REVIEW
History of Breast-Feeding in Relation to Breast Cancer
Risk: a Review of the Epidemiologic Literature
Loren Lipworth, L. Renee Bailey, Dimitrios Trichopoulos
The purpose of this review is to critically evaluate the col-
lective epidemiologic evidence that a history of breast-
feeding may decrease the risk of breast cancer. Original data
for inclusion were identified through a MEDLINE® 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 in-
creasing 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 hypoth-
esized 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 sup-
press lactation; however, the evidence is limited and should
be interpreted with caution. The biology underlying a pro-
tective effect of breast-feeding and why this should be re-
stricted to premenopausal women remain unknown, al-
though 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 mam-
mary 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 premeno-
pausal women with prolonged durations of breast-feeding
may be of marginal importance, particularly in Western so-
cieties. [J Natl Cancer Inst 2000;92:302–12]
More than 70 years ago, it was proposed that “the breast
which has never been called upon for normal function is cer-
tainly more liable to become cancerous” (1), and a history of
breast-feeding came to be considered as a protective factor for
breast cancer. This hypothesis is consistent with the pattern of
geographic variation in breast cancer incidence, which is mark-
edly lower among populations in which breast-feeding is the
most common and the most prolonged (2). In 1970, however,
MacMahon et al. (3) reported, on the basis of a large interna-
tional case–control study, that breast-feeding was unlikely to
have an independent influence on breast cancer risk after adjust-
ing for the effects of number of full-term pregnancies and age at
302 REVIEW Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000
first birth. These findings seemed, at the time, to close the issue,
and many subsequent epidemiologic studies disregarded the as-
sociation between breast-feeding and breast cancer.
More recently, the issue has undergone increasing scrutiny,
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and the attitude of the scientific community toward breast-
feeding in relation to breast cancer has changed. A number of
epidemiologic investigations have once again suggested that
breast-feeding, particularly for extended periods of time, may be
associated with a decreased risk of breast cancer, even after
adjusting for potential confounders, and that this protection may
be greatest among women under 50 years of age. It is difficult to
summarize the magnitude of the association, if any, because of
the variety of methodologies for reporting breast-feeding his-
tory; some studies report the effect of mean duration of breast-
feeding for each child, others report the effect of cumulative
duration following all births, and still others use different expo-
sure measures.
The purpose of this review is to critically evaluate the exist-
ing epidemiologic evidence that history of breast-feeding may
decrease the risk of breast cancer. Breast-feeding, if, in fact, it is
shown to be protective against the development of breast cancer,
is a potentially modifiable behavior and thus may represent one
of the few opportunities for intervention at present.
METHODS
Original data for inclusion in this review were identified through a
MEDLINE® search of the literature. All papers from 1966 through 1998 were
identified by use of either the term “breast-feeding” or the term “lactation,”
together with the term “breast cancer.” Moreover, all review papers addressing
reproductive factors in relation to breast cancer were identified, and references
were examined to supplement, if necessary, papers recovered through the initial
search. For the purposes of this review, only those studies that included more
than 200 cases overall and which explicitly controlled for number of full-term
pregnancies and age at first birth, both of which are associated with breast cancer
risk and potentially related to breast-feeding habits, were evaluated in detail.
Individual results were evaluated for bias, confounding, and chance and are
summarized in Tables 1–6. On the basis of the individual data, a qualitative
summary of the results is presented in the text.
EPIDEMIOLOGIC FINDINGS
Since the publication of the large international case–control
study (3), virtually all of the relevant epidemiologic data regard-
Affiliations of authors: L. Lipworth, International Epidemiology Institute,
Rockville, MD, and Vanderbilt-Ingram Cancer Center, Vanderbilt University
School of Medicine, Nashville, TN; L. R. Bailey, Program in Human Genetics,
Department of Molecular Physiology and Biophysics, Vanderbilt University
School of Medicine; D. Trichopoulos, Department of Epidemiology, Harvard
School of Public Health, Boston, MA
Correspondence to: Loren Lipworth, Sc.D., International Epidemiology In-
stitute, 1455 Research Blvd., Suite 550, Rockville, MD 20850 (e-mail:
loren3@earthlink.net).
See “Notes” following “References.”
© Oxford University Press
 Table 1. Hospital-based, case–control studies of breast-feeding and breast cancer among parous women of all ages*

No. of
Authors, year Study case No. of
(reference No.) Location period patients control subjects Measure of lactation OR 95% CI Comments

Yoo et al., 1992 Japan 1988–1989 430 455 noncancer Ever 0.62 0.37–1.04 Adjusted for age, family history of breast
(7) patients No. of children breast-fed cancer, age at menarche, menstrual
0 1.00 — regularity, menopausal status, age at
1 0.55 0.30–1.00 menopause, parity, age at first birth
2 0.66 0.38–1.16
3 0.71 0.34–1.51
艌4 0.93 0.12–6.96
Duration per child, mo
1–3 0.71 0.40–1.26
4–6 0.75 0.41–1.38
7–9 0.47 0.24–0.92

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10–12 0.59 0.34–1.02
艌13 0.53 0.26–1.05

Thomas and Australia, Germany, 1979–1986 2336 14 900 Total duration, mo Adjusted for age, study center, parity,
Noonan, 1993 Israel, Chile, nonobstetric/ 0 0.86 0.72–1.02 age at first birth
(25) China, Kenya, gynecologic 艋3 1.00 —
Colombia, patients 4–6 1.10 0.93–1.31
Mexico, 7–12 0.99 0.84–1.16
Philippines, 13–36 0.92 0.78–1.08
Thailand 37–72 0.84 0.68–1.03
73–107 0.72 0.53–0.96
艌108 0.99 0.70–1.42
Duration per child, mo
1.1–3.0 1.04 0.89–1.23
3.1–6.0 0.91 0.76–1.08
6.1–12.0 0.90 0.76–1.07
12.1–35.0 0.98 0.81–1.19
>35 1.17 0.62–2.22

