Abstract
Breast cancer survivors are at an increased risk of second primary cancers, and the risk factors for the latter may have clinical significance. The aims of our study were to evaluate the incidences and risk factors of second primary female genital cancers (corpus uteri, cervix uteri plus ovary) in a large cohort of breast cancer survivors. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined the standardized incidence ratio (SIR) and risk factors for second primary female genital cancers observed between 2000 and 2014. Breast cancer survivors had increased SIRs for second corpus uteri cancers and second ovarian cancers and a decreased SIR for second cervical cancers (SIR 1.17, 1.12, and 0.64, respectively). Risk factors of second corpus uteri cancers were the age at first cancer diagnosis, race (black vs. white, aHR = 1.142 95% CI 1.005–1.298), and progesterone receptor (PR) status (PR+ vs. PR−, aHR = 1.131 95% CI 1.004–1.273). In addition, the risk of second ovarian cancer was positively associated with age while inversely associated with race (black vs. white, aHR = 0.691 95% CI 0.555–0.859) and estrogen receptor (ER) status (ER+ vs. ER−, aHR = 0.655 95% CI 0.544–0.788). Age, race, and hormone receptor status are risk factors of developing second female genital cancers among breast cancer survivors. Older age, black race, and a PR+ status in survivors are associated with a higher risk of second corpus uteri cancers. Additionally, older age and an ER− status should increase vigilance for potential second ovarian cancers.
Highlights
According to statistics regarding cancer incidence and mortality, breast cancer is the most common malignancy diagnosed in females, accounting for nearly one in three cancers [1]
The italic values indicate the SIR for developing a second primary cancer was significantly decreased O observed numbers, SIR standardized incidence ratio, hazards ratios (HRs) hormone receptor, ER estrogen receptor, PR progesterone receptor *P < 0.05; confidence intervals are 95% 1 Women were considered perimenopausal if their age is in between 46 and 55 years, and the menopausal status is unknown endometrial cancers after first primary breast cancer (Supplementary Table 1)
When we considered risk factors for second primary corpus uteri cancer after breast cancer (Table 3), the risk of second primary corpus uteri cancer was positively associated with the age at first cancer (46–55 vs. ≤ 45 years, aHR = 2.343, P < 0.001; 56+ vs. ≤ 45 years, aHR = 3.218, P < 0.001) (Fig. 1a), race, and PR status (Fig. 1b), while an inverse association was found with the year of first cancer, and ER status showed no association with risk (P = 0.293)
Summary
According to statistics regarding cancer incidence and mortality, breast cancer is the most common malignancy diagnosed in females, accounting for nearly one in three cancers [1]. Previous studies have suggested a consensus in the increased risk of second primary female genital cancers among breast cancer survivors. A large cohort study reported that women with breast cancer had a 30% excess risk for second primary cancers, for endometrial cancer and ovarian cancer [5]. The problem of second primary female genital cancers among breast cancer survivors may be related to treatment side effects or to etiological associations for multiple cancers. One study has shown that patients with breast cancer have a higher risk of subsequent endometrial cancer regardless of ER or progesterone receptor (PR) status [8]. The aims of our study were to systemically evaluate the incidence of second primary female genital cancers in a large cohort of breast cancer patients and to identify risk factors for second primary corpus uteri cancer and ovarian cancer. We used multivariable analysis to examine the risk factors for the development of a second primary female genital cancer after breast cancer
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