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Bulletin of the World Health Organization. 1956; 15:5-41.The author reviews that mortality statistics from cancer of the breast in females and from malignant neoplasms of the uterus and of the other female genital organs for nineteen countries over the years 1920-53, first considering the general trend of the mortality series for each group of diseases for all ages and then analysing for each sector of mortality the changes which have occurred in the age-specific death-rates in some pivotal years during the same period. Considerable differences in the levels of total mortality from each group of tumours for various countries are noted. The important variations among age-specific death-rates for cancer of the breast in females and for uterine neoplasms in various countries are examined and their significance is commented upon. (excerpt)
A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer.
Anticancer Research. 2003 Jan-Feb; 23(1B):785-791.Objectives: To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with oxaliplatin (L-OHP) as first-line treatment of patients with advanced breast (ABC) and non-small cell lung cancer (NSCLC). Patients and methods: Fifty-two patients (26 with NSCLC and 26 with ABC), who had not received prior chemotherapy for metastatic disease, were enrolled. The patients' median age was 64 years, and 42 (71%) had a performance status (WHO) 0-1. Docetaxel was given as a 1-hour infusion after standard premedication on day 1 and L-OHP as a 2 to 6-hour infusion on day 2 every 3 weeks. Doses were escalated at increments of 10mg/m2. Results: The DLT1 was reached at the doses of docetaxel 75mg/m2 and L-OHP 80mg/m2. The addition of rhG-CSF permitted further dose escalation (DLT2: docetaxel 90mg/m2 and L-OHP 130mg/m2). The dose-limiting events were grade 4 neutropenia, febrile neutropenia, grades 3 or 4 diarrhea and grade 3 fatigue. Out of 239 delivered cycles, grades 3 or 4 neutropenia occurred in 22 (9%) cycles with 5 (2%) neutropenic febrile episodes. There was one septic death. Grades 3 or 4 fatigue was observed in seven (13%) patients and grades 3-4 diarrhea in five (10%). Out of 42 patients evaluable for response, seven (27%) patients with ABC and five (19%) patients with NSCLC experienced a partial response. Conclusion: The combination of docetaxel and oxaliplatin is a feasible and well-tolerated regimen. The recommended doses for future phase II studies are 75mg/m2 for docetaxel on day 1 and 70mg/m2 for L-OHP on day 2 without rhG-CSF support and 85mg/m2 and 130mg/m2, respectively, with rhG-CSF support. (author's)
World Health Organization Technical Report Series. 1981; (670):1-120.This report includes the collective views of a World Health Organization (WHO) Scientific Group on Research on the Menopause that met in Geneva during December 1980. It includes information on the following: 1) the endocrinology of the menopause and the postmenopausal period (changes in gonadotropins and estrogens immediately prior to the menopause and changes in gonadotropin and steroid hormone levels after the menopause); 2) the age distribution of the menopause (determining the age at menopause, factors influencing the age at menopause, and the range of ages at menopause and the definition of premature and delayed menopause); 3) sociocultural significance of the menopause in different settings; 4) symptoms associated with the menopause (vasomotor symptoms, psychological symptoms, disturbances of sexuality, and insomnia); 5) disorders resulting from, or possibly accelerated by, the menopause (osteoporosis, atherosclerotic cardiovascular disease, and arthritic disorders); 6) risks, with particular reference to neoplasia, of therapeutic estrogens and progestins given to peri- and postmenopausal women (endometrial cancer, breast cancer, and gallbladder disease); 7) fertility regulating methods for women approaching the menopause (fertility and the need for family planning in women approaching the menopause, problems of family planning in perimenopausal women, and considerations with regard to individual methods of family planning in women approaching the menopause); and 8) estrogen and the health care management of perimenopausal and postmenopausal women. At this time some controversy exists as to whether there is a menopausal syndrome of somatic and psychological symptoms and illness. There are virtually no data on the age distribution of the menopause and no information on its sociocultural significance in the developing countries. The subject of risks and benefits of estrogen therapy in peri- and postmenopausal women is of much importance in view of the large number of prescriptions issued for this medication in developed countries, which indicates their frequrnt use, and the different interpretations and opinions among epidemiologists and clinicians on both past and current studies on this subject. Specific recommendations made by the Scientific Group appear at the end of each section of the report. The following were among the general recommendations made: WHO sponsored research should be undertaken to determine the impact on health service needs of the rapidly increasing numbers of postmenopausal women in developing countries; uniform terminology should be adopted by health care workers with regard to the menopause; uniform endocrine standards should be developed which can be applied to the description of peri- and postmenopausal conditions and diseases; and descriptive epidemiological studies of the age at menopause should be performed in a variety of settings.
