Dojčenie a rakovinové ochorenia u matky

Väčšina prác nasvedčuje tomu, že dojčenie chráni ženu (najmä ak svoje prvé dieťa dojčila v mladšom veku) pred vznikom viacerých druhov nádorových ochorení – v prvom rade rakoviny prsníka, takisto však rakoviny maternice, vaječníkov a štítnej žľazy. Ochranný účinok sa zdá byť výraznejší v období do nástupu menopauzy.
 
Salud Publica Mex 2000 Jan-Feb;42(1):26-33
 
Risk factors of breast cancer in Mexican women. 
Calderon-Garciduenas AL, Paras-Barrientos FU, Cardenas-Ibarra L, Gonzalez-Guerrero JF, Villarreal-Rios E, Staines-Boone T, Barrera-Saldana HA 
Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Nuevo Leon (UANL), Mexico.
OBJECTIVE: To investigate the association between family history (FH) of neoplasia, gyneco-obstetric factors and breast cancer (BC) in a case-control study. In cases, to analyze those variables in relation with early onset of BC, the manner of detection (self-examination, prompted by pain, or casual), the size of tumor, and the elapsed time to seek medical attention. MATERIAL AND METHODS: Data from 151 prevalent BC cases and 235 age-matched controls were analyzed by multiple logistic regression, to assess the influence of BC risk factors. RESULTS: Ten per cent of patients and 1% of controls had first-degree relatives (FDR) with BC. Family history of FDR with BC (OR, 11.2; 95% CI 2.42-51.92) or with gastric or pancreatic cancer (OR, 17.7; 95% CI 2.2-142.6) was associated with BC risk. Breastfeeding at or under 25 years of age was protective against BC (OR, 0.40; 95% CI 0.24-0.66). The manner of tumor detection did not influence its size at the time of diagnosis. CONCLUSIONS: Our study confirms that FH of BC and/or of gastric or pancreatic carcinoma are risk factors for BC, while lactation at 25 years of age or earlier is protective.
 
Rev Saude Publica 1999 Jun;33(3):237-45
Reproductive risk factors associated with breast cancer in Colombian women. 
Olaya-Contreras P, Pierre B, Lazcano-Ponce E, Villamil-Rodriguez J, Posso-Valencia HJ 
Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica de Mexico, Cuernavaca, Morelos, Mexico. olayac@insp3.insp.mx
INTRODUCTION: As of 1992, breast cancer has been the second cause of death in Columbian women, with a rising trend in mortality due to this type of neoplasm (average annual rate 4.5*/100.000 inhabitants). Information about potential risk factors for breast cancer in Latin American countries is scarce. The objectives of the project were to test the breastfeeding protection against breast cancer and to establish the reproductive factors associated with breast cancer in Columbia. METHODS: A hospital case-control study was carried out from July 1995 to March 1996 in Bogota, Columbia, using paring by age groups. The study population consisted of 171 histopathologically confirmed cases and 171 controls. Reproductive history and sociodemographic data were collected through a questionnaire, and logistic regression models were used for statistical analysis of the data. RESULTS: The following associated factors were found as principal results: nuli-parousness as compared with women with over 3 children (OR=3.35 CI 1.40-8.0), age at first birth (OR=1.83 CI 0.70- 4.80), breast cancer history,breastfeeding the first child (OR=0.09 CI 0.01-0.64 for 1-11 months) and with a highly significant trend for accumulated breastfeeding above 24 months (p=0.001). CONCLUSIONS: This study indicates the importance of focusing on the promotion of prolonged breastfeeding by women identified as being at higher risk, and confirms that socio-economic level can determine life styles and reproductive events among women (such as breastfeeding time); this could explain the increase in breast cancer mortality in Latin American countries, similar to that in developed countries in terms of fertility and risk factors for breast cancer. The epidemiological information produced by this study will be useful for planning and carrying out early diagnosis and treatment of breast cancer in women identified as being at high risk of this disease.
 
Am J Public Health 1999 Aug;89(8):1244-7
Adolescent reproductive events and subsequent breast cancer risk. 
Marcus PM, Baird DD, Millikan RC, Moorman PG, Qaqish B, Newman B 
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA. pm145q@nih.gov
OBJECTIVES: This study investigated the relationship between reproductive events during adolescence and subsequent breast cancer risk. METHODS: Logistic regression models used self-reported data from 862 case patients and 790 controls in the Carolina Breast Cancer Study. RESULTS: Miscarriage, induced abortion, and full-term pregnancy before 20 years of age were not associated with breast cancer. Among premenopausal women, breast-feeding before 20 years of age was inversely associated with disease. Oral contraceptive use before 18 years of age was positively associated with disease risk among African American women only. CONCLUSIONS: Pregnancy during adolescence does not appear to influence breast cancer risk, but breast-feeding may. A possible increased breast cancer risk among African American women who used oral contraceptives as adolescents warrants further study.
 
Clin Perinatol 1999 Jun;26(2):491-503, viii-ix
Health sequelae of breastfeeding for the mother. 
Labbok MH 
Johns Hopkins School of Hygiene and Public Health, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Breastfeeding is known to demand use of maternal nutrient stores, but few comment on the positive health benefits of breastfeeding for the mother. Breastfeeding reduces the risk of postpartum blood loss by increasing the rate of uterine contraction, lowers the risk of premenopausal breast cancer and also reduces the risk of ovarian cancer, reduces lifetime menstrual blood loss, may reduce rate or severity of infections, may reduce the risk of spinal and hip fracture after menopause, and may support bonding with the infant as well as an improved sense of self-esteem and success with mothering. This article reviews the literature on short- and long-term sequelae of breastfeeding for women.
 
Br J Cancer 1997;76(1):118-23
Breastfeeding history, pregnancy experience and risk of breast cancer. 
Enger SM, Ross RK, Henderson B, Bernstein L 
Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, School of Medicine, Los Angeles 90033, USA.
Epidemiological evidence suggests that breastfeeding protects against breast cancer. Whether an effect of age at first breastfeeding is independent of an effect of age at first birth is unclear. We hypothesized that nausea and vomiting in pregnancy, which are associated with elevated serum oestradiol levels during pregnancy, may increase risk. Cases were 452 parous, premenopausal women, 40 years or younger, diagnosed with breast cancer in Los Angeles County from July 1983 to December 1988. Control subjects were matched to cases on age, race, parity and neighbourhood. Pregnancy and breastfeeding histories were obtained from in-person interviews. Odds of breast cancer among women who breastfed for at least 16 months relative to those among women who did not breastfeed was 0.66 [95% confidence interval (CI) 0.41-1.05]. Number of children breastfed was not associated with risk. Risk was lower in women who first breastfed at older ages. Having ever been treated for nausea or vomiting during pregnancy was associated with an increased risk, especially in women experiencing recent pregnancies (OR = 2.03, 95% CI 1.05-3.92). These results support a protective role of breastfeeding and an adverse role of nausea or vomiting during pregnancy in the development of premenopausal breast cancer, especially in the years immediately following pregnancy.
 