Negri et al., 1996 Italy 1991–1994 2167 2208, Ever 1.17 1.0–1.3 Adjusted for age, study center, education
(21) non-neoplastic, No. of children breast-fed level, parity, menopausal status, age at
nongynecologic, 1 1.14 1.0–1.4 menopause, age at first birth, family
non-hormone- 2 1.18 1.0–1.4 history of breast cancer, benign breast
related hospital 艌3 1.32 1.0–1.7 disease, body mass index, marital
admissions Total duration, mo status
1–5 1.19 1.0–1.4
6–11 1.15 1.0–1.4
12–17 1.34 1.1–1.7
18–23 1.10 0.8–1.5
艌24 0.86 0.5–1.3

Katsouyanni et al., Greece 1989–1991 657 1164 orthopedic Ever 0.92 0.67–1.27 Adjusted for age; place of birth; body
1996 (8) patients and Total duration, mo mass index; age at menarche;
hospital visitors <3 0.91 0.63–1.32 menopausal status; age at menopause;
3–11 1.00 0.71–1.42 parity; age at first birth; total daily
12–23 1.06 0.70–1.61 intake; history of benign breast
艌24 0.64 0.41–0.99 disease; family history of breast
cancer; intake of fruit, vegetables,
olive oil, and alcohol; induced
abortions; menopausal estrogen use

*OR ⳱ odds ratio; CI ⳱ confidence interval.

ing breast-feeding and breast cancer risk are derived from
case–control studies, the majority of which have been conducted
in North America or in Europe. The characteristics and results
of these hospital-based and population-based, case–control
studies, as well as those of the only cohort study to date (4)
and two retrospective assessments of breast-feeding in the
Nurses’ Health Study (5,6), are summarized in Tables 1–6.
Where available, relative risk (RR) estimates are presented for
women who ever breast-fed and for categories of cumulative
duration of breast-feeding, average duration of breast-feeding
per child, and number of children breast-fed. Clearly, even in
studies with more than 200 cases overall, many of the sub-
group analyses were based on smaller numbers. While several
studies were designed specifically to evaluate the role of breast-
feeding, they varied according to subject selection criteria and
classification of breast-feeding history. Many were based on
relatively small numbers of women who breast-fed for pro-
longed periods, making it difficult to meaningfully evaluate
the role of long-term breast-feeding in the etiology of breast
cancer.

Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000 REVIEW 303
 Table 2. Hospital-based, case–control studies of breast-feeding and breast cancer among premenopausal parous women*

No. of
Authors, year Study case No. of
(reference No.) Location period patients control subjects Measure of lactation OR 95% CI Comments

Yoo et al., 1992 Japan 1988–1989 198 225 noncancer Ever 0.64 0.32–1.30 Adjusted for age, family history of breast
(7) patients No. of children breast-fed cancer, age at menarche, menstrual
0 1.00 — regularity, parity, age at first birth
1 0.53 0.23–1.25
2 0.65 0.30–1.39
3 0.94 0.30–2.93
Duration per child, mo
1–3 0.85 0.39–1.83
4–6 0.63 0.27–1.44
7–9 0.39 0.15–0.97
10–12 0.58 0.27–1.25

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艌13 0.77 0.23–2.54

Thomas and Australia, Germany, 1979–1986 1852 11 265 Total duration, mo 0.87 0.72–1.06 Adjusted for age, study center, parity,
Noonan, 1993 Israel, Chile, nonobstetric/ 0 1.00 — age at first birth
(25) China, Kenya, gynecologic 艋3 1.20 1.00–1.44
Colombia, hospital 4–6 1.00 0.83–1.20
Mexico, admissions 7–12 0.90 0.75–1.08
Philippines, 13–36 0.81 0.64–1.03
Thailand 37–72 0.76 0.54–1.09
73–107 0.92 0.59–1.42
艌108

Katsouyanni et al., Greece 1989–1991 270 505 orthopedic Ever 0.76 0.48–1.19 Adjusted for age; place of birth; body
1996 (8) patients and Total duration, mo mass index; age at menarche; parity;
hospital visitors <3 0.58 0.34–0.98 age at first birth; total daily intake;
3–11 1.01 0.61–1.67 history of benign breast disease;
12–23 0.70 0.34–1.60 family history of breast cancer; intake
艌24 0.50 0.23–1.41 of fruit, vegetables, olive oil, and
alcohol; induced abortions

Stuver et al., 1997 Wales, United 1964–1968 1142 3529, nonbreast Ever 1.05 0.86–1.29 Adjusted for age, parity, age at first
(18) States, Greece, cancer patients Wales, United States, birth, age at menarche, body mass
Slovenia, Brazil, high risk index, education level, study center
Japan, Taiwan Ever 1.16 0.81–1.66
Total duration, mo
1–6 1.10 0.72–1.69
7–12 0.99 0.56–1.75
13–24 1.71 0.97–3.04
25–36 0.94 0.30–2.94
艌37 0.78 0.08–7.15
Greece, Slovenia, Brazil,
moderate risk
Ever 1.13 0.81–1.58
Total duration, mo
1–6 0.97 0.66–1.41
7–12 0.94 0.63–1.40
13–24 1.64 1.11–2.42
25–36 1.49 0.93–2.39
艌37 1.29 0.80–2.07
Japan, Taiwan, low risk
Ever 0.89 0.61–1.30
Total duration, mo
1–6 0.92 0.56–1.53
7–12 0.94 0.58–1.53
13–24 0.79 0.50–1.23
25–36 1.08 0.68–1.73
艌37 0.79 0.48–1.27

*OR ⳱ odds ratio; CI ⳱ confidence interval.

