Breast Cancer Patients at Increased Risk of Developing Type II Endometrial Cancer: Relative and Absolute Risk Estimation and Implications for Counseling

Abstract

Introduction Breast cancer (BC) is a recognized risk factor for endometrial cancer (EC). Emerging literature indicates that it confers a higher risk of type II EC (T2EC) than type I EC (T1EC). Although some surgeons offer a prophylactic hysterectomy to BC patients referred for risk-reducing bilateral salpingo-oophorectomy, insufficient evidence prevents this from being the standard practice. We aimed to quantify their absolute risk and relative risk (RR) of developing both EC subtypes and identify a higher-risk group that could be considered for prophylactic hysterectomy. Methodology This retrospective service evaluation compared patients diagnosed with BC between 2008 and 2014, who subsequently developed EC within 10 years to those who did not. Absolute risk and RR were calculated using the numbers of regional BC and EC cases within this group, alongside 2009 UK female population and EC incidence statistics. Binary logistic regression generated adjusted odds ratios (ORs) for patient- and disease-specific variables. Results A total of 45 BC patients developed EC, 24 had T1EC and 21 had T2EC. Their RR of developing EC was greater than that of the general population (RR: 12.44, p < 0.0001). Notably, this was higher for T2EC (RR: 33.96, p < 0.001) than T1EC (RR: 8.63, p < 0.0001). Nonetheless, the absolute risk remained low. Tamoxifen exposure was significantly more prevalent among T2EC patients (adjusted OR: 79.61, p = 0.003). Increased age at BC diagnosis was associated with T1EC (adjusted OR: 1.10, p = 0.043) and T2EC (adjusted OR: 1.13, p = 0.03). Neither smoking status nor family history of BC was significantly associated with any outcome. Conclusion Women with BC were more likely to develop T2EC than T1EC, and although the absolute risk was low, the cumulative risk was substantial enough to warrant vigilance. Tamoxifen exposure was significantly predictive of EC, particularly T2EC, and might facilitate risk estimation. Older women at BC diagnosis who receive tamoxifen treatment should be screened and closely monitored for EC. However, given the limitations of normal screening methods for the detection of T2EC, counseling for a prophylactic hysterectomy should also be considered. Clarification of the menopausal status will help make more meaningful recommendations.

Tamoxifen use and risk of endometrial cancer in breast cancer patients: A systematic review and dose–response meta‐analysis

“…According to the inclusion criteria, in title/abstract and full text screening, 3960 and 35 studies were excluded, respectively. Finally, 26 studies were eligible for inclusion in meta‐analysis 11–14,20–41 …”

“…Finally, 26 studies were eligible for inclusion in meta‐analysis. 11 , 12 , 13 , 14 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 …”

“…Mean age of participants was 58.4 years. Five studies were performed in the United States, 24 , 25 , 30 , 36 , 40 one in Canada and United States, 22 two in Italy, 13 , 14 three in Japan, 28 , 33 , 38 two in France, 27 , 29 two in Sweden, 20 , 26 two in Finland, 23 , 35 two in the United Kingdom, 37 , 41 and others in South Korea, Taiwan, United Kingdom, Netherlands, Slovenia, Austria, Israel, and Denmark. 11 , 12 , 21 , 31 , 32 , 34 , 39 Three studies had RCTs design, 21 , 22 , 26 eight studies had case–control design, 20 , 24 , 27 , 29 , 30 , 32 , 35 , 37 and 15 studies were cohorts.…”

Breast Cancer Patients Are at Increased Risk of Developing Uterine Serous Cancer: Implications for Counseling – A SEER Analysis

“…Guo et al [8] showed that the incidence of EC was increased by 15-16 fold in BC patients. Portella et al [13] found that in BC patients the risk for type I and type II EC was 12.4-and 33.9-fold higher as compared to the general population, respectively. Gehrig et al [10] found a 2.6-fold increased risk for USC compared to endometroid EC in BC survivors.…”

“…Several studies have investigated the association between BC and EC\USC [6,[8][9][10][11][12][13][14][15]. Guo et al [8] showed that the risk for EC after BC was approximately 15-16 times more than the general population in both estrogen receptor (ER)-positive and -negative BC subtypes.…”