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.

Sexual functioning, sexual enjoyment, and body image in Norwegian breast cancer survivors: a 12-year longitudinal follow-up study and comparison with the general female population.

BACKGROUND: Given the scarcity of evidence concerning the long-term sexual health of breast cancer (BC) survivors (BC-Pop), we aimed to assess how BC treatments affect short- and long-term sexual functioning, sexual enjoyment, and body image, and compare with aged-matched women in the Norwegian general population (F-GenPop). MATERIAL AND METHODS: The 349 patients in BC-Pop treated at Trondheim University Hospital in 2007-2014, were assessed in clinical controls at the hospital; before starting radiotherapy (T1, baseline), immediately after ending radiotherapy (T2), and after 3, 6, and 12 months (T3-T5), and at a long-term follow-up 7-12 years after baseline (T6). Meanwhile, F-GenPop included 2254 age-matched women in the Norwegian general population. The impact of BC treatment on sexual functioning was examined using a Linear Mixed Model. Sexual functioning, sexual enjoyment, and body image were assessed with the EORTC's QLQ-BR23 scales and compared between the populations in the four age groups (30-49, 50-59, 60-69, and 70+ years) using means with 95% confidence intervals and Student t-test. Linear regression, adjusted for age and comorbidity was applied to estimate individual scores. RESULT: BC survivors treated with mastectomy had overall lower sexual functioning than patients who had received breast-conserving surgery (p = 0.017). Although BC survivors treated with chemotherapy had lower sexual functioning than those treated without chemotherapy at T1-T5 (p = 0.044), both groups showed the same level of functioning at T6. BC-Pop exhibited significantly poorer sexual functioning (p < 0.001), lower sexual enjoyment (p < 0.05), and better body image (p < 0.001) than F-GenPop in all age groups. CONCLUSION: The impact of specific BC treatments on sexual functioning was modest; only mastectomy had a persistent negative influence. Nevertheless, all age groups in BC-Pop displayed significantly poorer sexual functioning than F-GenPop at both 12 months and up to 12 years after treatment.

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.

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.

The association of women's birth size with risk of molecular breast cancer subtypes: a cohort study.

BACKGROUND: Because birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes. METHODS: A cohort of 22,931 women born 1920-1966 were followed up for breast cancer occurrence from 1961 to 2012, and 870 were diagnosed during follow-up. Archival diagnostic material from 537 patients was available to determine molecular breast cancer subtype, specified as Luminal A, Luminal B (human epidermal growth factor receptor 2 (HER2)-), Luminal B (HER2+), HER2 type, and Triple negative (TN) breast cancer. Information on the women's birth weight, birth length and head circumference at birth was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for each molecular subtype, applying Cox regression, and stratified by maternal height. RESULTS: Birth length (per 2 cm increments) was positively associated with Luminal A (HR = 1.2, 95% CI, 1.0-1.3), Luminal B (HER2+) (HR = 1.3, 95% CI, 1.0-1.7), and TN breast cancer (HR = 1.4, 95% CI, 1.0-1.9). No clear association was found for birth weight and head circumference. The positive associations of birth length were restricted to women whose mothers were relatively tall (above population median). CONCLUSION: We found a positive association of birth length with risk of Luminal A, Luminal B (HER2+) and TN breast cancer that appears to be restricted to women whose mothers were relatively tall. This may support the hypothesis that breast cancer risk is influenced by determinants of longitudinal growth and that this finding deserves further scrutiny.

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.

Basal markers and prognosis in luminal breast cancer.

