Timing of Menarche and First Birth in Relation to Risk of Breast Cancer in A-Bomb Survivors

McDougall, Jean A.; Sakata, Ritsu; Sugiyama, Hiromi; Grant, Eric J.; Davis, Scott; Nishi, Nobuo; Soda, Midori; Shimizu, Yukiko; Tatsukawa, Yoshimi; Kasagi, Fumiyoshi; Suyama, Akihiko; Ross, Paul; Kopecky, Kenneth J.; Li, Christopher I.

doi:10.1158/1055-9965.epi-10-0246

Cited by 13 publications

(12 citation statements)

References 14 publications

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“…Breast tissue is largely undifferentiated and exposed to the mitogenic effects of ER and PR during this period, and is thus particularly susceptible to carcinogens . The interval between menarche to first live birth has been described as a “window of high susceptibility.” A shorter interval from menarche to first live birth is linked to higher endogenous hormone levels . A French prospective cohort study reported that the risk of breast cancer for women in the highest quartile of cumulative number of menstrual cycles before first birth was 1.42‐fold higher .…”

Section: Discussionmentioning

confidence: 99%

Associations of reproductive time events and intervals with breast cancer risk: A report from the Shanghai Breast Cancer Study

Huang

Beeghly–Fadiel

Gao

et al. 2013

Intl Journal of Cancer

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While there is clear evidence for an association between later age at first live birth and increased breast cancer risk, associations of other reproductive timings are less clear. As breast tissues undergo major structural and cellular changes during pregnancy, we examined associations between reproductive time events and intervals with breast cancer risk among parous women from the population-based Shanghai Breast Cancer Study (SBCS). Unconditional logistic regression was used to evaluate associations with breast cancer risk for 3,269 cases and 3,341 controls. In addition to later age at first live birth, later ages at first pregnancy and last pregnancy were significantly associated with increased breast cancer risk (P-trend=0.002, 0.015, 0.008, respectively); longer intervals from menarche to first or last live birth were also associated with increased risks (P-trend<0.001, = 0.018, respectively). Analyses stratified by menopausal status and estrogen receptor (ER) / progesterone receptor (PR) status revealed that associations for later age at first pregnancy or live birth and longer intervals from menarche to first or last live birth occurred among pre-menopausal women and ER+/PR+ breast cancers, whereas the association for later age at last pregnancy occurred among postmenopausal women and ER+/PR- or ER-/PR+ breast cancers. Due to high correlation with other reproductive variables, models did not include adjustment for age at first live birth; when included, significance of all associations was attenuated. These findings suggest while reproductive time events and intervals play an important role in breast cancer etiology, contributions may differ by menopausal status and hormone receptor status of breast cancers.

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Section: Discussionmentioning

confidence: 99%

Associations of reproductive time events and intervals with breast cancer risk: A report from the Shanghai Breast Cancer Study

Huang

Beeghly–Fadiel

Gao

et al. 2013

Intl Journal of Cancer

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“…Among Japanese A-bomb survivors, parity, first full-term pregnancy at a young age, multiple births and history of breastfeeding have all been shown to be associated with a lower excess risk of breast cancer after radiation exposure (13). A recent study of Japanese atomic bomb survivors, however, found that once the baseline breast cancer risk was taken into account, radiation-induced breast cancer risk did not vary appreciably by whether exposure occurred before menarche, between menarche and first pregnancy, or after first pregnancy, i.e., radiation-associated breast cancer risk did not vary by reproductive status at the time of exposure (16). …”

Section: Discussionmentioning

confidence: 99%

Reproductive Status at First Diagnosis Influences Risk of Radiation-Induced Second Primary Contralateral Breast Cancer in the WECARE Study

Brooks

Boice

Stovall

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

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Purpose Our study examines whether reproductive and hormonal factors prior to, at the time of, or subsequent to, radiation treatment for a first primary breast cancer, modify the risk of radiation-induced second primary breast cancer. Methods and Materials The Women’s Environmental, Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based study of 708 women (cases) with asynchronous contralateral breast cancer (CBC) and 1,399 women (controls) with unilateral breast cancer. Radiotherapy (RT) records, coupled with anthropomorphic phantom simulations, were used to estimate quadrant-specific radiation dose to the contralateral breast for each patient. Rate ratios (RR) and 95% confidence intervals (CI) were computed to assess the relationship between reproductive factors and risk of CBC. Results Women who were nulliparous at diagnosis and exposed to ≥1 gray (Gy) to the contralateral breast, had a greater risk of CBC than matched unexposed nulliparous women (RR=2.2, 95% CI 1.2–4.0). No increased risk was seen in RT-exposed parous women (RR=1.1, 95% CI 0.8–1.4). Women treated with RT who later became pregnant (n=8 cases and 9 controls) had a greater risk of CBC (RR=6.0, 95% CI 1.3, 28.4) than unexposed women (n=4 cases and 7 controls) who also became pregnant. The association of radiation with risk of CBC did not vary by number of pregnancies, history of breastfeeding or menopausal status at the time of first breast cancer diagnosis. Conclusion Nulliparous women treated with RT were at an increased risk of CBC. Although based on small numbers, women who become pregnant after first diagnosis also appear to be at an increased risk of radiation-induced CBC.

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“…However, this may be due to misclassification of menopausal status as opposed to an important biological effect involving menarche status at the time of radiation exposure. McDougall et al found no association of breast cancer risk and menarche status at the time of radiation exposure but did not consider serum marker levels 38.…”

Section: Discussionmentioning

confidence: 99%

Associations of Ionizing Radiation and Breast Cancer-Related Serum Hormone and Growth Factor Levels in Cancer-Free Female A-Bomb Survivors

et al. 2011

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Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N = 412, ages 26–79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1 Gy of radiation dose among samples collected from postmenopausal women (17%1Gy, 95% CI: 1%–36% and 21%1Gy, 95% CI: 4%–40%, respectively), while they decreased in samples collected from premenopausal women (−11%1Gy, 95% CI: −20%–1% and −12%1Gy, 95% CI: −20%– −2%, respectively). Interactions by menopausal status were significant (P = 0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%1Gy, 95% CI: 13%–49%) while they marginally decreased in premenopausal samples (−10%1Gy, 95% CI: −19%–0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%1Gy, 95% CI: 2%–18%) and there was a significant interaction by menopausal status (P = 0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.

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Timing of Menarche and First Birth in Relation to Risk of Breast Cancer in A-Bomb Survivors

Cited by 13 publications

References 14 publications

Associations of reproductive time events and intervals with breast cancer risk: A report from the Shanghai Breast Cancer Study

Associations of reproductive time events and intervals with breast cancer risk: A report from the Shanghai Breast Cancer Study

Reproductive Status at First Diagnosis Influences Risk of Radiation-Induced Second Primary Contralateral Breast Cancer in the WECARE Study

Associations of Ionizing Radiation and Breast Cancer-Related Serum Hormone and Growth Factor Levels in Cancer-Free Female A-Bomb Survivors

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