Biological Characteristics and Long-term Outcomes in Node-negative Breast Cancer

BackgroundBecause the risk of relapse of node-negative breast cancer (BC) is varying, we evaluated the prognosis of patients with this disease and the factors associated with increased risk of relapse.Patients and MethodsThe clinical charts of patients with BC with evidence of negative nodes and with a potential ≥ 5-year follow-up were retrospectively reviewed.ResultsWe analyzed 1276 patients. Over a median follow-up of 71.6 months (range, 1-227.2 months), we observed 159 events of relapse or death. The median RFS was 170 months. The median overall survival (OS) was 192 months. At univariate analysis, older age, negative hormonal receptors, larger tumor size and higher proliferation index (Ki67) were associated with worse recurrence-free survival (RFS) and OS (P < .05); higher grading was associated with worse RFS (P = .01). At multivariate analysis for RFS, age, Ki67 and tumor size confirmed their independent prognostic role. At multivariate analysis for OS, age and positive hormonal receptors showed an independent prognostic role. We observed no differences in prognosis between human epidermal growth factor receptor 2 (HER2) positive and triple-negative (TN) BC, but TNBC showed a worse OS compared with luminal-like BC.ConclusionsIn node-negative BC, age, hormone receptor status, tumor size and Ki67 were prognostic factors. The TNBC subtype was not associated with poorer prognosis compared with the HER2-positive subtype, but showed a worse OS compared with luminal-like BC.     

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.     

Progesterone receptor loss identifies Luminal B breast cancer subgroups at higher risk of relapse

BackgroundThe immunohistochemical (IHC) evaluation of estrogen receptor (ER), progesterone receptor (PgR), Ki-67 and HER2 is considered a surrogate means for identifying the molecular subtypes of breast cancer with different prognosis.Patients and methodsWe explored patterns of recurrence in 4837 women with breast cancer defined as Luminal B (ER-positive and/or PgR-positive, HER2 positive and/or Ki-67≥14%) by IHC classification. We evaluated four subgroups within the Luminal B subtype according to HER2 expression and PgR status.ResultsPatients within the ER+/PgR+/HER2- subgroup presented a 5-year breast cancer-related survival (BCS) of 97% (95% confidence interval (CI), 96–97) and overall survival (OS) of 95% [95% CI, 95–96], the best survivals of the Luminal B subgroups. In the multivariate analysis, the ER+/PgR-/HER2- subgroup was associated with a reduced BCS (HR 1.71; 95%CI, 1.25–2.35) and OS (HR 1.47; 95%CI, 1.10–1.96) when compared with the ER+/PgR+/HER2- subgroup. Also patients within the ER+/PgR-/HER2+ subgroup had a reduced BCS (HR 1.93; 95%CI, 1.32–2.83) and OS (HR 1.62; 95%CI, 1.14–2.30) when compared with ER+/PgR+/HER2- subgroup. On the other hand, no statistically significant differences were found with regard to BCS and OS among patients with ER+/PgR+/HER2+ and patients with ER+/PgR+/HER2- disease.ConclusionsPgR loss identifies Luminal B breast cancer subgroups at higher risk of relapse and death, both with HER-2-positive and HER-2-negative disease.     

HER2 as a potential biomarker guiding adjuvant chemotherapy in stage II colorectal cancer