Am J Epidemiol 1996 Mar 15;143(6):543-52
Breast cancer and lactation history in Mexican women. 
Romieu I, Hernandez-Avila M, Lazcano E, Lopez L, Romero-Jaime R 
Centro Pan-Americano de Ecologia Humana y Salud, Organizacion Pan-Americana de la Salud, Metepec, Mexico State, Mexico.
The authors conducted a case-control study in Mexico City between September 1990 and December 1992 to determine whether a dose-response relation could be observed between duration of lactation and the risk of breast cancer. Cases, women aged 20-75 years, were identified through six hospitals in Mexico City (n = 349) and were interviewed to obtain data on risk factors for breast cancer, including a detailed history of lactation. Controls (n = 1,005) were selected from the general population using the Mexican national sampling frame. Parous women who had ever lactated had a reduction in breast cancer risk (age-adjusted odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.25-0.62). A small decreasing trend of breast cancer risk in relation to duration of lactation (p < 0.001) was observed. Compared with parous women who had never breast-fed, women who had breast-fed for 12-24 months had an age-adjusted odds ratio of 0.47 (95% CI 0.27-0.83). A stronger protective effect was observed with lactation duration for the first live birth among pre- and postmenopausal women (for 4-12 months of lactation, OR = 0.56 (95 percent CI 0.32-0.96) and OR = 0.48 (95 percent CI 0.29-0.81) in pre- and postmenopausal women, respectively). Adjusting for potentially confounding factors modified these results only slightly. The declining trend in fertility and lactation among Mexican women could lead to a major epidemic of breast cancer such as that observed in Western countries.
 
Int J Cancer 1998 Apr 13;76(2):182-8
Reproductive factors and breast cancer in New Zealand. 
McCredie M, Paul C, Skegg DC, Williams S 
Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
A national population-based case-control study was used to assess the influence on breast cancer risk of reproductive factors and the possibility of an interaction with age at diagnosis. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. There was a declining risk of breast cancer with increasing age at menarche (p = 0.06), the strongest effect being seen in women aged less than 40. Parous women had a 27% lower risk of breast cancer than nulliparous women, a reduced risk being evident in all but the youngest age group. A falling risk of breast cancer with rising parity was clear only in women diagnosed when aged at least 45 years. Breast cancer risk tended to fall amongst parous women with increasing duration of breastfeeding (p = 0.14); the association was most apparent in the youngest women, while those over 40 years at diagnosis showed no clear negative trend. There was no association of breast cancer risk with age at first full-term pregnancy, time since last full-term pregnancy, abortion (spontaneous or induced), abortion before first full-term pregnancy, or ability to conceive, and there was no trend in risk with age at natural menopause. Women in the highest category of body mass index at age 20 had the lowest risk of breast cancer in the age group studied. When each reproductive factor was formally tested for effect modification by age at diagnosis, the interaction term in logistic models approached statistical significance only for parity (p = 0.07).
 
Br J Cancer 1996 Mar;73(6):814-8
A case-control study of lactation and cancer of the breast. 
Katsouyanni K, Lipworth L, Trichopoulou A, Samoli E, Stuver S, Trichopoulos D 
Department of Hygiene and Epidemiology, University of Athens Medical School, Greece.
We have examined the relation of lactation, by total duration, with breast cancer risk among pre- and post-menopausal women. In a hospital-based case-control study conducted in Athens (1989-91), involving 820 patients with confirmed breast cancer and 795 orthopaedic patient controls and 753 hospital visitor controls, logistic regression was used to analyse the data controlling for demographic, nutritional and reproductive factors, including parity and age at any birth. Among post-menopausal women, there was no association between breastfeeding and breast cancer risk, but among premenopausal women those who has breastfed for > or = 24 months had an odds ratio of 0.50 (95% confidence interval 0.23-1.41). A reduction of the odds ration was also evident among premenopausal women who had breastfed between 12 and 23 months (odds ratio 0.70; 95% confidence interval 0.34-1.60). In conjunction with several other recent reports these results support the hypothesis that breastfeeding of prolonged duration may reduce the risk of breast cancer among premenopausal women but not among post-menopausal women. The biology underlying this different effect remains unknown, and the practical implication of the finding is a marginal importance.
 
Int J Gynaecol Obstet 1994 Dec;47 Suppl:S11-20; discussion S20-1
 
Effects of breastfeeding on women's health. 
Kennedy KI 
Family Health International, Research Triangle Park, NC 27709.
Research about the effects of breastfeeding on maternal health has concentrated primarily on breast cancer, bone loss, and maternal depletion. Breastfeeding may provide some protection against breast cancer. Adequate maternal nutrition, a prolonged period of weaning, and adequate child spacing are expected to alleviate any potential bone loss or maternal depletion caused by breastfeeding. Regardless of how one chooses to weight the relative benefits and risks of breastfeeding to the mother, it seems clear that the programmatic tasks are to see that breastfeeding women are adequately fed and enabled to space their pregnancies.
 
Environ Health Perspect 1995 Nov;103 Suppl 8:185-9
Hormones and breast and endometrial cancers: preventive strategies and future research. 
Hulka BS, Brinton LA 
Department of Epidemiology, University of North Carolina, Chapel Hill, USA.
A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches.
 
Am J Epidemiol 1999 Jul 15;150(2):174-82
Lactation in relation to postmenopausal breast cancer. 
Newcomb PA, Egan KM, Titus-Ernstoff L, Trentham-Dietz A, Greenberg ER, Baron JA, Willett WC, Stampfer MJ 
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.
 
Cancer Epidemiol Biomarkers Prev 1998 May;7(5):365-9
Breastfeeding experience and breast cancer risk among postmenopausal women. 
Enger SM, Ross RK, Paganini-Hill A, Bernstein L 
Research and Evaluation Department, Kaiser Permanente Medical Care Program, Southern California, Pasadena 91188, USA.
Results of studies of breastfeeding and postmenopausal breast cancer risk have been inconsistent, with many investigators concluding that breastfeeding does not influence risk. We examined whether breastfeeding reduces postmenopausal breast cancer risk as well as the details of this relationship, including possible modification in risk by the age that a woman first breastfed a child and the number of children she breastfed. This population-based case-control study compared 974 women who were residents of Los Angeles County and newly diagnosed with breast cancer to 973 women with no history of breast cancer who were matched to patients by age (within 3 years) and neighborhood of residence. Subjects were parous and postmenopausal. Breast cancer patients were ages 55-64 years at diagnosis. Women who breastfed at least 16 months experienced a reduced odds of breast cancer relative to women who never breastfed (odds ratio, 0.73; 95% confidence interval, 0.52-1.01). Risk decreased as the number of children breastfed increased, but the association was attenuated after accounting for lifetime duration of breastfeeding. Breast cancer risk was 30% lower among women ages 20-24 years at first breastfeeding than women who had never breastfed(odds ratio, 0.69; 95% confidence interval, 0.54-0.88), independent of the effect of age at first birth. This study provides some evidence that the protective effect of breastfeeding persists into the postmenopausal years. The potential for nondifferential error in recall of breastfeeding habits among postmenopausal patients and controls may explain the inconsistent results observed across studies and underscores the need for careful assessment of this relationship.
 
