Torgil Möller

Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50 302 women with breast cancer and 96 973 women without the disease

Background Although childbearing is known to protect against breast cancer, whether or not breastfeeding contributes to this protective effect is unclear. Methods Individual data from 47 epidemiological studies in 30 countries that included information on breastfeeding patterns and other aspects of childbearing were collected, checked, and analysed centrally, for 50 302 women with invasive breast cancer and 96 973 controls. Estimates of the relative risk for breast cancer associated with breastfeeding in parous women were obtained after stratification by fine divisions of age, parity, and womens ages when their first child was born, as well as by study and menopausal status. Findings Women with breast cancer had, on average, fewer births than did controls (2·2 vs 2·6). Furthermore, fewer parous women with cancer than parous controls had ever breastfed (71% vs 79%), and their average lifetime duration of breastfeeding was shorter (9·8 vs 15·6 months). The relative risk of breast cancer decreased by 4·3% (95% CI 2·9–5·8; p<0·0001) for every 12 months of breastfeeding in addition to a decrease of 7·0% (5·0–9·0; p<0·0001) for each birth. The size of the decline in the relative risk of breast cancer associated with breastfeeding did not differ significantly for women in developed and developing countries, and did not vary significantly by age, menopausal status, ethnic origin, the number of births a woman had, her age when her first child was born, or any of nine other personal characteristics examined. It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6·3 to 2·7 per 100 women by age 70, if women had the average number of births and lifetime duration of breastfeeding that had been prevalent in developing countries until recently. Breastfeeding could account for almost two-thirds of this estimated reduction in breast cancer incidence. Interpretation The longer women breast feed the more they are protected against breast cancer. The lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries. (Less)BACKGROUND Although childbearing is known to protect against breast cancer, whether or not breastfeeding contributes to this protective effect is unclear. METHODS Individual data from 47 epidemiological studies in 30 countries that included information on breastfeeding patterns and other aspects of childbearing were collected, checked, and analysed centrally, for 50302 women with invasive breast cancer and 96973 controls. Estimates of the relative risk for breast cancer associated with breastfeeding in parous women were obtained after stratification by fine divisions of age, parity, and womens ages when their first child was born, as well as by study and menopausal status. FINDINGS Women with breast cancer had, on average, fewer births than did controls (2.2 vs 2.6). Furthermore, fewer parous women with cancer than parous controls had ever breastfed (71% vs 79%), and their average lifetime duration of breastfeeding was shorter (9.8 vs 15.6 months). The relative risk of breast cancer decreased by 4.3% (95% CI 2.9-5.8; p<0.0001) for every 12 months of breastfeeding in addition to a decrease of 7.0% (5.0-9.0; p<0.0001) for each birth. The size of the decline in the relative risk of breast cancer associated with breastfeeding did not differ significantly for women in developed and developing countries, and did not vary significantly by age, menopausal status, ethnic origin, the number of births a woman had, her age when her first child was born, or any of nine other personal characteristics examined. It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6.3 to 2.7 per 100 women by age 70, if women had the average number of births and lifetime duration of breastfeeding that had been prevalent in developing countries until recently. Breastfeeding could account for almost two-thirds of this estimated reduction in breast cancer incidence. INTERPRETATION The longer women breast feed the more they are protected against breast cancer. The lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries.

Decreasing Late Mortality Among Five-Year Survivors of Cancer in Childhood and Adolescence: A Population-Based Study in the Nordic Countries

PURPOSE To assess the risk of death in patients who survive more than 5 years after diagnosis of childhood cancer and to evaluate causes of death in fatal cases. PATIENTS AND METHODS This was a population-based study in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) using data of the nationwide cancer registries and the cause-of-death registries. The study cohort included 13,711 patients who were diagnosed with cancer before the age of 20 years between 1960 and 1989 and who survived at least 5 years from diagnosis. By December 31, 1995, 1,422 patients had died, and death certificates were assessed in 1,402. Standardized mortality ratios (SMRs) for validated causes of death were calculated based on 156,046 patient-years at risk. RESULTS The overall SMR was 10.8 (95% confidence interval [CI], 10.3 to 11.5), mainly due to high excess mortality from the primary cancer. SMR for second cancer was 4.9 (95% CI, 3.9 to 5.9) and was 3.1 (95% CI, 2.8 to 3.5) for noncancer death. The pattern of causes of death varied markedly between different groups of primary cancer diagnoses and was highly dependent on time passed since diagnosis. Overall late mortality was significantly lower in patients treated during the most recent period of time, 1980 to 1989, compared with those treated from 1960 to 1979 (hazard ratio, 0.61; 95% CI, 0.54 to 0.70), and there was no increase in rates of death due to cancer treatment. CONCLUSION Long-term survivors of childhood cancer had an increased mortality rate, mainly dying from primary cancers. However, modern treatments have reduced late cancer mortality without increasing the rate of therapy-related deaths.

