Expression and clinicopathological significance of FSIP1 in breast cancer

Aim

To investigate the clinicopathological significance of the expression of fibrous sheath interacting protein 1 (FSIP1) in breast cancer, serum samples, and wound fluid from patients with breast cancer.

Methods

Wound fluid and serum samples from female patients with primary breast cancer, recurrent and metastatic breast cancer, and benign tumors were analyzed for FSIP1 expression using ELISA. 286 paraffin-embedded surgical specimens from breast cancer patients with at least 5 years of follow-up were included for FSIP1 expression assay using immunohistochemistry.

Results

Expression of FSIP1 protein was significantly higher in breast cancer tissues compared to tumor-adjacent tissues (p = 0.001). Strong correlation was observed between FSIP1 expression and human epidermal growth factor receptor 2 (Her-2) or Ki67 expression in breast cancer (p = 0.027 and 0.002, respectively). Similarly, serum level of FSIP1 was higher in patients with recurrent and metastatic breast cancer compared to that of primary breast cancer (7, 713 ± 3, 065 vs. 4, 713 ± 3, 065 pg/ml, p = 0.003). Finally, patients with high FSIP1 expression showed a worse post-operative disease-specific survival (p = 0.024).

Conclusion

FSIP1 may play an important role in the tumorigenesis and invasion of breast cancer and is a potential biomarker for breast cancer diagnosis or prognosis.     

Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression

Purpose

Breast cancer displays varying molecular and clinical features. The ability to form breast tumors has been shown by several studies with aldehyde dehydrogenase 1 (ALDH1) positive cells. The aim of this study is to investigate the association between ALDH1 expression and clinicopathologic characteristics of invasive ductal carcinoma.

Methods

We investigated breast cancer tissues for the prevalence of ALDH1⁺ tumor cells and their prognostic value. The present study included paraffin-embedded tissues of 70 patients with or without recurrences. We applied immunohistochemical staining for the detection of ALDH1⁺ cells. Analysis of the association of clinical outcomes and molecular subtype with marker status was conducted.

Results

ALDH1⁺ and ALDH1^- tumors were more frequent in triple-negative breast cancers and in luminal A breast cancers, respectively (p<0.01). ALDH1 expression was found to exert significant impact on disease free survival (DFS) (ALDH1⁺ vs. ALDH1^-, 53.1±6.7 months vs. 79.2±4.7 months; p=0.03) and overall survival (OS) (ALDH1⁺ vs. ALDH1^-, 68.5±4.7 months vs. 95.3±1.1 months; p<0.01). In triple-negative breast cancer (TNBC) patients, DFS and OS showed no statistical differences according to ALDH1 expression (ALDH1⁺ vs. ALDH1^-, 45.3±9.4 months vs. 81.3±7.4 months, p=0.52; 69.0±7.5 months vs. 91.3±6.3 months, p=0.67). However, non-TNBC patients showed significant OS difference between ALDH1⁺ and ALDH1^- tumors (ALDH1⁺ vs. ALDH1^-, 77.6±3.6 months vs. 98.0±1.0 months; p=0.04) with no statistical difference of DFS (ALDH1⁺ vs. ALDH1^-, 60.5±8.0 months vs. 81.8±4.6 months; p=0.27).

Conclusion

Our findings suggest that the expression of ALDH1 in breast cancer may be associated with TNBC and poor clinical outcomes. On the basis of our findings, we propose that ALDH1 expression in breast cancer could be correlated with poor prognosis, and may contribute to a more aggressive cancer phenotype.     

Antiproliferatory Effects of Crab Shell Extract on Breast Cancer Cell Line (MCF7)

Purpose

Breast cancer is the most common type of cancer in women. Despite various pharmacological developments, the identification of new therapies is still required for treating breast cancer. Crab is often recommended as a traditional medicine for cancer. This study aimed to determine the in vitro effect of a hydroalcoholic crab shell extract on a breast cancer cell line.

Methods

In this experimental study, MCF7 breast cancer cell line was used. Crab shell was powdered and a hydroalcoholic (70° ethanol) extract was prepared. Five concentrations (100, 200, 400, 800, and 1,000 µg/mL) were added to the cells for three periods, 24, 48, and 72 hours. The viability of the cells were evaluated using trypan blue and 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Cell apoptosis was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. Nitric oxide (NO) level was assessed using the Griess method. Data were analyzed using analysis of variance, and p<0.05 was considered significant.

