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Simple Summary: Adolescents and young adults (AYAs) experiencing cancer have support needs that differ from older adult cancer patients. The aim of our qualitative study was to determine the holistic needs of AYA cancer survivors and to develop a patient-centered conceptual model of AYA survivorship care. Analysis of our interview results reveals eight key domains critical to holistic patient-centered AYA survivorship care. We offer a conceptual model that differs from current conceptual models of AYA survivorship care by centering the patient and their support systems, emphasizing the need for continuing supportive navigation, and the importance of repeated support along the identified domains over time. Purpose: Conceptual models provide frameworks to illustrate relationships among patient-, provider-, system-, and community-level factors that inform care delivery and research. Existing models of cancer survivorship care focus largely on pediatric or adult populations whose needs differ from adolescents and young adults (AYAs). We developed a patient-centered conceptual model of AYA survivorship care. Methods: We conducted a narrative literature review of current conceptual and theoretical models of care. We engaged AYA cancer survivors (n = 25) in semi-structured one-hour telephone interviews. Most participants were in their 20s and 30s, and the majority (84%) were women. Recruitment was stratified by age and time since cancer diagnosis. We conducted a thematic analysis of interview transcripts to identify themes that exemplified patient-centered care. Results: Most participants identified as white and female. Leukemia and breast cancer were the most common cancer types. Main themes included the need for (1) care coordination, (2) ongoing mental health support, (3) connection to AYA peer support, (4) support during fertility preservation efforts, (5) support with financial burden, (6) support for quality of life, (7) information about and support with side effects and late effects, and (8) attention to the unique needs of young adults. Conclusions: We present a patient-centered conceptual model of AYA survivorship care needs that can inform future cancer care delivery and research. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. Methods: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. Results: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED βQ4vsQ1: − 0.17, 95% CI − 0.27, − 0.08; DASH βQ4vsQ1: − 0.18, 95% CI − 0.28, − 0.08; aHEI βQ4vsQ1: − 0.20, 95% CI − 0.30, − 0.10; HEI-2015 βQ4vsQ1: − 0.19, 95% CI − 0.29, − 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. Conclusion: Healthy dietary patterns were associated with lower levels of oxidative stress. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer?Summary Answer: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects.What Is Known Already: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.Study Design, Size, Duration: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived.Participants/materials, Setting, Methods: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group.Main Results and the Role Of Chance: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer.Limitations, Reasons For Caution: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children.Wider Implications Of the Findings: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer.Study Funding/competing Interest(s): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting.Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors.Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women.Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM. [ABSTRACT FROM AUTHOR]

Context: We previously reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.Objective: This study assessed whether risk factors for breast cancer are correlates of AMH concentration.Methods: This cross-sectional study included 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49) from 10 cohort studies among the general population.Results: Adjusting for age and cohort, AMH positively associated with age at menarche (P < 0.0001) and parity (P = 0.0008) and inversely associated with hysterectomy/partial oophorectomy (P = 0.0008). Compared with women of normal weight, AMH was lower (relative geometric mean difference 27%, P < 0.0001) among women who were obese. Current oral contraceptive (OC) use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, P < 0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, P = 0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40 vs ≥40), associations of AMH with body mass index and OCs were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (P-interaction < 0.05).Conclusion: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and it suggests that most associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining. [ABSTRACT FROM AUTHOR]

Background: In a previous exploratory study, we reported lower concentrations of the ovarian reserve biomarker anti-Müllerian hormone (AMH) in adulthood with prenatal farm exposure. We now examine this association as well as childhood farm exposure using enrollment data from the Sister Study, a large US cohort of women.Methods: We collected prenatal and childhood farm exposure data by questionnaire and telephone interview. However, serum AMH data were available only for a nested subset: premenopausal women ages 35-54 subsequently diagnosed with breast cancer (n = 418 cases) and their matched controls (n = 866). To avoid potential bias from restricting analyses to only premenopausal controls, we leveraged the available cohort data. We used data from both premenopausal cases and controls as well as postmenopausal women ages 35-54 (n = 3,526) (all presumed to have undetectable AMH concentrations) and applied weights to produce a sample representative of the cohort ages 35-54 (n = 17,799). The high proportion of undetectable AMH concentrations (41%) was addressed using reverse-scale Cox regression. An adjusted hazard ratio (HR) <1.0 indicates that exposed individuals had lower AMH concentrations than unexposed individuals.Results: Prenatal exposure to maternal residence or work on a farm was associated with lower AMH concentrations (HR 0.66; 95% confidence intervals [CI] = 0.48 to 0.90). Associations between childhood farm residence exposures and AMH were null or weak, except childhood contact with pesticide-treated livestock or buildings (HR 0.69; 95% CI = 0.40 to 1.2).Conclusions: Replication of the prenatal farm exposure and lower adult AMH association raises concern that aspects of prenatal farm exposure may result in reduced adult ovarian reserve. [ABSTRACT FROM AUTHOR]