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.

PURPOSE To assess the risk of subsequent malignant neoplasms among Hodgkins disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). PATIENTS AND METHODS There were 1,641 Hodgkins disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. RESULTS A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkins lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkins disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkins disease in the 1980s. CONCLUSION Patients who survive Hodgkins disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkins disease in the teenage years calls for enhanced activity for early diagnosis.

Incidence and survival of squamous cell carcinoma of the tongue in Scandinavia, with special reference to young adults

In several countries, increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been suspected during the last decades. Some reports indicate a lower survival rate for young patients compared to older patients. In other reports, there has not been any considerable difference in survival when comparing young adults to older patients, whereas some authors have shown better survival for young adults. This disease is rare in young adults, and early reports were based on comparable small numbers and selected patients. Our aim was first to perform a population‐based study to determine if an increased incidence in SCC of the tongue could be verified in a larger population comprising the Scandinavian countries Denmark, Finland, Sweden and Norway. A second aim was to determine survival rates for young adults compared to older patients. The material was based on the annual cancer incidence and survival reports from the Scandinavian cancer registries. The study period was 1960–1994. During that period, 5,024 SCCs of the tongue were reported. Of these, 276 (5.5%) were young adults (20–39 years). The incidence increased at all ages except for women 65–79 years old. The increase was most pronounced in young adults: 0.06–0.32 for men and 0.03–0.19 for women, counted by 100,000 person‐years. Relative survival was significantly better for young adults compared to older patients.

Carcinoma of the parotid and submandibular glands-a study of survival in 2465 patients.

Salivary gland carcinomas demonstrate a wide diversity of histopathological types and biological behavior. The aim of this study was to analyze relative survival of patients with major salivary gland carcinomas with special reference to histopathology, gender and age. All new carcinomas of the major salivary glands reported to the National Swedish Cancer Registry 1960-1995 were searched for and the vital status of the cases was updated by record linkage to the Swedish Population Registry through December 31 1996. The study comprised 2465 patients with carcinoma of the parotid or submandibular glands. Relative survival differed markedly according to histopathological typing (P<0.001). For parotid tumors, acinic cell carcinomas had the best prognosis with a 10-year relative survival of 88%. The corresponding figures for mucoepidermoid carcinomas, adenoidcystic carcinomas and carcinoma ex pleomorphic adenoma were 80, 74 and 73%. Adenocarcinoma NOS and undifferentiated carcinoma had worse prognosis, with 10-year relative survival of 55 and 44%. Patients with submandibular gland cancer had similar relative survival to those with parotid cancers, besides those with mucoepidermoid cancer and adenocarcinoma NOS, who carried worse prognosis. Age and gender had an impact on relative survival for patients with mucoepidermoid carcinoma, adenocarcinoma and undifferentiated cancer of the parotid.

Effect of pregnancy on prognosis for young women with breast cancer

Breast cancer in women under 30 years old carries a poor prognosis, for reasons that have not been identified. This study aimed to identify prognostic factors in this age group. Special attention was paid to the history of pregnancy. The clinical presentation and course of breast cancer was documented for 407 women, aged 20-29 years, who registered between 1978 and 1988 at one of nine cancer centres. Eligible patients had histologically confirmed local or regional invasive breast carcinoma, and received part or all of their initial therapy at the participating hospital. For patients whose breast cancers were diagnosed during pregnancy, the risk of dying from breast cancer was significantly greater than that of women who had never been pregnant (relative risk 3.26 [95% CI 1.81-5.87], p = 0.0004). Adjustment for number of axillary nodes affected and tumour diameter reduced the relative risk only slightly (2.83 [1.24-6.45], p = 0.023). For each 1-year increment in the time between the latest previous pregnancy and breast cancer diagnosis, the risk of dying decreased by 15% (relative risk 0.85, p = 0.011). Thus concurrent or recent previous pregnancy adversely affects survival of breast cancer in young women. The size of the effect is such that it probably contributes substantially to the poor prognosis of breast cancer in this age group as a whole.

