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Clinical pathologies of breast cancer in the elderly and youths and their prognosis.

Byline: Hong Ji Ning Ai Qinghuai Li Kaili Zhang and Wang Di

: Objective To explore the correlation between the clinical pathologies of breast cancer in the elderly and youths as well as their prognosis.Methods: Two hundred and eighty breast cancer patients were divided into a youth group (less than 60 n=120) and an elderly group (= 60 n=160) according to the age. Their routine clinical pathological indices and immune indices were observed and determined and the prognosis was observed after effective treatment. Results: The positive expression rates of p63 CK5/6 CK14 and CK17 in the elderly group were significantly higher than those of the youth group (P less than 0.05). The tumor-free survival rate of the youth group (95.8%) was significantly higher than that of the elderly group (84.4%) (P less than 0.05). Multivariate Logistic regression analysis showed that the positive expressions of p63 and estrogen receptor age and postoperative chemotherapy were the independent risk factors of tumor-free survival rate (P less than 0.05).Conclusion: The immunohistochemical typing characteristics of the elderly and youths were different and the prognosis of young patients was better being correlated with the typing.

KEY WORDS: Age Breast cancer Immunohistochemistry Pathological characteristics Prognosis.

INTRODUCTION

Breast cancer which is malignant for women worldwide has led to considerable morbidity and mortality rates even in youths.12 In China the pa- tients are mostly 40-49 years old. Since early diag- nosis gives rise to satisfactory prognosis it is crucialto diagnose and treat them as soon as possible to elevate the survival rate.3-5 In contrast interim and advanced breast cancer patients usually require long-term treatment thus tremendously burden- ing them and their families physically and physi- ologically accompanied by high mortality rates.6Recently the expressions of estrogen receptor (ER) and progesterone receptor (PR) have been applied to determine the prognosis and treatment outcomes of breast cancer patients.7-9###Given that breast can- cer is highly heterogeneous the evaluation on early prognosis is subject to being affected by tumor me- tastasis recurrence and surgical tolerance etc.10Generally the patients older than 60 years old were prone to malignant tumors despite slow dis- ease progression whereas those younger than 60 commonly suffer from rapid progression. How- ever prognosis also evidently depends on the self- repair ability and immunity of different patients.11Therefore we herein explored the correlation be- tween the clinical pathologies of breast cancer in the elderly and youths as well as the prognosis by

Table-I: Clinical data of the two groups.

###Clinical data###Youth (n=120)###Elderly (n=160)###2 or t###P

###Tumor size (cm)###4.560.32###4.620.44###0.324###greater than 0.05

###Disease course (month)###7.120.15###7.260.33###0.488###greater than 0.05

###Tumor position (left/right)###68/52###90/60###0.511###greater than 0.05

###Lymphatic metastasis (yes/no)###36/84###60/100###0.412###greater than 0.05

###TNM stage (I/II/III)###72/38/10###100/45/15###0.321###greater than 0.05

###Family history (yes/no)###24/96###32/128###0.000###greater than 0.05

METHODS

Subjects: All the experiments have been approved by the ethic committees of the Second Hospital of Hebei Medical University and the Fourth Hospital of Hebei Medical University and written consent was obtained from all patients. Two hundred and eighty breast cancer patients enrolled in our hos- pitals from February 2008 to February 2013 were selected. Inclusion criteria: Primary breast cancer; pathologically confirmed invasive non-specific can- cer; unilateral disease; recurrence and metastasis confirmed by CT B-mode ultrasound imaging and MRI; complete clinical and follow-up data; com- pletion of radical or modified radical mastectomy; with signed written consent. Exclusion criteria: Completion of breast lump puncture one week be- fore admission; completion of neoadjuvant chemo- therapy; susceptible observation to inhomogeneous fat suppression; complicated with critical physical and mental diseases; older than 80 or younger than18 years old. They were divided into a youth group (less than 60 n=120) and an elderly group (=60 n=160) ac- cording to the age. Their tumor diameters disease courses tumor positions lymphatic metastasis TNM stages and family history did not differ sig- nificantly (Pgreater than 0.05) (Table-I).Immunohistochemical analysis: Tumor samples were fixed in 10% neutral formalin and embedded in paraffin. The eligible sections were stained after4m continuous removal. PBS primary antibody which was purchased from Beijing Zhongshan Jin- qiao Biotechnology Co. Ltd. was utilized as the negative control. Known invasive breast cancer sections were used as the positive control. Mouse monoclonal antibodies (ER PR p53 p63 CK5/6 CK14 CK17 and VEFR) and immunohistochemi- cal kits were bought from Fuzhou Maxim Biotech Inc. DAB chromogenic reagent was obtained from Sangon Biotech (Shanghai) Co. Ltd. All sections were observed under an optical microscope by a professional physiological doctor. ER PR p53 and p63 were positively expressed in cell nucleus while CK5/6 CK14 and CK17 were positively expressed in cytoplasm and EGFR was positively expressed in cell membrane.Treatment methods: All patients received radical or modified radical mastectomy of which 88 in the youth group and 110 in the elderly group received postoperative chemotherapy and 50 in the youth group and 65 in the elderly group received radio- therapy at chest wall regional lymph nodes and internal mammary area. They were follow-up until November 2013 with the contents regarding dis- ease course tumor diameter lymphatic metastasis TNM stage chemotherapy radiotherapy immuno- histochemical expression and survival.Statistical analysis: All data were analyzed by SAS13.0. The pathological characteristics and rou- tine data were compared by 2 or t test. Multivariate analysis was performed by using Logistic regres- sion model corrected confounding factors. Pless than 0.05 was considered statistically significant.

