Lower breast cancer survival in mothers of children with a malignancy: a national study.

As it is unclear if hereditary factors affect breast cancer survival, this was compared using fertility and cancer registry data, among all women so diagnosed during 1961-1999 in Sweden, having a child with childhood cancer (

Reduced mortality for women with mammography-detected breast cancer in east Denmark and south Sweden.

The 5-year relative survival from breast cancer in Denmark is 10 percentage points lower than in Sweden. This difference has been demonstrated previously as being caused partly by more involved lymph nodes and larger tumours in Denmark. Sweden has had nationwide mammography-screening coverage since 1991, whereas this is still in its infancy in Denmark. In the search for an explanation for the remaining survival difference, patient delay was a likely candidate. This study compared patient delay and mammography-detection between two national regions. Data on patient delay and mammography were obtained from hospital records from 1989 and 1994, and analysed using Cox proportional hazard analysis of death within the first 5 years, with the factors age, country, delay/mammography detection and established patho-anatomic variables. A comparison of patient delay and mammography detection in 1989 and 1994 showed more mammography-detected tumours in south Sweden and more women with long delay in east Denmark. Mammography detection, but not long patient delay, had a significant effect on the death hazard when adjusting for patho-anatomic risk factors. The hazard ratio was not eliminated in 1989, but in 1994, the hazard ratio between east Denmark and south Sweden was reduced from 1.3 to 1.1. In conclusion, patient delay did not appear to have any effect on 5-year survival when adjusting for patho-anatomic factors, but tumour detection by mammography affected survival favourably and partly explained the survival difference between east Denmark and south Sweden.

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients.

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0-32) years before and median 4 (0-35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0-1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1-33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS.

Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas.

OBJECTIVE: To determine whether TNF blockers increase tumour risk in patients with RA. MATERIALS AND METHODS: The South Swedish Arthritis Treatment Group register (SSATG) comprises over 90% of anti-TNF treated patients with RA in the area. 757 patients treated with etanercept or infliximab included between 1 February 1999 and 31 December 2002 were identified. 800 patients with conventional antirheumatic treatment in a community based cohort served as a comparison cohort. Tumours and deaths were identified in the cancer registry and population census registers. Patients were followed up from initiation of anti-TNF treatment or 1 July 1997 for the comparison group, until death or 31 December 2002. RESULTS: In the anti-TNF group, 16 tumours (5 lymphomas) were identified in 1603 person-years at risk, and in the comparison group 69 tumours (2 lymphomas) in 3948 person-years. Standardised incidence ratios (SIRs) for total tumour relative risk for the anti-TNF group and the comparison group were 1.1 (95% confidence interval (CI) 0.6 to 1.8) and 1.4 (95% CI 1.1 to 1.8), respectively. The lymphoma relative risk (RR) was 11.5 (95% CI 3.7 to 26.9) and 1.3 (95% CI 0.2 to 4.5), respectively The total tumour RR excluding lymphoma was 0.79 (95% CI 0.4 to 1.42) and 1.39 (95% CI 1.08 to 1.76), respectively. Proportional hazard analysis for lymphomas yielded RR 4.9 (95% CI 0.9 to 26.2) in anti-TNF treated versus untreated patients. CONCLUSION: Community based patients with RA treated conventionally had an increased overall tumour risk compared with the background population. A possible additional increased risk for lymphoma associated with TNF blockers was based on few cases and needs confirmation.

Familial risk of tumors associated with hereditary non-polyposis colorectal cancer: a Swedish population-based study.

