Preliminary Clinical Study On The Relationship Between Hepatitis B Virus Infection And Breast Cancer

Part I Study on the role of hepatitis B virus infection in the occurrence and development of breast cancerBackground and purpose:Hepatitis C virus (HCV) infection is common in Western countries and considered to be the risk factor of breast carcinoma. But in China, hepatitis B virus (HBV) infection is more common than HCV. China is an epidemic area with a high or moderate rate of HBV infection. While there are few studies on the relationship between HBV infection and breast cancer. In this paper the status of HBV infection and liver function among initially diagnosed breast cancer patient and benign breast diseases patient was studied to explore the role of HBV infection in the occurrence and development of breast cancer.Method:The clinical data of 2452 cases of initially diagnosed breast cancer and 1926 cases of benign breast disease, with the reports of HBV serological markers and liver function tests in the Department of Endocrine and Breast Surgery, The First Affiliated Hospital, Chongqing Medical University, from January 2011 to March 2015, were collected for comparative analysis.Rusult:1. The average age of the initially diagnosed of breast cancer patients was 50.5±11.3 years, with the first and second age peaks being 40-49 (39.7%) and 50-59 years old (25.5%), respectively.2. Among 2452 cases of breast cancer, HBsAg was positive in 201 patients (8.2%), HBeAg positive in 18 patients (0.7%), HBcAb positive in 1629 patients (66.4%), HBsAb positive in 1403 patients (57.2%), HBeAb positive in 793 (32.3%); Among 1926 cases of benign breast disease, HBsAg was positive in 150 cases (7.8%), HBeAg positive in 21 cases (1.1%), HBcAb positive in 1035 patients (53.7%), HBsAb positive in 1156 patients (60%), HBeAb positive in 530 patients (27.5%). Among breast cancer patients, the positive rates of HBcAb and HBeAb were significantly higher than those in patients with benign breast diseases (p<0.05).3. Analysis on the basis of age stratification showed:among breast cancer patients of≤29 years old group, HBcAb was positive in 18 cases (50%) and HBeAb positive in 13 cases (36.1%); Among patients with benign breast disease of≤29 years old group, HBcAb was positive in 184 cases (32.6%) and HBeAb positive in 116 patients (20.6%). The positive rates of HBcAb and HBeAb were significantly higher in breast cancer patients compared to patients with benign breast disease (p<0.05).4. Among breast cancer patients of 40-49 years old group, HBcAb was positive in 648 cases (66.5%) and HBeAb positive in 344 cases (35.3%); Among patients with benign breast disease of 40-49 years old group, HBcAb was positive in 372 cases (61.3%) and HBeAb positive in 167 patients (27.5%).The positive rates of HBcAb and HBeAb were significantly higher in breast cancer patients than those in benign breast disease patients (p<0.05).5. Among breast cancer patients of≤40 years old group, HBcAb was positive in 265 cases (60.1%) and HBeAb positive in 149 cases (33.8%); Among patients with benign breast disease of≤40 years old group, HBcAb was positive in 569 cases (40.8%) and HBeAb positive in 332 patients (28.0%).The positive rates of HBcAb and HBeAb were significantly higher in breast cancer patients than those in benign breast disease patients (p<0.05).6. According to the age groups (≤29years age group、30-39 years age group、40-49years age group、50-59 years age group), the median concentrations of HBeAg among breast cancer patients were 0.37500S/CO, 0.38625S/CO,0.38598S/CO,0.38476S/CO,0.37756S/CO, respectively, which were significantly lower than those patients with benign breast diseases in the same age group (p<0.05); The median concentrations of HBsAg among breast cancer patients with age group of 30-39 years and 40-49 years, were 0.0150IU/ml and 0.0145IU/ml respectively, which were significantly lower than those in patients with benign breast diseases (p<0.05); Among breast cancer patients with 40-49 age group, the median concentration of HBcAb was 4.045S/CO which was significantly higher than that in the same age group of patients with benign breast diseases (p<0.05).7. The average albumin concentration in the age groups of≤29 years,30-39 