Any History of Breast-Feeding
One measure of breast-feeding history that has been com-
monly used in epidemiologic studies is that of “ever versus
never” breast-feeding. Overall, the evidence of an inverse asso-
ciation between ever breast-feeding and breast cancer risk re-
mains limited and inconclusive, with results suggesting either no
association or a definite, although modest, protective effect.
Among studies (6–19) that have found a protective effect, re-
ported RRs among parous women who have ever breast-fed

304 REVIEW Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000
 Table 3. Population-based, case–control studies of breast-feeding and breast cancer among parous women of all ages*

No. of
Authors, year Study case No. of
(reference No.) Location period patients control subjects Measure of lactation OR 95% CI Comments

Lubin et al., Canada 1976–1977 489 731, social insurance 艌2 consecutive wks 0.6 0.5–0.8 Adjusted for age, parity, age at
1982 (19) files first birth

Brinton et al., United States 1973–1977 1143 1056, breast cancer Ever 0.94 0.8–1.1 Adjusted for age at first birth,
1983 (9) screening participants No. of children breast-fed parity
None 1.00 —
Some 0.99 0.8–1.2
All 0.90 0.7–1.1

Yuan et al., Shanghai, China 1984–1985 429 429, neighborhood Total duration, mo Adjusted for parity, age at first
1988 (27) sampling 0 1.05 0.64–1.72 birth

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1–36 1.00 —
37–72 0.81 0.53–1.25
73–108 0.35 0.16–0.79
艌109 0.37 0.14–0.98

Tao et al., Beijing, China 1980–1984 449 449, neighborhood Total duration, mo Adjusted for parity, age at first
1988 (26) sampling 0 1.00 — birth
1–36 0.75 0.50–1.13
37–72 0.49 0.27–0.89
73–108 0.49 0.23–1.03
艌109 0.43 0.18–1.01

Layde et al., United States 1980–1982 3830 3931 random-digit Total duration, mo Adjusted for parity, age at first
1989 (23) dialing 0 1.00 — birth, age, benign breast
<6 0.92 0.82–1.02 disease, menopausal status,
6–12 0.85 0.73–0.98 family history of breast cancer,
13–24 0.75 0.62–0.90 regularity of menstrual cycles
艌25 0.67 0.52–0.85 as a teenager, body mass index

Siskind et al., Australia 1981–1985 459 1091, electoral rolls Ever 0.87† 0.58–1.34 Adjusted for age, education level,
1989 (10) Total duration, wk place of birth, family history of
0 1.00† — breast cancer, parity, age at first
1–13 0.91 0.54–1.52 birth, age at menarche, benign
14–52 0.74 0.57–1.17 breast disease
53–104 0.91 0.57–1.46
>104 1.10 0.68–1.78
Duration per child, wk
<1 1.00† —
1–6 0.93 0.56–1.55
7–13 0.70 0.42–1.16
14–26 1.03 0.65–1.64
27–39 0.89 0.56–1.43
>39 1.16 0.68–2.00

Adami et al., Sweden, Norway 1984–1985 422 527, population register Total duration, mo Adjusted for parity, age at first
1990 (24) 0 1.0† — birth, years since last birth,
<6 1.1 0.6–1.9 education level, menopause,
6–11 0.8 0.5–1.5 benign breast disease, family
12–17 1.0 0.5–2.0 history of breast cancer, oral
18–23 1.3 0.6–3.0 contraceptive use, alcohol
艌24 0.6 0.3–1.4 intake, smoking

Wang et al., Tianjin, China 1985–1986 246 246, residence files Total duration, mo Adjusted for parity, age at first
1992 (28) 0 0.9 0.4–2.0 birth
1–36 1.0 —
37–72 0.9 0.6–1.6
73–108 0.7 0.3–1.7
艌109 0.5 0.1–1.8

Newcomb et United States 1989–1991 5434 7563, driver’s licenses Ever 0.97 0.90–1.05 Adjusted for age at first birth,
al., 1994 or Medicare Total duration, mo parity, benign breast disease,
(11) 艋3 0.98 0.90–1.08 family history of breast cancer,
4–12 1.00 0.89–1.11 body mass index, age at
13–24 0.89 0.77–1.04 menarche, menopausal status
>24 0.95 0.79–1.15

(Table continues)

Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000 REVIEW 305
 Table 3 (continued). Population-based, case–control studies of breast-feeding and breast cancer among parous women of all ages*

No. of
Authors, year Study case No. of
(reference No.) Location period patients control subjects Measure of lactation OR 95% CI Comments

Romieu et al., Mexico 1990–1992 301 968, household sampling Ever 0.54 0.33–0.89 Adjusted for age, socioeconomic
1996 (12) Total duration, mo status, family history of breast
1–3 0.47 0.23–0.95 cancer, menopausal status,
4–12 0.61 0.35–1.05 parity, age at first birth
13–24 0.52 0.29–0.92
25–36 0.72 0.39–1.32
37–60 0.33 0.18–0.62
>60 0.31 0.16–0.57
No. of children breast-fed
1–2 0.57 0.34–0.96
3–4 0.52 0.31–0.87

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>4 0.39 0.21–0.70

Wu et al., 1996 United States 1983–1987 597 966, random-digit <1 mo 1.00† — Adjusted for age, area, ethnicity,
(34) (Asian-American) dialing or household 艌1 mo 0.78 0.58–1.04 migration history, parity, age at
sampling first birth, cycle length, age at
menarche

Gilliland et al., New Mexico 1992–1994 610 740, random-digit Hispanic Adjusted for age, education level,
1998 (29) dialing Total duration, mo body mass index, age at
1–12 1.05 0.71–1.55 menarche, age at first birth,
>12 0.78 0.48–1.27 parity, induced abortion,
Non-Hispanic white spontaneous abortion,
Total duration, mo menopausal status
1–12 1.30 0.90–1.87
>12 0.58 0.35–0.97

*OR ⳱ odds ratio; CI ⳱ confidence interval.

