Prophylactic salpingectomy: The future of ovarian cancer prevention?
Ovarian cancer is notorious for its late stage at diagnosis and its poor prognosis. Many theories have circulated about the origin and development of ovarian cancer in both BRCA-positive and BRCA-negative women. Earlier theories emphasized that ovarian cancer originates in the ovary, with multiple cycles of ovulation, as well as possibly pelvic inflammation, triggering mutations that ultimately lead to loss of tumor suppressor control.
Newer research, however, shows that ovarian cancer may originate in the fallopian tube, and more specifically, the fimbriated end of the fallopian tube. This leads practitioners to ask the questions: Should I offer my patients prophylactic salpingectomies for primary ovarian cancer prevention? Should both tubes be removed in their entirety during elective surgeries, such as tubal ligations and hysterectomies?
Although there are no prospective randomized clinical trials that address this issue, we will examine the concept here.
The scope of the problem
Nearly 22,000 women are diagnosed with ovarian cancer each year in the United States alone and 190,000 globally; it contributes to nearly 16,000 deaths in the United States and 114,000 deaths worldwide each year.1 Although there are modifiable risk factors for ovarian cancer, such as use of oral contraceptives, family history is one factor that cannot be modified. At least 10% of ovarian cancers originate in BRCA-positive women, who have a 27%–56% lifetime risk of developing ovarian cancer. BRCA-positive women who choose to have prophylactic surgery have an approximately 96% rate of cancer-free survival, whereas those who opt for close surveillance have a 69% cancer-free rate.2
The success rate for prophylactic surgery in the BRCA population is based on one principle: removing tissue that has the potential to become malignant before it can do so. Where ovarian cancer originates is a question that must, therefore, first be answered so that prophylactic surgeries can be done to remove as little tissue as possible while maximizing the benefit for the patient.
Theories on ovarian cancer development
There are 2 widely circulated theories on the origins and progression of ovarian cancer. Endometroid and clear-cell carcinomas are thought to originate from multiple genetic events, such as mismatch repair mutations, that activate the KRAS/BRAF pathway, beta-catenein activation, and PTEN mutations, which then progress to cancer. Mutations in the KRAS/BRAF pathway tend to lead to a slower progression in ovarian cancer development.
Some researchers theorize that retrograde flow from the uterus creates endometriotic cysts on the ovaries that predispose to the changes in the cell cycle pathways.3 Others theorize that ovarian cancer originates from endometriosis, via damage from exposure to Mullerian factors during menstruation, or even from inclusion cysts on the ovary that invaginate and, in that process, accrue DNA damage. Still other researchers theorize that pelvic inflammation may cause similar oxidative stress and pathway alterations.4
The histology of other epithelial ovarian cancers may follow a more malignant pathway involving p53 tumor suppressor mutations. Such mutations lead to the development of serous carcinoma, which metastasizes rapidly by direct peritoneal spread.
The theories beyond what triggers these changes to tumor suppressor genes are many. In 1971, Fathalla developed the “incessant ovulation theory,” which held that constant damage, via oxidative stress, and repair of the ovarian epithelium after each cycle of ovulation led to an increased chance of tumor development.5
Cramer and Welch in 1983 hypothesized that regular gonadotropin stimulation and elevated estrogen levels stimulate proliferation of the ovarian epithelium; with stimulation comes the risk of DNA damage and progression to cancer.6
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