Marked lymphovascular invasion,progesterone receptor negativity,and high Ki67 labeling index predict poor outcome in breast cancer patients treated with endocrine therapy alone

Purpose

Whether postoperative chemotherapy should be added to endocrine therapy or not is an important issue in patients with hormone receptor-positive and human epidermal growth factor receptor (HER)2-negative breast cancer. To identify patients who should be treated with additional chemotherapy, prognostic factors were investigated in breast cancer patients postoperatively treated with endocrine therapy alone.

Patients and methods

Tumor samples and clinicopathological data were collected from patients who underwent curative surgery and were postoperatively treated with endocrine therapy alone between 1999 and 2003 in three different institutes. Expression levels of estrogen receptor (ER), progesterone receptor (PgR), and HER2 in primary tumors were centrally retested. Patients with ER-negative and/or HER2-positive tumors and/or with unknown nodal status were excluded from the study subjects. Immunohistochemical analysis of Ki67, HER1, insulin-like growth factor-1 receptor, and aldehyde dehydrogenase-1 was also performed. Prognostic factors were investigated by univariate and multivariate analyses.

Results

A total of 261 patients were the subjects of this study. The median age was 59 years old, the mean tumor size was 1.9 cm, the node-positive rate was 20 %, and 65 % received tamoxifen alone. Distant metastases were observed in 11 patients at a median follow-up of 98 months, and four patients had died of breast cancer at a median follow-up of 99 months. Univariate analysis showed that marked lymphovascular invasion (LVI), PgR negativity, high Ki67 labeling index (LI), and high nuclear grade were significantly worse prognostic factors for distant metastasis. Multivariate analysis revealed that marked LVI [hazard ratio (HR) 21.8] and PgR negativity (HR 10.3) were independently worse prognostic factors for distant metastasis, respectively. Multivariate analysis also revealed that marked LVI (HR 287.3), PgR negativity (HR 25.1), and high Ki67 LI (HR 19.6) were independently worse prognostic factors for breast cancer-specific death, respectively.

Conclusions

The results of this multi-institute cohort study indicated that endocrine therapy alone could not prevent distant metastasis in breast cancer patients with PgR-negative tumors and/or with tumors showing marked LVI or high cell proliferation. These patients may need postoperative adjuvant chemotherapy in addition to endocrine therapy.     

Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer

Purpose

Recently, Ki67 index (cell proliferation marker) has been attracting a considerable attention as a prognostic factor in breast cancer but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has rarely been examined.

Experimental design

Primary breast cancer patients (n = 102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited in the study. Ki67, estrogen receptor (ER) and progesterone receptor (PR) and breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry and HER2 was determined by FISH in tumor tissues obtained before and after NAC, and their association with patient prognosis (relapse-free survival) was examined.

Results

Of the 102 patients, pCR was achieved in 30 (29.4%). In the 72 non-pCR patients, Ki67 index significantly (P < 0.001) decreased after NAC. Ki67 index after NAC, but not Ki67 index before NAC, was significantly associated with a patient prognosis (P = 0.022). Multivariate analysis has shown that Ki67 index after NAC is a marginally significant (P = 0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein before and after NAC are not significant.

Conclusions

Ki67 after NAC, but not before NAC, is prognostic in breast cancer patients, and might be clinically useful in the prognosis prediction of patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein before and after NAC are unlikely to be useful as prognostic factors in these patients.     

Biological characteristics of luminal subtypes in pre- and postmenopausal estrogen receptor-positive and HER2-negative breast cancers

Background

Estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negetive breast cancers can be divided into luminal A and luminal B subtypes based on Ki67 expression levels. However, the biological differences in ER and progesterone receptor (PR) expression levels between these luminal subtypes are not clear.

Methods

We examined immunohistochemical expression levels of ER, PR, and Ki67 in 180 ER-positive/HER2-negative breast cancers while taking menopausal status into account. Breast cancers were divided according to ER and PR levels (H: >50%, L: ≤50%), and luminal A and B were classified by the Ki67 labeling index (A: Ki67 <14%, B: Ki67 ≥14%).