Background: African American women have the highest risk of breast cancer mortality compared to other racial groups. Differences in tumor characteristics have been implicated as a possible cause; however, the tumor microenvironment may also contribute to this disparity in mortality. Hepatocyte growth factor (HGF) is a stroma-derived marker of the tumor microenvironment that may affect tumor progression differentially by race.Objective: To examine whether an HGF gene expression signature is differentially expressed by race and tumor characteristics.Methods: Invasive breast tumors from 1957 patients were assessed for a 38-gene RNA-based HGF gene expression signature. Participants were black (n = 1033) and non-black (n = 924) women from the population-based Carolina Breast Cancer Study (1993-2013). Generalized linear models were used to estimate the relative frequency differences (RFD) in HGF status by race, clinical, and demographic factors.Results: Thirty-two percent of tumors were positive for the HGF signature. Black women were more likely [42% vs. 21%; RFD = + 19.93% (95% CI 16.00, 23.87)] to have HGF-positive tumors compared to non-black women. Triple-negative patients had a higher frequency of HGF positivity [82% vs. 13% in non-triple-negative; RFD = + 65.85% (95% CI 61.71, 69.98)], and HGF positivity was a defining feature of basal-like subtype [92% vs. 8% in non-basal; RFD = + 81.84% (95% CI 78.84, 84.83)]. HGF positivity was associated with younger age, stage, higher grade, and high genomic risk of recurrence (ROR-PT) score.Conclusion: HGF expression is a defining feature of basal-like tumors, and its association with black race and young women suggests it may be a candidate pathway for understanding breast cancer disparities. [ABSTRACT FROM AUTHOR]