BackgroundHER2 is a well-established therapeutic target in breast and gastric cancers, while the role of HER2 in colorectal cancer is unclear, and no studies have explored the impact of HER2 on the outcome of stage II colorectal cancer patients treated with 5-fluorouracial based adjuvant chemotherapy.MethodsWe analyzed HER2 mRNA expression of 206 patients in GSE39582 dataset and explored the impact of HER2 expression on benefit from adjuvant chemotherapy for stage II colon cancer patients. We further validated the finding by retrospectively analyzing HER2 detection of immunohistochemistry in a cohort of 282 patients in Fudan University Shanghai Cancer Center (FUSCC).ResultsIn GSE39582 dataset, chemo-treated HER2-high patients had a better overall survival (OS) and relapse-free survival (RFS) versus chemo-naïve HER2-high patients (5-year OS: 100% vs 69.5%, 5-year RFS: 100% and vs 64%, P = 0.027 and 0.025, respectively). On the contrary, chemo-treated HER2-low patients had a worse RFS compared with chemo-naïve HER2-low patients (5-year RFS: 65.6% vs 82.1%, P = 0.022). In FUSCC cohort, chemo-treated HER2-positive patients exhibited better OS vs chemo-naïve HER2-positive patients (5-year OS: 100% vs 73.8%, P < 0.001), and showed marginal evidence of a lower probability of recurrence (5-year RFS: 74.4% vs 58.7%, P = 0.072). After stratifying by mismatch repair (MMR) status, the results only kept consistency in patients with pMMR status.ConclusionsHER2-positve patients with stage II colorectal cancer can benefit from 5-fluorouracial based adjuvant chemotherapy, especially for patients with pMMR status.     

淋巴结转移数和淋巴结转移率与乳腺癌预后关系的分析比较

  目的  探讨淋巴结转移率(lymph node ratio, LNR)是否能更优于淋巴结转移数(positive lymph nodes, PLN), 用于评价乳腺癌术后患者的复发风险和总生存时间。  方法  回顾性分析1089例淋巴结清扫数目为10枚或以上、术后经病理证实淋巴结转移阳性的原发性浸润性乳腺癌患者临床病理资料。  结果  单因素生存分析, 肿瘤大小分期, 组织学分级、ER/PR/HER-2状态、PLN、LNR、切检淋巴结总数、结外软组织侵犯、辅助治疗与患者RFS(relapse free survival, RFS)、OS(overall survival, OS)均具有明显的相关性(P < 0.05);多因素生存分析, 当PLN和LNR作为协变量分别进入Cox比例风险模型时, PLN和LNR均为患者RFS和OS的独立预测指标(P < 0.001);当PLN和LNR作为协变量同时进入Cox比例风险模型时, LNR依然是患者RFS和OS的独立预测指标(RFS: P < 0.001.OS: P=0.001), 而PLN不再是其独立预测指标(RFS: P=0.944, 0S: P=0.315)。  结论  相对于PLN而言, LNR能更好的评价乳腺癌术后患者的复发风险和总生存时间, 为乳腺癌危险度分级和临床医生制定辅助治疗方案提供更有力的参考依据。      

The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up

Background

The routine assessment of progesterone receptor (PR) expression in breast cancer (BC) remains controversial. This study aimed to evaluate the role of PR expression in luminal BC, with emphasis on the definition of positivity and its prognostic significance as compared to Ki67 expression.

Methods

A large cohort (n = 1924) of estrogen receptor (ER)-positive/HER2-negative BC was included. PR was immunohistochemically (IHC) stained on full face sections and core needle biopsies (CNB) where the optimal scoring cutoff was evaluated. In addition, the association of PR with other clinicopathological factors, cellular proliferation, disease outcome, and response to adjuvant therapy were analyzed.

Results

Although several cutoffs showed prognostic significance, the optimal cutoff to categorize PR expression into two clinically distinct prognostic groups on CNB was 10%. PR negativity showed a significant association with features of aggressive tumor behavior and poor outcome. Multivariate analyses indicated that the association between PR negativity and poor outcome was independent of tumor grade, size, node stage, and Ki67. PR negativity showed independent association with shorter survival in patients who received endocrine therapy whereas Ki67did not.

Conclusion

PR IHC expression provides independent prognostic value superior to Ki67. Routine assessment of PR expression in BC using 10% cutoff in the clinical setting is recommended.

Plain Language Summary

• In this study, we have established an optimal approach to determine the prognostic value of progesterone receptor expression in estrogen receptor-positive breast cancer patients.
• To do this, the levels of progesterone receptor were measured in a large cohort of estrogen receptor-positive breast cancer patients.
• We have refined the definition of progesterone receptor positivity in estrogen receptor-positive breast cancer.
• We show that progesterone receptor expression adds prognostic and predictive value of endocrine therapy in estrogen receptor-positive breast cancer patients, and our results show that the absence of progesterone receptor is associated with poorer outcomes independent of tumor grade, size, node stage, and Ki67 expression.