The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries.
CONTRACEPTION. 1991 Jun; 43(6):695-710.A hospital-based case-control study was conducted in 8 developing and 3 developed countries to determine whether use of combined oral contraceptives (OCs) alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of OCs, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing countries. Both causal and noncausal interpretations of this finding have been offered. No associations were found between OCs and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas. However, the ability of this study to detect alterations in risks for these neoplasms in longterm users was low. (author's)
WORLD HEALTH STATISTICS QUARTERLY. RAPPORT TRIMESTRIEL DE STATISTIQUES SANITAIRES MONDIALES. 1987; 40(3):267-78.The primary cause of death in women in the world is cancer. In most developing countries cancer of the cervix is the most prevalent cancer. Breast cancer has this distinction in Latin America and the developed countries of North America, Europe, Australia, and New Zealand. It is also the most prevalent cancer worldwide. The most common cancer in Japan and the Soviet Union is stomach cancer. Effective early detection programs can reduce both breast and cervical cancer mortality and also the degree and duration of treatment required. In Iceland, cervical cancer mortality declined 60% between the periods of 1959-1970 and 1975-1978. Programs consist of mammography, physician breast and self examination, and Pap smear. The sophisticated early detection equipment and techniques are expensive and largely located in urban areas, however, and not accessible to urban poor women and rural women, especially in developing countries. Tobacco smoking attributes to 80-90% of all lung cancer deaths worldwide and 30% of all cancer deaths. Passive smoking increases the risk of lung cancer to 25-35% in nonsmokers who breathe in tobacco smoke. Since smoking rates of women are skyrocketing, health specialists fear that lung cancer will replace cervical and breast cancers as the most common cancer in women worldwide in 20-30 years. Tobacco use also contributes to the high incidence of oral cancer in Southern and South Eastern Asia. For example, in India, incidence of oral cancer in women is 3-7 times higher than in developed countries with the smoking and chewing of tobacco in betel quid contributing. Techniques already exist to prevent 1/3 of all cancers. If cases can be discovered early enough and adequate treatment applied, another 1/3 of the cases can be cured. In those cases where the cancer cannot be cured, drugs can relieve 80-90% of the pain.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1986; 64(3):375-82.This memorandum from a World Health Organization (WHO) meeting held in 1985 summarizes available epidemiologic data from human studies, including the WHO Collaborative Study of Neoplasia and Steroid Contraceptives, on the association between depot-medroxyprogesterone acetate (DMPA) use and neoplasia. The WHO Collaborative Study is collecting data on cases and controls from 14 collaborating centers in 11 countries. Analysis of preliminary findings regarding cancers of the endometrium, ovary, liver, and breast suggest that there is no increased risk in DMPA users. The relative risk estimates for these sites are 0.3 for endometrial cancer, 0.7 for ovarian cancer, 1.0 for liver cancer, and 1.0 for breast cancer. The issue of a causal association between DMPA use and cervical cancer is less clear. The adjusted relative risk for cervical cancer was a nonsignificant 1.2; however, somewhat higher risks were noted in subgroups of longterm (over 4 years) users. Although the WHO study is the 1st to provide reliable data on DMPA and neoplasia, its findings must be regarded as tentative. At this point the data are insufficient to assess the influence of DMPA on risk among longterm users or risk long after initial exposure.
Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. [WHO Collaborative Study of Neoplasia and Steroid Contraceptives] [letter].
Lancet. 1984 Nov 24; 2(8413):1207-8.This letter presents the preliminary findings of a collaborative, multinational, hospital-based, case-control study being conducted under the auspices of the World Health Organization to assess the influence of depot medroxyprogesterone acetate (DMPA) on risks of mammary, gynecological, and hepatobiliary malignancies. The frequency of ever-use of DMPA was greater in breast cancer cases (15/246, or 6,0%) than in controls (381/4162, or 9.2%). When adjusted for age, center, age of birth of 1st child, and nulliparity, the relative risk in women who had ever used DMPA was 0.7. The lowest risk was noted in women who had used DMPA for 3 or more years, but no decreasing trend in risk with duration of use was evident. The reducton in risk of breast cancer in DMPA users was largely confined to women with 1st exposure after age 30 years. In terms of cervical cancer, a history of DMPA use was reported by slightly more cases (67/469, or 14.3%) than controls (269/2704, or 9.9%). Use of oral contraceptives, number of cervical smears, and number of pregnancies were the variables most strongly related to cervical or having the greatest influence on relative risk estimates for users of DMPA. When controlled for these 4 factors and age and center, the relative risk in DMPA was 1.13. The highest relative risk was found in longterm users, although there was no clear trend of increasing risk with duration of DMPA use. These preliminary findings provide no evidence that DMPA increases the risk of breast cancer. The relative risk for cervical cancer for DMPA users obtained in this study could be due to chance or to incomplete control for the confounding effect of sexual variables. Although the absence of a trend of increasing risk with duration of use tends to rule out a causal connection between DMPA use and cervical cancer, the doubling of risk in women who used DMPA for 5 years or more is of potential concern.