Study Question: What is the association between ART conception and treatment parameters and the risk of birth defects?Summary Answer: Compared to naturally conceived singleton infants, the risk of a major nonchromosomal defect among ART singletons conceived with autologous oocytes and fresh embryos without use of ICSI was increased by 18%, with increases of 42% and 30% for use of ICSI with and without male factor diagnosis, respectively.What Is Known Already: Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects but have been limited by small sample size and inadequate statistical power, failure to differentiate results by plurality, differences in birth defect definitions and methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.Study Design, Size, Duration: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2015 that resulted in live births from 1 September 2004 to 31 December 2016 in Massachusetts and North Carolina and from 1 September 2004 to 31 December 2015 for Texas and New York: these were large and ethnically diverse States, with birth defect registries utilizing the same case definitions and data collected, and with high numbers of ART births annually. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Naturally conceived ART siblings were identified through the mother's information. Non-ART children were classified as being born to women who conceived with ovulation induction (OI)/IUI when there was an indication of infertility treatment on the birth certificate, but the woman did not link to the SART CORS; all others were classified as being naturally conceived.Participants/materials, Setting, Methods: The study population included 135 051 ART children (78 362 singletons and 56 689 twins), 23 647 naturally conceived ART siblings (22 301 singletons and 1346 twins) and 9396 children born to women treated with OI/IUI (6597 singletons and 2799 twins) and 1 067 922 naturally conceived children (1 037 757 singletons and 30 165 twins). All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal). Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CI to evaluate the risk of birth defects due to conception with ART (using autologous oocytes and fresh embryos), and with and without the use of ICSI in the absence or presence of male factor infertility, with naturally conceived children as the reference. Analyses within the ART group were stratified by combinations of oocyte source (autologous, donor) and embryo state (fresh, thawed), with births from autologous oocytes and fresh embryos as the reference. Analyses limited to fresh embryos were stratified by oocyte source (autologous, donor) and the use of ICSI. Triplets and higher-order multiples were excluded.Main Results and the Role Of Chance: A total of 21 998 singleton children (1.9%) and 3037 twin children (3.3%) had a major birth defect. Compared to naturally conceived children, ART singletons (conceived from autologous oocytes, fresh embryos without the use of ICSI) had increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% 1.05, 1.32), cardiovascular defects (AOR 1.20, 95% CI 1.03, 1.40), and any birth defect (AOR 1.18, 95% CI 1.09, 1.27). Compared to naturally conceived children, ART singletons conceived (from autologous oocytes, fresh embryos) with the use of ICSI, the risks were increased for a major nonchromosomal birth defect (AOR 1.30, 95% CI 1.16, 1.45 without male factor diagnosis; AOR 1.42, 95% CI 1.28, 1.57 with male factor diagnosis); blastogenesis defects (AOR 1.49, 95% CI 1.08, 2.05 without male factor; AOR 1.56, 95% CI 1.17, 2.08 with male factor); cardiovascular defects (AOR 1.28, 95% CI 1.10,1.48 without male factor; AOR 1.45, 95% CI 1.27, 1.66 with male factor); in addition, the risk for musculoskeletal defects was increased (AOR 1.34, 95% CI 1.01, 1.78 without male factor) and the risk for genitourinary defects in male infants was increased (AOR 1.33, 95% CI 1.08, 1.65 with male factor). Comparisons within ART singleton births conceived from autologous oocytes and fresh embryos indicated that the use of ICSI was associated with increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% CI 1.03, 1.35), blastogenesis defects (AOR 1.65, 95% CI 1.08, 2.51), gastrointestinal defects (AOR 2.21, 95% CI 1.28, 3.82) and any defect (AOR 1.11, 95% CI 1.01, 1.22). Compared to naturally conceived children, ART singleton siblings had increased risks of musculoskeletal defects (AOR 1.32, 95% CI 1.04, 1.67) and any defect (AOR 1.15, 95% CI 1.08, 1.23). ART twins (conceived with autologous oocytes, fresh embryos, without ICSI) were at increased risk of chromosomal defects (AOR 1.89, 95% CI 1.10, 3.24) and ART twin siblings were at increased risk of any defect (AOR 1.26, 95% CI 1.01, 1.57). The 18% increased risk of a major nonchromosomal birth defect in singleton infants conceived with ART without ICSI (∼36% of ART births), the 30% increased risk with ICSI without male factor (∼33% of ART births), and the 42% increased risk with ICSI and male factor (∼31% of ART births) translates into an estimated excess of 386 major birth defects among the 68 908 singleton children born by ART in 2017.Limitations, Reasons For Caution: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing vs vitrification), and data on ICSI was only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility.Wider Implications Of the Findings: The use of ART is associated with increased risks of a major nonchromosomal birth defect, cardiovascular defect and any defect in singleton children, and chromosomal defects in twins; the use of ICSI further increases this risk, the most with male factor infertility. These findings support the judicious use of ICSI only when medically indicated. The relative contribution of ART treatment parameters versus the biology of the subfertile couple to this increased risk remains unclear and warrants further study.Study Funding/competing Interest(s): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. E.W. is a contract vendor for SART; all other authors report no conflicts.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.Objective: To characterize breast cancer risk in relation to recent childbirth.Design: Pooled analysis of individual-level data from 15 prospective cohort studies.Setting: The international Premenopausal Breast Cancer Collaborative Group.Participants: Women younger than 55 years.Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer. OBJECTIVE: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003-2009). METHODS: Non-Hispanic black (4,452) and white women (n = 42,453) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence. RESULTS: A total of 2,326 women developed breast cancer during follow-up (average follow-up = 5.4 y). Among black women, none of the latent class hazard ratios was elevated, but there were <100 cases in any category, limiting power. Among white women, those classified as "moderate" and "frequent" users of beauty products had increased risk of breast cancer relative to "infrequent" users [HR= 1.13 (95% CI: 1.00, 1.27) and HR = 1.15 (95% CI: 1.02, 1.30), respectively]. Frequent users of skincare products also had increased risk of breast cancer relative to infrequent users [HR= 1.13 (95% CI: 1.00, 1.29)]. None of the hair product classes was associated with increased breast cancer risk. The associations with beauty and skin products were stronger in postmenopausal women than in premenopausal women, but not significantly so. CONCLUSIONS: This work generates novel hypotheses about personal care product use and breast cancer risk. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype.Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+).Results: In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype.Conclusions: Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: Diets with a high glycemic index (GI) and glycemic load (GL) have been hypothesized to increase oxidative stress, but the limited human studies are inconsistent.Objective: The aim of this cross-sectional study was to investigate associations between dietary GI, GL, and carbohydrate intake and oxidative stress, as measured by F2-isoprostanes (F2-IsoPs).Methods: Concentrations of F2-IsoP and its metabolite (15-F2t-IsoP-M) were measured in urine samples collected at enrollment from 866 premenopausal women (aged 35-54 y) participating in the Sister Study. Total carbohydrate intake and dietary GI and GL were assessed using a validated food frequency questionnaire. Urinary F2-IsoP and 15-F2t-IsoP-M concentrations were compared across quintiles of carbohydrate intake, GI, and GL using multivariable linear regression models.Results: Urinary F2-IsoP concentrations were positively associated with dietary GI (P-trend = 0.023), and both F2-IsoP and 15-F2t-IsoP-M concentrations were positively associated with GL (F2-IsoP: P-trend < 0.001; 15-F2t-IsoP-M: P-trend < 0.001) and total carbohydrate intake (F2-IsoP: P-trend = 0.012; 15-F2t-IsoP-M: P-trend < 0.001). Stratified analyses suggested that a positive association between GI and urinary 15-F2t-IsoP-M concentrations was present among women with a body mass index [BMI (in kg/m2)] ≥30.0, but not among those with a BMI of <25.0 or 25.0-29.9 (P-interaction = 0.01).Conclusions: Our cross-sectional analyses in a sample of premenopausal women support hypothesized relations between high dietary GI and GL and oxidative stress, as assessed by urinary F2-IsoP and 15-F2t-IsoP-M concentrations. Given potential associations between oxidative stress and the development of cardiovascular disease and type 2 diabetes, our findings may have important implications for reducing chronic disease risk. [ABSTRACT FROM AUTHOR]

