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Association of reproductive history with breast tissue characteristics and receptor status in the normal breast.

ABSTRACT: INTRODUCTION:Reproductive history has been associated with breast cancer risk, but more knowledge of the underlying biological mechanisms is needed. Because of limited data on normal breast tissue from healthy women, we examined associations of reproductive history and established breast cancer risk factors with breast tissue composition and markers of hormone receptors and proliferation in a nested study within the Karolinska Mammography project for risk prediction for breast cancer (Karma). MATERIALS AND METHODS:Tissues from 153 women were obtained by ultrasound-guided core needle biopsy as part of the Karma project. Immunohistochemical staining was used to assessed histological composition of epithelial, stromal and adipose tissue, epithelial and stromal oestrogen receptor (ER) and progesterone receptor (PR) status, and Ki-67 proliferation status. An individualised reproductive score including parity, number of pregnancies without birth, number of births, age at first birth, and duration of breastfeeding, was calculated based on self-reported reproductive history at the time of the Karma study entry. All analyses were adjusted for age and BMI. RESULTS:Cumulated reproductive score was associated with increased total epithelial content and greater expression of epithelial ER. Parity was associated with greater epithelial area, increased epithelial-stromal ratio, greater epithelial ER expression and a lower extent of stromal proliferation. Increasing numbers of pregnancies and births were associated with a greater epithelial area in the entire study set, which remained significant among postmenopausal women. Increasing numbers of pregnancies and births were also associated with a greater expression of epithelial ER among postmenopausal women. Longer duration of breastfeeding was associated with greater epithelial area and greater expression of epithelial PR both in the entire study set and among postmenopausal women. Breastfeeding was also positively associated with greater epithelial ER expression among postmenopausal women. Prior use of oral contraceptives was associated with lower epithelial-stromal ratio amongst all participants and among pre- and postmenopausal women separately. CONCLUSION:Reproductive risk factors significantly influence the epithelial tissue compartment and expression of hormone receptors in later life. These changes remain after menopause. This study provides deeper insights of the biological mechanisms by which reproductive history influences epithelial area and expression of hormone receptors, and as a consequence the risk of breast cancer.

SUBMITTER: Gabrielson M

PROVIDER: S-EPMC6022521 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Association of reproductive history with breast tissue characteristics and receptor status in the normal breast.

Gabrielson Marike M Chiesa Flaminia F Behmer Catharina C Rönnow Katarina K Czene Kamila K Hall Per P

Breast cancer research and treatment 20180330 3

<h4>Introduction</h4>Reproductive history has been associated with breast cancer risk, but more knowledge of the underlying biological mechanisms is needed. Because of limited data on normal breast tissue from healthy women, we examined associations of reproductive history and established breast cancer risk factors with breast tissue composition and markers of hormone receptors and proliferation in a nested study within the Karolinska Mammography project for risk prediction for breast cancer (Ka ...[more]

PMID: 29603032

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Project description:ImportanceBreast cancer (BC), the most prevalent cancer among women globally, is a heterogeneous disease, with prognosis differing by estrogen receptor (ER) status. Having a family history of BC increases the risk of BC; however, it is unclear whether family history is associated with the prognosis of overall and ER-specific BC.ObjectiveTo assess whether a family history of BC is associated with the prognosis of overall and ER-specific BC.Design, setting, and participantsThis cohort study was based on data from several national registers in Sweden. All female residents of Stockholm who were born after 1932; had their first BC diagnosis between January 1, 1991, and December 31, 2019; and had at least 1 identified female first-degree relative (FDR) were included. Women who were diagnosed with other types of cancer before their BC diagnosis, were older than 75 years at diagnosis, or had distant metastasis at diagnosis were excluded. A total of 28 649 women were included. Data were analyzed from January 10, 2022, to December 20, 2022.ExposuresFamily history of BC, defined as 1 or more female FDRs diagnosed with BC.Main outcomes and measuresPatients were followed up until BC-specific death, censoring, or end of follow-up on December 31, 2019. The role of family history in BC-specific mortality was investigated using flexible parametric survival models among the full cohort, ER-positive subgroup, and ER-negative subgroup, adjusting for demographic characteristics, tumor characteristics, and treatments received.ResultsAmong 28 649 patients, the mean (SD) age at BC diagnosis was 55.7 (10.4) years; 19 545 (68.2%) had ER-positive BC, and 4078 (14.2%) had ER-negative BC. Overall, 5081 patients (17.7%) had at least 1 female FDR diagnosed with BC, while 384 (1.3%) had a family history of early-onset BC (FDR diagnosed before age 40 years). During the follow-up period (median [IQR], 8.7 [4.1-15.1] years), 2748 patients (9.6%) died of BC. Multivariable analyses revealed that having a family history of BC was associated with a lower risk of BC-specific death among the full cohort (hazard ratio [HR], 0.78; 95% CI, 0.65-0.95) and the ER-negative subgroup (HR, 0.57; 95% CI, 0.40-0.82) in the first 5 years, after which no association was observed. However, having an early-onset family history was associated with a higher risk of BC-specific death (HR, 1.41; 95% CI, 1.03-2.34).Conclusions and relevanceIn this study, patients with a family history of BC did not necessarily have a worse prognosis. Those with ER-negative status and a family history of BC had more favorable outcomes in the first 5 years after diagnosis, possibly due to enhanced motivation to receive and adhere to treatment. However, patients with a family history of early-onset BC had worse survival, suggesting that genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research.

Project description:Study questionWhat is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women?Summary answerHigher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity.What is known alreadyPostmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI.Study design, size, durationThis study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis.Participants/materials, setting, methodsData were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI.Main results and the role of chanceWomen who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies.Limitations, reasons for cautionThe WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics.Wider implications of the findingsThis study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention.Study funding/competing interest(s)HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare.Trial registration numberN/A.

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Association of reproductive history with breast tissue characteristics and receptor status in the normal breast.

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Association of reproductive history with breast tissue characteristics and receptor status in the normal breast.

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