†Studies in which reference groups include nulliparous women.

compared with women who have never breast-fed range from
0.54 to just below 1.0 (Tables 1, 3, and 5). However, a history
of ever breast-feeding may be too crude an indicator, and it may
be more important to demonstrate a dose–response association
with increasing duration of breast-feeding in making causal in-
ferences.
Number of Children Breast-Fed
Recent studies have raised the question of whether the total
number of children that a woman has breast-fed may be etio-
logically relevant or whether breast-feeding additional children
after the first may provide incremental protection against breast
cancer development. Two investigations (12,20) have reported
that the more children a woman breast-fed over the course of her
lifetime, the lower her breast cancer risk. Romieu et al. (12)
found that, after adjustment for several other risk factors, women
who breast-fed four or more children had a statistically signifi-
cant 60% reduction in breast cancer risk (odds ratio [OR] ⳱
0.39; 95% confidence interval [CI] ⳱ 0.21–0.70) compared with
women who never breast-fed; women who breast-fed one or two
children had an intermediate 43% reduction in breast cancer risk
(Table 3). However, a number of studies (7,9,21,22) have found
no such trend of decreasing risk with increasing number of
breast-fed children.
Cumulative Duration of Breast-Feeding
In many studies to date, the summation of all breast-feeding
episodes is calculated as the total duration of breast-feeding for
each woman, taking into account breast-feeding after all births.
Using the cumulative duration as a measure of a woman’s com-
plete breast-feeding history allows for the examination of dose–
response trends in drawing causal inferences. However, study
populations have been drawn from different geographic areas
and cultures, which could have important consequences with
respect to the interpretation and comparison of findings from
different studies. For instance, the classification of long-term
breast-feeding ranged from 24 months or longer in several stud-
ies in Europe and in North America (5,6,8,10,11,14,20,21,23,24)
to 100 months or longer in studies conducted in Asia and in other
non-Western societies (25–28). Such diversity in the definition
of exposure and nonexposure may account for the large discrep-
ancies in the percentages of control women with extensive du-
rations of breast-feeding. As a result, the magnitude of risk
estimates could be greatly affected, and direct comparison of
findings from different studies is difficult.
Among case–control studies that have found a decreasing
trend in breast cancer risk with increasing duration of breast-
feeding among parous women, adjusted ORs for premenopausal
women who have breast-fed for at least 12 months range from
0.21 to slightly below 1.0 compared with parous women who
never breast-fed (8,12,23,25–27,29) (Tables 1–4). In the Cancer
and Steroid Hormone Study, breast-feeding for 25 months or
longer was associated with an OR of 0.67 (23) (Table 3).
Several studies (4–6,10,11,21,24,28) have failed to confirm
an inverse association between increasing total duration of
breast-feeding and breast cancer risk in parous women. Michels
et al. (6), through a retrospective assessment of breast-feeding in
almost 90 000 parous women in the Nurse’s Health Study, re-
ported that, in comparison to never breast-feeding, the RR was

306 REVIEW Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000
 Table 4. Population-based, case–control studies of breast-feeding and breast cancer among premenopausal parous women*

Authors, year Study No. of No. of

(reference No.) Location period case patients control subjects Measure of lactation OR 95% CI Comments

Byers et al., New York state 1957–1965 107 440, household sampling Total duration, mo Adjusted for age, parity, age at
1985 (13) Per 6 mo 0.78 menarche, age at first birth,
Per 12 mo 0.60 education level

McTiernan et al., Washington 1981–1982 163 146, random-digit Total duration, mo Adjusted for age, parity, age at
1986 (33) state dialing 1–3 0.66 0.35–1.20 first birth
4–12 0.45 0.24–0.87
艌13 0.45 0.21–0.96

Siskind et al., Australia 1981–1985 136 397, electoral rolls Ever 0.93† 0.48–1.80 Adjusted for age, education level,
1989 (10) Total duration, wk place of birth, family history of

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0 1.00† — breast cancer, age at first birth,
1–13 1.04 0.48–2.3 age at menarche, benign breast
14–52 0.77 0.37–1.58 disease
53–104 0.91 0.42–1.95
>104 1.02 0.44–2.40
Duration per child, wk
<1 1.00† —
1–6 1.02 0.47–2.20
7–13 0.79 0.36–1.72
14–26 1.06 0.50–2.20
27–39 0.99 0.44–2.20
>39 1.22 0.46–3.20

Yang et al., 1993 British 1988–1989 271 286, random-digit Breast-fed >2 mo 1.0 — Adjusted for age at parity, age at
(14) Columbia dialing Breast-fed <1 mo 1.8 1.3–2.5 first birth
Never breast-fed 1.3 0.9–2.0
Total duration, mo
2–3 1.0 —
4–6 0.7 0.4–1.3
7–12 0.9 0.5–1.7
13–24 0.6 0.3–1.2
艌25 0.4 0.2–1.2

