Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review

Table 4 Characteristics of available studies, reported in English, designed to assess the association between hepatitis C virus infection and breast cancer risk

Author/Journal/Publication year	Country	Study design/study period	Diagnosis	Sample size (HCV positive breast cancer cases)	Control source	HCV positive controls/controls	Matching factors	Percentage of HCV-positive cases with 95%CI	Main conclusions
Amin J J Hepatol 2006	Australia	Community-based cohort-study Period: 1990-2002	Patients’data obtained from: -New South Wales (NSW) Australia Health Department’s Notifiable Diseases Database (NDD) for notification of newly diagnosed HCV infection -NSW Central Cancer Registry (CCR) for notification of incident cancer cases -National Death Index (NDI) database, containing records of all deaths in Australia since 1980 Identification of breast cancer cases by means of ICD-10-diagnosis codes	Individuals with HCV infection: 75834 Breast cancers detected: 50 50/75834	Incidence observed in the study cohort was compared to expected incidence derived from NSW population cancer rates by calculating standardised incidence ratios	SIR: 0.3 (0.4-0.5)	NR	(0.05-0.09)	No evidence supporting an association between HCV infection and breast cancer development
Hwang JP J Oncol Pract 2014	United States	Cohort-study Period: January 2004 - April 2011	Patients’data, obtained from four institutional sources: Tumor registry: to assess patients’ demographic characteristics Pharmacy informatics: to evaluate chemotherapy drugs and dates administered. Patient accounts: to identify study patients’ International Classification of Diseases (ninth edition; ICD-9) codes Laboratory informatics: to determine HCV antibody (anti-HCV) and ALT test dates and results	141877 patients with cancer, who were newly registered at MD Anderson Cancer during the study period. Patients considered in the study: 16773. HCV screened subjects: 2330/16773 (13.9%) HCV screened females: 1038 HCV-positive patients with cancers: 35/2330 (1.5%) HCV-positive females with cancers: 12 (1) HCV-positive females with breast cancers: 3/12 (2) HCV-negative females with breast cancer: 102/1026	NR	NR	NR	(1) 25 (5.5-57.2) (2) 9.9 (8.1-11.8)	HCV screening rates were low, even among patients with risk factors, and the groups with the highest rates of screening did not match the groups with the highest rates of a positive test result
Larrey D World J Gastroenterol 2010	France	Case serie with control gorup Period: NR	Females with history of HCV-related chronic infection, observed in Liver Unit of Montpellier School of Medicine, France, for chronic liver diseases in several occasions for a period longer than 1 yr. Chronic hepatitis proved by liver biopsy and/or biological markers of inflammation and fibrosis	17/294 (5.8%)	Females sequentially and prospectively seen during the same period with chronic liver disease over 1 yr, with well defined clinical, radiological and histological characteristics [chronic- HBV, alcoholic-liver disease, auto-immune hepatitis, hemochromatosis, non alcoholic fatty liver disease (NAFLD), cholangitis]	5/107 (4.7%)	NR	5.8 (3.1-8.4)	Chronic HCV infection is not a strong promoter of breast carcinoma in adult females of any age
Omland LH Clinical Epidemiology 2010	Denmark	Cohort-study Period: 1994-2003	Patients and subjects with HCV infection identified by means of: The Danish National Hospital Registry (DNHR) -The Danish Cancer Registry People listed in DNHR with at least one diagnosis of acute or chronic HCV infection (ICD-10 B17.1 and 18.2) were included Cancer diagnoses based on the Danish version of the international classification of diseases, 8th revision (ICD-8) until Dec 31, 1993, and 10th version (ICD-10) thereafter	4349 patients with HCV infection in the DNHR 2 breast cancer detected 2/4349 (0.05%)	The expected number of cases of cancer after a diagnosis of HCV infection using Danish incidence rates of first cancer diagnoses according to sex, age, and year of diagnosis in 1-yr intervals was calculated	Expected number of breast cancers 8.05	NR	0.05 (0-0.1)	No association between HCV infection and higher risk of breast cancer development
Su FH BMC Cancer 2011	Taiwan	Population-based study Period: 2000-2008	Data retrieved from National Health Insurance Research Database (NHIRD), which is maintained by the National Health Research Institute (NHRI), Taiwan. Newly diagnosed breast cancer identified from the registry for Catastrophic Illness Patients Database (ICD-9-CM code 174 and 175). Identification of HCV infected subjects by means of ICD-9-CM diagnosis codes (ICD-9- CM 070.41, 070.44, 070.51, 070.54, and V02.62)	56/1958 (2.9%)	Randomly selected and matched individuals without a history of breast cancer (control to patient ratio was 4:1)	178/7832 (2.3%)	age- and sex	2.9 (2.1-3.5)	HCV infection associated with early onset risk of breast cancer in areas endemic for HCV
Swart A BMJ Open 2012	Australia	Cohort-study 1 January 1993 - 31 December 2007	Individuals registered on the Pharmaceutical Drugs of Addiction System, a record of all NSW Health Department authorities that administer methadone or buprenorphine to opioid-dependent people as opioid substitution therapy. Solid cancers classified according to the International Classification of Diseases (ICD), 10th revision, haematopoietic neoplasms and Kaposi sarcomas classified according to the ICD for Oncology, 3rd edition	Patients considered in the study: 29613 Subjects with HCV infection alone: 14892 Observed number of breast cancer in HCV-positive cohort: 48 48/14892 (0.03%)	Calculation of expected number of incident breast cancer	Expected number of breast cancers: 101	NR	0.03 (0.02-0.04)	No evidence supporting an association between HCV infection and breast cancer development

NR: Not reported; SIR: Standardised incidence ratio; HCV: Hepatitis C virus.