Background: Women may have incomplete understanding of a breast cancer diagnosis, leading to inaccurate reporting in epidemiological studies. However, it is not feasible to obtain consent for medical records from all women participating in a study. Therefore, it is important to determine how well self-reported breast cancer characteristics correspond with what is found in medical records, but few studies have evaluated agreement of self-reported breast cancer characteristics with abstracted medical records.Methods: We calculated the positive predictive value (PPV) of self-reports compared to medical records and explored whether participant characteristics may have influenced reporting accuracy. We analyzed data from 2518 reported breast cancer cases from the Sister Study, a large nationwide cohort of women with a family history of breast cancer.Results: Medical records or pathology reports were obtained for 2066 of 2518 (82%) women who reported incident breast cancer. Breast cancer was confirmed for over 99% (n = 2054) of women with medical records. Confirmation rates were high for invasive, ductal, hormone receptor positive, and HER2 negative breast cancers, with little variation by race/ethnicity or age. Self-reported in situ breast cancer had a lower PPV (64.2%), with medical records showing invasive breast cancer instead, especially for older and Hispanic women. Hormone receptor (ER and PR) negative and HER2 positive self-reports had lower PPVs (83.0%, 71.6%, and 66.1% respectively). Hispanic women and women ages 65 or older at diagnosis were less able to accurately report breast cancer stage, excluding stage I.Conclusions: Accuracy of reporting overall breast cancer and common subtypes is high. Despite having a family history of breast cancer and voluntarily enrolling in a study evaluating breast cancer risk factors, participants may have greater difficulty distinguishing between in situ and invasive breast cancer and may less accurately report other less common subtypes. Discrepancies may reflect women's poor understanding of information conveyed by health care providers or lack of consistent terminology used to describe subtypes. [ABSTRACT FROM AUTHOR]

Background: Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause.Methods: We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression.Results: After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (≥2.94 ng/mgCr) to <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m (OR: 0.98, CI: 0.39, 2.5, 138 cases).Conclusions: Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk. [ABSTRACT FROM AUTHOR]

