• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.43-45
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• 2013

Background: The aim of this epidemiological study was to establish the laterality of breast cancer (BC) and its association with size, receptor status of the primary tumor and bone metastasis (BM) in a local population. Materials and Methods: This retrospective study included cases of BC from Jan-2009 to Dec-2011 who were referred for metastatic work up or follow up survey with Technetium-99m MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521 were included and all reviewed for age, primary tumor size (PTS), laterality, receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2-Neu receptor, presence or absence of BM with sites of involvement and time interval between diagnosis of BC and appearance of BM. Results: The left to right sided BC proportion was significantly higher than unity (59%:41%; p<0.001). The right sided BC was observed in younger age group (46:52 years; p<0.0001) and with a smaller PTS than the left sided (3.43:4.15 cm; p<0.0001). The patients with BM had relatively higher negative receptor status with a significant predominance of right sided BC. The overall incidence of BM on BS was 28% and relatively higher in right than left breast (33%:24% p=0.068). The average number of BM sites was also significantly greater for the right side (6:4, P<0.0001). The % cumulative risk of BM in right breast was noted at significantly smaller PTS than left side with log rank value of 5.579; p<0.05. The Kaplan Meier survival plot for event free survival of BM in left sided BC was significantly higher than for the right side (log rank value=4.155, p<0.05), with an earlier appearance of BM in right BC. Conclusions: 1) A left sided predominance of BC was seen in local population; 2) right sided BC had a more aggressive behavior with extensive and earlier appearance of BM at relatively younger age, smaller PTS and receptor (s) negativity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1197-1201
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• 2012

Objective: To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. Materials and Methods: Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. Results: The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor)/PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+++) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. Conclusions: HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7533-7537
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• 2014

Background: Breast cancer (BC) is the most frequent cancer type, and the leading cause of death from cancer among women in Israel. The Bedouin-Arab (BA) population in southern Israel is characterized by a high rate of consanguinity, common hereditary disorders, and transition from a semi-nomadic, traditional society to a more sedentary and urbanized society. In this hospital-based study, the demographic and the clinicopathological characteristics of BC in BA were compared with Jewish patients. Materials and Methods: 85 BA patients treated at the Soroka Medical Center, Beer Sheba, during the years 2004-2012, were studied and compared with 180 consecutive Jewish patients treated during the year 2007. Clinicopathological features compared included age, menopausal state, number of births, a history of BC in first-degree relatives, tumor size (T), extent of lymph-node involvement (N), distant metastases (M), stage, grade, estrogen and progesterone receptor (ER/PR), and Her2 status. Types of treatment, relapse rate and site, as well as outcome were also studied. Cox's regression models were applied for studying disease-free, and overall survival. Results: Compared with Jewish patients, BA patients were younger (average age $49{\pm}12$ yrs vs $59{\pm}13$, p<0.001), had a lower rate of BC in first-degree relatives (p<0.001), and a larger number of births ($6{\pm}4.2$ vs $2.5{\pm}1.9$, p<0.001). BA patients had larger tumors (p=0.02), more extensive lymph-node involvement (p=0.002), and more advanced stage (p=0.003). Grade, ER, PR, and Her2 status were similar in the two ethnic groups. Relapse type was most commonly systemic in BA patients (p=0.05), and loco-regional in Jewish patients (p=0.02). Median survival was 63, and 35 months for Jewish and BA patients, respectively (log-rank test, p=0.02). In Cox multivariate analysis, stage and PR status (HR-0.14, p<0.0001; HR-3.11, p=0.046), but not ethnicity, influenced overall survival. Conclusions: BC presents a decade earlier, and with more advanced disease in BA compared with Jewish patients. Biologic parameters including grade, ER, PR, and Her2 status were similar in both groups. Although prognosis was worse in BA than in Jewish patients, it was affected only by stage and PR status, but not by ethnicity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4507-4511
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• 2014

Background: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed. Aim: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) - "TNBC" and "Others". Materials and Methods: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others". Results: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC. Conclusions: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.11
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• pp.1495-1503
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• 2009