Cancer Causes Control 1995 May;6(3):199-208
Breastfeeding and breast cancer risk. 
Brinton LA, Potischman NA, Swanson CA, Schoenberg JB, Coates RJ, Gammon MD, Malone KE, Stanford JL, Daling JR 
Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI] = 0.7-1.0). This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR = 0.67, CI = 0.4-1.1 for an average period per child of 72 or more weeks). Women who began to breastfeed at a young age (< 22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk (RR = 1.04). The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks). Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.

Lancet 1996 Feb 17;347(8999):431-6
Prospective assessment of breastfeeding and breast cancer incidence among 89,887 women. 
Michels KB, Willett WC, Rosner BA, Manson JE, Hunter DJ, Colditz GA, Hankinson SE, Speizer FE 
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
BACKGROUND: The relation between breastfeeding and breast cancer risk has been examined in many studies; some have reported no association, and others a reduced risk, particularly among premenopausal women. In the only prospective cohort study, no association was found. We have assessed prospectively the association between breastfeeding and incidence of breast cancer among 89,887 women in the US Nurses' Health Study. METHODS: In 1986, participants were asked about the number of months they breastfed for all their children combined. Parous women with no history of cancer were included in this analysis. During 6 years of follow-up (513,015 person-years), 1,459 invasive breast cancer cases were diagnosed. FINDINGS: Relative to women who had never breastfed, no significant overall association was found--after adjusting for established risk factors for breast cancer--between a history of having breastfed and subsequent development of breast cancer (relative risk [RR] 0.93, 95% CI 0.83 -1.03). No inverse trend was observed with duration of breastfeeding; women who breastfed for 2 years of longer had a RR of 1.11 (0.90-1.38). Among women who had given birth only once, women who had breastfed their child experienced a lower incidence of breast cancer (RR 0.68, 0.46-1.00). Among premenopausal women, who tended to be near menopause due to the age structure of the cohort, the RR of breast cancer for those who had lactated was 1.16 (0.89-1.50). Premenopausal women who had lactated for 1 year or more had a RR of 1.10 (0.78-1.57). INTERPRETATION: These data suggest that there is no important overall association between breast-feeding and the occurrence of breast cancer.
 
Int J Cancer 1997 Apr 10;71(2):166-9
The association between lactation and breast cancer in an international case-control study: a re-analysis by menopausal status. 
Stuver SO, Hsieh CC, Bertone E, Trichopoulos D 
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. sos@episun1.harvard.edu
In the large, hospital-based, international case-control study of breast cancer conducted by MacMahon and colleagues in the 1960s, no protective effect of lactation was observed. However, more recent reports have suggested that such an association may be limited to pre-menopausal women. Therefore, a re-analysis of the data from that original study was performed by menopausal status and with control for additional breast-cancer risk factors since identified. Overall, data from 4,671 parous pre-menopausal and 7,200 parous post-menopausal women were analyzed, from 7 different sites representing areas of high risk (Glamorgan, Wales; Boston, USA), moderate risk (Athens, Greece; Slovenia, ex-Yugoslavia; Sao Paolo, Brazil), and low risk (Tokyo, Japan; Taipei, Taiwan) of breast cancer. No significant effect of lactation was found for pre-menopausal or post-menopausal women from the high-, moderate-, or low-risk areas; the center-adjusted, combined odds ratio (OR) for having breast-fed was 1.05 (95% confidence interval, 0.86-1.29) among pre-menopausal and 1.04 (0.88-1.24) among post-menopausal women. Moreover, examination of cumulative duration of lactation did not support an inverse association between breast cancer and increased length of total breast-feeding. In conclusion, re-analysis of these data, by menopausal status and adjusting for age at first parity, age at menarche, age at menopause, body-mass index and years of schooling, did not reveal a protective effect of lactation or duration of lactation against breast-cancer occurrence among the pre-menopausal, parous women.
 
Int J Cancer 1999 Jan 18;80(2):231-6
The role of reproductive factors and use of oral contraceptives in the aetiology of breast cancer in women aged 50 to 74 years. 
Magnusson CM, Persson IR, Baron JA, Ekbom A, Bergstrom R, Adami HO 
Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden. Cecilia.Magnusson@mep.ki.se
It is unclear whether age at menarche is causally involved in breast-cancer aetiology, or serves a correlate of other early-life exposures. Other aspects of reproductive life, including cycle length and regularity, climacteric symptoms, reproductive history and oral contraceptive use, are also incompletely investigated. We examined these issues in a population-based case-control study, including 3,016 women aged 50 to 74 years with invasive breast cancer, and 3,263 controls of similar age. Mailed questionnaires and telephone interviews were used to collect information on menstrual and reproductive characteristics as well as use of oral contraceptives. We found a statistically significant negative association between increasing age at menarche and breast-cancer risk in women born before 1925 but not after. Length of the menstrual cycle at age 30 seemed to be adversely related to breast-cancer risk, with OR for women with cycle lengths < 24 days and > 30 days being 0.76 and 1.18, as compared with women with a cycle length of 28 days. There was a strong trend of decreasing breast-cancer risk with increasing parity (OR per borne child 0.85, 95% CI 0.80-0.90). Lactation, menopausal symptoms or past use of oral contraceptives did not appear associated with breast-cancer risk. Our findings provide some evidence of a role of environmental correlates of early menarche in breast-cancer aetiology, and underline the importance of childbirth, especially early in life, in the prevention of breast cancer. Our data are not readily compatible with an important influence of former oral contraceptive use on post-menopausal breast-cancer risk.
 
Epidemiology 1997 Mar;8(2):188-91
Breastfeeding, menopause, and epithelial ovarian cancer. 
Siskind V, Green A, Bain C, Purdie D 
Department of Social and Preventive Medicine, University of Queensland, Australia.
No previous study has examined the modifying effect of menopausal status on the association between lactation and ovarian cancer risk. We recruited 824 epithelial ovarian cancer cases and 855 community controls in three Australian states, collecting reproductive and lactation histories by means of a contraceptive calendar and pregnancy and breastfeeding record. We report results in women with at least one liveborn infant for unsupplemented breastfeeding, in line with a biological model linking suppression of ovulation to reduction in ovarian cancer risk. We derived odds ratios from multiple logistic regression models including number of liveborn children, age, age at first or last birth, and other potential confounders, overall and by menopausal status. Estimates of relative risk of ovarian cancer per month of full lactation were 0.99 [95% confidence interval (CI) = 0.97-1.00] overall and 1.00 (95% CI = 0.99-1.01) and 0.98 (95% CI = 0.95-1.01) among post- and premenopausal women, respectively. We tailored a lactation variable to the incessant ovulation hypothesis by progressively discounting breastfeeding the longer after birth it occurred, finding odds ratios similar to those for the unmodified duration variable. We found no association of note among postmenopausal women. Breastfeeding seems to be somewhat protective against ovarian cancer, but only before menopause.
 
