Full-term Pregnancy Induces a Specific Genomic Signature in the Human Breast

Russo, José; Balogh, Gabriela Andrea; Russo, Irma H.

doi:10.1158/1055-9965.epi-07-0678

Cited by 104 publications

(103 citation statements)

References 77 publications

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“…This work confirmed that pregnancy had a protective effect that was evident from the early teen years and persisted until the middle twenties [1]. Other studies have reported that additional pregnancies and breastfeeding confer greater protection to young women, including a statistically significantly reduced risk of breast cancer OPEN ACCESS in women with deleterious BRCA1 mutations who breast-fed for a cumulative total of more than one year [3,4]. Our studies, designed to unravel what specific changes occurred in the breast during pregnancy that confer a lifetime protection from developing cancer, led us to the discovery that endogenous endocrinological or environmental influences affecting breast development before the first full term pregnancy were important modulators of the susceptibility of the breast to undergo neoplastic transformation.…”

Section: Introductionsupporting

confidence: 71%

The Genomic Signature of Breast Cancer Prevention

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Abstract:The breast of parous postmenopausal women exhibits a specific signature that has been induced by a full term pregnancy. This signature is centered in chromatin remodeling and the epigenetic changes induced by methylation of specific genes which are important regulatory pathways induced by pregnancy. Through the analysis of the genes found to be differentially methylated between women of varying parity, multiple positions at which beta-catenin production and use is inhibited were recognized. The biological importance of the pathways identified in this specific population cannot be sufficiently emphasized because they could represent a safeguard mechanism mediating the protection of the breast conferred by full term pregnancy.

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Section: Introductionsupporting

confidence: 71%

The Genomic Signature of Breast Cancer Prevention

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“…In perhaps the only previous study to address the effect of parity on gene expression profiles in the normal breast, Russo and coworkers applied cDNA microarrays to ethanolfixed tissue obtained from postmenopausal women (34)(35)(36). In this discovery effort, a large number of genes were found to be differentially expressed between parous and nulliparous women, including a number of immune-related genes that were upregulated in the parous group.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Patterns in the Human Breast after Pregnancy

Asztalos

Gann

Hayes

et al. 2010

Cancer Prevention Research

118

117

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Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammationassociated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor α (ERα, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-β (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk. Cancer Prev Res; 3(3); 301-11. ©2010 AACR.

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“…Both pregnancy and breastfeeding have long-term protective effects against breast cancer because of the increased differentiation of breast tissue under the effect of female hormonesmainly progesterone. [48][49][50][51] Increased age of marriage leads to a lack of differentiation in the breast tissue making it more susceptible to harmful effects of nonestrogenic mutagens as well as genotoxic effects of estrogen, which has been known to cause ER2 breast cancers as well. 52,53 Moreover, being married and having children might also reduce the level of circulating hormones or increase the levels of sex hormone-binding globulin.…”

Section: Discussionmentioning

confidence: 99%

Risk factors according to estrogen receptor status of breast cancer patients in Trivandrum, South India

Dey

Boffetta

Mathews

et al. 2009

Intl Journal of Cancer

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Estrogen receptor (ER) status is an important biomarker in defining subtypes of breast cancer differing in antihormonal therapy response, risk factors and prognosis. However, little is known about association of ER status with various risk factors in the developing world. Our case-control study done in Kerala, India looked at the associations of ER status and risk factors of breast cancer. From 2002 to 2005, 1,208 cases and controls were selected at the Regional Cancer Center (RCC), Trivandrum, Kerala, India. Information was collected using a standardized questionnaire, and 3-way analyses compared ER1/ER2 cases, ER1 cases/controls and ER2 cases/controls using unconditional logistic regression to calculate odds ratios and 95% confidence intervals. The proportion of ER2 cases was higher (64.1%) than ER1 cases. Muslim women were more likely to have ER2 breast cancer compared to Hindus (OR 5 1.48, 95% CI 5 1.09, 2.02), an effect limited to premenopausal group (OR 5 1.87, 95% CI 5 1.26, 2.77). Women with higher socioeconomic status were more likely to have ER1 breast cancer (OR 5 1.48, 95% CI 5 1.11, 1.98). Increasing BMI increased likelihood of ER2 breast cancer in premenopausal women (p for trend < 0.001). Increasing age of marriage was positively associated with both ER1 and ER2 breast cancer. Increased breastfeeding and physical activity were in general protective for both ER1 and ER2 breast cancer. The findings of our study are significant in further understanding the relationship of ER status and risk factors of breast cancer in the context of the Indian subcontinent. ' UICCKey words: estrogen receptor; breast cancer; India Estrogen receptor (ER) status of breast tumors has been instrumental in defining an important subtype of breast cancer with differences observed in risk factors, treatment and prognosis. [1][2][3][4][5][6][7] Numerous studies in the past have looked at differences in etiology and risk factors pertaining to presence or absence of ER-alpha. Most of these studies were conducted in Western populations as early as 1980s. [1][2][3][4][5] Around the same time, it was also discovered that ER1 tumors that lacked progesterone receptor (PR) expression were less responsive to endocrine therapy compared to tumors that expressed PR. 8 This led to studies in the past decade that looked at the link of various risk factors of breast cancer and combined ER/PR information to better explain the underlying differences between the various subtypes of breast cancer. 9-13 Chen and Colditz 14 have emphasized the importance of taking into account the ER/PR status information of breast tumors both for effective treatment as well as risk prediction for instituting prophylactic measures. Although there might be numerous ways to subtype breast cancer, the classification into ER1 and ER2 cancer remains a key divider. 14 However, information related to ER status is lacking for populations in developing countries. In fact, in most developing countries, determination of hormone receptor status is not a part of standard pro...

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Full-term Pregnancy Induces a Specific Genomic Signature in the Human Breast

Cited by 104 publications

References 77 publications

The Genomic Signature of Breast Cancer Prevention

The Genomic Signature of Breast Cancer Prevention

Gene Expression Patterns in the Human Breast after Pregnancy

Risk factors according to estrogen receptor status of breast cancer patients in Trivandrum, South India

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