EPIDEMIOLOGY

Reproductive factors and the risk of breast cancer in old age:a Norwegian cohort study

Julie Horn • Bjørn Olav Asvold • Signe Opdahl •

Steinar Tretli • Lars J. Vatten

Received: 3 January 2013 / Accepted: 8 April 2013 / Published online: 19 April 2013

� Springer Science+Business Media New York 2013

Abstract Reproductive factors, including early age at

menarche, late age at first birth, low parity, and late age at

menopause, are associated with increased risk of breast

cancer, but it is not clear to which degree the associations

persist into old age. Altogether 58,426 Norwegian women

born between 1886 and 1928 were followed up for breast

cancer incidence from 1961 to 2008. Associations of

reproductive factors with breast cancer risk were analyzed

separately for the age intervals 55–69 and 70 years and

older, using Cox regression. The associations were of

similar strength in the two age strata. At 70 years and later,

hazard ratios (HR) for the following comparisons were

found: late (C17 years) versus early (\13 years) age at

menarche [HR 0.79, 95 % confidence interval (CI): 0.62,

1.01, P for trend \0.001]; late (C35 years) versus early

(\20 years) age at first birth (HR 1.54, 95 % CI: 1.13, 2.11,

P for trend \0.001); high (C5) versus low (1) parity (HR

0.68, 95 % CI: 0.54, 0.86, P for trend = 0.001) and late

(50–54 years) versus early (\45 years) age at menopause

(HR 1.44, 95 % CI: 1.10, 1.90, P for trend = 0.002). These

findings suggest that reproductive events may have life-

long effects on breast cancer risk.

Keywords Age factors � Breast cancer � Menarche �Age at first birth � Parity � Menopause

Introduction

Early age at menarche, late age at first birth, low parity, and

late age at menopause are established factors associated with

increased risk for breast cancer [1]. Nonetheless, the

underlying mechanisms are not well understood, and it is not

known to which degree these associations extend to old age,

suggesting a life-long influence on the incidence of breast

cancer. It has been hypothesized that pregnancy, despite

being associated with a transient increase in breast cancer

risk during the first years following a delivery [1], may cause

permanent morphological changes in breast tissue that pro-

vide a lasting protection against breast cancer, and that the

protection is strengthened by increasing number of preg-

nancies [2]. On the other hand, timing of menarche and age at

menopause may reflect biological traits that determine the

cumulative exposure to menstrual factors, and the total

number of regular menstrual periods may play a role for

breast cancer risk apart from the influence of factors related

to pregnancy [3]. Whereas a late age at menopause has been

considered an important risk factor in elderly women [4–6],

it is not clear to which degree events in the distant past,

including age at menarche and age at first birth, have life-

long effects on the risk. The results of some observational

studies suggest that associations of some of these repro-

ductive factors may be attenuated in old age [4, 7–9], but only

a few studies have addressed this issue in detail, and the

results have not been consistent.

J. Horn (&) � B. O. Asvold � S. Opdahl � S. Tretli � L. J. Vatten

Department of Public Health, Norwegian University of Science

and Technology, Trondheim, Norway

e-mail: julie.horn@ntnu.no

J. Horn

Department of Gynecology and Obstetrics, Levanger Hospital,

Health Trust Nord-Trøndelag, Levanger, Norway

B. O. Asvold

Department of Endocrinology, St. Olavs Hospital, Trondheim

University Hospital, Trondheim, Norway

S. Tretli

Cancer Registry of Norway, Institute of Population-based Cancer

Research, Oslo, Norway

123

Breast Cancer Res Treat (2013) 139:237–243

DOI 10.1007/s10549-013-2531-0

In the 1980s, Kvale et al. assessed reproductive factors

in relation to breast cancer risk in a cohort of more than

63,000 Norwegian women born between 1886 and 1928

[10–12], including 1,565 incident breast cancer cases

diagnosed from 1961 to 1980. The results confirmed that

early age at menarche, late age at first birth, low parity, and

late age at menopause are associated with increased risk,

however, the analyses had limited statistical power to

assess risk factors at old age. In the present study, we

followed Kvale’s cohort for an additional 28 years (until

2008) and assessed whether established associations of

reproductive factors with breast cancer risk persist into old

age.