This experiment was conducted to determine the effect of dietary supplementation with BCAA (branched-chain amino acids: leucine, isoleucine and valine) on improving the growth of rats in a malnutritional IUGR (Intrauterine Growth Retardation) model, which was established by feeding restriction. In the experimental treatment, rats were fed purified diets supplemented with BCAA (mixed) during the whole gestation period, while arginine and alanine supplementation were set as the positive and negative control group, respectively. The results showed that, compared to the effect of alanine, BCAA reversed IUGR by increasing the fetus weights by 18.4% and placental weights by 18.0% while fetal numbers were statistically increased. Analysis of gene and protein expression revealed that BCAA treatment increased embryonic liver IGF-I expression; the uterus expressed higher levels of estrogen receptor-$\alpha$ (ER-$\alpha$) and progesterone receptor (PR), and the placenta expressed higher levels of IGF-II. Amino acid analysis of dam plasma revealed that BCAA supplementation effectively enhanced the plasma BCAA levels caused by the feed restriction. BCAA also enhanced the embryonic liver gluconeogenesis by augmenting the expression of two key enzymes, namely fructose-1,6-biphosphatase (FBP) and phosphoenolpyruvate carboxykinase (PEPCK). In conclusion, supplementation of BCAA increased litter size, embryonic weight and litter embryonic weight by improving the dam uterus and placental functions as well as increasing gluconeogenesis in the embryonic liver, which further provided energy to enhance the embryonic growth.

• Clinical and Experimental Reproductive Medicine
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• v.16 no.1
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• pp.23-34
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• 1989

Estradiol (E)은 난소내 과립세포 (granulosa cell, GC)를 증가시키고 생식소 자극호르몬과 협동으로 배란을 유도한다. Androgen은 E의 작용과 반대의 작용을 나타내며 여포의 폐쇄요인으로 알려지고 있다. Testosterone(T)이 폐쇄여포의 여포액내 다량 존재하는 것이 알려짐에 따라 난소내에도 자가조절분비(autocrine)또는 paracrine regulation에 의해 작용을 나타낼 것으로 가정되어 난소내 여포가 폐쇄됨에 따라 그 수용체의 변화하는 양상을 조사하고져 하였다. 흰쥐의 과립세포의 세포질에는 $51.3{\pm}6.1$fmol/mg protein의 Estradiol 수용체(ER) ; $153.1{\pm}25.3$의 Testosterone수용체(TR) ; 또한 $35.1{\pm}8.1$의 Progesterone수용체(PR)가 존재하였다. 과립세포내 ER용 세포질내 E를 제거한 후에 정량이 가능하였고 또한 과립세포내에도 TR이 사람에서는 $23.4{\pm}7.2$ fmol/mg protein, 돼지는 $98.5{\pm}23.1$로 상당량 존재함을 관찰하였다. Dihydrotestosterone Enanthate(DHTE)를 100ug/흰쥐의 농도로 처리한 결과 난소내 TR의 농도는 변화가 없이 ER의 농도만 현저히 저하되고 쥐의 난소무게 역시 감소하는 것을 발견하였다. 위의 결과로 보아 난소내에도 스테로이드 호르몬은 autocrine(자가조절)방법으로 작용하며 An-drogen이 난소의 무게를 감소시키는 것은 ER의 수를 감소시켜 E의 작용이 억제되고 여포들이 폐쇄를 일으켜 그 증식이 저하된 때문으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3805-3809
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• 2014

Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using ${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5257-5261
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• 2012

Background: High incidence of breast cancer and its fatal effect has reached an alarming stage across the globe, including the third world countries. Many factors have been reported to be associated with the development of breast cancer but detailed structural and functional information is missing. CA 15-3 is one of the known potential tumor marker of breast cancer; however little is known about structure and functional site of this protein. Present study aims to investigate the functional role of CA 15-3 in breast cancer, especially in development and metastasis. Material and Methods: Hundred female breast cancer patients confirmed by histopathological reports were included in the study. Their physiological characters were recorded in a performa. Enzyme linked immunosorbent assay (ELISA) technique was used to estimate serum CA 15-3 level. Immunohistochemistry was done for estrogen (ER), progesterone (PR) and Her2/neu receptors expression. Results: The study revealed the details of physiological characteristics of female breast cancer. Mean age was $37.72{\pm}5.99$ and $55.05{\pm}7.28$ years and serum CA 15-3 (MUC1) level was $60.47{\pm}8.59$ and $63.17{\pm}4.58$ U/ml in pre and post-menopause respectively, and both groups of women had sedentary life style. Their receptor status especially of progesterone, estrogen and HER-2/neu were positive in 50% of premenopausal women and 65% of postmenopausal women. Conclusion: There are multiple physiological factors promoting breast cancer. High serum CA 15-3 level and hormonal imbalance of ER, PR and Her2/neu appears to be the main cause of breast cancer. It may be possible that the functional sites of these proteins may be altered which may increase the chances of metastasis in breast cancer.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.45-55
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• 2008