Gynecol Oncol 1994 Dec;55(3 Pt 2):S15-9
Characteristics relating to ovarian cancer risk: implications for prevention and detection. 
Whittemore AS 
Department of Health Research and Policy Stanford University School of Medicine, California 94305-5092.
Approximately 20,000 women are diagnosed with ovarian cancer in the United States each year, and some 12,000 women die because of it. Epithelial ovarian cancer, the most common histopathologic type, is uncommon before age 40 years, after which incidence rates increase steeply until age 70-79 years and then decrease somewhat. In the United States, the lifetime risk from birth to age 85 years is about 1.5%. There is general agreement that residence in North America or northern Europe, nulliparity, and having a mother or sister with ovarian cancer are associated with an elevated risk, and that increasing number of pregnancies (whether or not full term), increasing length of oral contraceptive use, and increasing duration of lactation are protective. A history of breast or endometrial cancer appears to be associated with a slight elevation in risk. Apart from oral contraceptive use, none of these characteristics can be modified easily to reduce ovarian cancer risk. However, long-term oral contraceptive use before the menopause could prevent as much as half of all ovarian cancer. At present, the subgroup of the population at highest risk consists of women with a mother or sister with the disease; the lifetime ovarian cancer risk in these women is about 9%. A small fraction of them have families with multiple cases of ovarian cancer and early-onset breast cancer, due largely or entirely to mutated alleles of the gene BRCA1. These women, who have a lifetime risk of breast or ovarian cancer of 85-100%, need aggressive screening and possibly prophylactic surgery.
 
Int J Epidemiol 1993 Apr;22(2):192-7
Lactation and the risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. 
Rosenblatt KA, Thomas DB 
Department of Health and Safety Studies, University of Illinois, Urbana-Champaign.
The relationship between lactation and the development of epithelial ovarian cancer was assessed in data from seven countries that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. Three hundred and ninety-three cases of ovarian cancer were compared to 2565 controls matched on age, hospital, and year of interview. A non-significant reduction in risk with short-term lactation was observed but no further reduction in risk was seen with long-term lactation. The reduction in risk associated with months of lactation was not as great as the reduction with months of pregnancy, which may be a result of lactation being a less effective form of ovulation suppression than pregnancy. The short-term lactation that takes place in developed countries, may provide as great a reduction in risk as the long-term lactation practised in the developing countries included in this study.
 
Int J Epidemiol 1995 Jun;24(3):499-503
Prolonged lactation and endometrial cancer. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. 
Rosenblatt KA, Thomas DB 
Department of Community Health, University of Illinois, Champaign 61820, USA.
BACKGROUND. The risk of endometrial cancer is related to oestrogen levels, showing an increased risk with increasing endogenous or exogenous oestrogen stimulation and a reduced risk when oestrogen is opposed by progesterone. During breastfeeding, the reduction of endogenous oestrogen exposure is larger than that of progesterone, suggesting that breastfeeding may possibly reduce the risk of endometrial cancer. METHODS. The relationship between lactation and endometrial cancer was assessed in data from six countries, including four developing countries, that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. In all, 136 cases were compared with 933 controls matched on age, hospital, and year of interview. Standardized questionnaires, administered in the local language, ascertained information on the length of time breastfed, age started and stopped breastfeeding, reproductive and contraceptive practices, and other risk factors for endometrial cancer. Conditional logistic regression was used to control for the confounding effects of gravidity and age at menarche. RESULTS. Significant decreasing trends in risk were observed with increasing duration of lactation, and with months of breastfeeding per pregnancy. Risk was lowest in women who had most recently lactated, and the apparent protective effect declined with time since cessation of breastfeeding, so that there was no evidence for a protective effect after age 55 even in women who had breastfed for over 5 years. CONCLUSIONS. The long-term lactation that takes place in developing countries probably reduces the risk of endometrial cancer, but this effect may not persist into the ages at which this disease is most common.
 
Cancer Epidemiol Biomarkers Prev 1999 Nov;8(11):991-7
Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females. 
Mack WJ, Preston-Martin S, Bernstein L, Qian D, Xiang M 
Department of Preventive Medicine, University of Southern California, Los Angeles 90089, USA.
We conducted an individually matched case-control study (292 pairs) of female thyroid cancer patients to examine the role of reproductive history and exogenous hormones in this disease. Radiation treatment to the head or neck [28 cases and 2 controls exposed; odds ratio (OR), 14.0; 95% confidence interval (CI), 3.5-121.3] and certain benign thyroid diseases (including adolescent thyroid enlargement, goiter, and nodules or tumors) were strongly associated with thyroid cancer. Irregular menstruation increased risk (OR, 1.8; 95% CI, 0.9-3.7). Age at menarche and pregnancy history were not related to disease. Women with natural menopause and hysterectomized women without oophorectomy had no increase in risk, but disease risk was elevated in women with bilateral oophorectomy (OR, 6.5; 95% CI, 1.1-38.1). In general, use of oral contraceptives and other exogenous estrogens was not associated with thyroid cancer. However, risk increased with number of pregnancies in women using lactation suppressants (P = 0.03) and decreased with duration of breastfeeding (P = 0.04). These data provide only limited support for the hypothesis that reproductive and hormonal exposures are responsible for the marked excess of thyroid cancer risk in adult females.
 
J Natl Cancer Inst 2000 Feb 16;92(4):302-12
 
History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature. 
Lipworth L, Bailey LR, Trichopoulos D 
International Epidemiology Institute, Rockville, MD 20850, USA. loren3@earthlink.net
The purpose of this review is to critically evaluate the collective epidemiologic evidence that a history of breast-feeding may decrease the risk of breast cancer. Original data for inclusion were identified through a MEDLINE(R) search of the English language literature from 1966 through 1998. To date, virtually all epidemiologic data regarding breast-feeding and breast cancer risk are derived from case-control studies, which vary according to classification of breast-feeding history. Overall, the evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. An inverse association between increasing cumulative duration of breast-feeding and breast cancer risk among parous women has been reported in some, but not all, studies; the failure to detect an association in some Western populations may be due to the low prevalence of prolonged breast-feeding. It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women. It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution. The biology underlying a protective effect of breast-feeding and why this should be restricted to premenopausal women remain unknown, although several mechanisms have been postulated (hormonal changes, such as reduced estrogen; removal of estrogens through breast fluid; excretion of carcinogens from breast tissue through breast-feeding; physical changes in the mammary epithelial cells, reflecting maximal differentiation; and delay of the re-establishment of ovulation). While breast-feeding is a potentially modifiable behavior, the practical implication of reduced breast cancer risk among premenopausal women with prolonged durations of breast-feeding may be of marginal importance, particularly in Western societies.
Väčšina prác nasvedčuje tomu, že dojčenie chráni ženu (najmä ak svoje prvé dieťa dojčila v mladšom veku) pred vznikom viacerých druhov nádorových ochorení – v prvom rade rakoviny prsníka, takisto však rakoviny maternice, vaječníkov a štítnej žľazy. Ochranný účinok sa zdá byť výraznejší v období do nástupu menopauzy.
 