Expanding research capacity of large research networks within health care delivery systems requires strategically training both embedded and external investigators in necessary skills for this purpose. Researchers new to these settings frequently lack the skills and specialized knowledge conducive to multi-site and multi-disciplinary research set in delivery systems. This report describes the goals and components of the Cancer Research Network (CRN) Scholars Program, a 26-month training program developed to increase the capacity for cancer research conducted within the network's participating sites, its progression from training embedded investigators to a mix of internal and external investigators, and the content evolution of the training program. The CRN Scholars program was launched in 2007 to assist junior investigators from member sites develop independent and sustainable research programs within the CRN. Resulting from CRN's increased emphasis on promoting external collaborations, the 2013 Scholars program began recruiting junior investigators from external institutions committed to conducting delivery system science. Based on involvement of this broader population and feedback from prior Scholar cohorts, the program has honed its focus on specific opportunities and issues encountered in conducting cancer research within health care delivery systems. Efficiency and effectiveness of working within networks is accelerated by strategic and mentored navigation of these networks. Investing in training programs specific to these settings provides the opportunity to improve multi-disciplinary and multi-institutional collaboration, particularly for early-stage investigators. Aspects of the CRN Scholars Program may help inform others considering developing similar programs to expand delivery system research or within large, multi-disciplinary research networks. [ABSTRACT FROM AUTHOR]

Purpose: Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers.Methods: Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort. Tumor characteristics and endocrine therapy use were collected from medical and prescription records. We calculated multivariable prevalence ratios (PR) and 95 % confidence intervals (CI) for the association of endocrine therapy (versus no endocrine therapy) and urinary incontinence, overall and by therapy type (tamoxifen or aromatase inhibitors). PROMIS Sexual Function and Satisfaction domain scores were compared across endocrine therapy groups.Results: Among the 548 women with a breast cancer diagnosis, 49 % received endocrine therapy. Overall, 18 % of women reported urinary incontinence symptoms. We observed no association between urinary incontinence and endocrine therapy use overall (PR = 0.97; 95 % CI 0.67, 1.43), tamoxifen (PR = 1.20; 95 % CI 0.74, 1.96), or aromatase inhibitors (PR = 0.89; 95 % CI 0.55, 1.42), compared to no use. Approximately 55 % of women were sexually active. Sexual function scores did not vary according to endocrine therapy use, although urinary incontinence was associated with lower satisfaction scores (p = 0.05).Conclusions: Our findings demonstrate a high prevalence of urinary incontinence after breast cancer diagnosis similar to the overall prevalence in older U.S. women, and this did not vary strongly according to use of endocrine therapy. [ABSTRACT FROM AUTHOR]

Black women experience higher rates of hysterectomy than other women in the United States. Although research indicates that premenopausal hysterectomy with bilateral oophorectomy decreases the risk of breast cancer in black women, it remains unclear how hysterectomy without ovary removal affects risk, whether menopausal hormone therapy use attenuates inverse associations, and whether associations vary by cancer subtype. In the population-based, case-control Carolina Breast Cancer Study of invasive breast cancer in 1,391 black (725 cases, 666 controls) and 1,727 white (939 cases, 788 controls) women in North Carolina (1993-2001 ), we investigated the associations of premenopausal hysterectomy and oophorectomy with breast cancer risk. Compared with no history of premenopausal surgery, bilateral oophorectomy and hysterectomy without oophorectomy were associated with lower odds of breast cancer (for bilateral oophorectomy, multivariable-adjusted odds ratios = 0.60, 95% confidence interval: 0.47, 0.77; for hysterectomy without oophorectomy, multivariable-adjusted odds ratios = 0.68, 95% confidence interval: 0.55, 0.84). Estimates did not vary by race and were similar for hormone receptor-positive and hormone receptor-negative cancers. Use of estrogen-only menopausal hormone therapy did not attenuate the associations. Premenopausal hysterectomy, even without ovary removal, may reduce the long-term risk of hormone receptor-positive and hormone receptor-negative breast cancers. Varying rates of hysterectomy are a potentially important contributor to differences in breast cancer incidence among racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Background: To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype-specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype.Methods: During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression.Results: HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0-18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval: 0.92, 1.7).Conclusion: These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women. [ABSTRACT FROM AUTHOR]