Results

Cell viability decreased depending on dose and time, and was significantly different in the groups that were treated with 400, 800, and 1,000 µg/mL doses compared to that in the control group (p<0.001). Increasing the dose significantly increased apoptosis (p<0.001). NO secretion from MCF7 cells significantly decreased in response to different concentrations of the extract in a dose- and time-dependent manner (p<0.050).

Conclusion

The crab shell extract inhibited the proliferation of MCF7 cells by increasing apoptosis and decreasing NO production.     

A Dosimetric Comparative Analysis of TomoDirect and Three-Dimensional Conformal Radiotherapy in Early Breast Cancer

Purpose

The purpose of this study is to compare dosimetric parameters of intensity-modulated mode of TomoDirect and three-dimensional conformal radiotherapy (3D-CRT) in patients with early breast cancer.

Methods

TomoDirect and 3D-CRT planning were carried out for 26 patients with early breast cancer who had received breast-conserving surgery. A total of 50.4 Gy in 28 fractions were prescribed to the planning target volume. The organs at risk (OAR) such as lung and heart were contoured. Planning target volume (PTV) dose coverage, radiation conformity index (RCI), radical dose homogeneity index (rDHI), and irradiation dose of organs at risk were compared between TomoDirect and 3D-CRT planning.

Results

The mean PTV dose (51.65±0.37 Gy) and V_47.8 (100%) in TomoDirect were significantly higher than the mean PTV dose (50.88±0.65 Gy) and V_47.8 (89.23%±0.06%) in 3D-CRT (all, p<0.001). The RCI value in TomoDirect was significantly better than that in 3D-CRT (1.00 vs. 1.13, p<0.001). However, the rDHI value in TomoDirect was not significantly better than that in 3D-CRT (0.72 vs. 0.67, p=0.056). The mean lung dose and V₁₀, V₂₀, V₃₀, and V₄₀ values of ipsilateral lung in TomoDirect were significantly lower than those in 3D-CRT (all, p<0.05). There is no significant difference in the V₁₀, V₂₀, V₃₀, and V₄₀ values of heart between TomoDirect and 3D-CRT. And the mean dose for heart in TomoDirect was marginally lower than that in 3D-CRT (1.05 Gy vs. 1.62 Gy, p=0.085). The mean dose for left anterior descending coronary artery in left breast cancer was significantly lower in TomoDirect than in 3D-CRT (7.2 Gy vs. 12.1 Gy, p<0.001).

Conclusion

Compared to 3D-CRT, TomoDirect could result in favorable target coverage while reducing the irradiation dose of the ipsilateral lung for patients with early breast cancer.     

Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition

Purpose

Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue.

Methods

Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively.

Results

Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 µM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant.

Conclusion

The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition may also, in addition to Δ9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.     

αB-Crystallin is a Novel Oncoprotein Associated with Poor Prognosis in Breast Cancer

Purpose

αB-crystallin, a small heat shock protein, is an anti-apoptotic protein associated with aggressive tumor behavior. A recent study revealed that αB-crystallin is overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The purpose of this study was to investigate whether αB-crystallin is related to other breast tumor markers and can predict a breast cancer prognosis.

Methods

Eighty-two patients who underwent breast cancer surgery at Hallym Sacred Heart Hospital were enrolled. αB-crystallin expression was determined by immunohistochemical staining. Estrogen receptor, progesterone receptor (PR), human epidermal growth factor receptor, lymphovascular invasion, histological grade, other tumor markers and time to recurrence were compared with αB-crystallin expression.

Results

αB-crystallin expression in breast cancer tissues was associated with PR (p=0.030), the number of metastatic lymph nodes (pN) (p=0.020), lymphovascular invasion (p=0.022), histological grade (p=0.004) and triple negative breast cancer (TNBC) (p=0.004). αB-crystallin expression significantly decreased time to recurrence (p=0.039).