Methods

Study population and follow-up

Between 1956 and 1959, all women living in three Nor-

wegian counties (Vestfold, Nord-Trøndelag, and Aust-

Agder) who were born between 1886 and 1928 (at

28–73 years of age), were invited to participate in a clinical

breast cancer screening. The original study has been

described in detail by Kvale et al. [10–12]. In brief, the

women had a clinical breast examination conducted by

physicians (not including a mammography), and informa-

tion on history of breast disease and reproductive history

was collected during a structured interview, including

questions related to age at menarche, age at first birth,

number of full-term pregnancies, and age at menopause.

Information about place of residence, marital status, and

occupation (own or husband’s) was collected from the

local population register.

With the aid of the unique 11-digit identity number that

was allocated to every Norwegian citizen in 1960, the

study participants were linked to incidence data at the

Cancer Registry of Norway and to data on vital status at

Statistics Norway. The Cancer Registry of Norway was

established in 1951 and the reporting of cancer diagnoses

from physicians and hospitals is compulsory. The popula-

tion registry at Statistics Norway provides complete and

updated information about vital status and date of

emigration.

Among the women who were invited to the screening,

84,981 were eligible for follow-up, since they were still

alive on January 1, 1961, at the start of follow-up. A total

of 63,041 (74.2 %) of these women had attended the breast

screening and had been interviewed.

Among the 63,041 participants, we excluded 759

(1.2 %) women with a history of breast cancer before the

age of 55 years. We also excluded 933 (1.5 %) women

who died or emigrated before 55 years of age, and 2,923

(4.6 %) women with missing information on parity or age

at menarche. Thus, 58,426 women were included in the

analyses. The analyses of age at first birth and number of

births were restricted to 45,374 women with known age at

first birth, and the analysis of age at menopause included

20,398 participants with known natural menopause at the

time of the breast survey.

Participants were followed from January 1, 1961, or

from the age of 55 years, whichever occurred last. They

contributed person-time until the date of a first breast

cancer diagnosis, until date of death or emigration, or until

December 31, 2008, whichever occurred first.

Statistical analysis

We used Cox proportional hazards regression to estimate

hazard ratios of breast cancer by categories of age at

menarche, age at first birth, parity, and age at menopause.

We assessed the association of each reproductive factor

separately, with adjustment for age (using age as the time

scale) and birth cohort (in 5-year categories). In a second

step, we also adjusted for reproductive events occurring

before the exposure under study. The two analytic

approaches yielded nearly identical estimates, and in the

results section, we describe the results from the second

step. In a separate analysis, the association of each repro-

ductive factor was adjusted for marital status (ever/never

married), women’s or husband’s occupation (professional/

private enterprise, manual work, domestic or other work),

county and place of residence (urban/rural) as proxies for

socioeconomic status, and for all other reproductive fac-

tors, but these adjustments did not materially influence the

estimates (data not shown). P values for trend across

exposure categories were calculated by treating the median

values within the categories as a continuous variable.

We estimated separate hazard ratios for the age intervals

55–69 years and 70 years and older. Participants contrib-

uted person time to one or both age intervals, depending on

their age at start and end of follow-up. To test if the

association between a reproductive factor, treated as a

categorical variable, and breast cancer risk differed by age

interval, we estimated the association in two different

models. The first model assumed a constant hazard ratio,

while the second model included time-dependent covari-

ates that allowed hazard ratios to differ between the two

age intervals. The difference between the models was

assessed by likelihood ratio tests, yielding a p value for

interaction. The proportional hazard assumption was met in

all analyses, as evaluated by log minus log plots and

Schoenfeld residuals. All analyses were performed using

STATA for Windows (Version 12.1� StataCorp LP,

1985–2011).

238 Breast Cancer Res Treat (2013) 139:237–243

123

The study was approved by the regional committee for

medical research ethics and by the Norwegian Data

Inspectorate.

Results

Characteristics of the participants at baseline and charac-

teristics of breast cancer cases by age at diagnosis are

summarized in Table 1. Among the 58,426 women inclu-

ded in the analyses, 49,155 women died and 52 emigrated

during follow-up. There were 691,607 person-years of

follow-up in the younger (55–69 years) and 714,052 per-

son-years in the older age interval (70 years and older). A

total of 1,077 women were diagnosed with invasive breast

cancer in the younger age interval (median age at diag-

nosis, 64 years), and 1,822 were diagnosed in the older age

interval (median age at diagnosis, 78 years).