Salud Publica Mex 2000 Jan-Feb;42(1):26-33
 
Risk factors of breast cancer in Mexican women. 
Calderon-Garciduenas AL, Paras-Barrientos FU, Cardenas-Ibarra L, Gonzalez-Guerrero JF, Villarreal-Rios E, Staines-Boone T, Barrera-Saldana HA 
Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Nuevo Leon (UANL), Mexico.
OBJECTIVE: To investigate the association between family history (FH) of neoplasia, gyneco-obstetric factors and breast cancer (BC) in a case-control study. In cases, to analyze those variables in relation with early onset of BC, the manner of detection (self-examination, prompted by pain, or casual), the size of tumor, and the elapsed time to seek medical attention. MATERIAL AND METHODS: Data from 151 prevalent BC cases and 235 age-matched controls were analyzed by multiple logistic regression, to assess the influence of BC risk factors. RESULTS: Ten per cent of patients and 1% of controls had first-degree relatives (FDR) with BC. Family history of FDR with BC (OR, 11.2; 95% CI 2.42-51.92) or with gastric or pancreatic cancer (OR, 17.7; 95% CI 2.2-142.6) was associated with BC risk. Breastfeeding at or under 25 years of age was protective against BC (OR, 0.40; 95% CI 0.24-0.66). The manner of tumor detection did not influence its size at the time of diagnosis. CONCLUSIONS: Our study confirms that FH of BC and/or of gastric or pancreatic carcinoma are risk factors for BC, while lactation at 25 years of age or earlier is protective.
 
Rev Saude Publica 1999 Jun;33(3):237-45
Reproductive risk factors associated with breast cancer in Colombian women. 
Olaya-Contreras P, Pierre B, Lazcano-Ponce E, Villamil-Rodriguez J, Posso-Valencia HJ 
Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica de Mexico, Cuernavaca, Morelos, Mexico. olayac@insp3.insp.mx
INTRODUCTION: As of 1992, breast cancer has been the second cause of death in Columbian women, with a rising trend in mortality due to this type of neoplasm (average annual rate 4.5*/100.000 inhabitants). Information about potential risk factors for breast cancer in Latin American countries is scarce. The objectives of the project were to test the breastfeeding protection against breast cancer and to establish the reproductive factors associated with breast cancer in Columbia. METHODS: A hospital case-control study was carried out from July 1995 to March 1996 in Bogota, Columbia, using paring by age groups. The study population consisted of 171 histopathologically confirmed cases and 171 controls. Reproductive history and sociodemographic data were collected through a questionnaire, and logistic regression models were used for statistical analysis of the data. RESULTS: The following associated factors were found as principal results: nuli-parousness as compared with women with over 3 children (OR=3.35 CI 1.40-8.0), age at first birth (OR=1.83 CI 0.70- 4.80), breast cancer history,breastfeeding the first child (OR=0.09 CI 0.01-0.64 for 1-11 months) and with a highly significant trend for accumulated breastfeeding above 24 months (p=0.001). CONCLUSIONS: This study indicates the importance of focusing on the promotion of prolonged breastfeeding by women identified as being at higher risk, and confirms that socio-economic level can determine life styles and reproductive events among women (such as breastfeeding time); this could explain the increase in breast cancer mortality in Latin American countries, similar to that in developed countries in terms of fertility and risk factors for breast cancer. The epidemiological information produced by this study will be useful for planning and carrying out early diagnosis and treatment of breast cancer in women identified as being at high risk of this disease.
 
Am J Public Health 1999 Aug;89(8):1244-7
Adolescent reproductive events and subsequent breast cancer risk. 
Marcus PM, Baird DD, Millikan RC, Moorman PG, Qaqish B, Newman B 
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA. pm145q@nih.gov
OBJECTIVES: This study investigated the relationship between reproductive events during adolescence and subsequent breast cancer risk. METHODS: Logistic regression models used self-reported data from 862 case patients and 790 controls in the Carolina Breast Cancer Study. RESULTS: Miscarriage, induced abortion, and full-term pregnancy before 20 years of age were not associated with breast cancer. Among premenopausal women, breast-feeding before 20 years of age was inversely associated with disease. Oral contraceptive use before 18 years of age was positively associated with disease risk among African American women only. CONCLUSIONS: Pregnancy during adolescence does not appear to influence breast cancer risk, but breast-feeding may. A possible increased breast cancer risk among African American women who used oral contraceptives as adolescents warrants further study.
 
Clin Perinatol 1999 Jun;26(2):491-503, viii-ix
Health sequelae of breastfeeding for the mother. 
Labbok MH 
Johns Hopkins School of Hygiene and Public Health, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Breastfeeding is known to demand use of maternal nutrient stores, but few comment on the positive health benefits of breastfeeding for the mother. Breastfeeding reduces the risk of postpartum blood loss by increasing the rate of uterine contraction, lowers the risk of premenopausal breast cancer and also reduces the risk of ovarian cancer, reduces lifetime menstrual blood loss, may reduce rate or severity of infections, may reduce the risk of spinal and hip fracture after menopause, and may support bonding with the infant as well as an improved sense of self-esteem and success with mothering. This article reviews the literature on short- and long-term sequelae of breastfeeding for women.
 
Br J Cancer 1997;76(1):118-23
Breastfeeding history, pregnancy experience and risk of breast cancer. 
Enger SM, Ross RK, Henderson B, Bernstein L 
Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, School of Medicine, Los Angeles 90033, USA.
Epidemiological evidence suggests that breastfeeding protects against breast cancer. Whether an effect of age at first breastfeeding is independent of an effect of age at first birth is unclear. We hypothesized that nausea and vomiting in pregnancy, which are associated with elevated serum oestradiol levels during pregnancy, may increase risk. Cases were 452 parous, premenopausal women, 40 years or younger, diagnosed with breast cancer in Los Angeles County from July 1983 to December 1988. Control subjects were matched to cases on age, race, parity and neighbourhood. Pregnancy and breastfeeding histories were obtained from in-person interviews. Odds of breast cancer among women who breastfed for at least 16 months relative to those among women who did not breastfeed was 0.66 [95% confidence interval (CI) 0.41-1.05]. Number of children breastfed was not associated with risk. Risk was lower in women who first breastfed at older ages. Having ever been treated for nausea or vomiting during pregnancy was associated with an increased risk, especially in women experiencing recent pregnancies (OR = 2.03, 95% CI 1.05-3.92). These results support a protective role of breastfeeding and an adverse role of nausea or vomiting during pregnancy in the development of premenopausal breast cancer, especially in the years immediately following pregnancy.
 