     

Role of Ki67 in predicting resistance to adjuvant tamoxifen in postmenopausal breast cancer patients

IntroductionBreast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology.AimTo correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen.MethodsThis cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods.ResultsThe median Ki67 value was 22.5% (IQR, 10%–50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ?30%. Ki67 ?30% was an independent predictor of recurrence, poor DFS and OS.ConclusionHigh Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions.     

Effects of Germline Pathogenic Variants,Cancer Subtypes,Tumor-related Characteristics,and Pregnancy-associated Diagnosis on Outcomes

BackgroundAlthough breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC.Materials and MethodsThis was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS.ResultsWith mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing.ConclusionsSimilar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.     

Ki67/SATB1 ratio is an independent prognostic factor of overall survival in patients with early hormone receptor-positive invasive ductal breast carcinoma

Biological diversity of breast cancer presents challenges for personalized therapy and necessitates multiparametric approaches to understand and manage the disease. Multiple protein biomarkers tested by immunohistochemistry (IHC), followed by digital image analysis and multivariate statistics of the data, have been shown to be effective in exploring latent profiles of tumor tissue immunophenotype. In this study, based on tissue microarrays of 107 patients with hormone receptor (HR) positive invasive ductal breast carcinoma, we investigated the prognostic value of the integrated immunophenotype to predict overall survival (OS) of the patients. A set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16) was used. The main factor of the variance was characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α; it was associated with histological grade but did not predict OS. The second factor was driven by SATB1 expression along with moderate positive HIF-1α and weak negative Ki67 loadings. Importantly, this factor did not correlate with any clinicopathologic parameters, but was an independent predictor of better OS. Ki67 and SATB1 did not reach statistical significance as single predictors; however, high Ki67/SATB1 ratio was an independent predictor of worse OS. In addition, our data indicate potential double prognostic meaning of HIF-1α expression in breast cancer and necessitate focused studies, taking into account the immunophenotype interactions and tissue heterogeneity aspects.     

Prognostic Factors and Survival According to Tumor Subtype in Women With Breast Cancer Brain Metastases

Breast cancer (BC) is the second most cause of central nervous system (CNS) metastases. Studies report that almost one third of patients (pts) with triple-negative, one-third with human epidermal growth factor receptor 2 (HER2)-positive and 15% of those with hormone receptor-positive, HER2-negative metastatic breast cancer will develop brain metastases. It is known that the development of symptomatic brain metastases in women with advanced breast cancer is associated with poor prognosis, irrespective of local and systemic treatments. In the present study, we aim to determine the association between BC subtypes and CNS metastases occurrence and prognosis. Retrospective analysis of 309 BC patients with CNS metastases, confirmed by pathological and/or radiological methods, treated in a Cancer Center between 2003 and 2021, was obtained to identify clinicopathologic factors associated with early onset of brain metastases and survival outcomes. For analysis purposes, 3 BC subtypes were considered according to hormone receptor status and HER-2 expression: ER and/or PR positive, HER-2 positive and triple negative. The median time between diagnosis of BC and detection of CNS metastases was 43 months, and it was significantly shorter in triple negative group (8 months). Twenty-one patients (6,8%) had CNS metastases at BC diagnosis, with CNS being the first site of recurrence in 35,3%, mainly in HER2 positive. Most of the patients had parenchymal metastases (n = 245) and 37 (12%) had leptomeningeal (LM) disease, with predominance in ER and/or PR positive subtype (70,3%). In patients submitted to CNS surgery, the concordance between primary tumor and metastases subtype was higher in triple negative (76,9%) compared to 63,2% in HER-2 positive and 38,9% in ER and/or PR positive group (P < 0.05). After CNS involvement, 25,4% (n = 34) of patients with triple negative disease did not receive any systemic therapy, compared to 30,6% (n = 41) in HER-2 positive and 44% (n = 59) in ER and/or PR positive groups (P = 0.05). Median survival after CNS metastases was 9 months, but significantly longer in HER-2 positive group (16 months) and in patients submitted to surgical resection of CNS metastases, irrespectively of subtype (22 months vs 5 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastases (HR 0.60, 95% CI: 0.41-0.87, P = 0.007), regardless the therapeutic strategy. Clinical behavior and prognosis of CNS metastases varies according to BC subtype. The association between LM disease and ER and/or PR positive tumors should be explored in upcoming studies. Also, these patients’ prognosis depends on the availability of specific treatment options, therefore, innovative and effective therapeutic approaches are needed, in order to improve survival and quality of life of these patients.     