Background. Endocrine therapy initiation after ductal carcinoma in situ (DCIS) is highly variable and largely unexplained. National guidelines recommend considering tamoxifen for women with estrogen receptor-positive (ER1) DCIS or who undergo excision alone. We evaluated endocrine therapy use after DCIS over a 15-year period in an integrated health care setting to identify factors related to initiation. Methods. Female Group Health Cooperative enrollees ages 18-89 years with a DCIS diagnosis during 1996-2011 were eligible for inclusion. Endocrine therapy was identified through pharmacy records. Tumor and treatment information were from tumor registry reports; demographics and other risk factors were from questionnaires and electronic medical records. Relative risks (RRs) and 95% confidence intervals (CIs) for endocrine therapy initiation were calculated using multivariable generalized linear models. Results. We identified 727 women with a DCIS diagnosis, including 163 (22%) who initiated endocrine therapy (149 tamoxifen, 14 aromatase inhibitor). Younger women were more likely to initiate endocrine therapy (RR 1.69; 95% CI 1.16-2.46 for ages 45-54 vs. 65-74 years). Compared with breast-conserving surgery (BCS) with radiation, women who had BCS alone (RR 0.46;95% CI 0.25-0.84) or mastectomy (RR 0.54; 95% CI 0.39-0.75) were less likely to use endocrine therapy. ER testing increased from 4% of DCIS cases in 2001 to 71% in 2011; however, endocrine therapy initiation decreased from 58% of ER1 DCIS in 2001-2005 to 37% in 2009-2011. Conclusion. Increasing ER testing since 2001 has not corresponded to parallel increases in endocrine therapy initiation. Age, surgery, and radiation were the primary factors associated with initiation. [ABSTRACT FROM AUTHOR]

Purpose: Adiposity has been linked with increased breast cancer risk and mortality. It is established that etiologic associations for adiposity vary by tumor subtype, but the influence of adiposity on subtype-specific survival is unknown. Methods: Study participants were 1,109 invasive breast cancer participants in the population-based Carolina Breast Cancer Study, diagnosed between 1993 and 2001, and with tissue blocks available for immunohistochemical subtyping. General and central adiposities were assessed by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, based on in-person measurements after diagnosis. Vital status as of 2011 was determined using the National Death Index (median follow-up = 13.5 years). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer (BC)-specific and all-cause mortalities. Results: Among all patients, high WHR (≥0.84), but not BMI, was associated with all-cause mortality (adjusted HR 1.50, 95% CI 1.11-2.05, <0.77 as reference). No significant association between adiposity and BC-specific mortality was detected, although there was a suggestion of increased mortality risk among high-BMI (≥30 kg/m(2)) patients with basal-like tumors (adjusted HR 2.44, 95% CI 0.97-6.12, <25 kg/m(2) as reference). Quantitative differences in all-cause mortality were observed by subtype, with BMI associated with basal-like mortality and WHR associated with luminal mortality. The associations were attenuated by tumor characteristics. Conclusions: Our study confirms the association of adiposity and unfavorable overall survival in breast cancer patients and suggests that this association may vary by intrinsic subtype and adiposity measure. [ABSTRACT FROM AUTHOR]

Background: Greater body mass index (BMI), a measure of overall adiposity, is associated with a higher risk of postmenopausal breast cancer. The role of central adiposity, often measured by waist circumference, is less well understood, especially among premenopausal women. The objective of the current study was to examine multiple measures of adiposity in relation to breast cancer in a prospective cohort study.Methods: A total of 50,884 Sister Study cohort participants aged 35 to 74 years were enrolled from 2003 through 2009. Inclusion criteria for the cohort included having a sister previously diagnosed with breast cancer. Trained study personnel measured height, weight, and waist and hip circumference during a home visit and study participants completed a detailed questionnaire. Using Cox regression analysis, we estimated multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with adiposity measurements, considering tumor subtype and menopausal status.Results: In total, 2009 breast cancers were diagnosed during follow-up (mean = 5.4 years). Weight, BMI, waist circumference, and waist-to-hip ratio were found to be positively associated with overall breast cancer risk and HRs were greater among postmenopausal women, those with hormonally responsive tumors, and women who were not currently using postmenopausal hormones. In models that adjusted for BMI, waist circumference associations persisted among both postmenopausal women (81-88 cm vs ≤80 cm: HR = 1.16 [95% CI 1.01-1.35] and >88 cm vs ≤80 cm: HR = 1.30 [95% CI 1.10-1.54]) and premenopausal women (81-88 cm vs ≤80 cm: HR = 1.56 [95% CI 1.19-2.04] and >88 cm vs ≤80 cm: HR = 1.30 [95% CI 0.91-1.87]).Conclusions: Findings from this large, prospective study with examiner-measured body size indicate that waist circumference is independently and positively associated with both premenopausal and postmenopausal breast cancer risk. [ABSTRACT FROM AUTHOR]

