Evidence Points to Fallopian-tube Origins of Ovarian Cancer

Veronica Hackethal, MD

April 21, 2015

Most cases of high-grade serous cancer (HSGC) ― the most lethal form of ovarian cancer ― arise from the fallopian tubes rather than the ovaries, concludes a literature review published in the April issue of Cancer Prevention Research.

"There has been a major breakthrough in our understanding of the origin of ovarian cancer with the identification of the fallopian tubes as the major source of the cancer," commented first author Mary Daly, MD, head of the Genetics Risk Assessment Division of Fox Chase Cancer Center in Philadelphia, Pennsylvania. She even suggested that in the future, ovarian cancer may be described as fallopian tube cancer.

"This raises the possibility of altering our risk-reducing surgery approach, specifically, by removing the fallopian tubes first, while a woman is still premenopausal, and then removing the ovaries at the time of onset of menopause," Dr Daly explained. "This would spare women the side effects and long-term health risks associated with early surgical menopause."

For women with hereditary risk for ovarian cancer, such as those with BRCA1/2 mutations, the standard of care has been removal of both ovaries and fallopian tubes (bilateral salpingo- oopherectomy [BSO]). Although this procedure reduces the risk for ovarian cancer, it can affect quality of life, precipitate early menopause, cause sexual dysfunction, and contribute to increased risk for cardiovascular disease, osteoporosis, and all-cause mortality.

Because HSGC constitutes the most common form of ovarian cancer among women with high genetic risk, the new approach (bilateral salpingectomy with ovarian retention [BSOR]) could also have a "large impact" on ovarian cancer mortality, Dr Daly and colleagues write in the article.

BSOR could also reduce ovarian cancer risk in women at average risk for ovarian cancer who are undergoing hysterectomy for benign conditions, such as fibroids. About 600,000 women undergo hysterectomies in the United States each year. Fifteen percent of women who have had a hysterectomy develop ovarian cancer, according to background information in the article.

However, in a related editorial, Mark Greene, MD, and Phuong Mai, MD, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, in Bethesda, Maryland, state, "in our view, BSOR is an investigational procedure that should not be routinely implemented in high-risk women until its risks and benefits are more clearly defined."

The editorialists call for more research on the outcomes of such surgery, including impact on quality of life and on ovarian function. But they are pleased to see research moving the field forward. Recalling that in the past, when ovaries were removed prophylactically, the fallopian tubes were often left behind, they note that the current standard is to remove both ovaries and fallopian tubes. This latest research points to the importance of the fallopian tubes in ovarian carcinogenesis and is providing "invaluable etiologic and clinical leads that promise to refine and improve both the prevention and management of ovarian cancer," they write.

Leading Cause of Gynecologic Cancer Deaths

Although relatively rare in the United States, ovarian cancer affects about 22,280 women each year and represents the leading cause of gynecologic cancer deaths. Ovarian cancer also ranks as the fifth leading cause of cancer-related deaths among women worldwide, according to background information in the article. Although the cure rates of early-stage disease are high, at diagnosis, most women already have late-stage disease, contributing to an overall 5-year survival of 43.8%. Limited screening options exist and are associated with increased morbidity.

The accepted view has been that ovarian cancer arises from the ovarian surface epithelium. Recent evidence, however, has suggested that 10% to 15% of fallopian tubes removed from women with BRCA1/2 mutations have precursor lesions, whereas the ovaries do not. Fifty percent to 60% of women without a genetic predisposition who developed sporadic ovarian cancer also have early tubal lesions and carcinomas. Genetic mutations and characteristics of early fallopian tube lesions lend further support to the fallopian tube origin of ovarian cancer. Moreover, studies have "consistently" found that tubal ligation reduces ovarian cancer risk by 50%, Dr. Daly and colleagues write.

Although current rates of BSOR in the United States are unknown, some clinicians may already perform the procedure. A recent survey quoted in the review article suggest that about 60% of physicians may counsel women undergoing hysterectomy about the benefits of the approach, and about 54% may perform the procedure.

"Because the idea [of BSOR] is so new, we have no data on how effective it is and what risks may be associated with it," Dr Daly commented. "Some surgeons are now doing it on a case-by-case basis if a woman strongly desires that option. That requires a frank discussion with the patient about our lack of data at this point."

Before the new BSOR approach could become the standard of care, the safety and effectiveness of it need evaluation, Dr Daly stressed.

"We have a window of time in which to develop protocols and document outcomes, which we should definitely capitalize on, before this becomes a standard approach," she concluded.

Dr Daly and colleagues called for a national cohort study and a consortium of physicians who would work to create a registry about the use of BSOR in women at genetic risk for ovarian cancer and as part of standard hysterectomy in women at average risk.

The authors and editorialists report no conflicts of interest.

Cancer Prev Res. 2015;8:1-7. Abstract, Editorial

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