ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT‐PCR‐based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2‐amplified cases, two were negative and one was equivocal, and all FISH HER2‐equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2‐amplified, Oncotype DX HER2‐negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2‐positive breast carcinomas. The preferential use of Oncotype DX biomarker results over IHC and FISH is discouraged.     

IHC4 score plus clinical treatment score predicts locoregional recurrence in early breast cancer

PurposeImmunohistochemical 4 (IHC4) score plus Clinical Treatment Score (CTS) is an inexpensive tool predicting risk of distant recurrence in women with early breast cancer (EBC). IHC4 score is based on ER, PR, HER2 and Ki67 index. This study explores the role of the combined score (IHC4 + CTS) in predicting risk of locoregional recurrence (LRR) in women with EBC who had breast conservation surgery (BCS) without adjuvant radiotherapy (study group). The secondary objective was to evaluate the clinicopathological differences between our study group and women who had adjuvant radiation following BCS (control group).Methods and materialsPatients were selected from the local database over a 13-year period. IHC testing was done where results were missing. Combined scores were calculated using the appropriate formulae.ResultsPatients in the study group (81 patients) had favorable clinicopathological features compared to the control group (1406 patients).The Cox regression indicated a statistically significant association between the combined score and the risk of LRR (p = 0.03). The incidence of LRR was zero, 20% and 33.3% in the low, intermediate and high risk groups respectively (p = 0.007).Margin status was the only variable not included in the combined score. The Cox regression analysis demonstrated that the combined score (p = 0.02) and the ordinal measure of margins (p = 0.03) were significant independent predictors of LRR.ConclusionThis is the first study of its kind. The IHC4 score + CTS can be used to identify low risk women who can potentially avoid adjuvant radiotherapy.     

Discordance in early breast cancer for tumour grade, estrogen receptor, progesteron receptors and human epidermal receptor-2 status between core needle biopsy and surgical excisional primary tumour

The aim of the present study was to compare the tumour grade, Estrogen Receptor (ER), Progesteron Receptor (PgR) and Human Epidermal Receptor-2 (HER-2) status in the core needle biopsy (CNB) with those observed in the subsequent excisional primary tumour (EPT).All patients diagnosed with an early breast cancer in our University Hospital Center between January 1, 2005 and December 31, 2006 were included but exclusion criteria of patients with large tumour requiring neoadjuvant chemotherapy and cases with more than one tumour (multicentricity/multifocality tumours). Histological tumour grade assessed according to Nottingham Grading System (SBRm), ER, Pgr and HER-2 tumoural status were assessed twice in CNB and in EPT.A total of 175 patients were assessed. The concordance between CNB and EPT for Grade, ER, PgR and HER2 status were 75.4% (p > 0.00001), 84% (p > 0.00002), 78.3% (p = 0.002) and 98.3% (p = 0.486) respectively.In conclusion CNB can be used with confidence for HER2 determination. For grade, PgR and ER due to substantial discordance results from CNB should be used with caution.     

Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab

PurposeThe aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab.MethodsMedical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively.ResultsMedian follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER− and PR−) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33–8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33–8.71) were significant risk factors for development of brain metastasis as the first site of recurrence.ConclusionsIn patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER− and PR−) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence.     

Immunohistochemical prediction of brain metastases in patients with advanced breast cancer: The role of Rad51

BackgroundThere are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC).MethodsThe study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4.ResultsKi-67 ≥14% (hazard ratio [HR] 2.76; P < 0.001), cytoplasmic expression of Rad51 (HR 1.87; P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 (P < 0.001).ConclusionsER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.     

HER-2/neu-positive breast cancer neoadjuvant chemotherapy response after implementation of 2018 ASCO/CAP focused update

Human Epidermal Growth Factor Receptor 2 (HER2), a routinely tested breast cancer marker, is associated with worse prognosis yet increased sensitivity to targeted neoadjuvant therapy (NAT) in breast cancer patients. The presence of HER2 in breast carcinoma can be detected with either immunohistochemistry (IHC) or in situ hybridization (ISH). In this study, we examine the relationship between clinicopathological features, HER2 detection method (IHC vs ISH), and prognostic outcomes in NAT-treated HER2-positive breast cancer patients. We included 99 HER2-positive patients from three academic institutions following 2018 HER2 testing updates and conducted a retrospective correlational study. Seventy-one (72%) were HER2-positive by IHC and 28 (28%) were positive following reflexive ISH. Multivariate analysis showed biomarker status to be significantly associated with pathologic complete response (pCR) (p = 0.003), Residual Cancer Burden (RCB) (p = 0.007), and tumor size downstaging (p = 0.002) and HER2 detection method of IHC to be significantly associated with pCR (p = 0.05), RCB (p = 0.004), and nodal downstaging (p= 0.03). In conclusion, HER2 detection method and biomarker subtype allow for further prognostic stratification of HER2-positive patients when 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline updates are applied.     