Bilateral oophorectomy is often performed during hysterectomy for benign conditions and can reduce breast cancer risk by 20%–50% when performed at younger ages. Accuracy of estimating the decrease in breast cancer risk associated with bilateral oophorectomy could be affected by common conditions that lead to surgery, such as uterine fibroids or endometriosis. The authors examined the potential for confounding by nonmalignant indications for surgery on breast cancer risk estimates in a population-based case-control study of invasive breast cancer newly diagnosed in 1992–1995. Breast cancer cases (N = 4,935) aged 50–79 years were identified from Wisconsin, Massachusetts, and New Hampshire tumor registries; similarly aged controls (N = 5,111) were selected from driver's license and Medicare lists. Reproductive and medical history was obtained from structured telephone interviews. Odds ratios and 95% confidence intervals were estimated with multivariate logistic regression. Women who underwent bilateral oophorectomy with hysterectomy at age ≤40 years had significantly reduced odds of breast cancer (odds ratio = 0.74, 95% confidence interval: 0.60, 0.90) compared with women with intact ovaries and uterus. Effect estimates were virtually unchanged after adjustment for uterine fibroids or endometriosis history. Results indicate that breast cancer risk reductions conferred by bilateral oophorectomy are not strongly confounded by failure to account for nonmalignant indications for surgery. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.Methods: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December 31, 2012, and conceived 12 or more months after breast cancer diagnosis. Individuals in the control group were covariate-matched women without a history of breast cancer who delivered during 2000-2012. The primary outcome was preterm birth at less than 37 weeks of gestation. Secondary outcomes were preterm birth at less than 32 weeks of gestation, small for gestational age (SGA), cesarean delivery, severe maternal morbidity, and neonatal morbidity. Subgroup analyses were used to assess the effect of time from initial treatment to fertilization and receipt of additional adjuvant therapy before pregnancy on outcomes of interest.Results: Of 30,021 women aged 18-45 years diagnosed with stage I-III breast cancer during 2000-2012, 553 met the study inclusion criteria. Those with a history of breast cancer and matched women in the control group had similar odds of preterm birth at less than 37 weeks of gestation (odds ratio [OR], 1.29; 95% CI 0.95-1.74), preterm birth at less than 32 weeks of gestation (OR 0.77; 95% CI 0.34-1.79), delivering an SGA neonate (less than the 5th percentile: OR 0.60; 95% CI 0.35-1.03; less than the 10th percentile: OR 0.94; 95% CI 0.68-1.30), and experiencing severe maternal morbidity (OR 1.61; 95% CI 0.74-3.50). Patients with a history of breast cancer had higher odds of undergoing cesarean delivery (OR 1.25; 95% CI 1.03-1.53); however, their offspring did not have increased odds of neonatal morbidity compared with women in the control group (OR 1.15; 95% CI 0.81-1.62).Conclusion: Breast cancer 1 or more years before fertilization was not strongly associated with obstetric and neonatal complications. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis."

Objective: To evaluate exposure to tobacco, marijuana, and indoor heating/cooking sources in relation to antimüllerian hormone (AMH) levels.Design: Cross-sectional analysis in a sample of premenopausal women (n = 913) enrolled in the Sister Study cohort (n = 50,884).Setting: Not applicable.Patient(s): Women, ages 35-54 years at time of enrollment, with an archived serum sample and at least one intact ovary and classified as premenopausal.Intervention(s): Not applicable.Main Outcome Measure(s): Serum AMH (ng/mL) levels ascertained by ultrasensitive ELISA assay.Result(s): Lower AMH levels were associated with sources of indoor heating, including burning wood (-36.0%; 95% confidence interval [CI], -55.7%, -7.8%) or artificial fire logs (-45.8%; 95% CI, -67.2%, -10.4%) at least 10 times/year in a residential indoor stove/fireplace. Lower AMH levels were also observed in women who were current smokers of ≥20 cigarettes/day relative to nonsmokers (-56.2%; 95% CI, -80.3%, -2.8%) and in women with 10+ years of adult environmental tobacco smoke (ETS) exposure (-31.3%; 95% CI, -51.3%, -3.1%), but no associations were observed for marijuana use.Conclusion(s): We confirmed previously reported findings of lower AMH levels in current heavy smokers and also found associations for long-term ETS exposure and indoor burning of wood or artificial fire logs. These findings suggest that combustion by-products from common exposures can have toxic effects on the human ovary. [ABSTRACT FROM AUTHOR]