In this study, we investigated differences in clinicopathologic outcomes between SPBC after ovarian cancer and PBC in Korea. We showed that the incidence of breast cancer is higher in patients with ovarian cancer than it is in healthy people and that survival outcomes were worse for SPBC than for PBC; increased mortality was related to older age and advanced cancer stage.
In the current study, SPBC after ovarian cancer accounted for only 0.07% of newly diagnosed breast cancers in Korea, based on KCCR data from a 19-year period. In a retrospective observational study using SEER data between 1973 and 2013, the incidence of SPBC in the ovarian cancer cohort was approximately 1.37% (1,821/133,149) and the incidence of SPBC decreased from 7.2% to 2.0% between 1973 and 2008 (P < 0.05). [13] From 1999 to 2017, the incidence of breast cancer continued to increase year by year. On the other hand, the incidence of SPBC after ovarian cancer did not remain constant. In this study, the incidence of SPBC after ovarian cancer increased about two-fold in 2016 and 2017 (Supplement 1). Increasing rates of SPBC may be due to interest in genetic testing and application of insurance reimbursement, which may have led to active screening for breast cancer.
Ovarian cancer and breast cancer are hereditary cancers, and BRCA1 and BRCA2 are well known as causative genes. [4] According to the National Comprehensive Cancer Network guideline, risk-reducing surgery is recommended for carriers of BRCA gene mutations at an appropriate time. [7] A previous meta-analysis reported that the risk of breast cancer was reduced by about 50% in carriers of BRCA1 and BRCA2 mutations who underwent risk-reducing bilateral salpingo-oophorectomy (RRSO). [8] In our previous study about patterns of risk-reducing surgery in carriers of BRCA mutations, the rate of RRSO was 42.5%. After insurance reimbursement started in 2013, the rate of risk-reducing surgery was significantly higher (46.3% after 2013 vs. 31.6% before 2013, p < 0.001). [14]
In the current study, the overall SIR for SPBC after ovarian cancer was 1.27 (95% CI, 1.09–1.46). In a study of invasive ovarian cancer, the SIR of breast cancer was 1.35 (95% CI, 0.85‒2.05). [10] In another study on an ovarian cancer cohort from the Stockholm‒Gotland Cancer Registry, the SIR of breast cancer was 1.41 (95% CI, 1.14‒1.75). [9] We found that the SIR of SPBCS was significantly higher at 1.34 between 1 and 4 years after the initial diagnosis of ovarian cancer. Thus, patients with ovarian cancer require more active surveillance for SPBC during this period.
This study showed that patients with SPBC after ovarian cancer had a markedly poor survival. Interestingly, when compared by age, our study confirmed that the survival rate of patients with PBC was relatively lower in the older age-group, whereas the survival rate of patients with SPBC was lower in the 40s age-group. Treatment of ovarian cancer with radiation therapy and chemotherapy may lead to aggressiveness of the second primary tumor. A previous study using the SEER program database showed that survival of patients with localized SPBC was similar to that of patients with PBC, while cases with advanced stage SPBC showed worse survival outcomes. [11] Our study showed similar results.
This study had several strengths. We analyzed a population-based cancer registry that included approximately 98% of Korean cancer cases. No previous study has reported the clinical outcomes of patients with breast cancer after ovarian cancer in Korea. However, our study had several limitations. First, this study lacked detailed clinical information regarding surgery type, such as mastectomy or breast-conserving surgery, and subtypes of tumor, such as luminal A, luminal B, HER2-positive, and triple-negative. Second, the study did not have access to personal history, family history and status of genetic mutations, such as those in BRCA1/BRCA2, which influence hereditary cancer. Further studies should perform detailed investigations regarding the breast cancer characteristics.