Is breast cancer from Sub Saharan Africa truly receptor poor? Prevalence of ER/PR/HER2 in breast cancer from Kenya

ObjectivesStudies on ER/PR/HER2 in breast cancer from Sub Saharan Africa (SSA) are fraught with inconsistencies in the prevalence of hormone receptor status. In Kenya, ER/PR/HER2 for breast cancers is not part of routine assessment and available in only three to four centers across the country. Variability in methodology and interpretation makes comparison between data difficult. Our aim was to accurately determine the prevalence of ER/PR/HER2 using standardized techniques and double reporting. Prognostic tumor parameters were also correlated with clinical features and receptor status.Materials and methodsConsecutive invasive breast cancers (IBC) accrued between September 2011 and December 2012 were analyzed at Aga Khan University Hospital, Nairobi (AKUHN). Tumor blocks were stained for ER/PR/HER2 on an automated platform. Double reporting of ER/PR/HER2 was done using the Allred system and the ASCO/CAP guidelines respectively.ResultsA total of 301 cases of IBC were analyzed for pathology and ER/PR/HER2. The age range of patients was 19–94 years with a median of 47.5 years. Invasive ductal carcinoma (NOS) was the most common histologic type (84.2%). ER positivity was seen in 72.8%, PR in 64.8% and HER2 in 17.6% of all cases. Triple negative breast cancers (TNBC) constituted 20.2% of the cases. There was a significant association between receptor status and histologic grade (p < 0.001) and statistically significant trend of increasing pathological stage of tumor (pT) associated with TNBC (p = 0.020).ConclusionsWe present a definitive prospective analysis of ER/PR/HER2 from a single center and demonstrate that prevalence of receptor status from SSA is comparable with that in the West.     

Receptor discordance and phenotype change in metastatic breast cancer

Backgroundchanges may occur in tumor phenotype and receptor status during the progression of breast cancer. Discordance between primary and metastases has implications for further treatment and prognosis.Methods185 patients confirmed breast cancer metastasis were retrospectively analyzed during 1999–2019. All the pathological assessments of receptors and phenotypes of both primaries and metastases were recorded.Resultsrates of receptor discordance were 18.65%, 30.57%, and 16.06% for ER, PR, and HER2, respectively and 31.62% for phenotype change. Patients with ER discordance experienced a worse OS and PMS, and those with ER loss had worse PMS compared with ER positive concordance. Patients with PR discordance experienced poorer OS and loss of PR positivity also had decreased OS and PMS when comparing with PR positive concordance. There was also significantly poorer PMS of hormon receptor (HR) discordance than HR positive concordance. In phenotype change, the luminal A type concordance group showed better PMS result.Conclusionsthis study demonstrated that discordance in subtype and receptor status between primary and metastatic lesions ultimately affects the survival and has a potential impact on treatment options.     

Significance of HER2 expression in patients with upper tract urothelial carcinoma: A meta-analysis

ObjectiveSeveral studies have explored the prognostic values of HER2 expression in upper tract urothelial carcinoma (UTUC), however, the results obtained are not consistent. We aimed to calculate the clinical significance of HER2 expression on the outcome of UTUC patients using a meta-analysis.Materials and methodsUsing published evidence, we performed a meta-analysis to examine the clinical values of HER2 expression in patients with UTUC. Thirty-five articles from 679 articles related to the epidermal growth factor receptor family expression assessment in UTUC patients were reviewed and seven papers were found to be fit for analyses. The estimates included the odds ratio (OR), distribution related to stage and grade, hazard ratios (HRs), and 95% confidence intervals (CIs) from survival analyses of intravesical recurrence, progression, and overall survival (OS).ResultsThe pooled results showed that HER2 expression is significantly associated with higher stage, but not with tumor grade in patients with UTUC (OR, 2.05; 95% CI, 1.15–3.68; p = 0.016 and OR, 4.73; 95% CI, 0.80–27.8; p = 0.086, respectively). In addition, the pooled survival analyses demonstrated that HER2 expression yielded a worse recurrence-free survival in UTUC patients (HR, 4.32; 95% CI, 2.17–8.60; p < 0.0001). However, there is lack of statistical significance in terms of progression-free survival and OS (HR, 2.08; 95% CI, 0.46–9.32; p = 0.339 and HR, 1.06; 95% CI, 0.48–2.37; p = 0.879, respectively).ConclusionExisting studies on UTUC are heterogeneous and limited. Our analysis suggests that HER2 expression plays an important role in cancer recurrence in the urinary bladder after the primary treatment of UTUC.     

