Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation

Abstract

ObjectiveTo investigate the risks of ovarian, breast, and corpus uteri cancer in women who have had assisted reproduction.DesignLarge, population based, data linkage cohort study.Setting and participantsAll women who had assisted reproduction in Great Britain, 1991-2010, as recorded by the Human Fertilisation and Embryology Authority (HFEA).InterventionsHFEA fertility records for cohort members were linked to national cancer registrations.Main outcome measuresObserved first diagnosis of ovarian, breast, and corpus uteri cancer in cohort members were compared with age, sex, and period specific expectation. Standardised incidence ratios (SIRs) were calculated by use of age, sex, and period specific national incidence rates.Results255 786 women contributed 2 257 789 person years’ follow-up. No significant increased risk of corpus uteri cancer (164 cancers observed v 146.9 cancers expected; SIR 1.12, 95% confidence interval 0.95 to 1.30) was found during an average of 8.8 years’ follow-up. This study found no significantly increased risks of breast cancer overall (2578 v 2641.2; SIR 0.98, 0.94 to 1.01) or invasive breast cancer (2272 v 2371.4; SIR 0.96, 0.92 to 1.00). An increased risk of in situ breast cancer (291 v 253.5; SIR 1.15, 1.02 to 1.29; absolute excess risk (AER) 1.7 cases per 100 000 person years, 95% confidence interval 0.2 to 3.2) was detected, associated with an increasing number of treatment cycles (P=0.03). There was an increased risk of ovarian cancer (405 v 291.82; SIR 1.39, 1.26 to 1.53; AER 5.0 cases per 100 000 person years, 3.3 to 6.9), both invasive (264 v 188.1; SIR 1.40, 1.24 to 1.58; AER 3.4 cases per 100 000 person years, 2.0 to 4.9) and borderline (141 v 103.7; SIR 1.36, 1.15 to 1.60; AER 1.7 cases per 100 000 person years, 0.7 to 2.8). Increased risks of ovarian tumours were limited to women with endometriosis, low parity, or both. This study found no increased risk of any ovarian tumour in women treated because of only male factor or unexplained infertility.ConclusionsNo increased risk of corpus uteri or invasive breast cancer was detected in women who had had assisted reproduction, but increased risks of in situ breast cancer and invasive and borderline ovarian tumours were found in this study. Our results suggest that ovarian tumour risks could be due to patient characteristics, rather than assisted reproduction itself, although both surveillance bias and the effect of treatment are also possibilities. Ongoing monitoring of this population is essential.

A cohort study of 49 933 women with surgically verified endometriosis: Increased incidence of breast cancer below the age of 40

“…[10][11][12][13][14] A large British cohort study published in 2018 found no association between breast cancer and endometriosis among women receiving infertility treatment with assisted reproductive technologies. 15 In contrast, an increased incidence of breast cancer has been observed in recent study with histologically proven endometriosis. 9 The differences in the overall incidence of breast cancer between different subtypes of endometriosis were small in our study.…”

“…Previous studies assessing the relationship between endometriosis and breast cancer have reported conflicting results. Some recent large studies have suggested that the risk of breast cancer among endometriosis patients is increased [7][8][9] , whereas several other studies reported no such risk [10][11][12][13][14][15] Moreover, a cross-sectional study from North America found a decreased prevalence. 16 We have previously assessed the risk of gynecological and non-gynecological cancers according to the type of endometriosis.…”

Health and Disease After Assisted Reproductive Technology

“…However, there may be a transient increase in the incidence of breast cancer in the first year due to earlier diagnosis (Salhab et al, 2005). Williams and colleagues describe no increased risk of invasive breast cancer but increased risks of in situ breast cancer in women who have had assisted reproduction (Williams et al, 2018). In another study, Van den Belt and colleagues describe a significantly lower risk of breast cancer among women who undergoing seven or more IVF cycles compared with women who underwent one or two (hazard ratio [HR]: 0.55) (van den Belt-Dusebout et al, 2016).…”

“…Kessous and colleagues describe an association between IVF treatment and ovarian and uterine cancer in a study of 4000 IVF patients (Kessous et al, 2016). Williams and colleagues showed no increased risk of corpus uteri cancer but increased risks of invasive and borderline ovarian tumours in women who had assisted reproduction (Williams et al, 2018). Results suggest that ovarian tumour risks could be due to patient characteristics, rather than assisted reproduction itself, although both surveillance bias and the effect of treatment are also possibilities.…”

Risk of cancer in infertile women: analysis of US claims data

“…Several studies suggest that infertile women are at higher risk of cancer than women from the general population, particularly hormonesensitive cancers of the breast, ovaries and endometrium (Brinton et al, 1989;Rossing et al, 1994;Venn et al, 1995;Meirow and Schenker, 1996;Modan et al, 1998;Althius et al, 2005b;Rizzuto et al, 2013;Practice Committee of ASRM, 2016;Skalkidou et al, 2017;Williams et al, 2018). There is some conflicting data, however, from additional studies showing no association between infertility and risk of breast and ovarian cancer (Venn et al, 1995;Kashyap et al, 2004;Jensen et al, 2007;van den Belt-Dusebout et al, 2016).…”