RESULTS

Comparison between immunohistochemical analysis results: The positive expression rates of ER PR EGFR and p53 in the two groups did not differ significantly (Pgreater than 0.05) whereas the rates of p63 CK5/6 CK14 and CK17 in the elderly group were significantly higher than those of the youth group (Pless than 0.05) (Table-II).

Table-II: Positive expression rates of immune markers in breast cancer patients (n).

Immunohisto###Youth###Elderly###2###P

chemical index###(n=120)###(n=160)

Positive ER###56 (46.7%)###72 (45.0%)###0.225###greater than 0.05

Positive PR###60 (50.0%)###79 (49.3%)###0.195###greater than 0.05

Positive p53###36 (30.0%)###50 (31.3%)###0.188###greater than 0.0

Positive p63###36 (30.0%)###102 (63.8%)###10.854###less than 0.05

Positive CK5/6###50 (41.7%)###100 (62.5%)###7.556###less than 0.05

Positive CK14###42 (35.0%)###121 (75.6%)###11.525###less than 0.05

Positive CK17###68 (56.7%)###144 (90.0%)###8.954###less than 0.05

Positive EGFR###61 (50.8%)###85 (53.1%)###0.369###greater than 0.05

Case analysis: Two cases from the two groups were analyzed (Fig. 1 and 2).Prognosis analysis: Until 30th November 2013 a total of 250 patients had the tumor-free survival times 5 years of which there were 115 from the youth group and 135 from the elderly group. The tumor-free survival rates of the youth group and the elderly group were 95.8% and 84.4% respectively with a significant difference (Pless than 0.05) (Table-III). Risk factors affecting prognosis: By using multivariate Logistic regression analysis the positive expressions of p63 and ER age and postoperative chemotherapy were screened as the independent risk factors of tumor-free survival rate (Pless than 0.05) (Table-IV).

Table-III: Tumor-free survival rates of the two groups after treatment (n).

Group Case###Tumor-free###5-year tumor-free

###No.###survival for###survival

###5 years###rate

Youth###120 115###95.8%

Elderly 160 135###84.4%###

2###10.569

P###less than 0.05

Fig.2: A 65-year-old female with invasive ductal carcinoma and without lymphatic metastasis. A): Dynamic contrast- enhanced image disclosed a ring-like tumor focus; B): Enhancement rate 230%; C): Ascending enhancing mode and dynamic contrast-enhanced curve; D and E): Optical microscopic observation showed comedonecrosis (white arrow) and fibrosis (black arrow) (HEA-100).

DISCUSSION

Breast cancer is the most devastating malignant tumor that threatens women worldwide.12 Many Chinese women especially those in metropolis are prone to breast cancer even at young age owing to active or passive uptake of endogenous and exogenous estrogen with the rapid economic and social development habitual changes environmental contamination and working pressure.13 Currently approximately 40 out of 100 thousand women in China are suffering from breast cancer. Generally the patients older than 60 years old were prone to malignant tumors despite of slow disease progression whereas the younger ones were commonly subjected to rapid progression.14It is well known that breast cancer is highly het- erogeneous thus rendering diagnosis and treat-

Table-IV: Multivariate Logistic regression analysis of prognosis.

Risk factor###P###OR###95%CI

Age###0.421 0.0050.6240.321-1.447

Positive p63###1.195 0.0040.3040.135-0.685

Positive ER###2.514 0.0860.0780.004-1.439

Postoperative###0.145 0.0090.2620.096-0.713

ment tricky with complex clinical manifestations pathological characteristics and prognosis.15 The tumor diameters disease courses tumor positions lymphatic metastasis TNM stages and family his- tory of the two groups in this study did not differ significantly (Pgreater than 0.05). To improve the prognosis specifically indices such as ER and PR have been applied to determine the onset progression and selection of treatment protocols. It has previously been reported that the breast cancer of patients younger than 35 years old is more invasive lead- ing to poor prognosis.16 In this study the positive expression rates of ER PR EGFR and p53 in the two groups did not differ significantly (Pgreater than 0.05) whereas the rates of p63 CK5/6 CK14 and CK17 in the elderly group were significantly higher than those of the youth group (Pless than 0.05). The expressions of CK5/6 and CK17 are independent prognostic factors of breast cancer without being affected by tumor size or axillary lymph node metastasis.The tumor-free survival rates of the youth group and the elderly group were 95.8% and 84.4% re- spectively with a significant difference (Pless than 0.05). As a member of p53 gene family p63 is highly expressed in the basal cell layer of normal tissue epithelia thus evidently influencing the prolifera- tion of basal stem cells and epithelial tissues. The expression of p63 is associated with tumor size his- tological grade lymphatic metastasis and negative ER expression. Of the patients receiving surgeries higher expression of p63 gave rise to better prog- nosis. Meanwhile some breast cancer patients who had high contents of endogenous estrogen in blood and low ER expression were more subject to death due to distant metastases and recurrence.17In summary the immunohistochemical typing characteristics of the elderly and youths were different and the prognosis of young patients was better.

Conflicts of Interest: All the coauthors declare thatthey have no conflicts of interest.

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Publication:Pakistan Journal of Medical Sciences
Date:Jun 30, 2014
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