Real-world data of HER2-low metastatic breast cancer: A population based cohort study

BackgroundWith the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression.MethodsWomen with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+.ResultsAmong women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively.Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes.ConclusionSubstantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported.     

Is necrotizing enterocolitis the same disease in term and preterm infants?

IntroductionNecrotizing enterocolitis predominantly affects preterm (PT) infants. The paucity of data regarding the clinical course in term infants makes it difficult to predict outcomes and counsel families. To identify predisposing factors and gain a better understanding of the clinical course of NEC in term infants, we reviewed our experience with term infants and compared it to outcomes in PT infants.MethodsWe performed a 10 year retrospective review of all infants admitted to our NICU with Bell stage 2 NEC or greater. Infants < 37 weeks gestation were considered PT. Term and PT infant comorbidities, outcomes and intraoperative findings were compared.ResultsFifteen (12%) of 125 infants were term. Compared to PT infants, term infants were more likely to have congenital heart disease (33% term vs. 10% PT, p = 0.02) and develop NEC sooner (4 days in term vs. 17 days in PT, p < 0.001) but were less likely to require operative intervention (20% term vs. 38% PT; p = 0.17). There was no significant difference in Bell stage, survival and development of intestinal failure. NEC totalis occurred exclusively in PT infants.ConclusionsNEC in term infants has unique clinical features that distinguishes it from NEC in PT infants.     

Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients

BackgroundRecently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients.MethodsPatients of different breast cancer subtypes diagnosed with metastatic disease (visceral and/or brain metastases) were identified from a breast cancer database. Tissue samples of the respective primary tumors were retrieved, and immunohistochemical staining for estrogen-receptor, progesterone-receptor, HER2, and HER3 was performed. In HER2 equivocal and selected HER3 positive cases, subsequent fluorescent in situ hybridization (FISH) analysis was performed.ResultsTissue specimens of 110 patients were available for this analysis. 21% had strong, complete, membranous HER3 staining of at least 10% of all tumor cells; HER3 protein expression was not associated with HER3 gene amplification. HER2/HER3 co-overexpression was observed in 12/110 (11%) specimens and HER3-overexpression showed a statistically significant association with HER2-overexpression (p = 0.02). No correlation was observed for HER3-overexpression and overall survival (OS), time to diagnosis of brain metastases, and incidence of brain metastases. Still, in patients with HER3 overexpression, a higher rate of ‘brain only’ metastatic behavior was observed (p = 0.042). In the HER2-positive subgroup, HER3-overexpression was significantly associated with shorter OS from diagnosis of metastatic disease (median 17 vs. 35 months; p = 0.04; log rank test).ConclusionsHER2/HER3 co-overexpression is significantly associated with impaired OS from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or the inhibition of HER2/HER3 hetero-dimerization may improve clinical outcome in this subgroup.     

Male breast cancer: Looking for better prognostic subgroups

PurposeMale Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.Patients/methodsRetrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.ResultsAccording to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0–3.4years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7–14.3years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2–3.1years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2–16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6–7.8 years).ConclusionFBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.     

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy

BackgroundThe level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy.MethodsWe retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory.ResultsWe retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002–1.025).ConclusionsThe level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy.     

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.     

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status

ObjectiveFor patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain.Patients and methodsThis multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla.ResultsMedian follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56).ConclusionOur study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.     

Radiation therapy utilization and outcomes for older women with breast cancer: Impact of molecular subtype and tumor grade

BackgroundRadiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers.MethodsThe Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation. Chi-squared analysis was performed to determine the difference in RT utilization between groups. Multivariable logistic regression analysis was performed to determine predictors for RT use. Kaplan-Meier curves were created and the log-rank test done to compare differences in breast cancer specific survival (BCSS) between groups.ResultsA total of 12,312 patients met the inclusion criteria. Receipt of RT for patients with distinct tumor biomarkers was as follows: 55.7% for patients with Estrogen Receptor (ER) +/HER2+; 57.1% for patients with ER+/HER2-; 65.6% for patients with ER-/HER2+; and 69.2% for ER-/HER2- patients (p < 0.001). Factors associated with RT use included ER-/HER2- status, 70–74 years of age, and high grade disease, while adjuvant RT was associated with improve BCSS in ER+/HER2- and ER-/HER2- patients.ConclusionsPatients 70–74 years old and those with ER-/HER2- are more likely to receive adjuvant RT. Moreover, adjuvant RT is associated with improvements in BCSS in ER+/HER2- and ER-/HER2- patients. Given possible poor compliance with hormonal therapy, the omission of RT in ER + patients, without consideration of HER2 status, should be undertaken with care.     