Results

When breast cancers were classified based on ER and PR levels, the distribution of pre- and postmenopausals was significantly different for luminal A (P < 0.0001), but not for luminal B cancers. As for luminal A, ER-H/PR-L cancers were rare among premenopausals (8%), but frequent among postmenopausals (54%). Correlation between ER and PR levels among luminal A cancers was strong in premenopausals but weak in postmenopausals. Since crosstalk with growth factor signaling is unlikely in luminal A, we speculate that intratumoral estrogen insufficiency contributed to the characteristics of postmenopausal ER-H/PR-L cancers.

Conclusion

We speculate that the biological characteristics of luminal A cancers are influenced by the estrogen environment, but its influence on luminal B cancers may be limited. We believe these considerations constitute useful information for a better understanding of the biology of ER-positive-HER2-negetive breast cancers.     

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

Introduction  

Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases.     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

Influence of body mass index on clinicopathological factors including estrogen receptor,progesterone receptor,and Ki67 expression levels in breast cancers

Background

High body mass index (BMI) is associated not only with a higher incidence of breast cancers but also with poorer prognosis. It is speculated that both enhanced production of estrogens and other factors associated with obesity are involved in these associations, but the biological characteristics associated with high BMI have yet to be thoroughly identified.

Methods

We studied 525 breast cancers, focusing on biological differences between tumors associated with high and low BMI and by immunohistochemically defined intrinsic subtype. Ki67 expression levels were used to differentiate luminal A from luminal B estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)-breast cancers.

Results

Premenopausal patients with high BMI showed a significantly higher frequency of lymph node metastasis (46.4 % vs. 22.9 %, P = 0.005) and tended to have a larger tumor size (P = 0.05) and higher nuclear grade (P = 0.07) than those with low BMI. These differences were not observed among postmenopausal patients. BMI was not associated with distribution of breast cancer subtypes, and ER, progesterone receptor (PR), and Ki67 expression levels of each subtype showed no differences between high and low BMI among premenopausal patients.

Conclusion

Higher BMI might influence aggressive tumor characteristics among premenopausal patients, but its influence on ER, PR, and Ki67 expression levels seems to be limited.     

Ki-67 is a prognostic marker for hormone receptor positive tumors

Purpose

To evaluate the utility of Ki67 as a prognostic marker in Luminal B node-negative breast cancer patients.

Methods

We identified 888 patients with invasive breast carcinomas who underwent surgery between 1997 and 2004. Several classical factors were collected: age, tumor size, node involvement, tumor grade, estrogen and progesterone receptors, HER2 and Ki-67 expression. We analyzed if these parameters could be considered as a prognostic factor. In early Luminal B group, we investigated which of the following biological features provide information about bad prognosis: lack of progesterone receptor expression, HER2 overexpression/amplification or high Ki-67 value.

Results

The majority of patients were alive and without relapse of tumor at the moment of the analysis (70 %). The prognostic factors founded in multivariate analysis were: tumor size, node involvement, grade 3 and Ki-67 expression. When we stratified the sample by immunohistochemistry (IHC) in tumor subtypes, we assessed 680 patients and we observed 191 Luminal B tumors. The biological parameter related to the worst survival in absence of nodal involvement was Ki-67 value.

Conclusions

Ki-67 represents an additional predictor of survival in Luminal B node negative breast cancer. Conversely, neither Progesterone-receptor nor HER2 status proved prognostic significance in this group in our study.

     

The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer

Background  

Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer.     

Expression of Immunohistochemical Markers before and after Neoadjuvant Chemotherapy in Breast Carcinoma,and Their Use as Predictors of Response

Purpose

For patients with breast carcinoma, immunohistochemical markers are important factors in determining the breast cancer subtype and for establishing a therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However, it is not clear whether the expression of certain markers changes after NACT.

Methods

We assessed estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in specimens from 345 breast cancer cases before and after NACT. We analyzed the association between response to NACT and the expression of the markers in pre-NACT specimens. We also compared the expression between pre- and post-NACT specimens.

Results

ER and PR expression was negatively associated with pathological complete response (pCR). HER2 was associated with pCR in all cases, but the association was lost when the cases were subdivided according to hormone receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller than that of cases with residual disease. HER2-enriched and triple-negative breast cancers were more likely to achieve pCR than luminal A type cancers. PR expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67 index was also demonstrated in hormone receptor positive and HER2-enriched subtypes, but no similar tendency was observed in the triple-negative subtype.

