AimsThe immune checkpoint marker, Programmed cell death-ligand 1 (PD-L1), is expressed by both ca... more AimsThe 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.MethodsUsing 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 χ2test, and prognosis by cumulative inci...
Purpose In this study of oestrogen receptor (ER) Low Positive breast cancers (BC) in three large ... more Purpose In this study of oestrogen receptor (ER) Low Positive breast cancers (BC) in three large cohorts of BC patients, we assess associations between levels of ER expression and tumour characteristics and prognosis. Methods Cases were stratified into patients unlikely to have received adjuvant therapy according to treatment guidelines at time of diagnosis (before 1995), and those who could have received adjuvant therapy (diagnosed in 1995 or later). ER status was divided into < 1%; ≥ 1 < 10%; ≥ 10%. Results were correlated with time of diagnosis, histopathological grade, proliferation status, and molecular subtypes, using Pearson’s Chi-square test. For prognosis, hazard ratios and cumulative incidence of death from BC were used. Results Of the 1955 tumours, 65 (3.3%) were ER Low Positive (ER ≥ 1 < 10%). Overall, the highest proportion of ER Low Positive tumours was observed among Luminal B (HER2 +) subtype (9.4%) and grade 3 tumours (4.3%). The risk of death from BC was l...
Background Because birth size appears to be positively associated with breast cancer risk, we hav... more 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...
BackgroundIn breast cancer (BC) Ki-67 cut-off levels, counting methods and inter- and intraobserv... more BackgroundIn breast cancer (BC) Ki-67 cut-off levels, counting methods and inter- and intraobserver variation are still unresolved. To reduce inter-laboratory differences, it has been proposed that cut-off levels for Ki-67 should be determined based on the in-house median of 500 counted tumour cell nuclei. Digital image analysis (DIA) has been proposed as a means to standardize assessment of Ki-67 staining in tumour tissue. In this study we compared digital and visual assessment (VA) of Ki-67 protein expression levels in full-face sections from a consecutive series of BCs. The aim was to identify the number of tumour cells necessary to count in order to reflect the growth potential of a given tumour in both methods, as measured by tumour grade, mitotic count and patient outcome.MethodsA series of whole sections from 248 invasive carcinomas of no special type were immunohistochemically stained for Ki-67 and then assessed by VA and DIA. Five 100-cell increments were counted in hot spo...
AimsThe immune checkpoint marker, Programmed cell death-ligand 1 (PD-L1), is expressed by both ca... more AimsThe 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.MethodsUsing 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 χ2test, and prognosis by cumulative inci...
Purpose In this study of oestrogen receptor (ER) Low Positive breast cancers (BC) in three large ... more Purpose In this study of oestrogen receptor (ER) Low Positive breast cancers (BC) in three large cohorts of BC patients, we assess associations between levels of ER expression and tumour characteristics and prognosis. Methods Cases were stratified into patients unlikely to have received adjuvant therapy according to treatment guidelines at time of diagnosis (before 1995), and those who could have received adjuvant therapy (diagnosed in 1995 or later). ER status was divided into < 1%; ≥ 1 < 10%; ≥ 10%. Results were correlated with time of diagnosis, histopathological grade, proliferation status, and molecular subtypes, using Pearson’s Chi-square test. For prognosis, hazard ratios and cumulative incidence of death from BC were used. Results Of the 1955 tumours, 65 (3.3%) were ER Low Positive (ER ≥ 1 < 10%). Overall, the highest proportion of ER Low Positive tumours was observed among Luminal B (HER2 +) subtype (9.4%) and grade 3 tumours (4.3%). The risk of death from BC was l...
Background Because birth size appears to be positively associated with breast cancer risk, we hav... more 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...
BackgroundIn breast cancer (BC) Ki-67 cut-off levels, counting methods and inter- and intraobserv... more BackgroundIn breast cancer (BC) Ki-67 cut-off levels, counting methods and inter- and intraobserver variation are still unresolved. To reduce inter-laboratory differences, it has been proposed that cut-off levels for Ki-67 should be determined based on the in-house median of 500 counted tumour cell nuclei. Digital image analysis (DIA) has been proposed as a means to standardize assessment of Ki-67 staining in tumour tissue. In this study we compared digital and visual assessment (VA) of Ki-67 protein expression levels in full-face sections from a consecutive series of BCs. The aim was to identify the number of tumour cells necessary to count in order to reflect the growth potential of a given tumour in both methods, as measured by tumour grade, mitotic count and patient outcome.MethodsA series of whole sections from 248 invasive carcinomas of no special type were immunohistochemically stained for Ki-67 and then assessed by VA and DIA. Five 100-cell increments were counted in hot spo...
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