BACKGROUND: Familial clustering, which may be due to inherited predisposition, is seen in several common cancer types. The aim of this study was to assess the familial risk of tumors that are associated with hereditary non-polyposis colorectal cancer (HNPCC), a familial cancer syndrome that confers an increased risk of several cancer types, and is associated with a low age at onset. METHODS: The National Swedish Cancer Registry and population registers were utilized to identify all tumors among the offspring of individuals who had developed any of the diagnoses included in the Amsterdam II criteria for HNPCC. In all, 204,358 offspring of 102,814 individuals with cancer of the colorectum, endometrium, upper urinary tract or small intestine were identified. RESULTS: Significantly increased risks for several tumor types were demonstrated. If the parent was below age 50 at diagnosis, the offspring Standard Incidence Ratios (SIRs) were 3.6 for colon cancer, 3.8 for rectal cancer, 2.8 for gastric cancer, and 2.3 for ovarian cancer. Offspring who had both a parent and a sibling with HNPCC-associated cancer showed even higher SIRs for cancer of the colorectum, endometrium, ovary, and urinary tract. The highest values were observed in the subgroup whose parent had developed multiple primary tumors; SIR 34.0 for colon cancer, 17.9 for rectal cancer, 21.8 for endometrial cancer, and 5.8 for ovarian cancer. CONCLUSIONS: The study demonstrates that there is an increased risk for several tumor types among individuals whose parents developed HNPCC-associated tumors, where a young age at diagnosis and development of multiple tumors in the parents lead to the highest SIRs.

Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy?

OBJECTIVE: [corrected] To investigate the relationship between hormone replacement therapy (HRT), smoking, and cancer incidence. METHODS: Baseline interviews were conducted from 1990 to 1992 in a population-based cohort of 29,508 Swedish women aged 25-65 years with no history of cancer. Cancer incidence in the cohort was assessed through December 31, 1999, with the Swedish Cancer Registry, the Population Census Registry, and the Cause of Death Registry. RESULTS: When follow-up ended, the cohort included 226,611 person-years. A total of 1145 malignancies were diagnosed (observed), and 1166.6 were expected (standardized incidence ratio 0.98; 95% confidence interval [CI] 0.93, 1.04). Women who had experienced a natural menopause and had ever used HRT had no increased incidence of cancer overall (standardized incidence ratio 1.03; 95% CI 0.88, 1.19). Long-term HRT users who smoked had a decreased incidence of smoking-related cancers, such as the oral cavity, pharynx, hypopharynx, larynx, esophagus, lung, cervix, and bladder (standardized incidence ratio 0.24; 95% CI 0.08, 0.76). The effect was seen regardless of the type of HRT (progestin versus non-progestin-containing preparations) used and number of cigarettes smoked. The protective role of HRT for colon cancer was evident among both smokers and nonsmokers. An increased incidence of endometrial cancer was seen only for nonsmokers who used HRT. CONCLUSION: Our data indicate that HRT use protects women against smoking-associated cancers. This effect occurs regardless of the type of HRT and the amount of smoking.

A cohort study of reproductive factors and family history of breast cancer in southern Sweden.

BACKGROUND: Studies have been contradictory regarding the hypothesis that reproductive risk factors of breast cancer as parity and age at first full-term pregnancy (AFFP) operate differently in women with and without a family history of breast cancer. METHODS: The overall tumour incidence and breast cancer incidence related to fertility factors were followed in a population based cohort of 29,508 women aged 25-65 when interviewed between 1990 and 1992 in south Sweden. At the end of the follow up in December 1999, the cohort constituted 226,611 person years. The risk of breast cancer in relation to reproductive factors were studied in women with at least one first degree relative with breast cancer and compared with women without a family history. FINDINGS: A total of 1145 malignant tumours were seen and 1166.6 were expected (SIR = 0.98, 95% CI = 0.93-1.04). Slightly more breast cancer cases were seen 434 than expected 387.69 (SIR = 1.12, 95% CI = 1.02-1.23). A family history of breast cancer among a first degree relative was present in 1615 women . Forty-five breast cancers were seen among these women while 24.27 was expectecd (SIR = 1.85, 95% CI = 1.35-2.48). Nulliparous women with a family history of breast cancer had a higher risk of breast cancer, SIR = 1.76, 95% CI = 0.64-3.82, compared with nulliparous women without a family history, SIR = 1.13, 95% CI = 0.99-1.29. Similarly women with parity 1-2 with a family history had a higher SIR = 1.81, 95% CI = 1.16-2.69 compared with women without a family history having 1-2 children, SIR = 1.13, 95% CI = 0.99-1.29. In women with > or = 3 children those with a family history continued to have a high SIR = 1.98, 95% CI = 1.11-3.27 compared with women without a family history SIR = 0.90, 95% CI = 0.73-1.09. An early full-term pregnancy was protective in both groups. A higher risk than nulliparous women were seen after age 25 in the family history group and after age 30 in the sporadic cancer group. INTERPRETATION: Women with a first degree family history of breast cancer do not experience the sameprotection from a high number of pregnancies as women without a family history. However, an early first full-term pregnancy seems to offer a substantial protection in the family history group if undertaken before age 20. This suggest that reproductive factors tend to operate differently in the two groups of women.