Conclusion

A patient with breast cancer scheduled for NACT should be assessed for the breast cancer subtype, as this will influence the treatment plans for the patient. The expression of PR and Ki-67 after NACT should be interpreted carefully because NACT tends to reduce the expression of these molecules.     

Prognostic value of estrogen receptor α and progesterone receptor conversion in distant breast cancer metastases

BACKGROUND:

Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor α (ERα) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ERα and PR on survival in a large group of distant non‐bone breast cancer metastases.

METHODS:

Receptor conversion was studied by immunohistochemistry in a group of 233 metastatic breast cancer patients. Kaplan‐Meier overall survival curves were plotted, and differences between the curves were analyzed by log‐rank analysis. The additional prognostic value of conversion to established prognosticators was studied by Cox regression.

RESULTS:

Overall survival of patients showing conversion from positive to negative ERα or PR, or from negative to positive ERα or PR, or remaining receptor negative was comparable, and significantly worse than patients remaining receptor positive. ERα or PR receptor conversion from positive in the primary breast tumor to negative in distant metastases has independent negative prognostic value.

CONCLUSIONS:

ERα or PR receptor conversion from positive in the primary breast cancer to negative in distant metastases has negative prognostic value. Cancer 2012. © 2012 American Cancer Society.     

ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67

Introduction  

Accurate assessment of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 is essential in the histopathologic diagnostics of breast cancer. Commercially available image analysis systems are usually bundled with dedicated analysis hardware and, to our knowledge, no easily installable, free software for immunostained slide scoring has been described. In this study, we describe a free, Internet-based web application for quantitative image analysis of ER, PR, and Ki-67 immunohistochemistry in breast cancer tissue sections.     

乳腺癌组织FAP表达病理生物学意义的研究

目的:探讨乳腺癌成纤维细胞活化蛋白(FAP)的表达与乳腺癌临床病理因素和生物学预后因子(ER、PR、p53、c-erbB-2、Ki-67)的相关性,评价FAP在乳腺癌的表达意义。方法:选取经病理确诊的乳腺癌患者82例,免疫组织化学法检测乳腺癌组织FAP的表达。收集乳腺癌患者的临床病理信息,分析FAP与乳腺癌临床病理因素和生物学预后因子的表达水平的关系。结果:FAP表达与患者年龄、肿瘤部位、肿瘤大小与FAP的表达无相关性(P>0.05),临床分期与FAP表达呈正相关(r=0.922,P=0.000),病理分级与FAP表达呈弱正相关,r=0.360,P=0.001。FAP表达在有无淋巴结转移组间差异统计学意义,t=11.003,P=0.00。FAP表达与p53(r=0.498,P=0.000)、c-erbB-2(r=0.326,P=0.004)、Ki-67(r=0.449,P=0.000)的表达呈正相关,FAP表达与ER、PR的表达无相关性,P>0.05。结论:FAP在女性乳腺癌发生、发展、侵袭转移方面起到了重要的作用。FAP可作为预测乳腺癌预后的重要因子。     

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction

Background

A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features.

Methods

We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied.

Results

Median follow up time was 74 months (range 3–165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR.

Conclusion

Luminal B/HER2 positive, triple negative subtypes and BMI ≥25 are independent prognostic factors for risk of LRR after IBR.     

Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma

Background:

Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.

Methods:

Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.

Results:

No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.

Conclusions:

Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.     

Overexpression of the p16 cell cycle inhibitor in breast cancer is associated with a more malignant phenotype

In order to study the role of the p16^INK4A(MTS1/CDKN2a) tumor suppressor in breast cancer, we analyzed p16 protein expression in 60 breast cancer samples which were also analyzed for expression of Rb, Ki67, HER2/neu, and estrogen and progesterone receptors (ER, PR). P16 expression was investigated by two methods: western blotting (WB) followed by densitometry, and immunohistochemistry (IHC). The Rb status was studied by western blotting, and expression of Ki67, HER2/neu, ER, and PR was analyzed immunohistochemically. P16-negative results were found in 18% of the carcinomas by WB, but in only one case by IHC and were not associated with established prognostic parameters. In contrast, p16 overexpression which was detected by WB and IHC in 15% and 25% of the tumors, respectively, was significantly associated with unfavorable prognostic indicators. High p16 expression as detected by both methods correlated significantly with high grading and a negative estrogen receptor status. In addition, a significant association of p16 staining with inverse progesterone receptor status and high Ki67 expression was found with IHC. No correlation of p16 expression with clinical stage, HER2/neu immunostaining, Rb expression or Rb phosphorylation was found. Comparison of western blot results and immunohistochemistry suggests that both nuclear and cytoplasmic immunoreactivity in tumor cells is specific and due to p16 expression. We conclude that high p16 reactivity (both nuclear and cytoplasmic) is indicative of a more undifferentiated, malignant phenotype in mammary carcinomas.     