Am J Epidemiol 1996 Mar 15;143(6):543-52
Breast cancer and lactation history in Mexican women. 
Romieu I, Hernandez-Avila M, Lazcano E, Lopez L, Romero-Jaime R 
Centro Pan-Americano de Ecologia Humana y Salud, Organizacion Pan-Americana de la Salud, Metepec, Mexico State, Mexico.
The authors conducted a case-control study in Mexico City between September 1990 and December 1992 to determine whether a dose-response relation could be observed between duration of lactation and the risk of breast cancer. Cases, women aged 20-75 years, were identified through six hospitals in Mexico City (n = 349) and were interviewed to obtain data on risk factors for breast cancer, including a detailed history of lactation. Controls (n = 1,005) were selected from the general population using the Mexican national sampling frame. Parous women who had ever lactated had a reduction in breast cancer risk (age-adjusted odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.25-0.62). A small decreasing trend of breast cancer risk in relation to duration of lactation (p < 0.001) was observed. Compared with parous women who had never breast-fed, women who had breast-fed for 12-24 months had an age-adjusted odds ratio of 0.47 (95% CI 0.27-0.83). A stronger protective effect was observed with lactation duration for the first live birth among pre- and postmenopausal women (for 4-12 months of lactation, OR = 0.56 (95 percent CI 0.32-0.96) and OR = 0.48 (95 percent CI 0.29-0.81) in pre- and postmenopausal women, respectively). Adjusting for potentially confounding factors modified these results only slightly. The declining trend in fertility and lactation among Mexican women could lead to a major epidemic of breast cancer such as that observed in Western countries.
 
Int J Cancer 1998 Apr 13;76(2):182-8
Reproductive factors and breast cancer in New Zealand. 
McCredie M, Paul C, Skegg DC, Williams S 
Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
A national population-based case-control study was used to assess the influence on breast cancer risk of reproductive factors and the possibility of an interaction with age at diagnosis. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. There was a declining risk of breast cancer with increasing age at menarche (p = 0.06), the strongest effect being seen in women aged less than 40. Parous women had a 27% lower risk of breast cancer than nulliparous women, a reduced risk being evident in all but the youngest age group. A falling risk of breast cancer with rising parity was clear only in women diagnosed when aged at least 45 years. Breast cancer risk tended to fall amongst parous women with increasing duration of breastfeeding (p = 0.14); the association was most apparent in the youngest women, while those over 40 years at diagnosis showed no clear negative trend. There was no association of breast cancer risk with age at first full-term pregnancy, time since last full-term pregnancy, abortion (spontaneous or induced), abortion before first full-term pregnancy, or ability to conceive, and there was no trend in risk with age at natural menopause. Women in the highest category of body mass index at age 20 had the lowest risk of breast cancer in the age group studied. When each reproductive factor was formally tested for effect modification by age at diagnosis, the interaction term in logistic models approached statistical significance only for parity (p = 0.07).
 
Br J Cancer 1996 Mar;73(6):814-8
A case-control study of lactation and cancer of the breast. 
Katsouyanni K, Lipworth L, Trichopoulou A, Samoli E, Stuver S, Trichopoulos D 
Department of Hygiene and Epidemiology, University of Athens Medical School, Greece.
We have examined the relation of lactation, by total duration, with breast cancer risk among pre- and post-menopausal women. In a hospital-based case-control study conducted in Athens (1989-91), involving 820 patients with confirmed breast cancer and 795 orthopaedic patient controls and 753 hospital visitor controls, logistic regression was used to analyse the data controlling for demographic, nutritional and reproductive factors, including parity and age at any birth. Among post-menopausal women, there was no association between breastfeeding and breast cancer risk, but among premenopausal women those who has breastfed for > or = 24 months had an odds ratio of 0.50 (95% confidence interval 0.23-1.41). A reduction of the odds ration was also evident among premenopausal women who had breastfed between 12 and 23 months (odds ratio 0.70; 95% confidence interval 0.34-1.60). In conjunction with several other recent reports these results support the hypothesis that breastfeeding of prolonged duration may reduce the risk of breast cancer among premenopausal women but not among post-menopausal women. The biology underlying this different effect remains unknown, and the practical implication of the finding is a marginal importance.
 
Int J Gynaecol Obstet 1994 Dec;47 Suppl:S11-20; discussion S20-1
 
Effects of breastfeeding on women's health. 
Kennedy KI 
Family Health International, Research Triangle Park, NC 27709.
Research about the effects of breastfeeding on maternal health has concentrated primarily on breast cancer, bone loss, and maternal depletion. Breastfeeding may provide some protection against breast cancer. Adequate maternal nutrition, a prolonged period of weaning, and adequate child spacing are expected to alleviate any potential bone loss or maternal depletion caused by breastfeeding. Regardless of how one chooses to weight the relative benefits and risks of breastfeeding to the mother, it seems clear that the programmatic tasks are to see that breastfeeding women are adequately fed and enabled to space their pregnancies.
 
Environ Health Perspect 1995 Nov;103 Suppl 8:185-9
Hormones and breast and endometrial cancers: preventive strategies and future research. 
Hulka BS, Brinton LA 
Department of Epidemiology, University of North Carolina, Chapel Hill, USA.
A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches.
 
Am J Epidemiol 1999 Jul 15;150(2):174-82
Lactation in relation to postmenopausal breast cancer. 
Newcomb PA, Egan KM, Titus-Ernstoff L, Trentham-Dietz A, Greenberg ER, Baron JA, Willett WC, Stampfer MJ 
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.
 
Cancer Epidemiol Biomarkers Prev 1998 May;7(5):365-9
Breastfeeding experience and breast cancer risk among postmenopausal women. 
Enger SM, Ross RK, Paganini-Hill A, Bernstein L 
Research and Evaluation Department, Kaiser Permanente Medical Care Program, Southern California, Pasadena 91188, USA.
Results of studies of breastfeeding and postmenopausal breast cancer risk have been inconsistent, with many investigators concluding that breastfeeding does not influence risk. We examined whether breastfeeding reduces postmenopausal breast cancer risk as well as the details of this relationship, including possible modification in risk by the age that a woman first breastfed a child and the number of children she breastfed. This population-based case-control study compared 974 women who were residents of Los Angeles County and newly diagnosed with breast cancer to 973 women with no history of breast cancer who were matched to patients by age (within 3 years) and neighborhood of residence. Subjects were parous and postmenopausal. Breast cancer patients were ages 55-64 years at diagnosis. Women who breastfed at least 16 months experienced a reduced odds of breast cancer relative to women who never breastfed (odds ratio, 0.73; 95% confidence interval, 0.52-1.01). Risk decreased as the number of children breastfed increased, but the association was attenuated after accounting for lifetime duration of breastfeeding. Breast cancer risk was 30% lower among women ages 20-24 years at first breastfeeding than women who had never breastfed(odds ratio, 0.69; 95% confidence interval, 0.54-0.88), independent of the effect of age at first birth. This study provides some evidence that the protective effect of breastfeeding persists into the postmenopausal years. The potential for nondifferential error in recall of breastfeeding habits among postmenopausal patients and controls may explain the inconsistent results observed across studies and underscores the need for careful assessment of this relationship.
 
