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From page 177... ... Index A Abortion, 131 Activation, of oncogenes, 45-46 Age and breast cancer rate, 10-11, 12, 20, 21, 29, 57-58 at diagnosis, 128-129 and duration of exposure, 97 and effect of hormones, 2 and epithelial proliferation, 32 at first live birth, 112, 114 less than 25, 87-88, 94-98, 118124, 137, 169, 170-172 and oral contraceptive use, 9,10, 13, 14 Alleles, 31 Amplification, of ins-2 and myc, 47 Animal studies direct tests of carcinogenicity, 153-159 of mechanisms of mammary carcinogenicity of sex steroid hormones, 160-162 of pharmacokinetics of various steroids, 160 potential contributions of, 19, 48 177 questions raised by, 163-164 Athymic mice, 53 B Barrier methods, recommendations on research with, 5 bcl-1 gene, 47 Beagle dogs direct tests of carcinogenicity in, 154-159 mechanisms of carcinogenicity in, 161-162 pharmacokinetics in, 160 risk factors in, 163 Benefits, of oral contraceptive use, 55-57, 165-172 Benign breast disease, 42-43, 89, 114-118, 136-137 Biological knowledge, recommendations on research for, 7, 65-66 Biological markers, recommendations on, 4, 7, 66 Birth cohort, oral contraceptive use by, 10,13, 14 Blood levels, of ethinyl estradiol and progestin, 148-149 Read the entire page →
From page 178... ... Study, 62, 76, 81, 87 Carcinogenesis potential, 13 Carcinogenicity in beagle dogs, 154-159, 161-162 direct tests of, 153-159 in mice and rats, 153-154, 155, 161, 162 studies of mechanisms for, 160162 Cardiovascular disease, oral contraceptives and, 20, 22, 57, 58, 166-167 Case-control studies, 26-27 of benign breast disease, 114-116, 117 design of, 92-93, 97 of developing countries, 109-111 disadvantages of, 26 of early use, 120-124 of ever use of oral contraceptives 104-105, 124-125 of latency, 107, 108 of long-term use, 106, 125-126 recommendations on, 7, 26-27 and relative risk, 26 size of, 26 of use before first full-term pregnancy, 116-120 Catechol estrogens, 39 Cell lines, 49-50 Cell types, relationships among, 40 Cervical cancer, oral contraceptives and, 23, 167, 168 Children, number of, 112, 114 Chlamydial infection, 56 Chlorethinyl-norgestrel, carcinogenicity of, 158, 159 Chlormadinone, 138 Read the entire page →
From page 179... ... , 153-154, 155 Comparison groups, 28 Confounding variables, 170 Consensus conferences, recommendations on, 6, 65 Contraceptives, developing broader array of, 64 Controls, selection of, 92, 170 Cost, of long-term prospective studies, 34, 67 Critical time periods, 41 Cultures organ, 52-53 short-term mammary epithelial cell, 50-52 Cysts, 42-43 Cytokeratin, 14, 52 D Deletion, of genes, 48 Depomedroxyprogesterone acetate (DMPA) , 138, 157-159 DES, 29 Desogestrel, 146-147 Detection bias, 94 Developed countries, risk in, 10~109 179 Developing countries benefits in, 166, 167 risk in, 16, 109-111, 136 Diethylstilbestrol (DES) Read the entire page →
From page 180... ... endogenous, 39 temporal effect of, 39 INDEX Estrogenicity, 147 Estrogen receptors, down-regulation by progestins of, 149-150 Estrone, 39 Ethinyl estradiol blood levels of, 148-149 direct tests of carcinogenicity of, 154, 155, 157 epidemiological studies on, 133, 134, 138 metabolism of, 39 in oral contraceptive formulations, 17 Ethynerone, carcinogenicity of, 154 Ethynodiol diacetate, carcinogenicity of, 158, 159 '`Ever" use, of oral contraceptives, 79, 80, 104-105, 124-127 Exposure opportunity, 93 Extracellular matrix (ECM) proteins, 37, 40 Family history, 29-31, 43, 112, 115 Femodene, 146, 148 Fibroadenomas, 42-43, 115 Fibroblast growth factor, 36, 37 Fibrocystic disease, 116 First full-term pregnancy (FFTP) Read the entire page →
From page 181... ... infection, 167 Human tissue models, see In vitro human tissue models Human trials, of drugs, 18 16a-Hydroxyestrone, 32, 39 17a-Hydroxyprogesterone derivatives, 133, 138 Hysterectomy, 11 Incidence I of breast cancer, 1, 9-10, 11, 75 of oral contraceptive use, 1, 9 Information, recommendations on dissemination of, 4, 6, 65 Insulin-like growth factors, 36, 37 ins-1 gene, 47 ins-2 gene, 47 In vitro human tissue models athymic mice, 53 organ cultures, 52-53 potential contributions of, 19 recommendations for, 7 short-term mammary epithelial cell cultures, 50-52 tumor cell lines, 49-50 Iron-deficiency anemia, 55-56 181 K 3-Keto-desogestrel, 146, 147-148 Kl-ras