People. 1984; 11(1):33.Recent suggestions that there might be a causal link between oral contraceptives (OCs) and breast and cervical cancer are not based on evidence strong enough to warrant any change in prescribing practice, according to the medical advisers of the International Planned Parenthood Federation (IPPF). A US study suggests that for women who use OCs for several years before the age of 25 there may be a slightly increased risk of developing breast cancer later in their lives. The risk of breast cancer was influenced by the type of OCs the women took. They suggest that those brands with a high level of progestogen potency are the culprits. The other study from the UK suggests that women who use OCs for several years are more likely to develop cancer of the uterine cervix than women who use IUDs for similar lengths of time. Both studies left the Medical Advisory Panel of IPPF convinced that there is insufficient evidence to make it advisable for family planning programs to change their prescribing policies. The breast cancer study has several methodological weaknesses which could have influenced its results and these differed from results published by other, large scale studies. There is strong disagreement in the medical profession about the validity of the way the US team assessed progestogen potency. The Panel agreed that the number of women in the study who used each brand of OC was too small to justify drawing any definite conclusions about which OCs to prescribe for women aged under 25. The Panel noted that the cervical cancer study failed to take into account the sexual history of the subjects even though the age at 1st intercourse and the number of sexual partners a woman has are known to affect the likelihood of her developing cervical cancer. This, combined with the fact that other studies have not shown a relationship between OC use and cervical cancer, led the Panel to recommend to change in current practice. Data from the 2 studies are currently being analyzed again, to look specifically at the association between breast cancer and OC use. This reanalysis will be closely monitored by the Panel which will review its own recommendations as further evidence becomes available.
LAKARTIDNINGEN. 1979 Apr 25; 76(17):1625-7.An overview of the risk of developing cancer related to oral contraceptive (o.c.) use is presented. A committee of experts affiliated with WHO studied the problem of developing cancer related to o.c. use. O.c. use for more than 2 years prevents the formation of benign breast tumors, even after discontinuing o.c. use. The effect is due to the progestin component. There is no clear indication that o.c. use increases the risk of breast cancer. A higher risk of endometrial cancer is associated with sequential preparation use, but not with the use of combination preparations. Cervical neoplasms and pituitary adenoma may be more frequent among predisposed women who use o.c.s. Studies show a reduced risk of ovarian cancer with o.c. use, but more studies are necessary. There is a marked increase in the relative risk of developing hepatocellular adenoma among women who use o.c.s for longer than 3 years. The risk increases with the hormone dosage, the duration of treatment, and the age of the patient. There is no reliable data to indicate that the risk of malignant melanoma increases with o.c. use. More study is needed to determine the possible cancer risks of injection preparations. Combination preparations can cause an increased risk of vaginal epithelial metaplasia. Diethylstilbestrol taken during early pregnancy can cause vaginal neoplasms in the offspring. More epidemiological studies and clinical and laboratory studies on the carcinogenic effects of o.c.s and the endocrinological effects of o.c.s on younger women should be undertaken. It is recommended that o.c.s with the lowest possible hormone dosages be used. O.c.s should not be prescribed to women with vaginal adenosis. (Summary in ENG)
Contraception. 1970 Jun; 1(6):409-445.This article reviews the validity of previously published material linking oral contraceptive usage to health hazards. The statistical methods involved in such studies are thoroughly examined, particularly those studies relating oral contraceptive usage to thromboembolic disease incidence. Problems inherent to the basic designs of such studies are discussed. Some relationship between thromembolic disease and oral contraceptive usage has been established. Studies on animals relating oral contraceptive usage with carcinogenesis are inconclusive due to the different metabolic rates obtained for different animals and different strains and the high dosage used to produce tumors. Review of the data relating oral contraceptives with alterations in carbohydrate metabolism, serum lipids, etc., show pure speculation of conclusion. Endrocrine effects persisting after discontinuation of oral contraceptives were rare; apparently both types of steroids play some part. It was suggested that most data on this subject is faulty and filled with fixed opinions which should be avoided.