Cancer Causes Control 1995 May;6(3):199-208
Breastfeeding and breast cancer risk. 
Brinton LA, Potischman NA, Swanson CA, Schoenberg JB, Coates RJ, Gammon MD, Malone KE, Stanford JL, Daling JR 
Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI] = 0.7-1.0). This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR = 0.67, CI = 0.4-1.1 for an average period per child of 72 or more weeks). Women who began to breastfeed at a young age (< 22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk (RR = 1.04). The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks). Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.

Lancet 1996 Feb 17;347(8999):431-6
Prospective assessment of breastfeeding and breast cancer incidence among 89,887 women. 
Michels KB, Willett WC, Rosner BA, Manson JE, Hunter DJ, Colditz GA, Hankinson SE, Speizer FE 
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
BACKGROUND: The relation between breastfeeding and breast cancer risk has been examined in many studies; some have reported no association, and others a reduced risk, particularly among premenopausal women. In the only prospective cohort study, no association was found. We have assessed prospectively the association between breastfeeding and incidence of breast cancer among 89,887 women in the US Nurses' Health Study. METHODS: In 1986, participants were asked about the number of months they breastfed for all their children combined. Parous women with no history of cancer were included in this analysis. During 6 years of follow-up (513,015 person-years), 1,459 invasive breast cancer cases were diagnosed. FINDINGS: Relative to women who had never breastfed, no significant overall association was found--after adjusting for established risk factors for breast cancer--between a history of having breastfed and subsequent development of breast cancer (relative risk [RR] 0.93, 95% CI 0.83 -1.03). No inverse trend was observed with duration of breastfeeding; women who breastfed for 2 years of longer had a RR of 1.11 (0.90-1.38). Among women who had given birth only once, women who had breastfed their child experienced a lower incidence of breast cancer (RR 0.68, 0.46-1.00). Among premenopausal women, who tended to be near menopause due to the age structure of the cohort, the RR of breast cancer for those who had lactated was 1.16 (0.89-1.50). Premenopausal women who had lactated for 1 year or more had a RR of 1.10 (0.78-1.57). INTERPRETATION: These data suggest that there is no important overall association between breast-feeding and the occurrence of breast cancer.
 
Int J Cancer 1997 Apr 10;71(2):166-9
The association between lactation and breast cancer in an international case-control study: a re-analysis by menopausal status. 
Stuver SO, Hsieh CC, Bertone E, Trichopoulos D 
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. sos@episun1.harvard.edu
In the large, hospital-based, international case-control study of breast cancer conducted by MacMahon and colleagues in the 1960s, no protective effect of lactation was observed. However, more recent reports have suggested that such an association may be limited to pre-menopausal women. Therefore, a re-analysis of the data from that original study was performed by menopausal status and with control for additional breast-cancer risk factors since identified. Overall, data from 4,671 parous pre-menopausal and 7,200 parous post-menopausal women were analyzed, from 7 different sites representing areas of high risk (Glamorgan, Wales; Boston, USA), moderate risk (Athens, Greece; Slovenia, ex-Yugoslavia; Sao Paolo, Brazil), and low risk (Tokyo, Japan; Taipei, Taiwan) of breast cancer. No significant effect of lactation was found for pre-menopausal or post-menopausal women from the high-, moderate-, or low-risk areas; the center-adjusted, combined odds ratio (OR) for having breast-fed was 1.05 (95% confidence interval, 0.86-1.29) among pre-menopausal and 1.04 (0.88-1.24) among post-menopausal women. Moreover, examination of cumulative duration of lactation did not support an inverse association between breast cancer and increased length of total breast-feeding. In conclusion, re-analysis of these data, by menopausal status and adjusting for age at first parity, age at menarche, age at menopause, body-mass index and years of schooling, did not reveal a protective effect of lactation or duration of lactation against breast-cancer occurrence among the pre-menopausal, parous women.
 
Int J Cancer 1999 Jan 18;80(2):231-6
The role of reproductive factors and use of oral contraceptives in the aetiology of breast cancer in women aged 50 to 74 years. 
Magnusson CM, Persson IR, Baron JA, Ekbom A, Bergstrom R, Adami HO 
Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden. Cecilia.Magnusson@mep.ki.se
It is unclear whether age at menarche is causally involved in breast-cancer aetiology, or serves a correlate of other early-life exposures. Other aspects of reproductive life, including cycle length and regularity, climacteric symptoms, reproductive history and oral contraceptive use, are also incompletely investigated. We examined these issues in a population-based case-control study, including 3,016 women aged 50 to 74 years with invasive breast cancer, and 3,263 controls of similar age. Mailed questionnaires and telephone interviews were used to collect information on menstrual and reproductive characteristics as well as use of oral contraceptives. We found a statistically significant negative association between increasing age at menarche and breast-cancer risk in women born before 1925 but not after. Length of the menstrual cycle at age 30 seemed to be adversely related to breast-cancer risk, with OR for women with cycle lengths < 24 days and > 30 days being 0.76 and 1.18, as compared with women with a cycle length of 28 days. There was a strong trend of decreasing breast-cancer risk with increasing parity (OR per borne child 0.85, 95% CI 0.80-0.90). Lactation, menopausal symptoms or past use of oral contraceptives did not appear associated with breast-cancer risk. Our findings provide some evidence of a role of environmental correlates of early menarche in breast-cancer aetiology, and underline the importance of childbirth, especially early in life, in the prevention of breast cancer. Our data are not readily compatible with an important influence of former oral contraceptive use on post-menopausal breast-cancer risk.
 
Epidemiology 1997 Mar;8(2):188-91
Breastfeeding, menopause, and epithelial ovarian cancer. 
Siskind V, Green A, Bain C, Purdie D 
Department of Social and Preventive Medicine, University of Queensland, Australia.
No previous study has examined the modifying effect of menopausal status on the association between lactation and ovarian cancer risk. We recruited 824 epithelial ovarian cancer cases and 855 community controls in three Australian states, collecting reproductive and lactation histories by means of a contraceptive calendar and pregnancy and breastfeeding record. We report results in women with at least one liveborn infant for unsupplemented breastfeeding, in line with a biological model linking suppression of ovulation to reduction in ovarian cancer risk. We derived odds ratios from multiple logistic regression models including number of liveborn children, age, age at first or last birth, and other potential confounders, overall and by menopausal status. Estimates of relative risk of ovarian cancer per month of full lactation were 0.99 [95% confidence interval (CI) = 0.97-1.00] overall and 1.00 (95% CI = 0.99-1.01) and 0.98 (95% CI = 0.95-1.01) among post- and premenopausal women, respectively. We tailored a lactation variable to the incessant ovulation hypothesis by progressively discounting breastfeeding the longer after birth it occurred, finding odds ratios similar to those for the unmodified duration variable. We found no association of note among postmenopausal women. Breastfeeding seems to be somewhat protective against ovarian cancer, but only before menopause.
 