Prognostic variables in invasive breast cancer: Contribution of comedo versus noncomedo in situ component

Background: Many invasive breast cancers are accompanied by a variety of noninvasive components. Histological distinctions have been made between these components, but to understand their importance, it is essential to examine their molecular biology. Methods: Proliferative indices, oncoproteins, and steroid receptor expression were compared for invasive breast cancers containing comedo-type ductal carcinoma in situ (n=35), noncomedo-type ductal carcinoma in situ (n=34), and pure invasive cancers (n=49). Ploidy, S-phase fraction, Ki-67 staining, estrogen receptor (ER), progesterone receptor (PR), and the expression of HER-2/neu and epidermal growth factor receptor (EGFR) were evaluated in these tumors. Results: The comedo-invasive subgroup differed significantly from the noncomedoinvasive subgroup, demonstrating significantly higher mean ploidy (1.6 vs. 1.3;p=0.0156), S-phase fraction (7.9% vs. 4.3%;p=0.0066), Ki-67 staining (20.3% vs. 12.0%;p=0.0058), and HER-2/neu values (2,247 fm/mg vs. 1,014 fm/mg;p=0.0412) and lower ER (76 fm/mg vs. 339 fm/mg;p=0.006) and PR values (99 fm/mg vs. 265 fm/mg;p=0.0608). A higher percentage of comedo-invasive carcinomas demonstrated aneuploidy (71%;p=0.0158), elevated levels of S-phase fraction (75%;p=0.0016) and Ki-67 staining (55%;p=0.0512), overexpression of HER-2/neu oncogene (47%;p=0.0011), and were ER negative (35%;p=0.0148), PR negative (47%;p=0.0073) when compared to noncomedo-invasive carcinomas. Comedo-invasive and noncomedo-invasive tumors were comparable for nodal status and tumor size, but differences were noted for tumor differentiation and percentage of tumors that were >1 cm. Comedo-invasive tumors were predominantly poorly differentiated (60 vs. 32%) and were >1 cm (94 vs. 77%,p<0.05). Results: Comedo-invasive cancers were comparable to pure invasive cancers for ploidy, S-phase fraction, Ki-67 staining, and ER, PR, and EGFR expression. However, comedoinvasive carcinomas had greater HER-2/neu overexpression when compared to pure invasive tumors (47 vs. 19%;p=0.0359). Conclusions: These results are consistent with the hypothesis that comedo carcinoma is a more aggressive type of ductal carcinoma in situ and may have independent prognostic value when seen in association with infiltrating ductal carcinoma. In invasive tumors, comedo carcinomas are associated with poor prognostic factors, including higher ploidy, S-phase fractions, Ki-67 staining, negative ER and PR status, poorer differentiation, larger tumors, and presence of HER-2/neu oncogene overexpression.The results of this study were presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

The association between referral source and outcome in patients with colorectal cancer

AimThe colorectal two-week wait fast track (FT) referral system was nationally implemented in the UK in 2000 to ensure patients with colorectal cancer (CRC) received prompt access to specialized services. The aim of this study was to determine the association between the mechanism of referral to colorectal services and the 5-year outcomes for patients with CRC.MethodsConsecutive patients with newly diagnosed CRC presenting between October 2002 and September 2004 were identified retrospectively. Analysis for survival and recurrence of disease at 5 years from presentation was undertaken. Outcomes for patients were compared between fast track (FT), non-fast track (NFT) and emergency referral (ER) routes, using Kaplan–Meier survival estimates.ResultsOut of 189 patients, 96 (51%) presented via the FT, 41 (22.5%) via the NFT and 52 (27.5%) via the ER referral route. The 5-year overall survival was 52.6% ± 5.1, 41.5% ± 7.7 and 38.5% ± 6.7 for the FT-, NFT- and ER groups respectively (p = 0.075). The 5-year cancer specific survival was 60.3% ± 5.2, 58.8% ± 5.3 and 43.5% ± 7.2 for the FT-, NFT- and ER groups respectively (p = 0.056). Patients referred as emergencies had worse 5-year overall survival; 49.3% ± 4.3 (FT&NFT) vs. 38.5% ± 6.7 (ER) (p = 0.042) and 5-year cancer specific survival 59.8% ± 4.4 (FT&NFT) vs. 43.5% ± 7.2 (ER) (p = 0.016). A total of 136 patients (FT n = 71, NFT n = 34, ER n = 31) underwent potentially curative surgery. Differences in 5-year survival did not reach statistical significance in these patients.ConclusionReferral route to specialist services for patients with CRC via the fast track pathway compared to non-fast track pathway was not associated with improved survival.