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Background: Fertility counseling is recommended for adolescent and young adult women facing gonadotoxic cancer therapy. However, fertility care is subspecialized medical care offered at a limited number of institutions, making geographic access a potential barrier to guideline-concordant care. We assessed the relationship between geographic access and receipt of fertility counseling among adolescent and young adult women with cancer., Methods: Using data from the North Carolina Central Cancer Registry, we identified women diagnosed with lymphoma, gynecologic cancer, or breast cancer at ages 15 to 39 years during 2004 to 2015. Eligible women were invited to complete an online survey on various topics, including fertility counseling. Geographic access was measured, using geocoded addresses, as vehicular travel time from residence to the nearest fertility clinic available at diagnosis. Multivariable regression models were used to examine the association between travel time and receipt of fertility counseling by provider type: health care provider versus fertility specialist., Results: Analyses included 380 women. The median travel time to a fertility clinic was 31 (IQR: 17-71) minutes. Overall, 75% received fertility counseling from a health care provider and 16% by a fertility specialist. Women who lived ≥30 minutes from a clinic were 13% less likely to receive fertility counseling by a health care provider (prevalence ratio: 0.87; 95% confidence interval, 0.75-1.00) and 49% less likely to receive counseling by a fertility specialist (prevalence ratio: 0.51; 95% confidence interval, 0.28-0.93)., Conclusions: Women who lived further away from fertility clinics were less likely to receive fertility counseling., Impact: Interventions to improve access to fertility counseling should include strategies to alleviate the burden of geographic access., (©2024 American Association for Cancer Research.)

Background: Fertility preservation (FP) may be underused after cancer diagnosis because of uncertainty around delays to cancer treatment and subsequent reproductive success., Methods: Women aged 15 to 39 years diagnosed with cancer between 2004 and 2015 were identified from the North Carolina Central Cancer Registry. Use of assisted reproductive technology (ART) after cancer diagnosis between 2004 and 2018 (including FP) was assessed through linkage to the Society for Assisted Reproductive Technology. Linear regression was used to examine time to cancer treatment among women who did (n = 95) or did not (n = 469) use FP. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% CIs for pregnancy and birth based on timing of ART initiation relative to cancer treatment (n = 18 initiated before treatment for FP vs n = 26 initiated after treatment without FP)., Results: The median time to cancer treatment was 9 to 33 days longer among women who used FP compared with women who did not, matched on clinical factors. Women who initiated ART before cancer treatment may be more likely to have a live birth given pregnancy compared with women who initiated ART after cancer treatment (age-adjusted RR, 1.47; 95% CI, 0.98-2.23), though this may be affected by the more frequent use of gestational carriers in the former group (47% vs 20% of transfer cycles, respectively)., Conclusions: FP delayed gonadotoxic cancer treatment by up to 4.5 weeks, a delay that would not be expected to alter prognosis for many women. Further study of the use of gestational carriers in cancer populations is warranted to better understand its effect on reproductive outcomes., (© 2022 American Cancer Society.)

Purpose: To examine trends in the surgical treatment of breast cancer by age, rurality, and among Black women in a populous, racially diverse, state in the Southeastern United States of America., Methods: We identified women diagnosed with localized or regional breast cancer between 2003 and 2016 in the North Carolina Central Cancer Registry (n = 86,776). Using Joinpoint regression we evaluated the average annual percentage change in proportion of women treated with mastectomy versus breast-conserving surgery overall, by age group, among Black women, and for women residing in rural areas., Results: Overall, the rate of mastectomy usage in the population declined 2.5% per year between 2003 and 2016 (95% CI - 3.2, - 1.7). Over this same time interval, breast-conserving surgery increased by 1.6% per year (95% CI 0.9, 2.2). These temporal trends in surgery were also observed among Black women and rural residing women. Trends in surgery type varied by age group: mastectomy declined over time among women > 50 years, but not among women aged 18-49 at diagnosis., Discussion: In contrast to national studies that reported increasing use of mastectomy, we found declining mastectomy rates in the early 2000s in a Southern US state with a racially and geographically diverse population. These decreasing trends were consistent among key subgroups affected by cancer inequities, including Black and White rural women., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. The Author(s).)

Background: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States., Methods: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data., Results: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall ( N = 1,679), and notably lower among minority groups compared with non-Hispanic white women., Conclusions: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements., Impact: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care., (©2021 American Association for Cancer Research.)

The long-term reproductive health impact of cancer treatments is a concern for premenopausal women with a history of breast cancer. This study examined the unmet sexual and reproductive health needs of breast cancer survivors, as well as concordances and discordances in needs by childbearing status and race. We interviewed 17 women diagnosed with breast cancer between the ages of 18 and 45 years and living in North Carolina. To analyze these data, we used the Sort and Sift, Think and Shift© method, a multidimensional qualitative analysis approach. We learned that breast cancer survivors (a) received limited reproductive health information, (b) desired realistic expectations of conceiving postcancer, (c) struggled with adjusting to their altered physical appearance, and (d) had menopause symptoms that led to sexual health and quality of life issues. Breast cancer survivors are in need of and desire more education and resources to address their sexual and reproductive health concerns.

Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF)., Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally., Design, Setting, and Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020., Exposures: Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries., Main Outcomes and Measures: Cancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups., Results: A total of 1 000 639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52 776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group., Conclusions and Relevance: This study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally.