U.K. National Britain 1982–1985 755 755, random sampling Total duration, mo Adjusted for parity, age at
Case–Control from general 1–3 0.83 menarche, family history of
Study Group, practitioner attending 4–9 0.77 breast cancer, benign breast
1993 (20) the case patient 10–15 0.53 disease, age at first birth, oral
16–21 0.68 contraceptive use
艌22 0.63
No. of children breast-fed
1 0.84
2 0.62
艌3 0.79

Newcomb et al., United States 1989–1991 1180 2185, driver’s licenses Ever 0.78 0.66–0.91 Adjusted for age at first birth,
1994 (11) or Medicare Total duration, mo parity, benign breast disease,
艋3 0.85 0.69–1.06 family history of breast cancer,
4–12 0.78 0.63–0.97 body mass index, age at
13–24 0.66 0.50–0.87 menarche
>24 0.72 0.51–0.99

Brinton et al., United States 1990–1992 1211 1120, random-digit Ever 0.87 0.7–1.0 Adjusted for site, age, race,
1995 (15) dialing Total duration, mo parity, age at first birth, oral
<6 0.97 0.8–1.2 contraceptive use
6–11 0.90 0.7–1.2
12–17 0.79 0.6–1.1
艌18 0.88 0.7–1.2
Duration per child, wk
<12 1.04 0.8–1.4
12–23 0.94 0.7–1.2
24–35 0.80 0.6–1.1
艌36 0.82 0.6–1.1
(Table continues)

Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000 REVIEW 307
 Table 4 (continued). Population-based, case–control studies of breast-feeding and breast cancer among premenopausal parous women*

Authors, year Study No. of No. of

(reference No.) Location period case patients control subjects Measure of lactation OR 95% CI Comments

Romieu et al., Mexico 1990–1992 112 513, household sampling Ever 0.58 0.30–1.11 Adjusted for age, socioeconomic
1996 (12) Total duration, mo status, family history of breast
1–3 0.40 0.15–1.05 cancer, parity, age at first birth
4–12 0.77 0.38–1.56
13–24 0.40 0.17–0.92
25–36 0.96 0.41–2.25
37–60 0.39 0.14–1.06
>60 0.40 0.14–1.13
No. of children breast-fed
1–2 0.56 0.28–1.12
3–4 0.64 0.31–1.30
>4 0.42 0.16–1.07

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Enger et al., Los Angeles, 1983–1988 452 452, neighborhood Ever 0.93 0.69–1.26 Adjusted for age at first birth,
1997 (22) CA Total duration, mo parity, age at menarche, family
1–6 1.15 0.80–1.65 history of breast cancer, oral
7–15 0.84 0.56–1.27 contraceptive use, race, alcohol
艌16 0.66 0.41–1.05 intake, physical activity
No. of children breast-fed
1 0.87 0.61–1.25
2 1.05 0.70–1.57
艌3 0.90 0.50–1.63

Freudenheim et New York state 1986–1991 253 266, driver’s licenses or Ever 0.80 0.54–1.17 Adjusted for age, education level,
al., 1997 (17) Health Care Financing Total duration, mo family history of breast cancer,
Agency <4 0.85 0.50–1.42 benign breast disease, age at
4–11 0.72 0.41–1.27 menarche, parity, age at first
12–20 1.08 0.78–1.96 birth, body mass index
>20 0.50 0.21–1.12

Gilliland et al., New Mexico 1992–1994 231 326, random-digit Hispanic Adjusted for age, education level,
1998 (29) dialing Total duration, mo body mass index, age at
1–12 0.74 0.39–1.42 menarche, age at first birth,
>12 0.41 0.17–0.98 parity, induced abortion,
Non-Hispanic white spontaneous abortion
Total duration, mo
1–12 0.90 0.41–1.99
>12 0.63 0.24–1.65

*OR ⳱ odds ratio; CI ⳱ confidence interval.

†Studies in which reference groups include nulliparous women.

0.86 for fewer than 3 months of breast-feeding, 1.02 for 406
months, 0.95 for 7–11 months, 0.86 for 12–23 months, and 1.11
for 24 months or longer (Table 5). The only prospective study
(4) of breast-feeding to date found no association among either
premenopausal or postmenopausal Norwegian women (Table 5),
despite the fact that it included a high percentage of women with
long durations of breast-feeding compared with studies in other
Western populations.
The failure to detect an association in some studies may be
due to the low prevalence of prolonged breast-feeding; for in-
stance, only 17% of the women in the Nurses’ Health Study
population breast-fed for at least 12 months (6). Thus, it is
difficult in Western studies to evaluate the influence of the ex-
tensive durations of breast-feeding experienced by the majority
of parous women in many non-Western populations. For ex-
ample, in China, where more than half of the women breast-feed
for at least 3 years, a 64% reduction in risk has been found
among mainly premenopausal women who breast-fed for at least
10 years compared with women who never breast-fed (26).
Breast-feeding for 3–5 years was associated with little decrease
in risk. In this study, more than 15% of the parous control
subjects had breast-fed for more than 6 years. Similarly, Yuan et
al. (27) reported adjusted ORs of 0.35 and 0.37 after 73–108
months and greater than 109 total months of breast-feeding,
respectively, among Chinese women (Table 3). Another large
study (25) conducted in 10 countries, the majority of which are
non-Western societies, also found a statistically significant re-
duction in breast cancer risk (OR ⳱ 0.72) among women with
a prolonged duration (73–107 months) of breast-feeding (Table
1). Although it is difficult to speculate at this stage that long-
term breast-feeding has substantial incremental benefit in all
populations, there appears to be evidence for a protective influ-
ence on breast cancer risk among women in non-Western soci-
eties with extensive cumulative durations of breast-feeding.
However, the potential for confounding by numerous factors,
including low body weight and height, low socioeconomic sta-
tus, poor nutritional status and possibly associated amenorrhea,
or age at any pregnancy (30), cannot be ruled out.
Average Duration of Breast-Feeding Per Child
Average months of breast-feeding per child has been used as
a measure of breast-feeding history in a number of studies, based

