Gonococcal mastitis. / Gonokokkmastitt.

A young woman experienced pain and swelling in a non-lactating breast. The culture test result showed an unusual microbe, which is increasingly prevalent in Norway and internationally.

PD-L1 protein expression in breast cancer.

AIMS: The immune checkpoint marker, Programmed cell death-ligand 1 (PD-L1), is expressed by both cancer epithelial cells and tumour-infiltrating immune cells (TICs) thus constituting a potential target for immunotherapy. This is of particular interest in triple negative breast cancer. In this study, we assessed the prognostic value of PD-L1 expression in tumour epithelial cells and TICs in a series of patients with breast cancer with long-term follow-up, and associations between PD-L1 expression and histopathological type and grade, proliferation and molecular subtype. METHODS: Using immunohistochemistry for PD-L1 in tissue microarrays, we assessed PD-L1 expression in 821 tumours. Expression of PD-L1 was assessed separately in the epithelial and stromal compartments and classified as <1%, ≥1% to <10% or ≥10% positive staining cells. We correlated PD-L1 expression in tumour epithelial cells and TICs with tumour characteristics using Pearson's χ2 test, and prognosis by cumulative incidence of death from breast cancer and Cox regression analyses. RESULTS: We found membranous staining in ≥1% of tumour epithelial cells in 53/821 cases (6.5%). Of these, 21 (2.6%) were ≥10%. Among TICs, staining (≥1%) was seen in 144/821 cases (17.6%). Of these, 62 were ≥10% (7.6%). PD-L1 was associated with high histopathological grade and proliferation, and the medullary and metaplastic patterns. In TICs, PD-L1 ≥1% found in 22/34 (34.4%) human epidermal growth factor receptor 2 type and 29/58 (50%) basal phenotype. An independent association between PD-L1 expression and prognosis was not observed. CONCLUSIONS: PD-L1 is expressed more frequently in TICs than tumour epithelial cells. Expression in TICs is associated with aggressive tumour characteristics and non-luminal tumours but not with prognosis.

Predictors of adherence and the role of primary non-adherence in antihormonal treatment of breast cancer.

BACKGROUND: Antihormonal treatment for hormone receptor (HR) positive breast cancer has highly beneficial effects on both recurrence rates and survival. We investigate adherence and persistence in this group of patients. METHODS: The study population comprised 1192 patients with HR-positive breast cancer who were prescribed adjuvant antihormonal treatment from 2004 to 2013. Adherence was defined as a medical possession ratio (MPR) of ≥80. RESULTS: Of the 1192 included patients, 903 (75.8%) were adherent and 289 (24.2%) were non-adherent. Primary non-adherence was seen in 101 (8.5%) patients. The extremes of age (< 40 and ≥ 80 years) were associated with poor adherence. Patients with metastasis to axillary lymph nodes and those who received radiotherapy and/or chemotherapy were more likely to be adherent. Better adherence was also shown for those who switched medication at 2 years after diagnosis. Primary non-adherence seems to be associated with cancers with a good prognosis. CONCLUSION: Adherence to antihormonal therapy for breast cancer is suboptimal. Primary non-adherence occurs among patients with a relatively good prognosis. Non-adherent patients tend to terminate their antihormonal therapy in the initial part of the treatment period. Targeted interventions to improve adherence should be focused on the first part of the treatment period.

The drug will not work if the patient fails to take it. / Medisinen virker ikke hvis pasienten ikke tar den.

Poor adherence leads to poorer patient treatment. Doctors in all specialties need to be aware of this phenomenon.

ZNF703 gene copy number and protein expression in breast cancer; associations with proliferation, prognosis and luminal subtypes.

PURPOSE: Amplification of 8p12 is frequent in breast cancer and associated with poor prognosis in luminal subtypes. ZNF703 has been identified as the driver gene of proliferation in the A1 amplicon situated in 8p12. In this study, the aims were to investigate associations between ZNF703 copy number alterations and molecular subtypes, proliferation and prognosis, and using immunohistochemistry, examine associations between ZNF703 copy number and ZNF703 protein expression. METHODS: Copy number alterations in 702 primary breast tumours and corresponding lymph node metastases were examined using fluorescence in situ hybridization with probes for ZNF703 and centromere 8. In addition, protein expression was studied in 869 tumours from the same cohort. Associations between copy number alterations and protein expression and tumour characteristics were assessed using Pearson chi square test. The prognostic impact of ZNF703 copy number increase and protein expression was assessed estimating cumulative incidence of breast cancer death and hazard ratios. RESULTS: We found mean ZNF703 copy number ≥ 6 in 7% of tumours, most frequently in Luminal B subtypes. We found a positive association between increased copy number, and high proliferation, high histological grade, and poor prognosis. Luminal A tumours with high copy number had high histological grade and poor prognosis (borderline significant). We found positive nuclear staining in 76% of primary tumours. There was an association between copy number status and protein expression, but no association between protein expression and prognosis. CONCLUSIONS: In breast cancer, high ZNF703 copy number is associated with increased proliferation, Luminal B subtypes and poor prognosis.

MRPS23 amplification and gene expression in breast cancer; association with proliferation and the non-basal subtypes.