Analysis of Ki‐67 expression with neoadjuvant anastrozole or tamoxifen in patients receiving goserelin for premenopausal breast cancer

BACKGROUND:

The increasing costs associated with large‐scale adjuvant trials mean that the prognostic value of biologic markers is increasingly important. The expression of nuclear antigen Ki‐67, a marker of cell proliferation, has been correlated with treatment efficacy and is being investigated for its value as a predictive marker of therapeutic response. In the current study, the authors explored correlations between Ki‐67 expression and tumor response, estrogen receptor (ER) status, progesterone receptor (PgR) status, and histopathologic response from the STAGE study (S_ tudy of T_ amoxifen or A_ rimidex, combined with G_ oserelin acetate to compare E_ fficacy and safety).

METHODS:

In a phase 3, double‐blind, randomized trial (National Clinical Trials identifier NCT00605267), premenopausal women with ER‐positive, early stage breast cancer received either anastrozole plus goserelin or tamoxifen plus goserelin for 24 weeks before surgery. The Ki‐67 index, hormone receptor (ER and PgR) status, and histopathologic responses were determined from histopathologic samples that were obtained from core‐needle biopsies at baseline and at surgery. Tumor response was determined by using magnetic resonance imaging or computed tomography.

RESULTS:

In total, 197 patients were randomized to receive either anastrozole plus goserelin (n = 98) or tamoxifen plus goserelin (n = 99). The best overall tumor response was better for the anastrozole group compared with the tamoxifen group both among patients who had a baseline Ki‐67 index ≥20% and among those who had a baseline Ki‐67 index <20%. There was no apparent correlation between baseline ER status and the Ki‐67 index in either group. Positive PgR status was reduced from baseline to week 24 in the anastrozole group.

CONCLUSIONS:

In premenopausal women with ER‐positive breast cancer, anastrozole produced a greater best overall tumor response compared with tamoxifen regardless of the baseline Ki‐67 index. Cancer 2013. © 2012 American Cancer Society.     

Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers

Background

Indication for chemotherapy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers is determined on the basis of Ki67 expression level. However, since Ki67-high cancers are not necessarily sensitive to chemotherapy, identification of such patients who do not need chemotherapy is an important issue.

Patients and methods

We used immunohistochemical staining to examine the expression levels of ER, progesterone receptor (PgR), Ki67, and geminin, a marker of S to G2/M phases, in 80 ER-positive/HER2-negative breast cancers. The labeling indices of Ki67 and geminin were determined and cutoff values were set at 15 and 6 %, respectively.

Results

Ki67 and geminin expression levels were significantly associated with nuclear grade. In the Ki67-low subset, 26 out of 28 (92.9 %) cancers were geminin low and in the Ki67-high subset, 31 out of 52 (59.6 %) were geminin high. Distant disease-free survival (DDFS) of the geminin-high subset was significantly poorer than that of the geminin-low subset (P = 0.009). In the Ki67-low subset, only one patient showed recurrence. Metastasis was detected in eight out of 31 (25.8 %) patients in the geminin-high group of the Ki67-high subset, but no recurrence was observed in the geminin-low group of the Ki67-high subset.

Conclusion

Geminin-high breast cancers are significantly associated with worse prognosis. Since poorer prognosis was recognized only in the geminin-high group in Ki67-high cancers, we speculate that geminin may be useful for identifying patients in the Ki67-high subset who can avoid unnecessary chemotherapy.