oncogenes, 45 L Lactation, see Breastfeeding Latency effects, 88-89, 96, 107, 108109, 118, 122 Levonogestrel androgenicity of, 147 carcinogenicity of, 157-159,160 Longitudinal studies, see Cohort studies M Mammary epithelial cell cultures 50-52 Mammary tissue, see Breast tissue Mammographic screening, 75-76, 129-131, 137 Mammoplasties, reduction, epithelial cell cultures from, 51 Manufacturers, premarketing and postmarketing testing by, 5, 18-19 Marital status, oral contraceptive use by, 10 Marvelon, 146, 147-148 Medicare data bases, 62 Medroxyprogesterone acetate (MPA) , carcinogenicity of, 159 Megestrol acetate, carcinogenicity of, 158, 159 Melatonin, 148 Menopause, oral contraceptive use near, 131-132, 137-138 Menorrhagia, 55-56 Menstrual cycle breast tissue during, 35 epithelial proliferation and, 32 estrogen levels during, 38-39 oral contraceptives and, 55-56 Mestranol direct tests of carcinogenicity of, 154, 155, 157 epidemiological studies on, 133, 134, 138 Read the entire page →
From page 182... ... consensus conferences, recommendations on, 6, 65 neu gene, 46-47 Nonresponse bias, 170 Nonsteroidal methods, recommendations on research wish, 5 Norethindrone acetate carcinogenicity of, 158, 159 progestogenicity of, 147 Norethynodrel, carcinogenicity of, 154, 155 Norgestimate, 146, 147 19-Nortestosterone, in oral contraceptive formulations, 17, 144146 N-ras oncogenes, 45 Nude mouse model, 53 Nulliparous women, 111-112, 113 Nurses' health study, 84, 170 o Obesity, 112-114, 116 2-OH metabolite, 32 INDEX Oncogenes, 44-45 Oophorectomy, 11 Oral contraceptive formulations blood levels of, 148-149 developing alternatives to, 4, 5-6, 64 direct tests of carcinogenicity of, 153-159 epidemiological studies on, 17, 33, 95-96, 132-135, 138 estrogen and progestin content of, 143-145, 150 implications for research on, 148150 list of current, 144, 145 mechanisms of carcinogenicity of, 160-162 most commonly prescribed, 143 number of, 1, 143 phasic, 77, 143-144, 145, 146 potential new 144-148 quantitative effect of, 38-39 steroid level vs. potency of, 149150 steroidal potency of, 89-90 trends in, 1, 77 types of, 76-77 Oral contraceptive use before age 25, 87-88, 94-98, 118124, 137, 169, 170-172 before first full-term pregnancy, 13, 14, 58-59, 84-88, 116-122, 169 benefits of, 55-57, 165-172 by birth cohort, 10, 13, 14 and cardiovascular disease, 20, 22 and cervical cancer, 23 changing profile of, 76-78 contraindications to, 59 current controversy over, 57-59 duration of, 13-15, 79-84, 106108, 125-128 duration since first, 88-89, 96, 107, 108-109, 118, 122 "ever" use, 79, 80, 104-105, 124127 in high-risk subgroups, 89 Read the entire page →
From page 183... ... , 31, 45 Pedigrees, 29-31 Pelvic inflammatory disease, 56 Phase III clinical trials, 63 Phasic oral contraceptives, 77, 143144, 145, 146 Pituitary mammary mitogen, 162163 Platelet-derived growth factor, 36, 37 183 Polycystic ovaries, 29 Polymerase chain reaction (PCR) , 31, 45 Postmarketing surveillance, 27-28, 63-64 Postmenopausal breast cancer increased incidence of, 12 oral contraceptive use and, 2-3 recommendations for research on, 7 Pregnancy and breast cancer, 41-42 breast tissue during, 35 ectopic, 56-57 estrogen level during, 39 first full-term, 13, 14, 58-59, 8488, 116-122, 169 protective effect of, 41-42 unplanned, 21, 166, 167-168 Premarketing testing, 5, 18, 63-64 Premenopausal breast cancer, oral contraceptive use and, 15 Progesterone, carcinogenicity of, 159 Progestin~s) Read the entire page →
From page 184... ... , 147 Short-term mammary epithelial cell cultures, 50-52 Side effects, of oral contraceptives, 21-22, 57, 58 Socioeconomic status, 111, 112 Special studies, 29-32 Stem cells, 40 Stillbirth, 131 Stroke, with oral contraceptives, 57, 58 postmarketing, 27-28, 63-64 recommendations on maintaining, 4, 5, 61-64 Surveillance, Epidemiology, and End Results (SEER) Program, 34, 62, 75 Survival rates, 137 Thymidine labeling index (TLI) Read the entire page →
From page 185... ... INDEX Transforming growth factors (TGFs) , 36, 37, 46 Triphasic oral contraceptives, 77, 143-144, 145, 146 Tumor cell lines, 49-50 Turner's syndrome, 29 Tyrosine kineses, overexpression of, 46-47 185 V Venous thrombosis, with oral contraceptives, 57, 58 W Weaning, cell cultures derived during, 51 World Health Organization (WHO) Read the entire page →