Hazard ratios (HR) for the associations of reproductive

factors with breast cancer risk in the two age intervals

(55–69 years and 70 years and older) are shown in

Table 2. At the age of 70 years and older, there was an

inverse association of age at menarche with breast cancer

risk (P for trend\0.001) that appeared to be stronger than

for the age interval 55–69 years (P for trend = 0.13).

However, the test for interaction between the age intervals

did not suggest that the difference was statistically signif-

icant (P for interaction = 0.67).

Age at first birth was positively associated with the risk

of breast cancer in both age intervals (P for trend\0.001).

Compared to women who gave their first birth before the

age of 20, the hazard ratio during the 55–69 year age

interval was 1.69 (95 % confidence interval (CI): 1.09,

2.64) for women who were 35 years or older at first birth,

and 1.54 (95 % CI: 1.13, 2.11) at 70 years and older.

Compared to parous women, nulliparous women were at

increased risk of breast cancer both at 55–69 years (HR

1.34; 95 % CI: 1.16, 1.55) and at 70 years and above (HR

1.31; 95 % CI: 1.17, 1.46). Among parous women, parity

was inversely associated with risk, both in the 55–69 year

interval and at 70 years and later (P for trend = 0.001).

Compared to women with 1 child, having 5 or more chil-

dren was associated with a risk reduction of 41 % in the

age interval 55–69 years (HR 0.59; 95 % CI: 0.42, 0.83)

and 32 % for women 70 years and above (HR 0.68; 95 %

CI: 0.54, 0.86).

Age at menopause was positively associated with breast

cancer risk both at 55–69 years of age (P for trend = 0.09)

and at 70 years and above (P for trend = 0.002). In the

younger age interval (55–69 years), menopause between

50–54 years of age was associated with 38 % higher risk

(HR 1.38; 95 % CI: 0.87, 2.19) compared to menopause

before 45 years. The corresponding increase in risk in the

older age interval (70 years and above) was 44 % (HR

1.44; 95 % CI: 1.10, 1.90).

Discussion

In this cohort study of 58,426 women, with breast cancer

follow-up into old age, we assessed whether reproductive

factors that are associated with breast cancer risk in middle

age, are also associated with risk in old age. During more

than 1.4 million person-years of follow-up, 2,899 women

developed breast cancer, and our findings show equally

strong associations for age at menarche, age at first birth,

parity, and age at menopause after 70 years of age as

between 55 and 69 years of age.

Strengths of this study include the population-based

prospective design with long-term follow-up and the large

number of incident breast cancers. Also, the high atten-

dance of eligible women and the high comparability at

baseline between women who participated and women who

declined to participate [10] strengthen the validity of the

findings. The reporting of new breast cancers to the Cancer

Registry of Norway is mandatory and regulated by law, and

the registration is considered to be nearly complete [13,

14].

The historical feature of the study is another interesting

aspect, since the participants are too old to have entered

any organized mammography screening program, and most

of the women are too old to have been given hormone

treatment around menopause. Thus, the Norwegian Mam-

mography Screening Program was gradually introduced

from 1996 [15], and only 7 % of the women in the cohort

were in the eligible age group. Similarly, hormone treat-

ment around menopause was not prevalent in Norway

before the 1990s [16, 17], and therefore, the study popu-

lation has largely been unaffected by modern interventions

that influence breast cancer incidence.

It is a weakness of the study that information on family

history of breast cancer was not available, and that baseline

measurements of body mass index were not conducted. In

relation to the information that was collected, some women

were still at childbearing age, and for these women number

of births may be misclassified. However, the consequence

of this potential misclassification is that the women would

be grouped in a lower parity category, which most likely

would have attenuated the estimated associations.

There are few other studies of reproductive factors and

breast cancer risk in old women, and results have not been

consistent [4, 6–9, 18]. However, other researchers have

also reported negative associations of age at menarche

[3, 6, 8, 9] and parity [4], and positive associations of age at

first birth [7, 18] and menopause [3, 4, 6, 18] in women

65 years and older. In some studies, age at menarche, age

Breast Cancer Res Treat (2013) 139:237–243 239

123

at first birth or parity were not associated with breast cancer

risk in old age, and the authors’ interpretation was that

effects of reproductive factors may be attenuated with

advancing age [4, 7, 9]. However, in those studies, the lack

of association with breast cancer risk in old age may be

explained by low statistical power. Compared to previous

studies, the larger population and the longer follow-up

allowed us to assess more reliably the associations of

reproductive factors with breast cancer risk in old age.