Gynecol Oncol 1994 Dec;55(3 Pt 2):S15-9
Characteristics relating to ovarian cancer risk: implications for prevention and detection. 
Whittemore AS 
Department of Health Research and Policy Stanford University School of Medicine, California 94305-5092.
Approximately 20,000 women are diagnosed with ovarian cancer in the United States each year, and some 12,000 women die because of it. Epithelial ovarian cancer, the most common histopathologic type, is uncommon before age 40 years, after which incidence rates increase steeply until age 70-79 years and then decrease somewhat. In the United States, the lifetime risk from birth to age 85 years is about 1.5%. There is general agreement that residence in North America or northern Europe, nulliparity, and having a mother or sister with ovarian cancer are associated with an elevated risk, and that increasing number of pregnancies (whether or not full term), increasing length of oral contraceptive use, and increasing duration of lactation are protective. A history of breast or endometrial cancer appears to be associated with a slight elevation in risk. Apart from oral contraceptive use, none of these characteristics can be modified easily to reduce ovarian cancer risk. However, long-term oral contraceptive use before the menopause could prevent as much as half of all ovarian cancer. At present, the subgroup of the population at highest risk consists of women with a mother or sister with the disease; the lifetime ovarian cancer risk in these women is about 9%. A small fraction of them have families with multiple cases of ovarian cancer and early-onset breast cancer, due largely or entirely to mutated alleles of the gene BRCA1. These women, who have a lifetime risk of breast or ovarian cancer of 85-100%, need aggressive screening and possibly prophylactic surgery.
 
Int J Epidemiol 1993 Apr;22(2):192-7
Lactation and the risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. 
Rosenblatt KA, Thomas DB 
Department of Health and Safety Studies, University of Illinois, Urbana-Champaign.
The relationship between lactation and the development of epithelial ovarian cancer was assessed in data from seven countries that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. Three hundred and ninety-three cases of ovarian cancer were compared to 2565 controls matched on age, hospital, and year of interview. A non-significant reduction in risk with short-term lactation was observed but no further reduction in risk was seen with long-term lactation. The reduction in risk associated with months of lactation was not as great as the reduction with months of pregnancy, which may be a result of lactation being a less effective form of ovulation suppression than pregnancy. The short-term lactation that takes place in developed countries, may provide as great a reduction in risk as the long-term lactation practised in the developing countries included in this study.
 
Int J Epidemiol 1995 Jun;24(3):499-503
Prolonged lactation and endometrial cancer. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. 
Rosenblatt KA, Thomas DB 
Department of Community Health, University of Illinois, Champaign 61820, USA.
BACKGROUND. The risk of endometrial cancer is related to oestrogen levels, showing an increased risk with increasing endogenous or exogenous oestrogen stimulation and a reduced risk when oestrogen is opposed by progesterone. During breastfeeding, the reduction of endogenous oestrogen exposure is larger than that of progesterone, suggesting that breastfeeding may possibly reduce the risk of endometrial cancer. METHODS. The relationship between lactation and endometrial cancer was assessed in data from six countries, including four developing countries, that were collected for a multinational hospital-based case-control study conducted between 1979 and 1988. In all, 136 cases were compared with 933 controls matched on age, hospital, and year of interview. Standardized questionnaires, administered in the local language, ascertained information on the length of time breastfed, age started and stopped breastfeeding, reproductive and contraceptive practices, and other risk factors for endometrial cancer. Conditional logistic regression was used to control for the confounding effects of gravidity and age at menarche. RESULTS. Significant decreasing trends in risk were observed with increasing duration of lactation, and with months of breastfeeding per pregnancy. Risk was lowest in women who had most recently lactated, and the apparent protective effect declined with time since cessation of breastfeeding, so that there was no evidence for a protective effect after age 55 even in women who had breastfed for over 5 years. CONCLUSIONS. The long-term lactation that takes place in developing countries probably reduces the risk of endometrial cancer, but this effect may not persist into the ages at which this disease is most common.
 
Cancer Epidemiol Biomarkers Prev 1999 Nov;8(11):991-7
Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females. 
Mack WJ, Preston-Martin S, Bernstein L, Qian D, Xiang M 
Department of Preventive Medicine, University of Southern California, Los Angeles 90089, USA.
We conducted an individually matched case-control study (292 pairs) of female thyroid cancer patients to examine the role of reproductive history and exogenous hormones in this disease. Radiation treatment to the head or neck [28 cases and 2 controls exposed; odds ratio (OR), 14.0; 95% confidence interval (CI), 3.5-121.3] and certain benign thyroid diseases (including adolescent thyroid enlargement, goiter, and nodules or tumors) were strongly associated with thyroid cancer. Irregular menstruation increased risk (OR, 1.8; 95% CI, 0.9-3.7). Age at menarche and pregnancy history were not related to disease. Women with natural menopause and hysterectomized women without oophorectomy had no increase in risk, but disease risk was elevated in women with bilateral oophorectomy (OR, 6.5; 95% CI, 1.1-38.1). In general, use of oral contraceptives and other exogenous estrogens was not associated with thyroid cancer. However, risk increased with number of pregnancies in women using lactation suppressants (P = 0.03) and decreased with duration of breastfeeding (P = 0.04). These data provide only limited support for the hypothesis that reproductive and hormonal exposures are responsible for the marked excess of thyroid cancer risk in adult females.
 
J Natl Cancer Inst 2000 Feb 16;92(4):302-12
 
History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature. 
Lipworth L, Bailey LR, Trichopoulos D 
International Epidemiology Institute, Rockville, MD 20850, USA. loren3@earthlink.net
The purpose of this review is to critically evaluate the collective epidemiologic evidence that a history of breast-feeding may decrease the risk of breast cancer. Original data for inclusion were identified through a MEDLINE(R) search of the English language literature from 1966 through 1998. To date, virtually all epidemiologic data regarding breast-feeding and breast cancer risk are derived from case-control studies, which vary according to classification of breast-feeding history. Overall, the evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. An inverse association between increasing cumulative duration of breast-feeding and breast cancer risk among parous women has been reported in some, but not all, studies; the failure to detect an association in some Western populations may be due to the low prevalence of prolonged breast-feeding. It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women. It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution. The biology underlying a protective effect of breast-feeding and why this should be restricted to premenopausal women remain unknown, although several mechanisms have been postulated (hormonal changes, such as reduced estrogen; removal of estrogens through breast fluid; excretion of carcinogens from breast tissue through breast-feeding; physical changes in the mammary epithelial cells, reflecting maximal differentiation; and delay of the re-establishment of ovulation). While breast-feeding is a potentially modifiable behavior, the practical implication of reduced breast cancer risk among premenopausal women with prolonged durations of breast-feeding may be of marginal importance, particularly in Western societies.