From page 177...

... Index A Abortion, 131 Activation, of oncogenes, 45-46 Age and breast cancer rate, 10-11, 12, 20, 21, 29, 57-58 at diagnosis, 128-129 and duration of exposure, 97 and effect of hormones, 2 and epithelial proliferation, 32 at first live birth, 112, 114 less than 25, 87-88, 94-98, 118124, 137, 169, 170-172 and oral contraceptive use, 9,10, 13, 14 Alleles, 31 Amplification, of ins-2 and myc, 47 Animal studies direct tests of carcinogenicity, 153-159 of mechanisms of mammary carcinogenicity of sex steroid hormones, 160-162 of pharmacokinetics of various steroids, 160 potential contributions of, 19, 48 177 questions raised by, 163-164 Athymic mice, 53 B Barrier methods, recommendations on research with, 5 bcl-1 gene, 47 Beagle dogs direct tests of carcinogenicity in, 154-159 mechanisms of carcinogenicity in, 161-162 pharmacokinetics in, 160 risk factors in, 163 Benefits, of oral contraceptive use, 55-57, 165-172 Benign breast disease, 42-43, 89, 114-118, 136-137 Biological knowledge, recommendations on research for, 7, 65-66 Biological markers, recommendations on, 4, 7, 66 Birth cohort, oral contraceptive use by, 10,13, 14 Blood levels, of ethinyl estradiol and progestin, 148-149

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From page 178...

... Study, 62, 76, 81, 87 Carcinogenesis potential, 13 Carcinogenicity in beagle dogs, 154-159, 161-162 direct tests of, 153-159 in mice and rats, 153-154, 155, 161, 162 studies of mechanisms for, 160162 Cardiovascular disease, oral contraceptives and, 20, 22, 57, 58, 166-167 Case-control studies, 26-27 of benign breast disease, 114-116, 117 design of, 92-93, 97 of developing countries, 109-111 disadvantages of, 26 of early use, 120-124 of ever use of oral contraceptives 104-105, 124-125 of latency, 107, 108 of long-term use, 106, 125-126 recommendations on, 7, 26-27 and relative risk, 26 size of, 26 of use before first full-term pregnancy, 116-120 Catechol estrogens, 39 Cell lines, 49-50 Cell types, relationships among, 40 Cervical cancer, oral contraceptives and, 23, 167, 168 Children, number of, 112, 114 Chlamydial infection, 56 Chlorethinyl-norgestrel, carcinogenicity of, 158, 159 Chlormadinone, 138

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From page 179...