years,40-49 years and 50-59 years were 42.4g/L,41.7g/L, 41.6g/L,41.5g/L, respectively, which were significantly lower than those in patients with benign breast disease (p<0.05); The ALT enzyme levels among breast cancer patients in the age groups of≤29 years,30-39 years,40-49 years,50-59 years, above 60 years old were 21.5U/L,20.5U/L, 22.4U/L,24.5U/L,23.6U/L respectively, which were significantly higher than those in patients with benign breast disease (p<0.05); among breast cancer patients with 40-49 years and above 60 years age groups, the AST levels were 21.2U/L and 23.9U/L, respectively, which were significantly higher than those in the same age group of patients with benign breast disease (p<0.05).8. The median concentrations of HBeAg among breast cancer patients with negative HBsAg and positive HBcAb in the age groups of≤29 years, 30-39 years,40-49 years and 50-59 years were 0.3500S/CO,0.3839S/CO, 0.3832S/CO,0.3842S/CO,0.3759S/CO, respectively which were significantly higher than those in the same age group of patients with benign breast disease (p<0.05). Among breast cancer patients of 40-49 years age group, the median concentration of HBsAg was 0.0124IU/ml, which was significantly lower than that in patients with benign breast disease,the median HBcAb concentration was 6.690 S/CO, which was significantly higher than that in patients with benign breast disease (p<0.05).9. Of 1926 cases of benign breast disease, there were 67 cases with age of no more than 18 years old, who have actively taken HBV vaccination in their neonatal period since active HBV vaccination was carried out in China in 1992. Among these patients, HBsAg was positive in 3 cases (4.5%), HBeAg positive in 3 cases (4.5%), HBcAb was positive in 10 cases (14.9%), HBsAb positive in 43 cases (64.2%), simple HBsAb positive in 43 cases (50.7%), HBeAb positive in 6 cases (9.0%) and all HBV markers negative in 22 cases (32.8%).Conclusion:1. The mean age at diagnosis for female breast cancer patients in China was 50.5 years and breast cancer peaked in the age group of 40-49 years (39.7%) and 50-59 years old (25.5%). As high as 14.6% of the female breast cancer patients were no more than the age of 40 years. It is indicated that the age of onset and occurrence peak of age group of female breast cancer patients in china is significantly earlier than that of Europe and United states.2. Among 40-49 years age group,≤29 years age group and 40-49 years age group, the rates of positive HBcAb in breast cancer patients were significantly higher than those in patients with benign breast diseases. History of HBV infection or latent infection could be a risk factor for breast cancer, and also may be the reason of the presence of earlier age peak in breast cancer morbidity among Chinese females compared to that in Europe and USA3. The liver function of breast cancer patients significantly impaired at the time of diagnosis, and latent HBV infection and/or various tumour related factors may be the possible reasons.4. HBV infection is common in breast cancer patients with comparatively lower concentrations of HBeAg and HBsAg than those in patients with benign breast disease. Meanwhile, comparatively high rate of pre core gene mutation may be the reason for low concentration of HBeAg. There is a definite lopsidedness for assessment of breast cancer risk through HBV detection only with HBsAg test.5. The HBV screening and efficacy of HBV vaccination monitoring should be enhanced from the neonatal period, which can probably prevent or delay the occurrence of breast cancer.Part II Preliminary clinical study of HBV reactivation in breast cancer patients during chemotherapy.Background and purpose:HBV reactivation is commonly seen in cancer patients undergoing chemotherapy. Some associations have issued guidelines stressing on the importance of screening every cancer patients undergoing chemotherapy with hepatitis B surface antigen (HBsAg) and hepatitis B virus core antibody (HBcAb). Patients with positive HBsAg should be started with anti viral therapy before chemotherapy, and those patients with negative HBsAg should be further screened for HBcAb. Patients with positive HBcAb should be closely monitored with HBV DNA and HBsAg. If any result of the HBV