Elevated risks of subsequent endometrial cancer development among breast cancer survivors with different hormone receptor status: a SEER analysis

Abstract

Estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen are known to have an elevated risk of subsequent endometrial cancer. However, it is unclear if ER-negative patients also have a higher risk of endometrial cancer. This population-based study aims to evaluate whether breast cancer patients with distinctive ER and PR status possess differential risks in developing delayed endometrial malignancy. Data were obtained from the Surveillance, Epidemiology, and End Results program (1992–2009). Standardized incidence ratio (SIR) was calculated as the observed cases of endometrial cancers among breast cancer survivors compared with the expected cases in the general population. Data were stratified by latency periods, race, age, and calendar year of breast cancer diagnosis. We identified 2044 patients who developed a second primary endometrial cancer among 289,933 breast cancer survivors. The overall SIRs for subsequent endometrial cancers were increased in all of the four subtypes (ER+PR+, ER+PR−, ER−PR+, and ER−PR−) of breast cancer. SIR was increased for all latency periods except for the initial 6–11 months after breast cancer diagnosis. Stratifying by age of diagnosis, elevated SIRs in all ER/PR groups were statistically significant among patients diagnosed with breast cancer after the age of 40. Demographically, non-Hispanic whites had increased SIRs in all subtypes of breast cancer, while Hispanic whites had no statistically elevated SIRs. Here we showed that patients with invasive breast cancer have a higher risk of developing subsequent endometrial cancer regardless of ER or PR status. The increased risk among hormone receptor-negative breast cancer survivors raises concerns whether common etiological factors among these breast cancer subtypes increase the susceptibility to develop endometrial cancer. Lower threshold for routine endometrial cancer surveillance may be warranted.

The bidirectional association among female hormone‐related cancers: breast, ovary, and uterine corpus

“…Estrogen receptor-positive breast cancer patients treated with tamoxifen are known to have an elevated risk of subsequent uterine cancer [31]. Notably, patients with invasive breast cancer have a higher risk of developing subsequent uterine cancer, regardless of hormone receptor status [7]. Mellemkjaer et al [4] found that higher risk was noted before 1975 when tamoxifen was rarely used.…”

The characteristics of breast cancer patients with metachronous primary malignancies

“…Published data indicate that age as well as menopausal status at diagnosis of breast cancer are important predictors of second primaries [16,[24][25][26][27][28][29][30][31][32][33][34]. Langballe et al, who investigated the risk of second malignancies in relation to menopausal status in women with breast cancer, noted that premenopausal women had an 18% increase in risk of appearance of second malignancy and this increased risk was confined to endometrial and ovarian cancers.…”

“…application of tamoxifen. It is known that the elevated risk of subsequent cancer which developed in breast cancer survivors is related to hormonal (estrogen and progesteron) receptor status [26,35].…”

“…Tamoxifen is used for treatment of ER/PR-positive breast cancers and for primary breast cancer prevention. However, this drug may increase the risk of other primary malignancies [26,[36][37][38]. Endometrium and gastrointestinal organs (colorectum, stomach and liver) may be target sites for tamoxifen-induced carcinogenesis [36].…”

“…The above-mentioned hormonotherapy as well as cytotoxic and radiation therapy used in breast cancer patients can increase the risk of occurrence of second malignancies [3,4,6,20,22,24,26,36,37,[39][40][41][42][43][44][45][46].…”