Conclusion

The results revealed a strong relationship between αB-crystallin and poor prognostic factors such as the number of metastatic lymph nodes (especially pN2), TNBC, and rapid time to recurrence. We believe that αB-crystallin could be a novel oncoprotein biomarker of a poor prognosis in breast cancer.     

The Metastatic Rate of Internal Mammary Lymph Nodes When Metastasis of Internal Mammary Lymph Node Is Suspected on PET/CT

Purpose

Metastatic status of internal mammary lymph node (IMLN) has a clinical importance in assessing the stage and prognosis of breast cancer. But, when metastasis of IMLN is suspected; the management is controversial. We retrospectively reviewed 36 breast cancer patients who underwent IMLN biopsy, and investigated the pathologic status of IMLN which suspected metastasis with positron emission tomography and computed tomography (PET/CT).

Methods

From January 2007 to December 2012, 36 patients underwent IMLN biopsy for suspected IMLN metastasis on PET/CT, when diagnosed with primary or recurrent breast cancer. Clinicopathologic features of these patients and metastatic status of IMLNs were investigated.

Results

A total of 36 patients were included in this study. Twenty-four patients diagnosed with primary breast cancer and 12 patients diagnosed with recurrent breast cancer underwent IMLN biopsy. The mean number of IMLNs was 2.72±2.05, and the total metastatic rate of IMLNs was 72.2% (26 out of 36). IMLN metastasis was confirmed on pathologic examination in 19 patients (79.2%, 19 out of 24) with primary breast cancer and in 7 patients (58.3%, 7 out of 12) with recurrent breast cancer. The mean standardized uptake values of metastatic and nonmetastatic IMLNs in primary breast cancer were 3.50±2.51 and 3.72±3.55, respectively and those of metastatic and nonmetastatic IMLN in recurrent breast cancer were 3.92±2.67 and 4.12±3.57, respectively. In both groups, there was no statistically significant difference between the SUVs of metastatic and nonmetastatic IMLNs (p=0.291 and p=0.951, respectively).

Conclusion

Due to the recent advances in diagnostic and surgical skills, IMLN biopsy can be performed safely without any complications without performing radical mastectomy. If IMLN metastasis is suspected on PET/CT, IMLN biopsy is useful to assess the exact stage and to determine the treatment for breast cancer. Further follow-up studies are needed to assess the locoregional recurrence and to compare the improvement in overall survival and disease-free survival.     

Diagnostic Value of Contrast-Enhanced Ultrasound Parametric Imaging in Breast Tumors

Purpose

This study aimed to evaluate the diagnostic value of SonoLiver software for parametric imaging in breast tumors.

Methods

Contrast-enhanced ultrasound (CEUS) was performed in 216 breast lesions (113 malignant, 103 benign). The CEUS parameters were compared between benign and malignant lesions. The rise time, the time to peak, the mean transit time and dynamic vessel pattern (DVP) were analyzed using SonoLiver software.

Results

Quantitative analysis showed that the rise time was 16.52±4.15 seconds in the benign group vs. 13.86±3.36 seconds in the malignant group (p=0.007), and the time to peak was 19.86±4.87 seconds in the benign group vs. 16.52±4.85 seconds in the malignant group (p=0.009). The mean transit time was 80.55±18.65 seconds in the benign group vs. 65.16±20.28 seconds in the malignant group (p=0.006). The difference between the distribution of DVP in benign and malignant tumors was statistically significant. One hundred one malignant tumors (89.4%) performed an irregular red/yellow fill in the region of interest (ROI) and 85 benign tumors (82.5%) performed a single blue/green fill in the ROI. The sensitivity, specificity, and accuracy of parametric imaging in breast tumors were 84.1%, 85.4%, 84.7%, respectively.

Conclusion

The CEUS parametric imaging can distinguish differences between malignant and benign breast tumors as well as provide diagnostic information on breast lesions.     

Survival Outcomes of Different Treatment Methods for the Ipsilateral Breast of Occult Breast Cancer Patients with Axillary Lymph Node Metastasis: A Single Center Experience

Purpose

This study compared the survival outcomes of different treatment methods for the ipsilateral breast of occult breast cancer (OBC) patients with axillary lymph node metastasis.