PURPOSE: Basal marker expression in triple-negative breast cancers identifies basal-like tumours, and thus separates the TN group into two prognostic groups. However, the expression and prognostic significance of basal markers in luminal breast cancers are poorly described. The aim of this study was to investigate the expression and prognostic value of basal markers (CK5, CK14 and EGFR) in luminal breast cancer. METHODS: A total of 1423 formalin-fixed, paraffin-embedded breast cancer tumours from a well-characterized cohort of Norwegian women, previously reclassified into molecular subtypes using IHC and ISH, were included in the study. For the present study, tumours expressing at least one of the basal markers CK5, CK14 or EGFR were defined as basal marker positive. Cumulative incidence of death from breast cancer and hazard ratio analyses were used to assess prognosis according to basal marker expression. RESULTS AND CONCLUSION: In total, 470 cases (33.0%) were basal marker positive. A higher proportion of the basal marker-positive tumours were of histopathological grade 3 compared to basal marker negative. For hormone receptor-positive, HER2-negative cases, we found better prognosis for basal marker-positive breast cancer compared to basal marker negative. For all subtypes combined, poorer prognosis for basal marker-negative cases was found in histopathological grade 2 tumours but not among grade 1 and 3.

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.

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.

HER2 gene copy number and breast cancer-specific survival.

AIMS: HER2 amplification occurs in 10-15% of breast cancers. It is associated with poor breast cancer-specific survival (BCSS) and is an important prognostic and predictive marker. While it has been accepted that the HER2:chromosome 17 centromere (CEP17) ratio determines HER2 status, recent guidelines acknowledge the significance of HER2 copy number alone. The aims of this study were to assess BCSS according to mean HER2 copy number and HER2 status expressed as a HER2:CEP17 ratio with and without increased CEP17 copy number. METHODS AND RESULTS: The study population comprised breast cancer patients treated with surgery only and with long-term follow-up. In situ hybridization for HER2:CEP17 was performed on tissue microarrays and was successful in 679 cases. These were included in the study. Kaplan-Meier methods were used to estimate BCSS. A total of 47 cases had ≥4 < 6 HER2 copies; 16 were HER2+ and 31 were HER2- by ratio. Eighty-five cases had ≥6 copies of HER2 and only two of these were HER2- by ratio. The risk of death from breast cancer was increased among those with ≥6 HER2 compared to cases with 0-3.9 HER2 signals [hazard ratio (HR): 2.05; confidence interval (CI): 1.49-2.82 (unadjusted)]. After adjusting for stage, there was increased risk of death from breast cancer during the first 5 years after diagnosis in cases that were HER2- by ratio but with ≥4 < 6 HER2 (HR: 2.38; CI: 1.23-4.60). CONCLUSIONS: Increased copy number of HER2 may confer an increased risk of death from breast cancer despite negative HER2 status by ratio.

Invasive lobular breast cancer: the prognostic impact of histopathological grade, E-cadherin and molecular subtypes.

AIMS: The aim of this study was to compare breast cancer specific survival (BCSS) for invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and, further, to evaluate critically the prognostic value of histopathological grading of ILC and examine E-cadherin as a prognostic marker in ILC. METHODS AND RESULTS: The study comprised 116 lobular and 611 ductal breast carcinomas occurring between 1961 and 2008. All cases had been classified previously according to histopathological type and grade, stained for oestrogen receptor (ER), progesterone receptor (PR), antigen Ki67 (Ki67), epithelial growth factor receptor (EGFR), cytokeratin 5 (CK5) and human epidermal growth factor receptor 2 (HER2) and classified into molecular subtypes. For the present study, immunohistochemical staining for E-cadherin was performed. The Kaplan-Meier method and Cox proportional hazards models were used in the analyses. Grade 2 tumours comprised 85.3% of the lobular tumours and 51.9% of the ductal tumours. BCSS in ILC grade 2 was comparable to that of IDC grade 3. E-cadherin-negative ILC had a poorer prognosis compared to E-cadherin positive ILC and to IDC regardless of E-cadherin status. CONCLUSIONS: The implication of histopathological grading may differ in ILC compared to IDC. E-cadherin may be useful in prognostication in ILC and thereby influence the determination of treatment strategies for this group of women.

Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women.