308 REVIEW Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000
 Table 5. Follow-up studies of breast-feeding and breast cancer among parous women of all ages*

Authors, year Period of No. of

(reference No.) Location follow-up Population case patients Measure of lactation RR 95% CI Comments

Kvale and Norway 1961–1980 50 274 parous 1136 Total duration, mo: per 6 mo 1.01 0.97–1.05 Adjusted for age, place of residence,
Heuch, 1987 women Duration per child, mo: per 1.01 0.98–1.05 parity, age at first birth
(4) 2 mo

London et al., United States 1976–1986 89 413 parous 1262 Total duration, mo Adjusted for age, parity, age at first
1990 (5) nurses <7 0.94 0.82–1.06 birth, age at menarche, family
7–11 0.83 0.67–1.03 history of breast cancer, benign
12–23 0.90 0.74–1.09 breast disease, oral contraceptives,
艌24 0.95 0.73–1.23 menopausal status
Michels et al., United States 1986–1992 89 887 parous 1459 Ever 0.93 0.83–1.03 Adjusted for age, parity, age at first
1996 (6) nurses Total duration, mo birth, age at menarche, family
艋3 0.86 0.75–0.99 history of breast cancer, benign

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4–6 1.02 0.87–1.21 breast disease, oral contraceptives,
7–11 0.95 0.79–1.14 body mass index, age at
12–23 0.86 0.72–1.03 menopause, postmenopausal
艌24 1.11 0.90–1.38 hormone use, alcohol intake,
vitamin A, physical activity

*RR ⳱ relative risk; CI ⳱ confidence interval.

Table 6. Follow-up studies of breast-feeding and breast cancer among premenopausal parous women*

Authors, year Period of No. of

(reference No.) Location follow-up Population case patients Measure of lactation RR 95% CI Comments

London et al., United States 1976–1986 89 413 parous nurses, 624 Total duration, mo Adjusted for age, parity, age at
1990 (5) age 30–55 y <7 1.00 0.83–1.20 first birth, age at menarche,
7–11 0.85 0.63–1.14 family history of breast cancer,
12–23 0.90 0.69–1.18 benign breast disease, oral
艌24 1.06 0.75–1.50 contraceptives

Michels et al., United States 1986–1992 89 887 parous nurses 256 Ever 1.14 0.87–1.50 Adjusted for age, parity, age at
1996 (6) Total duration, mo first birth, age at menarche,
艋3 1.10 0.77–1.56 family history of breast cancer,
4–6 1.31 0.88–1.96 benign breast disease, oral
7–11 1.12 0.73–1.71 contraceptives, body mass
12–23 1.21 0.82–1.78 index, alcohol, vitamin A,
艌24 0.90 0.53–1.54 physical activity

*RR ⳱ relative risk; CI ⳱ confidence interval.

on the hypothesis that a higher average duration of breast-
feeding per child may confer greater protection against breast
cancer. However, four studies (4,7,10,25) have failed to show
any significant association between breast cancer risk and this
measure of breast-feeding, while only one study (15) reported a
statistically significant trend of decreasing risk with increasing
average length of breast-feeding per child (Table 4).
Reasons for Cessation of Breast-Feeding
It has been hypothesized that the apparently protective effect
of breast-feeding against breast cancer may be due to an elevated
risk among women who either have difficulties in starting
breast-feeding or who discontinue breast-feeding after a short
interval (13), perhaps as a result of abnormalities in estrogen
levels or other endocrine or psychosocial factors. A common
reason for stopping breast-feeding, particularly among women
who cease within the first month, is “insufficient milk supply,”
while breast infections, cracked nipples, and nonmedical cir-
cumstances such as returning to work are among other reasons
given (13,15).
Byers et al. (13) reported a twofold increase in risk of breast
cancer among premenopausal women who cited insufficient
milk as the reason for having stopped breast-feeding compared
with women who cited all other reasons combined. While
adjusting for insufficient milk eliminated the increased risk
observed among women in the category of shortest cumula-
tive breast-feeding duration, it did not markedly reduce the
overall strength of the inverse association between breast-
feeding duration and breast cancer. These findings suggest
that there may still be a protective effect of breast-feeding in-
dependent of those factors that lead women to cease breast-
feeding because of a perception of insufficient milk (13). A
population-based, case–control study conducted in British
Columbia (14) reported significantly elevated risks of breast
cancer among premenopausal women who tried to breast-
feed for more than 1 month but were unsuccessful because
of either “insufficient milk” (OR ⳱ 3.1) or other reasons (OR ⳱
3.0) compared with women who breast-fed for at least 2
months. In both studies (13,14), the association between
breast cancer and “insufficient milk” was less pronounced
among postmenopausal women. In a number of other studies
(10,11,15,17), however, there was no evidence that women
who reported stopping breast-feeding because of a perception

Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000 REVIEW 309
of insufficient milk were at markedly elevated risk of breast
cancer.
It has also been suggested that breast cancer risk may be
increased among women who do not breast-feed as a result of
exposure to lactation suppressants. In a number of studies
(11,15), a substantial proportion of women, often as many as
44%, reported having been given treatment to induce cessation
of lactation after one or more births. However, the use of hor-
monal medication to suppress breast-feeding has not been con-
sistently linked with an increased risk of breast cancer, either
before or after adjustment for duration of breast-feeding
(11,14,15,17,20,22,25).
Estrogen Receptor Status
Breast tumors that are estrogen receptor (ER) positive have
been shown to be slower growing tumors, and patients with
these types of tumors have fewer recurrences, longer survival,
and seem to respond better to therapy than patients with ER-
negative tumors (31). It has been suggested that the risk factor
profiles for these breast tumor subtypes may differ, but there are
limited data with respect to whether the ER status (ER positive
versus ER negative) of breast tumors, as well as the actual con-
centration of ER protein, varies according to breast-feeding his-
tory. In an intracase analysis among parous women (32), those
with ER-positive breast tumors were more likely than ER-
negative cases to have breast-fed at least one child, although the
results were of borderline significance. After adjustment for sev-
eral known breast cancer risk factors, women who ever breast-
fed were three times more likely than those who never breast-fed
to have an ER-positive tumor as opposed to an ER-negative
tumor (OR ⳱ 3.4; 95% CI ⳱ 1.3–8.7); similarly, a history of
ever having breast-fed was significantly associated with the ER
concentration of the tumor. In their case–control analysis, Hil-
dreth et al. (32) showed that a history of ever having breast-fed
was not associated with an increased risk for ER-positive breast
tumors, while the association with ER-negative tumors was, if
anything, inverse.
Another case–control study (33), which compared risk factors
for ER-rich and ER-poor breast cancers, reported an inverse
association between cumulative duration of breast-feeding and
both ER-positive and ER-negative tumors. In particular, women
who breast-fed for longer than 13 cumulative months had a
decreased OR of 0.43 (95% CI ⳱ 0.20–0.95) for ER-positive
breast cancer and 0.71 (95% CI ⳱ 0.31–1.6) for ER-negative
breast cancer. To date, a plausible biologic mechanism for dif-
ferential influences of breast-feeding on the ER status of a tumor
has not been put forth, and the findings should be interpreted
with caution until they are confirmed in other studies.
Ethnic Differences
There is striking geographic variation in breast cancer inci-
dence rates, with the highest rates seen in North America and in
Europe and the lowest rates in Asia and in Africa. While a
number of studies (7,25–28) have evaluated breast cancer risk
factors, including breast-feeding, among Asian and African
populations, the epidemiologic data with respect to the potential
association between breast-feeding and breast cancer risk among
various racial and ethnic groups within the United States are
substantially more limited.
Studies of migrants suggest that environmental factors are
largely responsible for the international variation in breast can-
310 REVIEW Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000
cer incidence rates. Patterns among migrants to the United States
show that women born in countries with low breast cancer rates,
such as China and Japan, experience an increase in rates above
those of their country of birth but still below U.S. rates (2). Wu
et al. (34) conducted a study among Asian-Americans, both
American-born and migrants, to investigate if breast-feeding had
a protective effect on breast cancer risk in this population. No
statistically significant trend of decreasing breast cancer risk
with increasing duration of breast-feeding was observed.
Mayberry et al. (35) conducted a case–control study of Af-
rican-American and Caucasian women to determine if there
were different breast cancer risk profiles between the two races.
The multivariate analysis of breast-feeding among parous
women of both races indicated that increasing total months of
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breast-feeding was associated with decreased breast cancer risk
among both African-Americans and Caucasians. However, the
magnitude of the protective effect was larger among African-
American than among Caucasian women, with adjusted ORs of
0.45 and 0.76, respectively, for women who breast-fed for 16
months or longer compared with those who breast-fed for fewer
than 4 months.
Similarly, a study of risk factors for breast cancer among
Hispanic and non-Hispanic white women found that the protec-
tive effect of longer cumulative duration of breast-feeding varied
between these two groups (29). Non-Hispanic white women who
breast-fed for longer than 12 months had a statistically signifi-
cant reduced OR of 0.58, while Hispanic women who breast-fed
the same length of time had an OR of 0.78 that was not statis-
tically significant.
Menopausal Status
Examination of the pattern of breast cancer risk among par-
ous women by menopausal status has produced inconsistent re-
sults. However, in most studies (7,8,10–14,17,18,22–26,36), any
apparently protective effect of breast-feeding was stronger
among, or confined to, premenopausal women, despite differ-
ences in the classification of menopausal status. Adjusted ORs
for premenopausal parous women who have ever breast-fed
compared with those who never breast-fed ranged from 0.58 to
1.14 (Tables 2, 4, and 6). The findings of the United Kingdom
National Case–Control Study (20), as well as a number of other
investigations (11,14,22,36), indicate a statistically significantly
decreasing risk for breast cancer among young women with
increasing duration of breast-feeding or with number of children
breast-fed. If, indeed, there is an inverse association between
breast-feeding and breast cancer that is confined to young
women, the small number of premenopausal women in the pro-
spective study of Kvale and Heuch (4) may have reduced the
statistical power to detect a modest association.
Few investigations have reported a statistically significant
inverse association between breast-feeding and postmenopausal
breast cancer. One case–control study in Los Angeles (16) found
that postmenopausal women who breast-fed for at least 16
months had a reduced risk of breast cancer (OR ⳱ 0.73; 95% CI
⳱ 0.52–1.01) relative to postmenopausal women who never
breast-fed, suggesting that a protective effect of breast-feeding