DNA or HBsAg changes into positive, the patients should be given anti viral therapy. In the past, researches on HBV reactivation in chemotherapeutic breast cancer patients were mainly about the liver function damage and liver failure caused by HBV reactivation but few about the changes in serum markers of HBV and its relation with HBV reactivation in patients receiving neoadjuvant chemotherapy. This study was designed to investigate the changes of HBV serum markers and liver function as well as their relationships with HBV reactivation in breast cancer patients during neoadjuvant chemotherapy.Method:From January 2012 to February 2014 there were 1251 cases of breast cancer treated in Department of Endocrine and Breast Surgery, The First Affiliated Hospital, Chongqing Medical University, of which the data of HBV serum markers and liver function tests in 413 cases of breast cancer receiving neoadjuvant chemotherapy at initial diagnosis and before operation were comparatively analyzed. Meanwhile, fractional analysis was also done according to the status of HBsAg and HBcAb.Result:1. Among 413 breast cancer patients who received neoadjuvant chemotherapy, HBsAg was positive in 32 patients (7.7%), hepatitis B virus e antigen (HBeAg) positive in 2 cases (0.5%), HBcAb positive in 282 patients (68.3%), hepatitis B virus surface antibody (HBsAb) positive in 228 cases (55.2%).2. After chemotherapy, there were 24 cases (5.8%) with hepatitis B virus e antibody (HBeAb) changed from positive to negative (p<0.05), while, there were no significant changes in the detection of HBsAg, HBsAb, HBeAg, HBcAb (p>0.05).3. Serum HBsAg concentration after chemotherapy increased significantly (p<0.05), HBsAb, HBeAb, and HBcAb concentrations significantly decreased (p<0.05),the albumin content was significantly decreased (p<0.05), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) significantly increased (p<0.05).4. According to the fractional analysis of HBsAg:in 32 HBsAg positive breast cancer patients after chemotherapy, the HBsAg concentration significantly increased (p<0.05) and the concentration of HBcAb significantly decreased (p<0.05), the albumin content significantly decreased (p<0.05), ALT and AST significantly increased (p<0.05); In 381 cases of HBsAg negative breast cancer patients after chemotherapy, The HBsAg concentration significantly increased (p<0.05), the HBsAb, HBeAb, and HBcAb concentrations significantly decreased (p<0.05), the albumin content significantly decreased (p<0.05), ALT and AST significantly increased (p<0.05).5. According to the fractional analysis of HBcAb:in HBcAb positive breast cancer patients after chemotherapy, HBsAg significantly increased (p<0.05), HBsAb, HBeAb, and HBcAb concentrations significantly decreased (p<0.05),the albumin content significantly decreased (p<0.05), ALT and AST significantly increased (p<0.05);In HBcAb negative breast cancer patients after chemotherapy, the HBsAg concentration did not change obviously, the concentrations of HBsAb and HBcAb significantly decreased (p<0.05), the albumin content significantly decreased (p<0.05), ALT and AST significantly increased (p<0.05).Conclusion:There is a higher proportion of HBsAg and/or HBcAb positivity in breast cancer patients. During chemotherapy, HBsAg concentration will get significantly higher with the trend of HBV reactivation, hence HBV reactivation should be closely monitored during chemotherapy. During the period of chemotherapy in breast cancer patients with positive or negative HBsAg, the concentration of HBsAg significantly increased, negative detection of HBsAg could not completely exclude the HBV reactivation during chemotherapy; HBsAg concentration significantly increased in HBcAb positive breast cancer patients with the presence of HBV reactivation trend during chemotherapy. HBsAg concentrations did not show significant changes in HBcAb negative breast cancer patients, suggesting that HBcAb negative breast cancer patients during chemotherapy did not have the trend of significant HBV reactivation, hence breast cancer patients with negative HBcAb detection at the initial time or before chemotherapy would possibly rule out the possibility of HBV reactivation in patients during the period of chemotherapy.