Risk of Breast Cancer in Patients with Thyroid Cancer Receiving or Not Receiving 131I Treatment: A Nationwide Population-Based Cohort Study

Abstract STUDY QUESTION Do female adolescents and young adults (AYAs) with cancer have a higher risk of subsequent infertility diagnosis than AYAs without cancer? SUMMARY ANSWER Female AYAs with breast, hematological, thyroid and melanoma cancer have a higher risk of subsequent infertility diagnosis. WHAT IS KNOWN ALREADY Cancer therapies have improved substantially, leading to dramatic increases in survival. As survival improves, there is an increasing emphasis on optimizing the quality of life among cancer survivors. Many cancer therapies increase the risk of infertility, but we lack population-based studies that quantify the risk of subsequent infertility diagnosis in female AYAs with non-gynecological cancers. The literature is limited to population-based studies comparing pregnancy or birth rates after cancer against unexposed women, or smaller studies using markers of the ovarian reserve as a proxy of infertility among female survivors of cancer. STUDY DESIGN, SIZE, DURATION We conducted a population-based cohort study using universal health care databases in the province of Ontario, Canada. Using data from the Ontario Cancer Registry, we identified all women 15–39 years of age diagnosed with the most common cancers in AYAs (brain, breast, colorectal, leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, thyroid and melanoma) from 1992 to 2011 who lived at least 5 years recurrence-free (Exposed, n = 14,316). Women with a tubal ligation, bilateral oophorectomy or hysterectomy previous to their cancer diagnosis were excluded. We matched each exposed woman by age, census subdivision, and parity to five randomly selected unexposed women (n = 60,975) and followed subjects until 31 December 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertility diagnosis after 1 year of cancer was identified using information on physician billing codes through the Ontario Health Insurance Plan database (ICD-9 628). Modified Poisson regression models were used to assess the risk of infertility diagnosis (relative risk, RR) adjusted for income quintile and further stratified by parity at the time of cancer diagnosis (nulliparous and parous). MAIN RESULTS AND THE ROLE OF CHANCE Mean age at cancer diagnosis was 31.4 years. Overall, the proportion of infertility diagnosis was higher in cancer survivors compared to unexposed women. Mean age of infertility diagnosis was similar among cancer survivors and unexposed women (34.8 years and 34.9 years, respectively). The overall risk of infertility diagnosis was higher in cancer survivors (RR 1.30; 95% CI 1.23–1.37). Differences in infertility risk varied by type of cancer. Survivors of breast cancer (RR 1.46; 95% CI 1.30–1.65), leukemia (RR 1.56; 95% CI 1.09–2.22), Hodgkin lymphoma (RR 1.49; 95% CI 1.28–1.74), non-Hodgkin lymphoma (RR 1.42; 95% CI 1.14, 1.76), thyroid cancer (RR 1.20; 95% CI 1.10–1.30) and melanoma (RR 1.17; 95% CI 1.01, 1.35) had a higher risk of infertility diagnosis compared to women without cancer. After stratification by parity, the association remained in nulliparous women survivors of breast cancer, leukemia, lymphoma and melanoma, whereas it was attenuated in parous women. In survivors of thyroid cancer, the association remained statistically significant in both nulliparous and parous women. In survivors of brain or colorectal cancer, the association was not significant, overall or after stratification by parity. LIMITATIONS, REASONS FOR CAUTION Non-biological factors that may influence the likelihood of seeking a fertility assessment may not be captured in administrative databases. The effects of additional risk factors, including cancer treatment, which may modify the associations, need to be assessed in future studies. WIDER IMPLICATIONS OF THE FINDINGS Reproductive health surveillance in female AYAs with cancer is a priority, especially those with breast cancer, leukemia and lymphoma. Our finding of a potential effects of thyroid cancer (subject to over-diagnosis) and, to a lesser extent, melanoma need to be further studied, and, if an effect is confirmed, possible mechanisms need to be elucidated. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the Faculty of Health Sciences and Department of Obstetrics and Gynecology, Queen’s University. There are no competing interests to declare. TRIAL REGISTRATION NUMBER N/A

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Prenatal Biochemical Screening and a Woman’s Long-Term Risk of Cancer: A Population-Based Cohort Study

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz077 ◽

2019 ◽

Vol 4 (1) ◽

Author(s):

Alison L Park ◽

Tianhua Huang ◽

Wendy S Meschino ◽

Javaid Iqbal ◽

Joel G Ray

Keyword(s):

Breast Cancer ◽

Endometrial Cancer ◽

Cohort Study ◽

Thyroid Cancer ◽

Plasma Protein ◽

Protein A ◽

Population Based ◽

Hazard Ratio ◽

Hormone Sensitive ◽

In Pregnancy

Abstract Background Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman’s subsequent risk of hormone-sensitive cancer. Methods This population-based cohort study included women aged 12–55 years who underwent prenatal screening between 11 weeks + 0 days of gestation to 20 weeks + 6 days of gestation in Ontario, Canada, 1993–2011, where universal health care is available. The hazard ratio of newly diagnosed breast, ovarian, endometrial, and thyroid cancer—arising at 21 weeks + 0 days of gestation or thereafter—was estimated in association with an abnormally low (≤5th) or high (>95th) percentile multiple of the median (MoM) for alpha-fetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol, pregnancy-associated plasma protein A, and dimeric inhibin A. Results Among 677 247 pregnant women followed for a median of 11.0 years (interquartile range = 7.5–16.1), 7231 (1.07%) developed breast cancer, 515 (0.08%) ovarian cancer, 508 (0.08%) endometrial cancer, and 4105 (0.61%) thyroid cancer. In multivariable adjusted models, abnormally high hCG greater than the 95th percentile MoM was associated with a doubling in the risk of endometrial cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.33 to 2.95), and abnormally low AFP at the fifth percentile or less MoM conferred a moderately greater risk of thyroid cancer (aHR = 1.21, 95% CI = 1.07 to 1.38). Abnormally low pregnancy-associated plasma protein A at the fifth percentile or less MoM was not statistically significantly associated with breast cancer after multivariable adjustment (aHR = 1.19, 95% CI = 0.98 to 1.36). Conclusions Women with abnormally high levels of serum hCG or low AFP in early pregnancy may be at a greater future risk of certain types of hormone-sensitive cancers.

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