Methods

A retrospective study was conducted in which forty OBC patients with axillary lymph node metastasis were identified out of 15,029 patients who had been diagnosed with a primary breast cancer at between 1992 and 2010. The patients were categorized into three treatment groups based on ipsilateral breast management: breast-conserving surgery (BCS) (n=17), mastectomy (n=12), and nonsurgical intervention with or without radiation therapy (No surgery with or without radiation therapy [No Op±RT]) (n=11). All patients underwent axillary lymph node dissection. Cases were evaluated based on treatment and potential prognostic factors with respect to overall survival (OS) and disease-free survival (DFS).

Results

During the follow-up period (median follow-up of 71.5 months), the overall OS and DFS were 76.9% and 74.9%, respectively. The 5-year treatment-specific OS was 72.0% for the BCS group, 74.0% for the mastectomy group, and 87.5% for the No Op±RT group (log-rank p=0.49). The 5-year DFS was 70.6% for the BCS group, 66.7% for the mastectomy group, and 90.9% for the No Op±RT group (log-rank p=0.36). Recurrence rates for the BCS and No Op±RT groups were 5.9% and 18.2%, respectively. Histologic grade and lymph node status were inversely correlated with DFS (log-rank p=0.04 and p<0.01, respectively).

Conclusion

There was no difference in survival outcomes between the three treatment methods for the ipsilateral breast (mastectomy, BCS, and No Op±RT) of OBC patients with axillary lymph node metastasis. A large-scale multicenter study is needed to validate the results from this small retrospective study.     

Lecithin: Cholesterol Acyltransferase and Na+-K+-ATPase Activity in Patients with Breast Cancer

Purpose

The aim of this study was to determine whether plasma lecithin:cholesterol acyltransferase (pLCAT) and erythrocyte membrane Na⁺-K⁺-ATPase ase (emNaKATPs) activity have a correlation in breast cancer. This study compared these parameters at time points before and after treatment with radiotherapy.

Methods

The levels of pLCAT and emNaKATPs were assessed in 30 patients with breast carcinoma and 20 control subjects. While emNaKATPs was measured with spectrophotometric method, pLCAT levels was measured using a specific enzyme-linked immunosorbent assay.

Results

pLCAT levels, both before and after radiotherapy, were found to be decreased in breast cancer patients than in the controls groups (p<0.001 and p<0.001, respectively). Also, pLCAT levels after radiotherapy were found to be decreased in breast cancer patients than the pLCAT levels before radiotherapy (p<0.001). The emNaKATPs activity were higher in the control group than in the breast cancer patients before/after radiotherapy (RT) (p<0.001 and p<0.001, respectively). At the same time, emNaKATPs activity before RT was higher in the breast cancer patients than emNaKATPs activity after RT (p<0.001). There was a significant correlation between pLCAT and emNaKATPs activity in breast cancer patients receiving radiotherapy (r=0.63, p<0.001), but no correlation between in breast cancer patients before RT and control group (r=0.023, p>0.05).

Conclusion

The results of the present study demonstrated that decreased pLCAT and emNaKATPs activity levels in breast cancer patients after/before RT than control group. In addition, decreased emNaKATPs activity in breast cancer patients receiving radiotherapy may be due to decreased pLCAT concentrations and RT beam. In our opinion, altered activities of pLCAT and emNaKATPs are linked to the treatment effect of radiotherapy. These data may clarify the development of cell membrane dysfunction and lipid metabolism in breast cancer patients receiving radiotherapy.     

Breast Cancer Risk Factors in a Defined Population: Weighted Logistic Regression Approach for Rare Events

Purpose

This study aimed to determine out risk factors for female breast cancer in a low socioeconomic population in Iran.

Methods

Between 2007 and 2009, a total of 25,592 women who were ensured by the Imam Khomeini Relief Foundation participated in this screening program. The characteristics of patients diagnosed with breast cancer (n=111) were compared with those of control cases (n=25,481). In this study, we used relogit analysis (rare event logistic regression) with a weighting method using program Zelig.