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2-)], Luminal B (HER2+), HER2 subtype, basal-like phenotype (BP) and five-negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend , 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend , 0.002), Luminal B (HER2-) (ptrend , 0.02), Luminal B (HER2+) (ptrend , 0.06), and also for the HER2 subtype (ptrend , 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women.

PURPOSE: Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes. METHODS: We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2-) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype. RESULTS: We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype. CONCLUSIONS: The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.

Quantification of multiple steroid hormones in serum and human breast cancer tissue by liquid chromatography-tandem mass spectrometry analysis.

Introduction: Systemic and local steroid hormone levels may function as novel prognostic and predictive biomarkers in breast cancer patients. We aimed at developing a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous measurement of multiple, biologically pivotal steroid hormones in human serum and breast cancer tissue. Methods: The quantitative method consisted of liquid-liquid extraction, Sephadex LH-20 chromatography for tissue extracts, and analysis of steroid hormones by liquid-chromatography-tandem mass spectrometry. We analyzed serum and tissue steroid hormone levels in 16 and 40 breast cancer patients, respectively, and assessed their correlations with clinical parameters. Results: The method included quantification of nine steroid hormones in serum [including cortisol, cortisone, corticosterone, estrone (E1), 17ß-estradiol (E2), 17α-hydroxyprogesterone, androstenedione (A4), testosterone and progesterone) and six (including cortisone, corticosterone, E1, E2, A4, and testosterone) in cancer tissue. The lower limits of quantification were between 0.003-10 ng/ml for serum (250 µl) and 0.038-125 pg/mg for tissue (20 mg), respectively. Accuracy was between 98%-126%, intra-assay coefficient of variations (CV) was below 15%, and inter-assay CV were below 11%. The analytical recoveries for tissue were between 76%-110%. Tissue levels of E1 were positively correlated with tissue E2 levels (p<0.001), and with serum levels of E1, E2 and A4 (p<0.01). Tissue E2 levels were positively associated with serum E1 levels (p=0.02), but not with serum E2 levels (p=0.12). The levels of tissue E2 and ratios of E1 to A4 levels (an index for aromatase activity) were significantly higher in patients with larger tumors (p=0.03 and p=0.02, respectively). Conclusions: The method was convenient and suitable for a specific and accurate profiling of clinically important steroid hormones in serum. However, the sensitivity of the profile method in steroid analysis in tissue samples is limited, but it can be used for the analysis of steroids in breast cancer tissues if the size of the sample or its steroid content is sufficient.

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.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer.

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7-12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17ß-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography-tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan-Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (

Characterization of FGD5 Expression in Primary Breast Cancers and Lymph Node Metastases.

Faciogenital dysplasia 5 ( FGD5) amplification drives tumor cell proliferation, and is present in 9.5% of breast cancers. We describe FGD5 expression, assess associations between FGD5 amplification and FGD5 expression, and assess FGD5 expression in relation to proliferation and prognosis. FGD5 immunohistochemistry was done on primary tumors ( n=829) and lymph node metastases ( n=231) from a cohort of Norwegian patients. We explored associations between FGD5 amplification, FGD5 expression, and proliferation, and analyzed the prognostic value of FGD5 expression by estimating cumulative risks of death and hazard ratios (HRs). We identified nuclear and cytoplasmic expression in 64% and 73% of primary tumors, respectively, and found an association between gene amplification and nuclear expression ( p=0.02). The proportion of cases with FGD5 expression was higher in lymph node metastases, compared with primary tumors ( p=0.004 for nuclear and p=0.001 for cytoplasmic staining). Neither proliferation nor prognosis was associated with FGD5 expression (age-adjusted HR 1.12 [95% confidence interval = 0.89-1.41] for nuclear expression; and 0.88 [95% CI = 0.70-1.12] for cytoplasmic expression). FGD5 is expressed in a high proportion of breast cancers and lymph node metastases. There was a correlation between FGD5 amplification and nuclear expression, but no association between FGD5 expression and proliferation or 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.