National Academies Press: OpenBook
« Previous: Appendix F: List of Background Documents
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

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, 118–124, 137, 169, 170–172

and oral contraceptive use, 9, 10, 13, 14

Alleles, 31

Amplification, of int-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

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

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

Body mass index, 114, 116

Breast(s), development of, 18, 35, 36–37

Breast cancer

age and, 10–11, 12, 20, 21, 29, 57–58

age at diagnosis of, 128–129

breastfeeding and, 23

carcinogenesis potential for, 13

cell lines, 49–50

in developed countries, 104–109

in developing countries, 16, 109–111, 136

endogenous hormones and, 12, 102

etiology of, 12–13, 78

genetic susceptibility to, 29–31, 43, 112, 115

histological typing of, 43–44, 111, 129

incidence of, 1, 9–10, 11, 75

molecular changes associated with , 45–48

mortality rate for, 1, 10

ovariectomy and, 38

postmenopausal, 2–3, 7, 12

premenopausal, 15

risk factors for, 57–58, 78, 102, 111–116, 136

survival rates for, 137

in women vs. men, 38

Breastfeeding

and breast cancer, 23

breast tissue during, 35

protective effect of, 41–42

Breast self-examination, 129–131

Breast tissue

during breastfeeding, 35, 41–42

calcium in, 44

critical time periods for, 41

estrogen effect on, 78

during menstrual cycle, 35

pathological, 42–44

during pregnancy, 35, 41–42

progestin effect on, 78

receptors in, 40–41

relationships among cell types in, 40

signal complexity in development and differentiation of , 36–37

time domain and, 35, 40

2-Bromo-α-ergocryptine, and mammary tumors , 161, 162

C

Calcium deposits, in breast, 44

Cancer and steroid hormones (CASH) 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, 160–162

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

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

Cigarette smoking, oral contraceptives and , 22

Cilest, 144–146, 148

Clinical practice, recommendations

on assessing knowledge for

use in, 4, 6, 64–65

c-myc gene, 47

Cohort effect, of oral contraceptives, 16

Cohort studies, 27–28

cost of, 34

of ever use of oral contraceptives, 105, 126, 127

of latency, 108–109

of long-term use, 106–108

vs. postmarketing studies, 18–19

recommendations on, 7

of use before first full-term pregnancy , 117, 121

Combination pills, 76

Committee on Safety of Medicines (CSM) , 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, 104–109

Developing countries

benefits in, 166, 167

risk in, 16, 109–111, 136

Diethylstilbestrol (DES), 29

DMPA, 138, 157–159

DNA repair deficiency, 30

Dogs

direct tests of carcinogenicity in, 154–159

mechanisms of carcinogenicity in, 161–162

pharmacokinetics in, 160

risk factors in, 163

Dose-response relationship, 79–84

Duration

of oral contraceptive use, 13–15, 79–84, 106–108, 125–128

since first oral contraceptive use, 88–89, 96, 107, 108–109, 118, 122

E

Early diagnostic bias, with casecontrol studies , 27

ECM (extracellular matrix) proteins, 37, 40

Ecological studies, 19, 28–29

Ectopic pregnancy, 56–57

EGF (epidermal growth factor), 36, 37

receptor for, 46

Endogenous hormones

and breast cancer, 12, 102

synthetic vs., 39

Endometrial carcinoma, 56, 166

Epidemiological studies

case-control method, 26–27

cohort studies, 27–28

comparison groups in, 28

cost of, 34

defined, 25

design and conduct of, 90–93

discussion of, 94–96

on duration of use, 79–84

on duration since first use, 88–89, 96

early, 78–79

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

ecological studies, 28–29

on estrogen metabolism, 31–32

on “ever” use of oral contraceptives 79, 80

on genetic susceptibility, 29–31

on high-risk subgroups, 89

on hormones other than oral contraceptives 29

issues to consider with, 90–93

on oral contraceptive formulations 33, 89–90

on progestins, 32

recommendations on, 7, 33–34, 66, 96–97

response rates for, 90–91

results of, 2–3

sample size of, 92

special studies, 29–32

on use before first full-term

pregnancy or before age 25, 84–88, 94–96

Epidermal growth factor (EGF), 36, 37

receptor for, 46

Epithelial cell cultures, 50–52

Epithelial proliferation, and menstrual cycle 32

erbB-2 gene, 46–47

erbB-3 gene, 47

Estriol, 39

Estrogen(s)