Similar to most other studies, we could not distinguish

between tumor types, as indicated by hormone receptor

status or other subtypes. There is evidence that the distri-

bution of hormone receptor status of breast tumors may

change over the life span, and that among elderly women,

the proportion of estrogen and progesterone receptor

positive tumor types may be higher than in middle age

[19]. We cannot exclude that a similar tendency could be

present in our study. It has also been suggested that the

effect of various risk factors may vary by estrogen and

progesterone receptor status, and that reproductive factors

typically show stronger associations with hormone receptor

positive than with hormone receptor negative tumors

[20–22]. Therefore, an analysis of reproductive factors with

separate breast cancer subtypes could be useful, and pro-

vide a more differentiated assessment of breast cancer risk

in older women.

Russo et al. [23] have suggested that pregnancies,

especially an early first pregnancy, may lead to permanent

morphological changes that make the breast tissue more

resistant to carcinogenic events. Our results suggest that

effects of reproductive factors persist into old age, and

Russo et al’s suggestion that early age at first birth and

parity provide a permanent protective effect against breast

cancer seems to be compatible with our findings.

Age at menarche and age at menopause determine a

woman’s reproductive period, including the number of

ovulatory cycles, and may be an indicator of the cumula-

tive estrogen exposure during reproductive age [1, 24].

Table 1 Baseline characteristics of the study population (58,426 Norwegian women followed up from 1961 to 2008) and breast cancer cases by

age at diagnosis

Baseline characteristics Participants at risk

(n = 58,426)

Breast cancer cases 55–69 years

(n = 1,077)

Breast cancer cases C 70 years

(n = 1,822)

Year of birth, median (IQR) 1911 (1902–1920) 1915 (1908–1921) 1911 (1902–1919)

Place of residence (%)

Urban 21.3 24.2 21.7

Rural 78.7 75.8 78.3

Occupation, own or husband’s (%)

Professional, clerical 27.8 32.2 30.4

Farming, fishing, industrial 42.8 38.7 41.1

Domestic, others 29.4 29.1 28.5

Marital status (%)a

Never married 10.7 12.9 12.7

Ever married 89.3 87.1 87.3

Age at menarche (years), mean (SD) 14.2 (1.4) 14.1 (1.3) 14.1 (1.4)

Age at first birth (years), mean (SD)b 26.3 (4.9) 26.8 (4.9) 27.1 (5.3)

Nulliparous (%) 18.5 21.7 22.1

Number of children among parous women (%)b

1 21.2 26.5 23.1

2 33.1 36.9 35.3

3 22.2 22.4 22.0

4 11.8 8.5 11.1

C5 11.7 5.7 8.4

Age at menopause (years), mean (SD)c 48.1 (4.5) 48.3 (4.2) 48.8 (4.1)

Age at diagnosis (years), median (IQR) 64 (60–67) 78 (74–84)

Year at diagnosis, median (IQR) 1978 (1970–1985) 1991 (1982–1998)

IQR inter quartile range, SD standard deviationa Among women with known marital status (n = 58,191)b Among women with known age at first birth (n = 45,374)c Among women with known age at menopause (n = 20,398)

240 Breast Cancer Res Treat (2013) 139:237–243

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Breast Cancer Res Treat (2013) 139:237–243 241

123

Therefore, the increased breast cancer risk associated with

early age at menarche and late age at menopause that we

found among elderly women may be attributed to effects

that could be mediated by endocrine exposures during

reproductive age.

Furthermore, age at menarche and age at menopause

may also affect breast cancer risk in some degree through

other biological traits. It has been suggested that estrogen

concentrations in postmenopausal women may be posi-

tively associated with breast cancer risk [24, 25]. However,

in a meta-analysis of 13 studies, Key et al. [26] reported

only a weak association of age at menarche and the level of

postmenopausal estrogens. Similarly, the association

between age at menopause and estrogen levels was atten-

uated after adjustment for time since menopause [27, 28].

Therefore, these results appear to weaken the possibility

that associations of age at menarche and age at menopause

in elderly women are mediated by postmenopausal estro-

gen concentrations.

In conclusion, our results provide evidence that the

associations of early age at menarche, late age at first birth,

low parity, and late age at menopause with breast cancer

risk persist into old age. The findings suggest that repro-

ductive events may have life-long effects on breast cancer

risk and support the hypothesis that pregnancy reduces

breast cancer risk through permanent changes in breast

tissue.