Is quantitative oestrogen receptor expression useful in the evaluation of the clinical prognosis? Analysis of a homogeneous series of 797 patients with prospective determination of the ER status using simultaneous EIA and IHC

ObjectiveOestrogen receptor (ER) determination in breast cancer (BC) is a major yardstick for the prognosis and for response to hormonal therapy (HT). As several techniques have been proposed for ER quantification, the purpose of our study was to assess whether the qualitative or quantitative analysis of ER expression might influence the prognosis and response to treatment.Materials and methodsWe analysed overall survival (OS) and disease-free survival (DFS) in 797 primary BC cases with ER determination by enzyme immunoassay (EIA) and immunohistochemistry (IHC). The clinical impact according to qualitative or quantitative analysis of ER expression was assessed. Response to HT was evaluated according to quantitative EIA-determined ER expression levels.ResultsAccording to the qualitative analysis of ER expression, patients with EIA-determined and IHC-determined ER-positive tumours had significantly longer OS and DFS (p < 0.001). The analysis stratified on quartiles of ER levels showed significantly different outcomes according to EIA- and IHC-determined subgroups. In the group of patients who received adjuvant treatment, 5-year OS was significantly different between the groups, with a clear benefit for the highest EIA-determined ER quartiles (p < 0.001). Comparatively, in terms of 5-year DFS, a clear separation was noted between groups for adjuvant treatment (p < 0.001). The group with moderate ER+ values was clearly distinct from the ER-negative population. Quantitative ER expression helped to better distinguish the beneficial or detrimental effect of HT within quartiles of ER-expressing tumours. Based on the STEPP analysis which showed a trend towards an ER effect on DFS as a function of HT assignment, we confirm the benefit of HT in patients with a very high EIA-determined ER level and a detrimental impact on negative and weakly positive groups.ConclusionQuantitative ER expression in BC helps to better discriminate heterogeneity in clinical outcome and response to HT.     

Prognostic Significance of the Ki67 Scoring Categories in Breast Cancer Subgroups

BackgroundImmunohistochemical (IHC) expression of Ki67 has a prognostic and predictive value for breast cancer, and the IHC Ki67 labeling index is estimated by counting the number of positive and negative cells. It has not been clarified whether IHC Ki67 estimated using a semiquantitative scoring system has a prognostic value. We aimed to estimate the usefulness of scoring categories of IHC Ki67 as a prognostic factor for breast cancer subgroups.Patients and MethodsWe retrospectively identified patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000 and December 31, 2010. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test.ResultsOf the 1331 primary breast cancer patients included in the study, In patients with estrogen receptor (ER)-positive and HER2-negative tumors (n = 971), high and intermediate Ki67 scores were associated with poorer relapse-free survival than low Ki67 scores (P < .001 and P = .002, respectively). Furthermore, in the multivariate analyses of this subgroup, progression-free survival (PFS) was significantly longer in patients with low Ki67 scores than in patients with high Ki67 scores (hazard ratio, 0.387; 95% confidence interval, 0.233-0.643; P < .001). In the multivariate analyses, the Ki67 score was not significantly associated with PFS in the ER-positive and HER2-positive, ER-negative and HER2-positive, or ER-negative and HER2-negative subgroups.ConclusionOur data demonstrated that low, intermediate, and high Ki67 scores have a prognostic value in breast cancer patients with ER-positive and HER2-negative tumors.     