     

Differences in subtype distribution between screen-detected and symptomatic invasive breast cancer and their impact on survival

Purpose

Stage shift is considered a major reason for more favorable outcomes in patients with screen-detected breast cancer. However, even after adjusting for clinical stage, unresolved issues concerning the reasons for a survival benefit associated with screening programs remain. This study aims to evaluate differences in subtype distribution and outcomes among patients with screen-detected and symptomatic invasive breast cancer and assess whether variations in subtype distribution could explain differences in prognosis.

Methods

Survival analysis was performed to estimate the likelihood of distant recurrence and death in 1132 patients. Subtypes were defined as luminal A [estrogen receptor (ER)+ and/or progesterone receptor (PR)+, human epidermal growth factor receptor 2 (HER2)?, and Ki67 low], luminal B (HER2?) (ER+ and/or PR+, HER2?, and Ki67 high), luminal B (HER2+) (ER+ and/or PR+ and HER2+), HER2 overexpressing (ER?, PR?, and HER2+), and triple negative (ER?, PR?, and HER2?).

Results

Screen-detected cancers had favorable clinicopathological characteristics, such as smaller tumor size and a lower frequency of lymph node involvement. Women with screen-detected cancers had a survival advantage. Subtype distribution differed significantly among women with screen-detected and symptomatic cancer. Screen-detected cancers were more likely to be luminal A and less likely to be HER2 overexpressing or triple negative cancer compared with symptomatic cancers (luminal A 61.3 vs. 44.2%, HER2 overexpressing 4.0 vs. 8.0%, triple negative 8.0 vs. 15.9%). Node status, mode of detection, and subtype were independent prognostic factors in the multivariate analysis.

Conclusions

Differences in subtype distribution between screen-detected and symptomatic cancer could partially explain differences in outcomes.

     

Prognostic Impact and Clinicopathological Correlation of CD133 and ALDH1 Expression in Invasive Breast Cancer

Purpose

CD133 and aldehyde dehydrogenase 1 (ALDH1) expression are reliable poor-prognosis markers associated with the presence of adverse biomarkers and subtypes of breast cancer. The aim of our study was to investigate and compare the clinical impact of CD133 and ALDH1 expression in invasive breast cancer.

Methods

A total of 291 consecutive patients with invasive breast cancer who underwent breast cancer operations from 2005 to 2010 at a single institution were included in this retrospective review. CD133 and ALDH1 expression were determined by immunohistochemistry.

Results

CD133 and ALDH1 expression were positive in 24.7% and 22.0% of the patients, respectively, and were associated with tumor size, cancer stage, estrogen receptor negativity, nonluminal subtype, triple-negative breast cancer, and recurrence. CD133 expression was significantly associated with lymph node metastasis, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, chemotherapy, and poor disease-free (p=0.002) and overall survival (p=0.014), but ALDH1 expression was not. Cancer stage (p<0.001) was an independent prognostic factor for disease-free survival in multivariate analysis. Cancer stage (p<0.001) and receipt of radiotherapy (p=0.045) were independent prognostic factors for overall survival in multivariate analysis.

Conclusion

CD133 or the combination of CD133 and ALDH1 expression were more widely associated with the presence of adverse biomarkers and subtypes of breast cancer, compared to ALDH1 expression alone, and these markers may have a potential predictive role and be a helpful tool in the management for patients with invasive breast cancer.     

Higher rate of progesterone receptor positivity in skeletal metastases of breast cancer with a pathological fracture vs those without fracture

Identifying risk factors for fracture occurrence in breast cancer (BC) skeletal metastases (SM) may guide the management of such bone deposits. There is sparse evidence regarding receptor status in SM and their relationship to fracture occurrence. Our study aimed to determine the relationship between estrogen (ER), progesterone (PR) and HER2 receptor status and Ki-67 index and fracture occurrence in SM of BC. Exactly 152 samples of SM of BC obtained from individual patients were evaluated. The status of the aforementioned receptors and Ki67 index were determined in SMs samples. Their expression was compared between SM that did and did not develop a fracture. Ninety-one cases sustained a pathological fracture at the SM site, and 61 did not. Patients who sustained a pathological fracture had a higher rate of PR positivity at their SMs as compared to those with no fracture. There was no significant difference between the two groups concerning ER, HER2+ or Ki67 status. SMs secondary to BC with a fracture are more likely to be PR positive than those with no fracture. Determining the receptor status in SMs may identify high-risk groups for fracture occurrence, and determining the PR status may also guide surgical and hormonal therapy.