... , 153-154, 155 Comparison groups, 28 Confounding variables, 170 Consensus conferences, recommendations on, 6, 65 Contraceptives, developing broader array of, 64 Controls, selection of, 92, 170 Cost, of long-term prospective studies, 34, 67 Critical time periods, 41 Cultures organ, 52-53 short-term mammary epithelial cell, 50-52 Cysts, 42-43 Cytokeratin, 14, 52 D Deletion, of genes, 48 Depomedroxyprogesterone acetate (DMPA) , 138, 157-159 DES, 29 Desogestrel, 146-147 Detection bias, 94 Developed countries, risk in, 10~109 179 Developing countries benefits in, 166, 167 risk in, 16, 109-111, 136 Diethylstilbestrol (DES)

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From page 180...

... endogenous, 39 temporal effect of, 39 INDEX Estrogenicity, 147 Estrogen receptors, down-regulation by progestins of, 149-150 Estrone, 39 Ethinyl estradiol blood levels of, 148-149 direct tests of carcinogenicity of, 154, 155, 157 epidemiological studies on, 133, 134, 138 metabolism of, 39 in oral contraceptive formulations, 17 Ethynerone, carcinogenicity of, 154 Ethynodiol diacetate, carcinogenicity of, 158, 159 '`Ever" use, of oral contraceptives, 79, 80, 104-105, 124-127 Exposure opportunity, 93 Extracellular matrix (ECM) proteins, 37, 40 Family history, 29-31, 43, 112, 115 Femodene, 146, 148 Fibroadenomas, 42-43, 115 Fibroblast growth factor, 36, 37 Fibrocystic disease, 116 First full-term pregnancy (FFTP)

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From page 181...

... infection, 167 Human tissue models, see In vitro human tissue models Human trials, of drugs, 18 16a-Hydroxyestrone, 32, 39 17a-Hydroxyprogesterone derivatives, 133, 138 Hysterectomy, 11 Incidence I of breast cancer, 1, 9-10, 11, 75 of oral contraceptive use, 1, 9 Information, recommendations on dissemination of, 4, 6, 65 Insulin-like growth factors, 36, 37 ins-1 gene, 47 ins-2 gene, 47 In vitro human tissue models athymic mice, 53 organ cultures, 52-53 potential contributions of, 19 recommendations for, 7 short-term mammary epithelial cell cultures, 50-52 tumor cell lines, 49-50 Iron-deficiency anemia, 55-56 181 K 3-Keto-desogestrel, 146, 147-148 Kl-ras oncogenes, 45 L Lactation, see Breastfeeding Latency effects, 88-89, 96, 107, 108109, 118, 122 Levonogestrel androgenicity of, 147 carcinogenicity of, 157-159,160 Longitudinal studies, see Cohort studies M Mammary epithelial cell cultures 50-52 Mammary tissue, see Breast tissue Mammographic screening, 75-76, 129-131, 137 Mammoplasties, reduction, epithelial cell cultures from, 51 Manufacturers, premarketing and postmarketing testing by, 5, 18-19 Marital status, oral contraceptive use by, 10 Marvelon, 146, 147-148 Medicare data bases, 62 Medroxyprogesterone acetate (MPA) , carcinogenicity of, 159 Megestrol acetate, carcinogenicity of, 158, 159 Melatonin, 148 Menopause, oral contraceptive use near, 131-132, 137-138 Menorrhagia, 55-56 Menstrual cycle breast tissue during, 35 epithelial proliferation and, 32 estrogen levels during, 38-39 oral contraceptives and, 55-56 Mestranol direct tests of carcinogenicity of, 154, 155, 157 epidemiological studies on, 133, 134, 138

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From page 182...