Acknowledgments This study was funded by the Norwegian Can-

cer Society.

Conflict of interest The authors declare that they have no conflict

of interest.

References

1. Kelsey JL, Gammon MD, John EM (1993) Reproductive factors

and breast cancer. Epidemiol Rev 15(1):36–47

2. Russo J, Moral R, Balogh GA, Mailo D, Russo IH (2005) The

protective role of pregnancy in breast cancer. BCR 7(3):131–

142. doi:10.1186/bcr1029

3. Britt K (2012) Menarche, menopause, and breast cancer risk.

Lancet Oncol 13(11):1071–1072. doi:10.1016/S1470-2045(12)

70456-4

4. Sweeney C, Blair CK, Anderson KE, Lazovich D, Folsom AR

(2004) Risk factors for breast cancer in elderly women. Am J

Epidemiol 160(9):868–875. doi:10.1093/aje/kwh276

5. Trichopoulos D, MacMahon B, Cole P (1972) Menopause and

breast cancer risk. J Natl Cancer Inst 48(3):605–613

6. La Vecchia C, Negri E, Bruzzi P, Dardanoni G, Decarli A,

Franceschi S, Palli D, Talamini R (1992) The role of age at

menarche and at menopause on breast cancer risk: combined

evidence from four case-control studies. Ann Oncol 3(8):625–629

7. Shantakumar S, Terry MB, Teitelbaum SL, Britton JA, Millikan

RC, Moorman PG, Neugut AI, Gammon MD (2007) Reproductive

factors and breast cancer risk among older women. Breast Cancer

Res Treat 102(3):365–374. doi:10.1007/s10549-006-9343-4Ta

ble

2co

nti

nu

ed Ag

eat

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242 Breast Cancer Res Treat (2013) 139:237–243

123

8. Bouchardy C, Le MG, Hill C (1990) Risk factors for breast

cancer according to age at diagnosis in a French case-control

study. J Clin Epidemiol 43(3):267–275

9. Vacek PM, Skelly JM, Geller BM (2011) Breast cancer risk

assessment in women aged 70 and older. Breast Cancer Res Treat

130(1):291–299. doi:10.1007/s10549-011-1576-1

10. Kvale G, Heuch I, Eide GE (1987) A prospective study of

reproductive factors and breast cancer. I. Parity. Am J Epidemiol

126(5):831–841

11. Kvale G, Heuch I (1987) A prospective study of reproductive

factors and breast cancer. II. Age at first and last birth. Am J

Epidemiol 126(5):842–850

12. Kvale G, Heuch I (1988) Menstrual factors and breast cancer risk.

Cancer 62(8):1625–1631

13. Bakken IJ, Gystad SO, Christensen OO, Huse UE, Laronningen

S, Nygard J, Holmstrom L, Johannesen TB, Moller B, Larsen IK

(2012) Comparison of data from the Norwegian Patient Register

and the Cancer Registry of Norway. Tidsskr Nor Laegeforen

132(11):1336–1340. doi:10.4045/tidsskr.11.1099

14. Larsen IK, Smastuen M, Johannesen TB, Langmark F, Parkin

DM, Bray F, Moller B (2009) Data quality at the Cancer Registry

of Norway: an overview of comparability, completeness, validity

and timeliness. Eur J Cancer 45(7):1218–1231. doi:10.1016/

j.ejca.2008.10.037

15. Kalager M, Adami HO, Bretthauer M, Tamimi RM (2012) Over-

diagnosis of invasive breast cancer due to mammography screen-

ing: results from the Norwegian screening program. Ann Intern

Med 156(7):491–499. doi:10.1059/0003-4819-156-7-201204030-

00005

16. Bergsjø P (1984) Comments on the use of oestrogens 1979–83.

In: Øydvin K (ed) Drug consumption in Norway. Norsk medis-

inaldepot, Oslo, pp 114–115

17. Hofvind S, Sakshaug S, Ursin G, Graff-Iversen S (2012) Breast

cancer incidence trends in Norway—explained by hormone

therapy or mammographic screening? Int J Cancer 130(12):

2930–2938. doi:10.1002/ijc.26280

18. Lubin JH, Burns PE, Blot WJ, Lees AW, May C, Morris LE,

Fraumeni JF Jr (1982) Risk factors for breast cancer in women in

northern Alberta, Canada, as related to age at diagnosis. J Natl

Cancer Inst 68(2):211–217

19. Anderson WF, Chatterjee N, Ershler WB, Brawley OW (2002)

Estrogen receptor breast cancer phenotypes in the surveillance,

epidemiology, and end results database. Breast Cancer Res Treat

76(1):27–36

20. Althuis MD, Fergenbaum JH, Garcia-Closas M, Brinton LA,

Madigan MP, Sherman ME (2004) Etiology of hormone receptor-

defined breast cancer: a systematic review of the literature.