Male gynecomastia and risk for malignant tumours--a cohort study.

BACKGROUND: Men with gynecomastia may suffer from absolute or relative estrogen excess and their risk of different malignancies may be increased. We tested whether men with gynecomastia were at greater risk of developing cancer. METHODS: A cohort was formed of all the men having a histopathological diagnosis of gynecomastia at the Department of Pathology, University of Lund, following an operation for either uni- or bilateral breast enlargement between 1970-1979. All possible causes of gynecomastia were accepted, such as endogenous or exogenous hormonal exposure as well as cases of unknown etiology. Prior to diagnosis of gynecomastia eight men had a diagnosis of prostate carcinoma, two men a diagnosis of unilateral breast cancer and one had Hodgkin's disease. These patients were included in the analyses. The final cohort of 446 men was matched to the Swedish Cancer Registry, Death Registry and General Population Registry. RESULTS: At the end of the follow up in December 1999, the cohort constituted 8375.2 person years of follow-up time. A total of 68 malignancies versus 66.07 expected were observed; SIR = 1.03 (95% CI 0.80-1.30). A significantly increased risk for testicular cancer; SIR = 5.82 (95% CI 1.20-17.00) and squamous cell carcinoma of the skin; SIR = 3.21 (95% CI 1.71-5.48) were noted. The increased risk appeared after 2 years of follow-up. A non-significantly increased risk for esophageal cancer was also seen while no new cases of male breast cancer were observed. However, in the prospective cohort, diagnostic operations for gynecomastia may substantially have reduced this risk CONCLUSIONS: There is a significant increased risk of testicular cancer and squamous cell carcinoma of the skin in men who have been operated on for gynecomastia.

A population-based cohort study of HRT use and breast cancer in southern Sweden.

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI 1.32-2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use.

Familial breast and ovarian cancer: a Swedish population-based register study.

A cohort of offspring of mothers with breast or ovarian cancer diagnosed in 1958-1993 was established using Swedish population-based registers. The children (n = 158,041) were born between 1941 and 1993, and their cancer incidence was followed between 1961 and 1993. A total of 3,257 tumors in 3,102 children were found. Observed numbers of cases were compared with expected numbers based on national calendar year-, age-, and sex-specific incidences. For daughters of women with breast cancer, the standardized morbidity ratios for being diagnosed with breast cancer and ovarian cancer before age 50 years were 1.99 (95% confidence interval (CI): 1.86, 2.14) and 1.28 (95% CI: 1.05, 1.54), respectively. The corresponding figures for daughters of women with ovarian cancer were 1.79 (95% CI: 1.55, 2.07) and 2.38 (95% CI: 1.77, 3.12). The risks were raised if the mother's cancer was diagnosed at a young age, the mother had multiple breast/ovarian diagnoses, or there was a sister with breast/ovarian cancer. Among all offspring, increased risks were found for thyroid cancer, testicular cancer, and malignant melanoma, while lung cancer risk was decreased if the mother had had breast cancer. The authors developed a variance estimator for the standardized morbidity ratio to cope with overdispersion due to dependency within families.

Increased cancer risk in offspring of women with colorectal carcinoma: a Swedish register-based cohort study.

BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background. METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference. RESULTS: A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population. CONCLUSIONS: This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.