... consensus conferences, recommendations on, 6, 65 neu gene, 46-47 Nonresponse bias, 170 Nonsteroidal methods, recommendations on research wish, 5 Norethindrone acetate carcinogenicity of, 158, 159 progestogenicity of, 147 Norethynodrel, carcinogenicity of, 154, 155 Norgestimate, 146, 147 19-Nortestosterone, in oral contraceptive formulations, 17, 144146 N-ras oncogenes, 45 Nude mouse model, 53 Nulliparous women, 111-112, 113 Nurses' health study, 84, 170 o Obesity, 112-114, 116 2-OH metabolite, 32 INDEX Oncogenes, 44-45 Oophorectomy, 11 Oral contraceptive formulations blood levels of, 148-149 developing alternatives to, 4, 5-6, 64 direct tests of carcinogenicity of, 153-159 epidemiological studies on, 17, 33, 95-96, 132-135, 138 estrogen and progestin content of, 143-145, 150 implications for research on, 148150 list of current, 144, 145 mechanisms of carcinogenicity of, 160-162 most commonly prescribed, 143 number of, 1, 143 phasic, 77, 143-144, 145, 146 potential new 144-148 quantitative effect of, 38-39 steroid level vs. potency of, 149150 steroidal potency of, 89-90 trends in, 1, 77 types of, 76-77 Oral contraceptive use before age 25, 87-88, 94-98, 118124, 137, 169, 170-172 before first full-term pregnancy, 13, 14, 58-59, 84-88, 116-122, 169 benefits of, 55-57, 165-172 by birth cohort, 10, 13, 14 and cardiovascular disease, 20, 22 and cervical cancer, 23 changing profile of, 76-78 contraindications to, 59 current controversy over, 57-59 duration of, 13-15, 79-84, 106108, 125-128 duration since first, 88-89, 96, 107, 108-109, 118, 122 "ever" use, 79, 80, 104-105, 124127 in high-risk subgroups, 89

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From page 183...

... , 31, 45 Pedigrees, 29-31 Pelvic inflammatory disease, 56 Phase III clinical trials, 63 Phasic oral contraceptives, 77, 143144, 145, 146 Pituitary mammary mitogen, 162163 Platelet-derived growth factor, 36, 37 183 Polycystic ovaries, 29 Polymerase chain reaction (PCR) , 31, 45 Postmarketing surveillance, 27-28, 63-64 Postmenopausal breast cancer increased incidence of, 12 oral contraceptive use and, 2-3 recommendations for research on, 7 Pregnancy and breast cancer, 41-42 breast tissue during, 35 ectopic, 56-57 estrogen level during, 39 first full-term, 13, 14, 58-59, 8488, 116-122, 169 protective effect of, 41-42 unplanned, 21, 166, 167-168 Premarketing testing, 5, 18, 63-64 Premenopausal breast cancer, oral contraceptive use and, 15 Progesterone, carcinogenicity of, 159 Progestin~s)

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From page 184...

... , 147 Short-term mammary epithelial cell cultures, 50-52 Side effects, of oral contraceptives, 21-22, 57, 58 Socioeconomic status, 111, 112 Special studies, 29-32 Stem cells, 40 Stillbirth, 131 Stroke, with oral contraceptives, 57, 58 postmarketing, 27-28, 63-64 recommendations on maintaining, 4, 5, 61-64 Surveillance, Epidemiology, and End Results (SEER) Program, 34, 62, 75 Survival rates, 137 Thymidine labeling index (TLI)

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From page 185...

... INDEX Transforming growth factors (TGFs) , 36, 37, 46 Triphasic oral contraceptives, 77, 143-144, 145, 146 Tumor cell lines, 49-50 Turner's syndrome, 29 Tyrosine kineses, overexpression of, 46-47 185 V Venous thrombosis, with oral contraceptives, 57, 58 W Weaning, cell cultures derived during, 51 World Health Organization (WHO)

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Index Pages 177-186

Index
Pages 177-186