle core biopsy diagnosis.

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.

Epithelioid myxofibrosarcoma developing at the injection site of Adalimumab therapy for psoriatic synovitis.

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 management of chronic inflammatory autoimmune diseases. While the overall rates of malignancy in patients using anti TNF therapies are not elevated, increased risk has been established for cutaneous malignancy, particularly carcinoma. In subsets of patients, such as those with rheumatoid arthritis, a modestly increased incidence of melanoma is also documented. Herewith, we present the first reported instance of a sarcoma of the dermis and superficial subcutaneous tissue at the injection site of Adalimumab in a woman being treated for psoriatic synovitis. We review the literature and suggest that a more nuanced documentation of adverse events is needed to clarify the iatrogenic risk of rare cancers, such as soft tissue sarcomas, in patients taking these biological therapies.

Molecular subtypes of screen-detected breast cancer.

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.