Relationship between estrogen receptor,progesterone receptor,HER-2 and Ki67 expression and efficacy of aromatase inhibitors in advanced breast cancer

BackgroundSurprisingly few data are published on the relevance of even commonly used biomarkers of response to aromatase inhibitors (AIs) in advanced breast cancer. Here, we aim to determine the effectiveness of AIs in that setting according to quantitative levels of estrogen receptor (ER), progesterone receptor (PgR) and Ki67 or human epithelial growth factor receptor-2 (HER-2) status.Patients and methodsER, PgR, HER-2 and Ki67 protein expressions were centrally assessed in 177 archival formalin-fixed paraffin-embedded primary or locally recurrent breast tumours from women who subsequently received AI treatment of advanced disease.ResultsAmong ER-positive patients (n = 146), higher PgR, but not ER, levels were associated with increased time to AI treatment failure (TTF). Higher Ki67 staining was associated with decreased TTF. ER-positive/HER-2-positive patients showed a non-significant trend for decreased TTF compared with ER-positive/HER-2-negative patients. PgR level, but not Ki67, remained a significant predictor of TTF in multivariate analysis of ER-positive patients.ConclusionsHigher PgR and Ki67 levels are significantly associated with increased and decreased TTF, respectively, in ER-positive patients receiving AI treatment of advanced disease. The higher proliferation seen in PgR-negative tumours does not explain the poorer clinical responsiveness of this subgroup.     

Long-term follow-up of HER2-overexpressing stage II or III breast cancer treated by anthracycline-free neoadjuvant chemotherapy

BackgroundVery effective trastuzumab-based primary systemic therapy (PST) can be proposed for conservative surgery purpose to human epidermal growth factor receptor 2 (HER2)-positive breast cancer (HER2+BC). Long-term follow-up (LTFU) warrants further data.Patients and methodsLTFU of patients, with stage II/III HER2+BC, treated by trastuzumab associated with docetaxel (Taxotere®) and/or carboplatin used as anthracycline-free PST was studied.ResultsAmong 135 patients, with a median follow-up of 48.3 months [95% confidence interval (CI) 45.3–52.4 months], the relapse-free survival (RFS) rate was 73.2% (95% CI 63.76% to 80.55%) while the overall survival (OS) rate was 91.87% (95% CI 84.23% to 95.90%). Adjuvant trastuzumab favorably influenced RFS in univariate analysis while the pathological nodal invasion unfavorably influenced RFS [Cox multivariate analysis (hazard ratio = 2.80, 95% CI 1.36–5.76, P = 0.0052)] and OS. Cardiac toxicity was minor (2.2% transient, reversible asymptomatic decrease in left ventricular ejection fraction).ConclusionThis is the first report of LTFU showing that anthracycline-free trastuzumab-based PST combined either with docetaxel and/or carboplatin can achieve, without cardiac toxicity, very competitive results in terms of pathological complete response, RFS and OS, in HER2+BC. The choice of this schedule could be proposed to patients with vascular contraindication for anthracyclines or because patient's or physician's preference for a taxane-only schedule.     

Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials

Five years of adjuvant hormonal therapy is the standard of care in early breast cancer (BC) expressing oestrogen receptors (ER+). Prolonged duration of adjuvant endocrine therapy is implemented to prevent recurrence and death; in particular, its carryover effect may prevent very late events. This meta-analysis compares the efficacy of 5 years of hormonal therapy alone with that of additional years of hormonal therapy, in patients with early BC. Randomised trials comparing 5 years versus more than 5 years of hormonal therapy in BC were identified by electronic searches of PubMed, EMBASE, ISI Web of Science and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using the fixed- or random-effects models. The primary endpoints were overall survival (OS), BC-specific survival (BCSS) and relapse-free survival (RFS) reported as odds ratios (ORs) and 95 % confidence interval (CI). Eight trials, including 29,138 patients, were identified. Overall, in ER+ BCs, extended endocrine therapy beyond 5 years of tamoxifen significantly improved OS (OR, 0.89; 95 % CI 0.80–0.99; P = 0.03), BCSS (OR, 0.78; 95 % CI 0.69–0.9; P = 0.0003) and RFS (OR 0.72; 95 % CI 0.56–0.92; P = 0.01) compared with 5 years of hormonal therapy alone. Loco-regional and distant relapses were reduced by 36 and 13 %, respectively. Compared with 5 years of tamoxifen, additional adjuvant endocrine therapy reduced risk of death and relapse of ER+ BC by ~10 and 30 %, respectively. This strategy should be considered in patients free of disease after 5 years of hormonal therapy.     