Purpose: This study evaluates the association of estrogen receptor(ER), progesterone receptor(PR), Her-2, COX-2, and survivin with the clinicopathological features and outcomes in young Korean women with breast cancer using recently developed tissue microarray(TMA) technology. Materials and Methods: A cohort of 212 young patients with breast cancer diagnosed at the age of 45 years or younger from March 1994 to August 2005, were enrolled in this study. The age range of patients was $23{\sim}45$ years(median age, 39 years). The minimum and median follow-up periods were 24 months and 60 months, respectively. Serial sections of primary tumors were processed by the use of a TMA for immunohistochemical staining for five biomarkers. The correlation of these five biomarkers and the clinicopathological features and outcomes were analyzed by statistical methods. Results: The majority of the patients were stage T1(90 patients) or T2(101 patients), and 105 patients(49.5%) had an axillary node metastasis. The 5-year overall and relapse free survival rates for all of the patients were 90.4% and 82.3%, respectively, and 36 patients had a locoregional or distant metastasis as a first event. Positive expression of ER, PR, Her-2, COX-2, and survivin was determined in 38.2%, 45.3%, 25.9%, 41.5%, and 43.4%, of the tumor samples, respectively. Tumor stage, nodal status, age, as well as expression of ER, PR, and HER-2 status were significantly associated with the disease free survival rate. Tumor stage, nodal status, as well as expression of ER, PR, and HER-2 were significantly related with the overall survival rate. Expression of COX-2 and survivin were not single independent prognostic factors for the disease free and overall survival rate although co-expression of HER-2 and COX-2 had a tendency as a poor prognostic factor. By multivariate analysis, only T stage and lymph node status were significant prognostic factors, and ER status was a marginally significant prognostic factor(p=0.075). Conclusion: Expression of ER, PR and HER-2 were significant prognostic factors for the relapse free and overall survival rate. Expression of COX-2 and survivin were not prognostic factors for young women with breast cancer.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.111-118
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• 2009

Puopose : Exposure to dietary phytoestrogens such as genistein during early childhood is a growing public health concern. We examined the effect of early exposure to genistein on sexual maturation in immature rats. Methods : Weaning (3wk-old) Sprague-Dawley female rats were assigned to three groups (n=6 for each): fed by high dose of genistein (100 mg/kg/d), low dose of genistein (10 mg/kg/d) and control group. First vaginal opening (VO) day was observed. Structural alterations in the ovary and uterus were assessed by histologically. Expression of genes of $ER{\alpha}$, $ER{\beta}$, and progesterone receptor (PR) in the ovary and uterus were investigated by RT-PCR. Results : High genistein group had earlier VO than control and low genistein group. Graafian follicles and corpora lutea were observed from the ovary of genistein-treated groups, while primary, secondary follicles and small atretic follicles were observed in the control group. Hypertrophy of luminal and glandular uterine epithelia were found in the genistein-treated groups while poor development of gland and fewer myometrial cell layers were evident in control group. In ovary, the transcriptional activities of $ER{\alpha}$ and $ER{\beta}$ were higher in high genistein group than in controls. In uterus, the transcriptional activities of $ER{\alpha}$, $ER{\beta}$ and PR were higher in low genistein group than in controls. Conclusion : Acute exposure to genistein during the prepubertal period could activate the reproductive endocrine system resulting in the early onset of puberty in female rats. Further clinical investigation on the effect of genistein on the sexual maturation in children is warranted.