and breast cancer, 12

and breast tissue, 78

catechol, 39

content in oral contraceptives, 143–145, 150

and growth factors, 36–37

in hormone replacement therapy, 16–17

during menstrual cycle, 38–39

metabolism of, 31–32, 39

with ovariectomy, 39

during pregnancy, 39

qualitative effect of, 39

quantitative effect of, 38–39

synthetic vs. endogenous, 39

temporal effect of, 39

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

F

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), 13, 14, 58–59, 84–88, 116–122, 169

Food and Drug Administration (FDA)

recommendations on

premarketing and

postmarketing requirements

by, 5, 63, 64

surveillance requirements of, 63–64

Funding, recommendations on, 4, 8

G

Genetic susceptibility, 29–31, 43, 112, 115

Gestodene, 146–147

G-proteins, 45

Growth factors

in breast cancer, 40, 161–162, 163

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

in breast development and

differentiation, 36–37

Growth stimulation, 128–129, 137

H

Ha-ras oncogenes, 31, 45

Hepatocellular adenoma, oral contraceptives and, 57, 58, 167

Hepatocellular carcinoma, oral contraceptives and, 57, 58, 167

her-2 gene, 46–47

High-risk groups, oral contraceptive use in, 89

Histological typing, of breast cancer, 43–44, 111, 129

Hormone replacement therapy (HRT), 11, 16–17

hst gene, 47

Human immunodeficiency virus (HIV) infection, 167

Human tissue models, see In vitro human tissue models

Human trials, of drugs, 18

16α-Hydroxyestrone, 32, 39

17α-Hydroxyprogesterone derivatives, 133, 138

Hysterectomy, 11

I

Incidence

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

int-1 gene, 47

int-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

K

3-Keto-desogestrel, 146, 147–148

Kl-ras oncogenes, 45

L

Lactation, see Breastfeeding

Latency effects, 88–89, 96, 107, 108–109, 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

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

metabolism of, 39

in oral contraceptive formulations , 17

Mice

athymic, 53

direct tests of carcinogenicity in, 153–154, 155

mechanisms of carcinogenicity in, 161, 162

risk factors in, 163

Milk, cell cultures derived from, 51

Minipills, 77

MK-665, carcinogenicity of, 154

Molecular changes, associated with breast cancer , 45–48

Mortality rate, for breast cancer, 1, 10

MPA (medroxyprogesterone acetate), carcinogenicity of , 159

Myocardial infarction, with oral contraceptives , 57, 58, 167

N

National Institute of Health (NIH)

consensus conferences, recommendations on, 6, 65

neu gene, 46–47

Nonresponse bias, 170

Nonsteroidal methods, recommendations on research with , 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, 144–146

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

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, 148–150

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, 149–150

steroidal potency of, 89–90

trends in, 1, 77

types of, 76–77

Oral contraceptive use

before age 25, 87–88, 94–98, 118–124, 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, 106–108, 125–128

duration since first, 88–89, 96, 107, 108–109, 118, 122

“ever” use, 79, 80, 104–105, 124–127

in high-risk subgroups, 89

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

and hormone replacement therapy, 16–17

incidence of, 1, 9

information needed on, 15–16

latency of, 88–89, 96, 107, 108–109, 118, 122

by marital status, 10

misconceptions over, 55

near menopause, 131–132, 137–138

and premenopausal breast cancer, 15

prescribing problems for, 59–60

promotional vs. cohort effect of, 16

protective effect of, 20–21, 22, 55–57

recent, 171

and reproductive cancers, 20, 21, 22

risk factors for, 59, 89

risks of, 57, 58, 165–172

side effects of, 21–22, 57, 58

and unplanned pregnancies, 21

Organ culture, 52–53

Ortho-Cyclen, 144–146

Ovarian cancer, oral contraceptives and, 20, 21, 22, 56, 166, 168

Ovariectomy

and breast cancer, 38

and estrogen level, 39

Overexpression, of tyrosine kinases, 46–47

P

Parity, and epithelial proliferation, 32

Patient information, recommendations on, 4, 6

PCR (polymerase chain reaction), 31, 45

Pedigrees, 29–31

Pelvic inflammatory disease, 56

Phase III clinical trials, 63

Phasic oral contraceptives, 77, 143–144, 145, 146

Pituitary mammary mitogen, 162–163

Platelet-derived growth factor, 36, 37

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, 84–88, 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)