Results

Of 25,592 women, 3.9/1,000 had breast cancer, from which 38 were diagnosed during screening and 73 had already been diagnosed. The mean and standard deviation of age in breast cancer patients and in healthy controls were 49.18±8.86 years and 46.65±9.40 years, respectively. The findings based on the multivariate model revealed that the past history of ovarian cancer, hormone therapy, and first relatives with breast cancer were associated with increased risk for breast cancer. However, the use of oral contraceptive pills was found to be associated with reduced risk for breast cancer.

Conclusion

Due to the rarity of the event in the population, relogit with a weighting method was used to investigate the major risk factors for breast cancer. These factors include oral contraceptive pill use, a history of ovarian cancer of the person under study, first relatives with breast cancer and hormone therapy.     

Arthralgia among women taking aromatase inhibitors: is there a shared inflammatory mechanism with co-morbid fatigue and insomnia?

Introduction

Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs.

Methods

Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations.

Results

Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (β = 93.1; 95 % confidence interval (CI): 25.1–161.1; p = 0.008), eotaxin (β = 79.9; 95 % CI: 32.5–127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (β = 151.2; 95 % CI: 32.7–269.8; p = 0.013), and vitamin D–binding protein (VDBP) (β = 19,422; 95 % CI: 5500.5–33,344; p = 0.006).

Conclusions

Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0599-7) contains supplementary material, which is available to authorized users.     

The usefulness of F-18 FDG PET/CT-mammography for preoperative staging of breast cancer: comparison with conventional PET/CT and MR-mammography

Background

The objective of the study was to compare the diagnostic efficacy of an integrated Fluorine-18 fluorodeoxyglucose (F-18 FDG) PET/CT-mammography (mammo-PET/CT) with conventional torso PET/CT (supine-PET/CT) and MR-mammography for initial assessment of breast cancer patients.

Patients and methods

Forty women (52.0 ± 12.0 years) with breast cancer who underwent supine-PET/CT, mammo-PET/CT, and MR-mammography from April 2009 to August 2009 were enrolled in the study. We compared the size of the tumour, tumour to chest wall distance, tumour to skin distance, volume of axillary fossa, and number of meta-static axillary lymph nodes between supine-PET/CT and mammo-PET/CT. Next, we assessed the difference of focality of primary breast tumour and tumour size in mammo-PET/CT and MR-mammography. Histopathologic findings served as the standard of reference.

Results

In the comparison between supine-PET/CT and mammo-PET/CT, significant differences were found in the tumour size (supine-PET/CT: 1.3 ± 0.6 cm, mammo-PET/CT: 1.5 ± 0.6 cm, p < 0.001), tumour to thoracic wall distance (1.8 ± 0.9 cm, 2.2 ± 2.1 cm, p < 0.001), and tumour to skin distance (1.5 ± 0.8 cm, 2.1 ± 1.4 cm, p < 0.001). The volume of axillary fossa was significantly wider in mammo-PET/CT than supine-PET/CT (21.7 ± 8.7 cm³ vs. 23.4 ± 10.4 cm³, p = 0.03). Mammo-PET/CT provided more correct definition of the T-stage of the primary tumour than did supine-PET/CT (72.5% vs. 67.5%). No significant difference was found in the number of metastatic axillary lymph nodes. Compared with MR-mammography, mammo-PET/CT provided more correct classification of the focality of lesion than did MR-mammography (95% vs. 90%). In the T-stage, 72.5% of cases with mammo-PET/CT and 70% of cases with MR-mammography showed correspondence with pathologic results.

Conclusions

Mammo-PET/CT provided more correct definition of the T-stage and evaluation of axillary fossa may also be delineated more clearly than with supine-PET/CT. The initial assessment of mammo-PET/CT would be more useful than MR-mammography because the mammo-PET/CT indicates similar accuracy with MR-mammography for decision of T-stage of primary breast tumour and more correct than MR-mammography for defining focality of lesion.     

Expression of Leptin,Leptin Receptor,Adiponectin, and Adiponectin Receptor in Ductal Carcinoma In Situ and Invasive Breast Cancer

Purpose

Adipocytokines, such as leptin, resistin, and adiponectin, are associated with obesity and breast cancer. Several studies have indicated that adipocytokines may influence tumor growth or differentiation. The aims of this study were to determine the expression of leptin, leptin receptor (ObR), adiponectin and adiponectin receptor (AdipoR) in human breast cancer, to evaluate their prognostic significance in the breast cancer.