may persist into the postmenopausal years. However, the col-
lective evidence for an inverse relation between breast-feeding
and postmenopausal breast cancer is limited, with numerous
studies (5,7,8,10,11,13,14,25,36) reporting no such association.
It is possible that postmenopausal women may have more dif-
ficulty recalling past breast-feeding habits, thereby attenuating
any association with breast cancer risk.
BIOLOGIC MECHANISMS
The biologic basis for an inverse association between breast-
feeding and breast cancer risk has not been adequately eluci-
dated, although several mechanisms have been postulated. One
hypothesis is that lactation causes long-term endogenous hor-
monal changes, possibly reduced estrogen, and increased pro-
lactin production, which may decrease a woman’s cumulative
exposure to estrogen, thereby inhibiting the initiation or growth
of breast cancer cells (13,37). This effect, if indeed it were real,
would be more pronounced among premenopausal women. An-
other proposed mechanism is estrogen synthesis by the lactating
breast and removal of estrogens through breast fluid. Breast fluid
estrogen levels, independent of serum estrogen levels, were
found to be lower in premenopausal parous women who were
breast-feeding when compared with levels among parous
women who did not breast-feed or among nulliparous women. In
fact, breast fluid estrogen levels in the women who breast-fed
appeared to gradually increase over a period of several years
since last breast-feeding to reach levels found in nulliparous
women (38). Again, this underlying mechanism could explain
why an apparently protective effect of breast-feeding would be
stronger among premenopausal women.
It has also been suggested that a protective effect of breast-
feeding on breast cancer risk may be attributed to the excretion
of carcinogenic agents from the breast ductal tissue through
breast-feeding (39). For instance, there is some evidence that the
level of a potential carcinogen, cholesterol–␤-epoxide, is lower
in the breast fluid of women during and up to 2 years after
breast-feeding (40). However, it would be expected that these
carcinogens would, in turn, affect the child being breast-fed, an
association that has not been reported in epidemiologic studies.
Milk from unsuckled breasts has been shown to have a
slightly higher pH in comparison to that from suckled breasts,
which remains acidic during breast-feeding (41). Studies (39)
have shown that epithelial cells in an alkaline environment un-
dergo preneoplastic alterations, such as hyperplasia, cell atypia,
and increased mitotic activity at a more frequent rate.
Alternatively, physical changes in the epithelial cells of the
mammary ducts, including extended terminal differentiation in-
duced by lactation, may directly affect risk by making the breast
tissue more resistant to carcinogenesis (42). The lactational pe-
riod of the mammary gland is characterized by the presence of
lobule type 4, a lobular structure that represents maximal devel-
opment and differentiation and which is not present among nul-
liparous women (42).
Finally, the effect of breast-feeding may be attributed to its
role in delaying the re-establishment of ovulation (43), although
the relation between cumulative number of ovulatory cycles and
breast cancer risk remains controversial. Moreover, it has not
been shown that breast cancer risk relates more strongly to du-
ration of exclusive breast-feeding (until supplementation) than
to duration of total breast-feeding (15), which would be expected
if this were the underlying mechanism.
DISCUSSION
The collective epidemiologic evidence to date, while cer-
tainly not conclusive, is compatible with a protective effect of
prolonged breast-feeding against breast cancer risk among pre-
Journal of the National Cancer Institute, Vol. 92, No. 4, February 16, 2000
menopausal women. However, the effect, even if it were real,
appears to be relatively weak and limited to a minority of women
at risk of breast cancer. It is not clear why breast-feeding should
reduce the risk of breast cancer at the biologic level, nor is there
a convincing etiologic explanation for why this association
should be restricted to premenopausal women.
Future research should address the possibility that breast-
feeding delays the occurrence of breast cancer among premeno-
pausal women and that the postponed breast cancer cases occur
postmenopausally and mask a similarly generated protective ef-
fect among postmenopausal women. Moreover, if, in fact, an
inverse association does exist between breast-feeding and breast
cancer, it may be important to examine the joint effect on breast
cancer risk of breast-feeding on the one hand and family history
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of breast cancer or genetic susceptibility on the other. Finally, it
should be investigated whether breast-feeding from smaller
breasts, representing smaller mammary gland mass, may be
more protective.
Clearly, assessment of the effects of breast-feeding on breast
cancer risk is complicated, and most studies have limited data on
breast-feeding histories, including reasons for starting or discon-
tinuing breast-feeding and the manner of introduction of supple-
mental formula. This may be of particular importance when
comparing results from populations with different breast-feeding
practices. For instance, in non-Western populations in which
extended breast-feeding is the norm and there are relatively few
women who never breast-feed, a reference group of parous
women who have never breast-fed is likely to have different
characteristics compared with the same reference group from a
population in which breast-feeding is less common (17).
Breast-feeding is a potentially modifiable behavior, and an
understanding of its contribution to the etiology of breast cancer
is clearly a major research and public health priority. However,
breast-feeding may not be a practical intervention for women in
the United States and in other Western societies if, in fact, a
protective effect of breast-feeding on breast cancer risk is ap-
parent only after prolonged periods of breast-feeding. The
choice to breast-feed is primarily determined by socioeconomic
considerations and concerns for the health of the child, and only
if there were convincing evidence for a strong effect of breast-
feeding against breast cancer risk would a public health recom-
mendation of breast-feeding for the benefit of the mother be
justified.
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NOTES
Supported in part by Public Health Service grant CA68485 from the National
Cancer Institute, National Institutes of Health, Department of Health and Human
Services.
We thank Johnson Eyadiel for his help with literature research.
Manuscript received March 28, 1999; revised November 29, 1999; accepted
December 7, 1999.