Clinical Analysis Of The Susceptibility And Prognosis For Young Patients With Breast Cancer

Objective Compared with breast cancer of old patients, this disease in youngpatients is more aggressive, easier to have lymphatic or hematogenous metastasis andwith higher-degree malignancy and worse prognosis. Its prognosis is effected bymany factors, at present, in our country the relevant literature concentrate more on thesurvival rate comparing with non-young patients with breast cancer and the analysisof clinical prognostic factor, mainly on the clinical pathologic aspects, such as clinicalstage, tumor size, pathologic type and lymph node status. However, the biologicalcharacteristic related to it is studied less. This study not only analyzes the clinicalpathologic factors related to the development and turnover of breast cancer, but alsoattempts to select relevant biological factors of worse prognosis. Through thisresearch, we try to study the problem of breast cancer in young patients in anall-round way, indicate relevant risk factors from different aspects such as clinical,pathological, biological, hoping for early discovery, early treatment and theimprovement of survival rate.Methods Collected 191 patients with primary breast cancer (≤35 years)between 1994.1～1998.4 in Tianjin cancer hospital, of which 99 cases has clinicaldata, pathological slice, regular follow-up and the opportunity of operation, amongthose 99 paraffin block, 63 were examined by immunohistochemistry for bioligicalindex. To stage them again according to UICC (2002) TNM phase standard. Reviewthe morphological index of those pathological slice including pathologicalclassification, pathological grading, lymphatic vessel involvement, soft tissueinvolvement, EIC, lymph node involvement. Pathologic histological classification isaccording to the WHO (2003) standard. The expression of ER (estrogen receptor),PR (progesterone receptor),,AR (androgen receptor),C-erbB2,P53,Ki67 and BRCA1 were examined by immunohistochemistry in 63 carcinomas. The cases weredivided into two groups according to 5-year survival rate, compared the pathologicaland biological differences between the two groups. The data were analyzed bystatistics, the comparison of 5-year survival rates was by x~2 test, and pathologicaland biological index subtype survival curve by Kaplan-Meier. Single factor analysiswas adopted to recognize prognostic factors at first, then bad prognosis factors wereintroduced into multifactor COX regression model to analyze the survival, finallyselect the parameter which indicates the worse prognosis.Results 99 patients with breast cancer (≤35 years) were followed up for 5years with a rate of 100％. Young patients with breast cancer accounts for 6.6％ofthe total cases of breast cancer of the same period (191/2890). 10 cases have familyhistory, accounts for 10.1％(10/99). 3 ductal carcinoma in situ, 2 ductalmicroinvasive carcinoma, 89 invasive ductal carcinoma, 5 other types; Tissuegrading: 11 cases of gradeⅠ, 49 cases of gradeⅡ, 34 cases of gradeⅢ. Withlymphatic vessel involvement 26 cases (26.3％), soft tissue involement 34 cases(34.3％), EIC positive 39 cases (39.4％), lymph node metastasis rate was 59.6％(59/99). The expression rate ofER, PR, AR, C-erbB2, Ki67, P53, BRCA1 is 57.1％(36/63), 49.2％(31/63), 43.5％(27/62), 41.3％(26/63), 19.4％(12/62), 35.6％(21/59),21.1％(12/57) respectively. 5-year metastasis and 5-year survival rate were 28.0％(26/93), 72.7％(72/99),respectively. No relationship was found between BRCA1expression and age and family history of breast cancer (P＞0.05). Revealed by x~2test, different TNM stage has different survival rate, stageⅢhas the highermortality of 60.6％(P＜0.05); The survival rate of different treatments has statisticsdifference, among them, those accepting radically correction and castration treatmenthave the most high mortality (P＜0.05). Single factor analysis reveals, the lymphaticvessel involvement,soft tissue involvement,EIC,the lymph nodeinvolvement,AR and C-erbB2 expression situation influence prognosis.Multifactor COX regression analysis reveals that the death risk of lymph node involvement number 1-3, 4-6,＞6 are 1.49, 6.70, 15.36 times of lymph nodenegative respectively. Death risk of AR positive cases is 0.245 times that of thenegative ones. Death risk of C-erbB2 (+), (++), (+++) are 15.12, 10.61, 8.31 times ofC-erbB2(-) separately, indicating lymph node involvement, AR, C-erbB2 areindependent prognostic factors for young patients with breast cancer.Conclusions The incidence of young patients with breast cancer is on the rise,and the patients are younger day by day. The lymph node status and C-erbB2expression are the independent prognostic factors in young patients with breast cancer.AR may be an adjuvant prognostic factor. Age is not a basic prognosis factor. Thetherapeutic measurement do not benefit the survival radically. Objective The onset of young patients with breast cancer is very early whichclosely relates to the mutation of heredity susceptibility gene. The articles studyingheredity susceptibility gene at present mainly pay close attention to family breastcancer or non-young sporadic breast cancer(＞40 years), only few literature ofbreast cancer with early onset breast cancer. BRCA1 gene is an identified breastcancer susceptibility gene, has a mutation rate of 8％-20％among young patientswith breast cancer. BRCA1 gene is a big one which has multi-form and multi-sitemutation, and new form mutation is being found constantly, the variation that hasalready detected so far is not less than 600 kinds. This research collected cases ofsporadic breast cancer(≤35 year), chose relatively representative BRCA1 geneticcode area from the literature researched, looked for pathogenic mutation site, in orderto detect the prevalence of BRCA1 gene mutations and SNPs among youngpatients with breast cancer, in China and to study the hot spot of BRCA1 mutationsand the relationship between the mutations and the young patients. Hoping to showthe form and site of BRCA1 gene mutation of Chinese young patients with breastcancer, improve present mutation profile, discuss the clinical significance ofBRCAlmutation for risk assessment, onset detection and early diagnosis of breastcancer.Methods 30 Samples with early onset breast cancer (≤35 years)of breastcancer tissue were collected between 1994～2006, of which 14 are paraffin block and16 fresh tissue, 5 cases had at least one first-degree relative affected. The pathologicaltyping is invasive ductal carcinoma, account for 86.7％(26/30). The mutationscreening was performed in exon 2, 11C,11F,11L,11I,16,20 ofBRCA1 geneby using polymerase chain reaction and subsequent DNA direct sequencing. We checked the sequence results by the analytical tool of DNA Star-MagAlign.Results The order checking length is 2105 bp, accounts for 37.6％(2105/5600)of the total length. 14 order variation were detected, 4 of them with changes of aminoacid, 10 with not. The number of variation distributing in 2, 11C,11F,11I,11L exonswere 3,3,2,2,4, respectively. No mutation was found in the exon 16 and 20. Threedisease-causing mutations in BRCA1 were detected. The mutation frequency ofBRCA1 in young patients was 10％and all of that were frameshiftmutation(cDNA2639, 2640delTA and 3343 delG, 3398delT). Additional oneunclassified variant(2806T＞C )and 10 single nucleotide polymorphisms (SNPs) weredetected (cDNA 2570 C＞T,cDNA 2620 A＞T,1473 A＞G,1561 C＞T,1594G＞A,2206 A＞G,2227 T＞C,2659 C＞A,3307 A＞G 3375 G＞A).Conclusions The BRCA1 mutation was located the exon 11 mainly. Themutation frequency of young patients with family history was higher. Thedisease-causing sites may be related to early onset breast cancer. Our data contributeto information on spectrum of BRCA1 gene in Chinese population. As to the highrisk group with first-degree relative affected, BRCA1 gene mutation screening isbadly needed, in order to follow up and monitor..