Survival outcome of weak estrogen/progesterone receptor expression in HER2 negative breast cancer is similar to triple negative breast cancer

Background

Recent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with “weak” estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%–20%, and ER or PR >20% by hormone therapy.

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may helpto identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determinedby Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: Weobtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes weredefined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive,HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent ofHG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14%separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations betweenKi67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patientswere treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information tobe included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). Weperformed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before andafter chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), bothcategorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patientshad pathologic complete response (cPR). Conclusions: In our experience we did not find associations betweenKi67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.     

Novel implications of combined arterial resection for locally advanced pancreatic cancer in the era of newer chemo-regimens

IntroductionIn this study, we assessed the prognostic efficacy and feasibility of combined arterial resection (AR) for locally advanced pancreatic cancer (LAPC), and aimed to identify significant prognostic factors for patients who underwent combined AR.MethodsBetween 1981 and 2018, 733 consecutive patients who underwent pancreatic surgery for PC were identified. The 730 cases with detailed information were enrolled in the analysis.ResultsAmong 730 resected PC patients, 44 (6%) underwent AR including 21 hepatic (48%), 12 celiac (27%), five splenic (12%), four superior mesenteric (9%), and two other arteries (4%). The combined AR surgery showed significantly longer operative time (median, 608 vs 451 min, P < 0.0001), and the incidence of intraoperative blood transfusion was significantly higher in AR than surgery without AR (P = 0.0002), whereas there was no significant difference in the intraoperative blood loss (970 vs 1200 mL, P = 0.2) and occurrence of major complications (P = 0.5). In prognostic analysis of AR cases, multivariate Cox proportional hazard models revealed preoperative and postoperative therapy were the independent factors for both recurrence-free survival (RFS) and overall survival (OS) (preoperative therapy: RFS, HR = 0.21, P = 0.007; OS, HR = 0.18, P = 0.01; postoperative therapy: RFS, HR = 0.31, P = 0.003; OS, HR = 0.19, P = 0.002).ConclusionThis study showed the feasibility of combined AR for LAPC and robust association of pre- and postoperative therapy and survival after AR surgery. Preoperative therapy following combined AR surgery is potentially powerful strategy for LAPC.     

A biomarker study in Peruvian males with breast cancer

BACKGROUNDBreast cancer (BC) frequency in males is extremely low and tumor features vary from its female counterpart. Breast cancer clinical and pathological features differ by race in women. Tumor infiltrating lymphocyte (TIL) levels, mismatch repair (MMR) protein loss, androgen receptor (AR) expression, and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC. There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC. AIMTo investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population. METHODSThis study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018. Standard pathological features, TIL levels, MMR proteins, AR immunohistochemistry staining, and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material. Percentage of AR and estrogen receptor (ER) positive cells was additionally calculated by software after slide scanning. Statistical analyses included association tests, intraclass correlation test and Kaplan Meier overall survival curves.RESULTSThe median age was 63 years and most cases were ER-positive (85.7%), HER2 negative (87.2%), Luminal-A phenotype (60%) and clinical stage II (41.5%) among our male breast tumors. Median TIL was 10% and higher levels tended to be associated with Luminal-B phenotype and higher grade. AR-positive was found in 85.3% and was correlated with ER (intraclass index of 0.835, P < 0.001). Loss of MMR proteins was found in 15.4% and PIK3CA mutation (H1047R) in 14.3% (belonged to the Luminal-A phenotype). Loss of MMR proteins was associated with AR-negative (P = 0.018) but not with ER (P = 0.43) or TIL (P = 0.84). Early stages (P < 0.001) and lower grade (P = 0.006) were associated with longer overall survival. ER status, phenotype, AR status, TIL level, MMR protein loss nor PIK3CA mutation was not associated with survival (P > 0.05).CONCLUSIONMale BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.