• Breast cancer and hormonal contraceptives: further results. Collaborative Group on Hormonal Factors in Breast Cancer.

    3 July 2018

    The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on breast cancer risk and use of hormonal contraceptives. Original data from 54 studies, representing about 90% of the information available on the topic, were collected, checked and analysed centrally. The 54 studies were performed in 26 countries and include a total of 53,297 women with breast cancer and 100,239 women without breast cancer. The studies were varied in their design, setting and timing. Most information came from case-control studies with controls chosen from the general population; most women resided in Europe or North America and most cancers were diagnosed during the 1980s. Overall 41% of the women with breast cancer and 40% of the women without breast cancer had used oral contraceptives at some time; the median age at first use was 26 years, the median duration of use was 3 years, the median year of first use was 1968, the median time since first use was 16 years, and the median time since last use was 9 years. The main findings, summarised elsewhere, are that there is a small increase in the risk of having breast cancer diagnosed in current users of combined oral contraceptives and in women who had stopped use in the past 10 years but that there is no evidence of an increase in the risk more than 10 years after stopping use. In addition, the cancers diagnosed in women who had used oral contraceptives tended to be less advanced clinically than the cancers diagnosed in women who had not used them. Despite the large number of possibilities investigated, few factors appeared to modify the main findings either in recent or in past users. For recent users who began use before age 20 the relative risks are higher than for recent users who began at older ages. For women whose use of oral contraceptives ceased more than 10 years before there was some suggestion of a reduction in breast cancer risk in certain subgroups, with a deficit of tumors that had spread beyond the breast, especially among women who had used preparations containing the highest doses of oestrogen and progestogen. These findings are unexpected and need to be confirmed. Although these data represent most of the epidemiological evidence on the topic to date, there is still insufficient information to comment reliably about the effects of specific types of oestrogen or of progestogen. What evidence there is suggests, however, no major differences in the effects for specific types of oestrogen or of progestogen and that the pattern of risk associated with use of hormonal contraceptives containing progestogens alone may be similar to that observed for preparations containing both oestrogens and progestogens. On the basis of these results, there is little difference between women who have and have not used combined oral contraceptives in terms of the estimated cumulative number of breast cancers diagnosed during the period from starting use up to 20 years after stopping. The cancers diagnosed in women who have used oral contraceptives are, however, less advanced clinically than the cancers diagnosed in never users. Further research is needed to establish whether the associations described here are due to earlier diagnosis of breast cancer in women who have used oral contraceptives, to the biological effects of the hormonal contraceptives or to a combination of both. Little information is as yet available about the effects on breast cancer risk of oral contraceptive use that ceased more than 20 years before and as such data accumulate it will be necessary to re-examine the worldwide evidence.

  • Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies.

    3 July 2018

    OBJECTIVE: To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. STUDY DESIGN: The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. RESULTS: Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. CONCLUSIONS: Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.

  • Alcohol consumption and outcome of pregnancy.

    3 July 2018

    In a prospective study 1256 pregnant women at their first antenatal visit were asked if they drank alcohol every day, occasionally, or not at all, both at that time and before the diagnosis of pregnancy. There were no significant differences, among the three alcohol groups, in the proportions having miscarriages, perinatal deaths, congenital anomalies, or premature births. Women who reported drinking every day before pregnancy was diagnosed had heavier babies than those who did not drink at all, but there were no differences in mean birth weight according to alcohol use at the first antenatal visit. There were statistically significant differences among the three groups in important background characteristics, such as social class, age, smoking, and marital status. When adjustment was made for these factors, both occasional and daily consumption of alcohol before pregnancy appeared to have significantly positive effects on birth weight. These results illustrate the difficulty of evaluating the effects of alcohol in observational studies, and imply a need for caution in attributing either negative or positive effects of alcohol on the outcome of pregnancy.

  • Randomised trial of high doses of stilboestrol and ethisterone therapy in pregnancy: long-term follow-up of the children.

    3 July 2018

    The 27-year follow-up is reported of 136 children whose mothers were involved in a randomised trial of high doses of stilboestrol and ethisterone therapy during pregnancy. The children were not contacted directly. Information about them was obtained from hospitals, general practitioners, and other official sources; and the persons who responded to our inquiries were unaware of who had been exposed to hormones in utero and whose mothers had received an inactive tablet. All children were traced. Urogenital anomalies were reported more frequently in the hormone-exposed than the unexposed children (14% and 9% respectively). The earlier in pregnancy the therapy began, the higher the prevalence rate of abnormalities (X2 for trend, p less than 0.02). No malignant tumours were reported. For males, the proportion reported to be married or living as married was lower in the exposed than in the unexposed group (32% and 62% respectively). The proportion was lower the earlier in pregnancy hormonal exposure occurred and the higher the total hormone dose to which they were exposed (X2 for trend, p less than 0.02). These findings suggest that some interference with sexual function may not be uncommon in males exposed to high doses of stilboestrol and ethisterone while in utero.

  • Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk.

    3 July 2018

    BACKGROUND: Epidemiological studies have shown that taller people are at increased risk of cancer, but it is unclear if height-associated risks vary by cancer site, or by other factors such as smoking and socioeconomic status. Our aim was to investigate these associations in a large UK prospective cohort with sufficient information on incident cancer to allow direct comparison of height-associated risk across cancer sites and in relation to major potential confounding and modifying factors. METHODS: Information on height and other factors relevant for cancer was obtained in 1996-2001 for middle-aged women without previous cancer who were followed up for cancer incidence. We used Cox regression models to calculate adjusted relative risks (RRs) per 10 cm increase in measured height for total incident cancer and for 17 specific cancer sites, taking attained age as the underlying time variable. We also did a meta-analysis of published results from prospective studies of total cancer risk in relation to height. FINDINGS: 1 297 124 women included in our analysis were followed up for a total of 11·7 million person-years (median 9·4 years per woman, IQR 8·4-10·2), during which time 97 376 incident cancers occurred. The RR for total cancer was of 1·16 (95% CI 1·14-1·17; p<0·0001) for every 10 cm increase in height. Risk increased for 15 of the 17 cancer sites we assessed, and was statistically significant for ten sites: colon (RR per 10 cm increase in height 1·25, 95% CI 1·19-1·30), rectum (1·14, 1·07-1·22), malignant melanoma (1·32, 1·24-1·40), breast (1·17, 1·15-1·19), endometrium (1·19, 1·13-1·24), ovary (1·17, 1·11-1·23), kidney (1·29, 1·19-1·41), CNS (1·20, 1·12-1·29), non-Hodgkin lymphoma (1·21, 1·14-1·29), and leukaemia (1·26, 1·15-1·38). The increase in total cancer RR per 10 cm increase in height did not vary significantly by socioeconomic status or by ten other personal characteristics we assessed, but was significantly lower in current than in never smokers (p<0·0001). In current smokers, smoking-related cancers were not as strongly related to height as were other cancers (RR per 10 cm increase in height 1·05, 95% CI 1·01-1·09, and 1·17, 1·13-1·22, respectively; p=0·0004). In a meta-analysis of our study and ten other prospective studies, height-associated RRs for total cancer showed little variation across Europe, North America, Australasia, and Asia. INTERPRETATION: Cancer incidence increases with increasing adult height for most cancer sites. The relation between height and total cancer RR is similar in different populations. FUNDING: Cancer Research UK and the UK Medical Research Council.