Methods

Specimens from 198 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed using TMA, and the clinicopathologic characteristics were evaluated from the patient''s medical records.

Results

Stage 0 breast cancer accounted for 41 cases, and 157 cases were invasive cancer. Positive rates of leptin and ObR expression in the ductal carcinoma in situ (DCIS) group were significantly higher than those of the invasive cancer group (97.4% vs. 34.0%, p<0.001; 74.4% vs. 29.8%, p<0.001). However, positive rates of adiponectin and AdipoR expression in the invasive cancer group were significantly higher than those in the DCIS group (53.7% vs. 33.3%, p=0.024; 59.9% vs. 26.3%, p<0.001). High leptin expression was significantly associated with high Ki-67 expression (p=0.016). High adiponectin expression was significantly correlated with smaller tumor size (p=0.001).

Conclusion

We suggest that losses of leptin and ObR expression could be associated with invasive cancer, whereas high adiponectin and AdipoR expression may be associated with breast cancer invasiveness.     

Concurrent Gonadotropin-Releasing Hormone Agonist Administration with Chemotherapy Improves Neoadjuvant Chemotherapy Responses in Young Premenopausal Breast Cancer Patients

Purpose

This study aimed to determine the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment concurrent with chemotherapy in a neoadjuvant setting.

Methods

A retrospective analysis was performed on 332 cases of invasive breast cancer in patients who were <40 years old at diagnosis and received GnRH agonists concurrent with neoadjuvant chemotherapy (GnRH agonist group) or neoadjuvant chemotherapy alone (neochemotherapy-alone group) from December 2010 to September 2014. Pathologic complete response rates (pCR) and Ki-67 changes were evaluated between the two groups.

Results

Median age was 32±3.9 and 36±3.0 years in the GnRH agonist group and neochemotherapy-alone group, respectively (p<0.001). After adjustment for tumor size, grade, lymph node metastasis, hormone receptor (HR) status, and chemotherapy regimen, the GnRH agonist group exhibited a higher pCR rate with an odds ratio (OR) of 2.98 (95% confidence interval [CI], 1.37-6.34) and a greater decrease in Ki-67 expression after treatment (p=0.05) than the neochemotherapy-alone group. For HR-negative tumors, the GnRH agonist group showed a higher pCR rate (multivariate OR, 3.50; 95% CI, 1.37-8.95) and a greater decrease in Ki-67 expression (p=0.047). For HR-positive breast cancer, the pCR rate, change in Ki-67 index, and clinical response were higher, and preoperative endocrine prognostic index scores were lower, in the GnRH agonist group, but these did not reach statistical significance.

Conclusion

Concurrent administration of GnRH agonists during neoadjuvant chemotherapy improved pCR rates and suppressed Ki-67 expression, especially in HR-negative tumors.     

The Expression of Aldehyde Dehydrogenase Family in Breast Cancer

Purpose

It is widely accepted that aldehyde dehydrogenase (ALDH) activity is a signature of breast cancer stem cells, and high activity has been reported to be associated with poor clinical outcome. The aim of this study was to assess the expression of members of the ALDH family of isozymes in breast cancer tissues and to evaluate the implications of the results.

Methods

We analyzed paraffin-embedded tumor tissue from 160 patients with breast cancer. Immunohistochemistry (IHC) staining was performed on the slides using antibodies against different ALDH family members. We collated the IHC results with patient clinical characteristics and determined their prognostic value. In addition, we analyzed normal, hyperplastic, and carcinomatous tissues in situ to check their ALDH distributions.

Results

All the tested ALDH members were detected in the various tissue types, but at different levels. Only ALDH 1A3 was found to be significantly associated with distant metastasis (p=0.001), disease-free survival (p<0.001), and overall survival (p<0.001).

Conclusion

The level of ALDH 1A3 in breast cancer tissue is a predictive marker of a poor clinical outcome.     

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.     

Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Purpose:

The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk.

Patients and methods:

Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

Results:

Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8% P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36% P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30–0.76; P=0.002).

Conclusion:

The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.     

Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study

Purpose

The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed.

Methods

Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006.

Results

The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses).

Conclusion

Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.