Abstract
Ovarian cancer is the leading cause of gynecologic cancer death in the world, and its prevention and early diagnosis remain the key to its treatment, especially for high‐grade serous carcinoma (HGSC). Accumulating epidemiological and molecular evidence has shown that HGSC originates from fallopian tube secretory cells through serous tubal intraepithelial carcinoma. Comprehensive molecular analyses and mouse studies have uncovered the key driver events for serous carcinogenesis, providing novel molecular targets. Risk‐reducing bilateral salpingo‐oophorectomy (RRSO) has been proposed to reduce the subsequent occurrence of serous carcinoma in high‐risk patients with BRCA mutations. However, there is no management strategy for isolated precursors detected at RRSO, and the role of subsequent surgery or chemotherapy in preventing serous carcinoma remains unclear. Surgical menopause due to RRSO provides a variety of problems related to patients’ quality of life, and the risks and benefits of hormone replacement are under investigation, especially for women without a previous history of breast cancer. An additional surgical option, salpingectomy with delayed oophorectomy, has been proposed to prevent surgical menopause. The number of opportunistic salpingectomies at the time of surgery for benign disease to prevent the future occurrence of HGSC has increased worldwide. Thus, the changing concept of the origin of serous carcinoma has provided us a great opportunity to develop novel diagnostic and therapeutic approaches.
Highlights
In the United States of America and Japan, ovarian cancer accounts for 2.5% and 3.1% of cancer diagnoses and is the fouth and ninth leading cause of cancer-related death, respectively.1,2 While the cure rate of patients with disease confined to the ovary is over 90%,3,4 those with disseminated or metastatic lesions have 5-year survival rates of25%-30%.5-7 The prognosis of high-grade serous carcinoma (HGSC) is poor among the histological types, and prevention and early detection of this subtype are urgently needed
Determining precisely where these tumors initiate will affect strategies for early detection, such as improved methods of diagnostic imaging that focus on the distal fallopian tube, in addition to the ovary
One can imagine that fallopian tubes or fimbriae may be a target of cytology or biopsy with a specialized apparatus in outpatients, possibly as a screening test especially for high-risk patients or patients with an ovarian mass or ascites suspicious of HGSC
Summary
In the United States of America and Japan, ovarian cancer accounts for 2.5% and 3.1% of cancer diagnoses and is the fouth and ninth leading cause of cancer-related death, respectively. While the cure rate of patients with disease confined to the ovary is over 90%,3,4 those with disseminated or metastatic lesions have 5-year survival rates of. The pathway analyses showed that RB-related (67%) and RAS/ PI3K-related (45%) signaling pathways were activated, and homologous recombination defects (HRDs) were observed in up to 49% of cases, via BRCA1 promoter hypermethylation and silencing, as well as its germline and somatic mutations These findings indicate that the mutational spectrum marks HGSC as completely distinct from other histological subtypes of ovarian cancer, with extremely high TP53 mutations and frequent HRDs. Mouse models have been established to uncover the potential origin and the molecular pathways for serous carcinogenesis. Based on the accumulating evidence that HGSC may originate from the fallopian tubes, bilateral salpingectomy (without oophorectomy) may offer a reduced risk of ovarian cancer in BRCA1 or BRCA2 mutation carriers and greater peace of mind, while enabling women to delay or avoid surgical menopause and maintain fertility.
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