In: McDaniel EB, ed. Second Asian Regional Workshop on Injectable Contraceptives. Oklahoma City, Oklahoma, World Neighbors, 1982. 39-44.The best available data on the possible side effects of Depot Medroxyprogesterone Acetate (DMPA) are examined so that physicians and health officials can decide for themselves whether DMPA is appropriate for use in their countries. Several evaluations of the scientific evidence on the safety of DMPA have taken place in the last few years. The US Food and Drug Administration (FDA) announced in 1978 that it would not approve DMPA for use in the US. Subsequently, the World Health Organization's (WHO) Toxicology Review Panel conducted a review and found no reason to recommend that DMPA be withdrawn from use. In 1980 an Ad Hoc Consultative Panel presented its findings and recommendations to the US Agency for International Development (USAID). The Panel recommended that USAID make DMPA available to national family planning programs upon request. This recommendation was based on careful consideration of the medical and ethical issues involved by Panel members with expertise in the fields of obstetrics and gynecology, animal physiology and toxicology, epidemiology, pathology, law, and health policy. DMPA is currently approved for contraceptive use in more than 80 developed and developing countries. Each of the 6 reasons for FDA's denial of approval of DMPA are reviewed: studies using beagle dogs showed an increased incidence of mammary tumors associated with DMPA use; the availability of a number of alternative methods of contraception in the US and the lack of clear evidence that a significant patient population in need of DMPA exists in the US; the possibility that bleeding disturbances caused by the drug may lead to the administration of estrogen, thus decreasing the benefits of a progestogen only contraceptive; the possibility that exposure of fetuses to DMPA, if pregnancy occurs, poses a risk of congenital malformation; and reservations about the ability of the post marketing study for breast and cervical carcinoma. As a result of species differences in reactions to DMPA, the WHO Toxicology Review Panel, the Ad Hoc Panel, and the UK Commission on Safety of Medicines have stated that it is not possible to conclude from the beagle studies that DMPA poses any increased risk of breast cancer to women. The Ad Hoc Panel found little information on the effects of progestogen alone and concluded that the data fail to suggest that DMPA poses more of a threat of fetal malformation than do other hormonal contraceptives. Thorough discussion of menstrual changes with prospective DMPA users and supportive patient counseling are the best methods of dealing with concerns about irregular bleeding and amenorrhea. Regarding endometrial cancer, preliminary evidence suggests that progestogens may even protect against endometrial cancer.
Ippf Medical Bulletin. 1983 Dec; 17(6):1-2.The response of the International Medical Advisory Panel (IMAP) of the International Planned Parenthood Federation to 2 recent papers suggesting a link between cancer and oral contraceptive (OC) use is reported. The 1st paper by Pike et al. suggested an increased risk of breast cancer in women who use OCs containing high potency progestogens before age 25 for at least 4 years. It is noted that several methodological problems with the study design could have introduced a degree of selection of ascertainment bias. These issues include the procedures used for age matching between cases and controls, the 1/3 loss to follow-up among cancer cases, and the use of telephone interviews to ascertain OC use history. Moreover, data from other studies suggest that ever-users of OCs who develop breast cancer may be more likely to survive than women with breast cancer who have never used OCs, leading to the overrepresentation of women in the former group among surviving cases. The ranking of OCs by progestogen potency does not take the estrogen content into consideration. In addition, assessment of progestogen potency by use of a delay of menses test may not correlate with the degree of effect on the breast and has produced conflicting results when used by different researchers. Finally, the numbers of women using some OC brands were too small and the possibility that women may have changed OC brand over the study period was not considered. Largescale studies such as the UK Oxford-Family Planning Association contraceptive study and the Centers for Disease Control Cancer and Steroidal Hormone Study are curently being reanalyzed, controlling for type and amount of progestogen in the OCs. Until new data become available, IMAP believes there is insufficient evidence to recommend modification of existing practice. The 2nd study by Vessey et al. suggested a higher incidence of cervical cancer in OC users as compared to IUD users. However, several key modifying factors on the risk of cervical cancer, including age at 1st sexual intercourse and number of partners, could not be controlled for. Moreover, a high proportion of OC use involved preparations containing 50 mcg or more of estrogen. Although regular cervical smears are recommended for OC users, the IMAP again does not recommend any change in current practice. The IMAP noted that the possible cancer-related risks of OCs must be weighed against the protective effects of OCs against cancers of the endometrium and ovary, pelvic inflammatory disease, and unwanted pregnancies.