SECOND MALIGNANT NEOPLASMS AFTER CANCER IN CHILDHOOD AND ADOLESCENCE: A POPULATION-BASED CASE-CONTROL STUDY IN THE 5 NORDIC COUNTRIES

Our purpose was to assess the risk of developing a second malignant neoplasm (SMN) after cancer in childhood and adolescence associated with different treatment modalities. Our investigation was performed as a nested case‐control study within a Nordic cohort of 25,120 patients younger than 20 years old at first malignant neoplasm (FMN) diagnosed in 1960 through 1987. SMNs were diagnosed in 1960 through 1991. For each case of SMN, 3 controls were sampled, matched by sex, age, calendar year of diagnosis and length of follow‐up. For the final analysis, there were 234 cases and 678 controls. Relative risks (RRs) of various exposures were estimated by means of conditional logistic regression, with non‐exposed as the reference. The RR of developing SMN in the radiated volume was 4.3 (95% confidence interval 3.0–6.2). The risk was highest in children diagnosed before the age of 5 years; it increased with the dose of radiation and with increasing follow‐up time after FMN. Chemotherapy alone was not associated with an increased RR, but it significantly potentiated the effect of radiotherapy. RRs were unchanged between the periods 1960–1973 and 1974–1987, and since the use of chemotherapy increased in the latter period, the number of SMNs may increase. Hereditary factors were important for the occurrence of SMN independently of therapy. We conclude that radiation was the most important treatment‐related risk factor for the development of SMN. Chemotherapy appeared to play only an accessory role during the study period, potentiating the carcinogenic effect of radiotherapy. Int. J. Cancer 88:672–678, 2000.

Risk of cancer among offspring of childhood-cancer survivors

BACKGROUND Increasing numbers of children with cancer survive and reach reproductive age. However, the risk of cancer (other than retinoblastoma) in the offspring of survivors of childhood and adolescent cancer is uncertain. METHODS Using data from national cancer and birth registries, we assessed the risk of cancer among 5847 offspring of 14,652 survivors of cancer in childhood or adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland, Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for 86,780 person-years, and standardized incidence ratios were calculated. RESULTS Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17 retinoblastomas, yielding a standardized incidence ratio of 37. There were 27 neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The second most common primary site of cancer among the offspring was the brain and nervous system, in which eight tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases of cancer in other primary sites among the offspring. Excluding 4 likely cases of hereditary cancer and 2 subsequent cancers among the offspring with hereditary retinoblastoma, there were 22 sporadic cancers, for a standardized incidence ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0). CONCLUSIONS There is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of survivors of cancer in childhood.

Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening

The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.

Lifelong Cancer Incidence in 47 697 Patients Treated for Childhood Cancer in the Nordic Countries

BACKGROUND The pattern of cancer in long-term survivors from childhood cancer has not been investigated comprehensively. METHODS We obtained a cohort of 47,697 children and adolescents aged 0-19 years with cancer as defined by the country-wide cancer registries of Denmark, Finland, Iceland, Norway, and Sweden during 1943-2005. Cohort members were followed through age 79 years for subsequent primary cancers notified to the registries, and the age-specific risk pattern of the survivors was compared with that of the national populations using country and sex standardized incidence ratios (SIRs). We used a multiplicative Poisson regression model to estimate relative risk of cancer for attained age, with adjustment for calendar period and age at diagnosis of primary cancer. We also calculated excess absolute risk (EAR) attributable to status as childhood cancer survivor and determined the cumulative incidence of second primary cancer as a function of attained age for three subcohorts defined by period of treatment for childhood cancer. RESULTS A total of 1180 asynchronous second primary cancers were observed in 1088 persons, yielding an overall SIR of 3.3 (95% confidence interval = 3.1 to 3.5). The relative risk was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. The EAR for second primary cancer among survivors increased gradually from one additional case per 1000 person-years of observation in early life to six additional cases per 1000 person-years in the age group 60-69 years. For children treated in the prechemotherapy era (1943-1959), the cumulative risk for a second primary cancer reached 18%, 34%, and 48% at ages 60, 70, and 80 years, respectively. The age-specific incidence rates were highest for cohort members treated in the era of intensive, multiple-agent chemotherapy (1975-2005). CONCLUSION Survivors of childhood cancer have a persistent excess risk for a second primary cancer throughout their lives, accompanied by continuous changes in the risk of cancers at specific sites.