Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies

Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users

Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58 515 women with invasive breast cancer and 95 067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19–1.45, P<0.00001) for an intake of 35–44 g per day alcohol, and 1.46 (1.33–1.61, P<0.00001) for ⩾45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5–8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98–1.07, and for current smokers=0.99, 0.92–1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver

Opposing effects of quinacrine and chloroquine on the development of TA3 transplanted tumors in mice

Both quinacrine and chloroquine had been used as antimalarial agents. Furthermore, antineoplastic and antiviral effects have been described for quinacrine, while chloroquine has been described to induce viral replication and promote tumor growth. To search for differences in the growing rate of transplanted tumors, chloroquine or quinacrine were administered orally to AJ mice from 30 days previous to the inoculation of TA3 transplantable tumor cells, treatment being continued up to the end of the experiment. A control group, transplanted with tumor cells received tap drinking water. Marked differences between the three groups were found. Quinacrine had antitumoral effect, while chloroquine promoted a faster tumoral growth than controls (p &lt; 0.01). Results suggest caution in the use of chloroquine, because it might have a similar promoting effect on human neoplasia

Ovulation induction: ovarian response to human gonadotropins and synthetic gonadotropin-releasing hormone.

Human ovarian responses to FSH- and LH-releasing hormone (FSH/LH-RH) were observed at laparotomy and studies by histologic and histochemical examination of ovarian biopsy specimens. The responses were compared to those induced by human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) singly and together. The subjects were healthy, fertile, young women rendered anovulatory by injections of depomedroxyprogesterone acetate (DMPA) or depochlormadinone acetate (CA). Supplementary studies included measurement of urinary pregnanediol, examination of the cervix and vagina for estrogenic and progestational responses, and endometrial biopsy, Both HMG and HCG induced follicular growth and proliferation of granulosa and theca cells, but neither, when given alone, induced ovulation or corpus luteum formation. When given in conjunction they induced single or multiple ovulations and corpora lutea in 11 of 18 women treated. FSH/LH-RH CONSISTENTLY STIMULATED FOLLICULAR DEVELOPMENT AND INDUCED OVULATION IN 2 OF 16 WOMEN TREATED. Preovulatory mature follicles were found in 3 more. FSH/LH-RH may prove to be useful in the treatment of some cases of anovulatory sterility of hypothalamic origin

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver

Monthly injectable steroid contraceptives and cervical carcinoma

The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives is a large multinational hospital-based case-control study of steroid contraceptives and gynecologic, hepatobiliary, and mammary neoplasms. Monthly injectable steroid contraceptives which contained the long-acting pro-gestogen dihydroxyprogesterone acetofenide plus a shorter-acting estrogen (usually estradiol enanthate) were used by women in two of the countries (Chile and Mexico) from which data were collected. In preliminary analyses of data from Chile (1979-1983), a strong association was observed between use of these products and invasive cervical cancer. Therefore, three additional data sets from these two countries were analyzed in further detail for this report. Analyses of additional data from Chile on invasive cervical cancer (1983-1985) and cervical carcinoma in situ (1979-1986) and of data on invasive cervical cancer from Mexico (1979-1986) failed to confirm the initially observed asso

Intrauterine devices and endometrial cancer

The relationship between intrauterine device (IUD) use and the development of endometrial cancer was assessed in data from seven countries that were collected between 1979 and 1988 for a multinational hospital-based case-control study. Two hundred twenty-six cases of endometrial cancer were compared with 1,529 controls matched for age, hospital, and year of interview. No significant association between use of an IUD and risk of endometrial cancer was observed (OR = 0.74, 95% CI = 0.4-1.33). There were no trends in risk with respect to duration of use, time since first use, or ages at first or last use. No cases had used a copper IUD (OR = 0, 95% CI = 0- 1.71). Although women over age 55 who had used an IUD were at significantly increased risk, this unexpected finding is based on small numbers of users and requires independent confirmation. These results, along with those from other studies, provide reassurance that risk of endometrial cancer is unlikely to be increased by use of an IU

Histologic types of breast carcinoma in relation to international variation and breast cancer risk factors

Associations between breast cancer risk factors and histologic types of invasive breast carcinoma were studied in 2,728 patients. Lobular and tubular carcinomas occurred with increased relative frequency in most high‐risk groups. The proportion of these types increased with age to a maximum at 45–49 years and decreased in the following decade. Significantly increased proportions of lobular and tubular carcinomas were also associated with high‐risk countries, prior benign breast biopsy, bilateral breast cancer, concurrent mammary dysplasia, high age at first live birth, never‐pregnant patients compared to those with a first live birth before age 20, private pay status, and length of education. Nonsignificant increases were associated with family history of breast cancer, less than 5 live births, less than 25 months total of breast feeding, use of oral contraceptives or IUD, and high occupational class. As a general trend, the higher the overall relative risk, the higher the proportion