PURPOSE: MRPS23 is recognized as a driver of proliferation in luminal breast cancer. The aims of the present study were to describe MRPS23 copy number change in breast cancer, and to assess associations between MRPS23 copy number change and molecular subtype, proliferation and prognosis, and between MRPS23 gene expression and molecular subtype and prognosis. METHODS: Using fluorescence in situ hybridization (FISH), we examined MRPS23 and centromere 17 copy number in 590 formalin-fixed, paraffin-embedded primary tumours and 144 corresponding lymph node metastases from a cohort of Norwegian breast cancer patients. Furthermore, we analysed MRPS23 gene expression data in 1971 primary breast cancer tumours from the METABRIC dataset. We used Pearson's χ2 test to assess associations between MRPS23 copy number and molecular subtype and proliferation, and between MRPS23 expression and molecular subtype. We studied prognosis by estimating hazard ratios and cumulative incidence of death from breast cancer according to MRPS23 copy number and MRPS23 expression status. RESULTS: We found MRPS23 amplification (mean MRPS23 copy number ≥ 6 and/or MRPS23/chromosome 17 ratio ≥ 2) in 8% of primary tumours. Copy number increase associated with non-basal subtypes and higher tumour cell proliferation (Ki67). Higher MRPS23 expression associated with the Luminal B subtype. We found no significant association between MRPS23 amplification or MRSP23 gene expression, and prognosis. CONCLUSION: Amplification of MRPS23 is associated with higher proliferation and non-basal subtypes in breast cancer. High MRPS23 expression is associated with the Luminal B subtype.

The prognostic value of androgen receptors in breast cancer subtypes.

PURPOSE: Androgen receptor (AR) expression is frequent in breast cancer and has been associated with good prognosis in several studies. The present study investigates AR-expression in relation to molecular subtypes, clinicopathological features and prognosis in 1297 primary tumours and 336 paired axillary lymph node metastases (LNM) from two cohorts of Norwegian patients. METHODS: Immunohistochemistry for AR was performed on tumours previously reclassified into molecular subtypes using immunohistochemistry and in situ hybridisation. Associations between AR-expression and clinical features were studied using Chi-square tests. Cumulative incidence of breast cancer death and Cox regression analyses were used to assess prognosis. RESULTS: AR-positivity was found in 78.0% of all cases, 84.9% of luminal and 45.1% of non-luminal tumours. The highest proportion of AR-positivity was found in Luminal B tumours, and the lowest in the Basal phenotype. Discordance in AR-status between primary tumours and lymph node metastases was observed in 21.4% of cases. A switch from AR- primary tumour to AR+ lymph node metastasis was seen in 60/72 discrepant cases. AR-expression in primary tumours was an independent and favourable prognostic marker (HR 0.70, 95% CI 0.55-0.90), particularly in the Luminal A subtype, and in grade 3 tumours. CONCLUSIONS: AR is an independent predictor of good prognosis in BC, particularly in grade 3 and Luminal A tumours. Discordant AR-expression between primary tumour and LNM was observed in 21.4% of cases and most often there was a switch from AR- primary tumour to AR+ axillary LNM.

FGD5 amplification in breast cancer patients is associated with tumour proliferation and a poorer prognosis.

PURPOSE: Proliferation is a hallmark of cancer. Using a combined genomic approach, FGD5 amplification has been identified as a driver of proliferation in Luminal breast cancer. We aimed to describe FGD5 copy number change in breast cancer, and to assess a possible association with tumour proliferation and prognosis. METHODS: We used fluorescence in situ hybridization targeting FGD5 and chromosome 3 centromere (CEP3) on formalin-fixed, paraffin-embedded tissue from 430 primary breast cancers and 108 lymph node metastases, from a cohort of Norwegian breast cancer patients. We tested the association between FGD5 copy number status and proliferation (assessed by Ki67 levels and mitotic count) using Pearson's Chi square test, and assessed the prognostic impact of FGD5 copy number change by estimating cumulative risks of death and hazard ratios. RESULTS: We identified FGD5 amplification (defined as FGD5/CEP3 ratio ≥2 or mean FGD5/tumour cell ≥4) in 9.5% of tumours. Mitotic count and Ki67 levels were higher in tumours with FGD5 copy number increase, compared to tumours with no copy number change. After 10 years of follow-up, cumulative risk of death from breast cancer was higher among cases with FGD5 amplification [48.1% (95% CI 33.8-64.7)], compared to non-amplified cases [27.7% (95% CI 23.4-32.6)]. CONCLUSIONS: FGD5 is a new prognostic marker in breast cancer, and increased copy number is associated with higher tumour proliferation and poorer long-term prognosis.

Molecular Subtypes of Breast Cancer: Long-term Incidence Trends and Prognostic Differences.

BACKGROUND: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886-1977. METHODS: A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886-1928 and 1929-1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs. RESULTS: Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2-) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50-54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8-6.9 and 2.5; 95% CI, 1.2-5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3-0.5), Luminal B (HER2-; HR 0.5; 95% CI, 0.3-0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2-0.9). CONCLUSIONS: We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2-) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype. IMPACT: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625-34. ©2016 AACR.