blood levels of, 148–149

and breast cancer, 12

and breast tissue, 78

content in oral contraceptives of, 144, 145

down-regulation of estrogen receptor by, 149–150

epidemiological studies on, 32, 132–133, 134, 138

in hormone replacement therapy, 16–17

level vs. potency of, 149–150

19-nortestosterone, 144–146

progestogenic activity of, 149–150

Progestin-only pills, 77

Progestogen

direct tests of carcinogenicity of, 154, 155

and melatonin in formulation, 148

pharmacokinetics of, 160

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

Progestogenic activity, 149–150

Prolactin, and mammary tumors, 161, 162, 163

Promotional effect, of oral contraceptives, 16

Prospective studies, see Cohort studies

Protective effects, of oral contraceptives, 20–21, 22, 55–57

Puerto Rico contraceptive study, 165

Pulmonary embolism, with oral contraceptives, 57, 58

R

ras oncogenes, 31, 45–46

Rats

direct tests of carcinogenicity in, 153–154, 155

mechanisms of carcinogenicity in, 161, 162

risk factors in, 163

Recall bias, 92, 95, 97

Receptors, in breast tissue, 40–41

Recommendations, 3, 4

on assessing knowledge for use in clinical practice, 4, 6, 64–65

on developing broader array of contraceptives, 4, 5–6, 64

on filling gaps in biological and

epidemiological knowledge, 4, 7–8, 65–67

on maintaining surveillance, 4, 5, 61–64

Reduction mammoplasties, epithelial cell cultures from, 51

Relative risks, in case-control studies, 26

Research

costs of, 34, 67

international, cooperative, 5, 63

multidisciplinary, 7

recommendations on, 4, 5–7

Response rates, 90–91

Restriction fragment length polymorphisms (RFLPs), 31, 45

Retrospective studies, see Case-control studies

Risk assessment methodology, 3, 19–20

Risk factors

for breast cancer, 57–58, 78, 102, 111–116, 136

in epidemiological study design, 93

in mice, rats, dogs, and humans, 163

for oral contraceptive use, 59, 89, 165–172

S

Sample size, 92

Screening bias, 75–76, 129–131, 137

sea gene, 47

SEER Program, 34, 62, 75

Selection bias, 92, 170

Selectivity index, 147–148

Sequential pills, 76–77

Sex hormone-binding globulin (SHBG), 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

Surveillance

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

T

Thymidine labeling index (TLI), 32, 150

Time domain, and breast physiology, 35, 40

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×

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 kinases, overexpression of, 46–47

V

Venous thrombosis, with oral contraceptives, 57, 58

W

Weaning, cell cultures derived during, 51

World Health Organization (WHO) study, 81, 109, 111, 131

Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
This page in the original is blank.
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 177
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 178
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 179
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 180
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 181
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 182
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 183
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 184
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 185
Suggested Citation:"Index." Institute of Medicine. 1991. Oral Contraceptives and Breast Cancer. Washington, DC: The National Academies Press. doi: 10.17226/1814.
×
Page 186
Oral Contraceptives and Breast Cancer Get This Book
×
Buy Hardback | $44.95
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

At least 10.7 million American women use oral contraceptives (OCs). The potential connection with breast cancer has caused concern among these OC users and uncertainty among many of their physicians. This new volume offers the most up-to-date information available on this critical topic.

While the best available knowledge does not support any fundamental change in clinical practice with respect to the use of OCs, this book offers specific recommendations for more research to fully resolve the relationship between OCs and breast cancer. Noting consumer confusion, the volume includes a concise summary of benefits, risks, and other practical information for contraceptive users and their doctors.

The volume presents current data on changes in patterns of OC use, differences in risk at different ages, the benefits of OCs, and more.

Oral Contraceptives and Breast Cancer will be important reading for obstetricians/gynecologists and other health professionals, their patients who use OCs, contraceptive manufacturers, women's health advocates, policymakers, and researchers.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!