Purpose: In the United States, hysterectomies and oophorectomies are frequently performed before menopause for benign conditions. The procedures are associated with reduced breast cancer-specific mortality among White women. The relationship between premenopausal gynecologic surgery and mortality in Black women with breast cancer is unknown., Methods: This investigation used incident invasive cases of breast cancer from Phases 1 and 2 of the Carolina Breast Cancer Study a population-based study that recruited Black and White women in North Carolina between 1993 and 2001. Premenopausal gynecologic surgery was operationalized in three categories: no surgery; hysterectomy with bilateral oophorectomy; hysterectomy with conservation of ≥ 1 ovary. Mortality was ascertained using the National Death Index, last updated in 2016. Multivariable-adjusted Cox Proportional Hazard Models were used to estimate the effect of premenopausal surgery on breast cancer-specific and all-cause mortality RESULTS: Hysterectomy with bilateral oophorectomy was associated with reduced breast cancer-specific mortality (HR 0.68; 95% CI 0.49, 0.96). White and Black women had a similar reduction in breast cancer-specific mortality. (HR among white: 0.66; 95% CI 0.43, 1.02), (HR among Black: 0.67; 95% CI 0.37, 1.21)., Conclusions: There was a similar reduction in breast cancer-specific mortality following premenopausal, pre-diagnosis hysterectomy with bilateral oophorectomy across both Black and White women.

Purpose: Cancer survivors are at increased risk for the early development of age-related chronic medical conditions compared with peers without a history of cancer; however, little is known regarding the burden of these conditions among survivors of adolescent and young adult (AYA) cancers. In response, we sought to determine the prevalence of specific comorbidities and frailty among AYAs (15-39 years old at diagnosis) enrolled in a cancer survivorship cohort., Methods: Using a cross-sectional survey of a tertiary medical center-based cancer survivorship cohort, we determined the prevalence of specific comorbidities and frailty using the survey-based FRAIL assessment. In separate models adjusting for age, we estimated prevalence ratios (PRs) for the associations between patient characteristics and (1) any comorbidity and (2) frailty or prefrailty using log-binomial models., Results: We identified 271 AYA cancer survivors, most of whom were 30-39 years old at survey (57%). A majority of survivors (n = 163, 60%) reported having at least one comorbidity with the most common being depression (28%), anxiety (27%), asthma (17%), high cholesterol (15%), and hypertension (15%). Of the 184 AYA survivors at least 1 year from cancer diagnosis, 19 (10%) were classified as frail and 39 (21%) as prefrail. Survivors who were smokers (PR 2.0, 95% confidence interval [CI]: 1.16-3.56); obese (PR 1.7, 95% CI: 1.10-2.55); uninsured (PR 2.7, 95% CI: 1.63-4.59); or who reported comorbid depression or anxiety (PR 2.4, 95% CI: 1.51-3.67) were more likely to be frail or prefrail., Conclusions: The prevalence of frailty and comorbidities is high among AYA cancer survivors suggestive of accelerated aging.

Reproductive outcomes are an important survivorship concern for women diagnosed with cancer as adolescents and young adults (AYAs). We examined the incidence of live birth and the prevalence of adverse birth outcomes according to tumor and treatment characteristics among AYAs with breast cancer. Women diagnosed with breast cancer at ages 15-39 during 2000-2013 were identified using the North Carolina Central Cancer Registry (n = 4,978). Cancer registry records were linked to state birth certificate files from 2000 to 2014 to identify births to women with and without a breast cancer history. The breast cancer cohort was followed until live birth, death, age 46, or December 31, 2014, whichever occurred first. For each birth to breast cancer survivors (n = 338), we sampled 20 births to women without a recorded cancer diagnosis, with frequency matching on maternal age and year of delivery. The cumulative incidence of live births after breast cancer was 8% at 10 years. Births were less common among women treated with chemotherapy. Overall, the prevalence of preterm birth, low birth weight, small-for-gestational age (SGA) and Cesarean delivery did not differ substantially between births to women with and without breast cancer. However, births to women with ER-negative disease were more likely to be preterm (PR = 1.84; 95% CI: 1.11-3.06). In this population-based study, <10% of AYA breast cancer survivors had a live birth within 10 years of their diagnosis. The increase in risk of preterm delivery among ER-negative survivors in our cohort warrants further investigation in larger studies., (© 2017 UICC.)

Purpose: A cancer diagnosis in adolescence and young adulthood (AYA, ages 15-39) may affect future pregnancy outcomes. Previous studies have reported an increased risk of preterm delivery (< 37 weeks of gestation) after maternal cancer treatment. In this analysis, we evaluated whether non-cancer characteristics modify the association between an AYA cancer history and preterm birth., Methods: North Carolina Central Cancer Registry records (2000-2013) were linked to state birth certificate files (2000-2014) to identify births to AYA cancer survivors (n = 1,980). A comparison cohort of births to women without a cancer diagnosis was selected from birth certificate files (n = 11,860). Log-binomial regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. Effect modification by early prenatal care (1st trimester; yes/no), race/ethnicity (white/black/other), previous live births (0/1+), maternal age (< 25/25-29/30-34/35+), smoking during pregnancy (any/none), and education (high school or less/some college/Bachelor's degree or higher) was evaluated using likelihood ratio tests (LRT)., Results: Overall, preterm births were more common among AYA survivors than the comparison group (RR = 1.24, CI 1.07-1.43). The association was stronger among those who did not receive early prenatal care (RR = 1.73, CI 1.26-2.37) than among those who did (RR = 1.15, CI 0.98-1.35; LRT p = 0.03). Maternal age < 25 was also associated with a greater increase in preterm birth (< 25: RR = 1.80, CI 1.27-2.54; LRT p = 0.07). Associations did not vary strongly by other factors evaluated., Conclusions: An AYA cancer diagnosis may be associated with an increased risk of preterm birth, particularly among women who are younger and receive late or no prenatal care.

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., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)