Ovarian Cancer Doesn’t Begin in the Ovaries, Researchers Say

Ovarian cancer begins with lesions in the fallopian tubes, which if treated early could prevent the cancer from spreading, researchers say

A growing body of evidence suggests that ovarian cancer begins in the fallopian tubes and not the ovaries, giving researchers hope for developing better strategies to prevent and detect the deadly cancer.

Among women with cancer, ovarian cancer is the fifth-leading cause of death, killing 14,000 American women a year. With no real way to screen for it, it usually isn’t diagnosed until it has spread and is in the later stages.

Two studies published last fall in the journal Nature Communications focused on high-grade serous ovarian cancer, the most common and serious type.

Douglas Levine, director of gynecologic oncology at the Perlmutter Cancer Center at NYU Langone Health in New York City, with co-researchers examined precursor lesions, which are an abundance of abnormal cells, and the genetic profiles of tumors from 96 women with ovarian cancer.

Researchers compared ovarian cancer tumors with tissue from healthy women’s fallopian tubes, ovaries and abdominal lining and found the cancer cells were most similar to the fallopian tube tissue. Abnormal cells leave the fallopian tube and shed onto the ovary, progressing from precancer cells to cancer. They then took collections of tissue from a separate group of healthy women and looked at their fallopian tubes, ovaries and the lining inside the abdomen. They developed molecular bar codes, or “signatures,” to see which tissue the cancerous cells were more genetically similar to. The finding in almost every case, the cancerous cells were most similar to the fallopian tube tissue. “Ovarian cancer really comes from the fallopian tube,” says Dr. Levine. “Technically it’s fallopian tube cancer even though we’re not going to change the name.”

About 15% to 20% of ovarian cancers are inherited. Women who test positive for genetic mutations in the BRCA1 and BRCA2 genes have an increased risk of developing ovarian cancer.  For such women, because there is no way to screen for ovarian cancer doctors usually recommend preventive surgery between ages 35 and 40, when a woman has decided to have no more children or 10 years before the earliest ovarian cancer death in her family. The surgery entails removing the ovaries and fallopian tubes, resulting in premature menopause.

Given that the average age of menopause is 52, going through it 12 or more years early can significantly reduce a women’s quality of life, experts say.

Dr. Levine is part of a clinical trial led by researchers from MD Anderson Cancer Center in Houston that is comparing the standard treatment, removing ovaries and fallopian tubes at the same time, with an experimental treatment, removing only the fallopian tubes followed years later by the ovaries.

Karen Lu, senior vice president and chief clinical officer at MD Anderson Cancer Center in Houston and lead investigator of the clinical trial, said, “Surgical menopause is no walk in the park.”

“It’s a much more rapid decrease in estrogen,” she says. That can result in rapid onset of symptoms such as night sweats and hot flashes. Some symptoms can be counteracted with hormone replacement therapy. But many women surveyed have complained of a decrease in sex drive, she says.

“What our advocates really said was that the quality of life factor that mattered most was the decreased sex drive,” says Dr. Lu.

Researchers will evaluate several quality of life measures from 270 women in the study, including sex drive and menopausal symptoms. They also are looking at the number of cancers that develop in each group to evaluate the risk of developing cancer.

Carla Valencia, a 41-year-old who lives in New York City, is among the trial participants who opted for removals of just her fallopian tubes.

She tested positive for the BRCA1 gene mutation after her mother was diagnosed with ovarian cancer. She ended up getting a preventive double mastectomy about seven years ago.

After she turned 40, she started thinking about getting preventive surgery for ovarian cancer. “Initially I was looking at removing the ovaries but then as I did research I saw that the early onset of menopause can cause so many things,” Ms. Valencia said. “So I decided do the fallopian tubes now and give myself some time before I do the ovaries.”

In the second study in Nature Communications, Victor Velculescu, professor of oncology and co-director of Cancer Biology at the Johns Hopkins University School of Medicine, with co-researchers examined multiple tumor samples from women with high-grade serous ovarian cancer.

They looked at small lesions in the fallopian tube; fallopian tube tumors; ovarian cancers; and metastases, which are tumors that have spread. They sequenced the genomes of the tumors from each individual to identify the order in which the lesions arose.

They estimate that seven years elapsed between development of the early fallopian tube lesions and ovarian cancer. Then, within a year, the cancer quickly spread.

“If we can catch these lesions early, we can intervene before the cancer metastasizes,” Dr. Velculescu said. The researchers are trying to confirm their findings on a larger scale and see if women with other subtypes of ovarian cancer show the same pattern, Dr. Velculescu said.

Britton Trabert, an investigator in the metabolic epidemiology branch of the National Cancer Institute, part of the National Institutes of Health, said evidence of the fallopian-tube origin of ovarian cancer is compelling but hasn’t been “reproduced universally,” for all kinds of ovarian cancer in all kinds of women.

“It’s definitely looking in that direction, but in terms of going to the next step and saying you can remove the tubes and not the ovaries, I think that’s a stretch,” Dr. Trabert said. “It’s a great hypothesis that will help us understand a lot” about the origins of ovarian cancer, she added. “But I don’t think it’s going to explain everything.”


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