Cancer Epidemiol Biomarkers Prev 13(10):1558–1568

21. Ma H, Henderson KD, Sullivan-Halley J, Duan L, Marshall SF,

Ursin G, Horn-Ross PL, Largent J, Deapen DM, Lacey JV Jr,

Bernstein L (2010) Pregnancy-related factors and the risk of

breast carcinoma in situ and invasive breast cancer among post-

menopausal women in the California Teachers Study cohort.

BCR 12(3):R35. doi:10.1186/bcr2589

22. Colditz GA, Rosner BA, Chen WY, Holmes MD, Hankinson SE

(2004) Risk factors for breast cancer according to estrogen and

progesterone receptor status. J Natl Cancer Inst 96(3):218–228

23. Russo J, Hu YF, Silva ID, Russo IH (2001) Cancer risk related to

mammary gland structure and development. Microsc Res Tech

52(2):204–223. doi:10.1002/1097-0029(20010115)52:2\204:AID-

JEMT1006[3.0.CO;2-F

24. Bernstein L (2002) Epidemiology of endocrine-related risk fac-

tors for breast cancer. J Mammary Gland Biol Neoplasia 7(1):

3–15

25. Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PH, Biessy C,

Dossus L, Lukanova A, Bingham S, Khaw KT, Allen NE, Bueno-

de-Mesquita HB, van Gils CH, Grobbee D, Boeing H, Lahmann

PH, Nagel G, Chang-Claude J, Clavel-Chapelon F, Fournier A,

Thiebaut A, Gonzalez CA, Quiros JR, Tormo MJ, Ardanaz E,

Amiano P, Krogh V, Palli D, Panico S, Tumino R, Vineis P,

Trichopoulou A, Kalapothaki V, Trichopoulos D, Ferrari P, Norat

T, Saracci R, Riboli E (2005) Postmenopausal serum androgens,

oestrogens and breast cancer risk: the European prospective

investigation into cancer and nutrition. Endocr Relat Cancer

12(4):1071–1082. doi:10.1677/erc.1.01038

26. Key TJ, Appleby PN, Reeves GK, Roddam AW, Helzlsouer KJ,

Alberg AJ, Rollison DE, Dorgan JF, Brinton LA, Overvad K,

Kaaks R, Trichopoulou A, Clavel-Chapelon F, Panico S, Duell

EJ, Peeters PH, Rinaldi S, Fentiman IS, Dowsett M, Manjer J,

Lenner P, Hallmans G, Baglietto L, English DR, Giles GG,

Hopper JL, Severi G, Morris HA, Hankinson SE, Tworoger SS,

Koenig K, Zeleniuch-Jacquotte A, Arslan AA, Toniolo P, Shore

RE, Krogh V, Micheli A, Berrino F, Barrett-Connor E, Laughlin

GA, Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE,

Cauley JA, Lui LY, Cummings SR, Gunter MJ, Rohan TE,

Strickler HD (2011) Circulating sex hormones and breast cancer

risk factors in postmenopausal women: reanalysis of 13 studies.

Br J Cancer 105(5):709–722. doi:10.1038/bjc.2011.254

27. Chubak J, Tworoger SS, Yasui Y, Ulrich CM, Stanczyk FZ,

McTiernan A (2004) Associations between reproductive and

menstrual factors and postmenopausal sex hormone concentra-

tions. Cancer Epidemiol Biomarkers Prev 13(8):1296–1301

28. Sowers MR, Zheng H, McConnell D, Nan B, Harlow SD,

Randolph JF Jr (2008) Estradiol rates of change in relation to the

final menstrual period in a population-based cohort of women.

J Clin Endocrinol Metab 93(10):3847–3852. doi:10.1210/

jc.2008-1056

Breast Cancer Res Treat (2013) 139:237–243 243

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