Monthly Archives: October 2010

Estrogen Replacement Therapy Speeds Growth of ER+ Ovarian Cancer & Increases Risk of Lymph Node Metastasis

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Estrogen therapy used by menopausal women causes “estrogen receptor positive” (ER+) ovarian cancer to grow five times faster, according to a new study being published by researchers at the University of Colorado Cancer Center in the November 1 issue of Cancer Research.

Estrogen therapy used by menopausal women causes so-called “estrogen receptor positive” (ER+) ovarian cancer to grow five times faster, according to a new study being published tomorrow by researchers at the University of Colorado Cancer Center.

Menopausal estrogen replacement therapy (ERT) also significantly increases the likelihood of the cancer metastasizing to the lymph nodes, according to the study, which will be published in the November 1 issue of Cancer Research. The study was released online on Oct. 19, 2010. Cancer Research, published by the American Association for Cancer Research, is the world’s largest (based upon circulation) medical journal devoted specifically to cancer research.

The effect of ERT was shown in mouse models of estrogen receptor positive (ER+) ovarian cancer, which accounts for about 60 percent of all human ovarian cancer cases. Ovarian cancer is one of the deadliest cancers affecting women. This year alone, nearly 22,000 women will be newly diagnosed with ovarian cancer and an estimated 13,850 women will die from the disease, according to the National Cancer Institute.

Monique Spillman, M.D., Ph.D., Gynecologic Oncologist, University of Colorado Hospital; Assistant Professor, Obstetrics & Gynecology, University of Colorado School of Medicine.

“We showed that estrogen replacement substantially increases proliferation and risk of distant lymph node metastasis in ER+ tumors,” says Monique Spillman, M.D., Ph.D., the study’s lead researcher, a gynecologic oncologist at University of Colorado Hospital and assistant professor at of obstetrics and gynecology at the University of Colorado School of Medicine.

For the first time, Spillman and her team measured ovarian cancer growth in the abdomen of mice using novel techniques for visualizing the cancer. In mice with ER+ ovarian cancer cells, which were tagged with a firefly-like fluorescent protein that allowed them to be tracked, the introduction of estrogen therapy made the tumors grow five times faster than in mice that did not receive the ERT. The risk of the cancer moving to the lymph nodes increased to 26 percent in these mice compared with 6 percent in mice that did not receive ERT.

The team also found that the estrogen-regulated genes in ovarian cancer reacted differently than ER+ genes found in breast cancer, helping to explain why current anti-estrogen therapies used with breast cancer, such as tamoxifen, are largely ineffective against ovarian cancer.

“Breast cancer and ovarian cancer are often linked when talking about hormone replacement therapy, but we found that only 10 percent of the ER+ genes overlapped,” Spillman says. “We were able to identify estrogen-regulated genes specific to ER+ ovarian cancer that are not shared with ER+ breast cancers. We believe these genes can be specifically targeted with new anti-estrogen therapies that could more effectively treat ER+ ovarian cancers.”

“Breast cancer and ovarian cancer are often linked when talking about hormone replacement therapy, but we found that only 10 percent of the ER+ genes overlapped.  We were able to identify estrogen-regulated genes specific to ER+ ovarian cancer that are not shared with ER+ breast cancers. We believe these genes can be specifically targeted with new anti-estrogen therapies that could more effectively treat ER+ ovarian cancers.”

— Monique Spillman, M.D., Ph.D., Gynecologic Oncologist, University of Colorado Hospital; Assistant Professor, Obstetrics & Gynecology, University of Colorado School of Medicine.

Spillman and her team now will begin to screen current anti-estrogen therapies against the newly identified ovarian cancer genes to identify the [biological] pathways and compounds relevant to the treatment for ER+ ovarian cancer.

This study looked at the effect of estrogen replacement therapy in mice that already possessed ER+ ovarian cancer cells. It did not test whether the estrogen replacement actually could cause the development of these cancer cells. The study also dealt only with estrogen replacement, which is linked to higher risks of ovarian cancer, not combined estrogen/progesterone therapy that is used with women who retain their uteruses.

This research is too early to draw implications for use of estrogen replacement therapy in women, Spillman cautions. “We cannot make clinical recommendations based on what is happening in mice,” says Spillman, one of just eight gynecological oncologists in Colorado. “Every woman is different and needs to talk to her doctor about the decision to use hormone replacement therapy.”

The study was funded by a Gynecologic Cancer Foundation Career Development Award and the Liz Tilberis Scholars Award from the Ovarian Cancer Research Foundation. This competitive award, a $450,000 three-year grant, is given to early-career researchers who are developing techniques for early diagnosis and improved care for women with ovarian cancer.

About the University of Colorado Cancer Center

The University of Colorado Cancer Center is the Rocky Mountain region’s only National Cancer Institute-designated comprehensive cancer center. NCI has given only 40 cancer centers this designation, deeming membership as “the best of the best.” Headquartered on the University of Colorado Denver Anschutz Medical Campus, UCCC is a consortium of three state universities (Colorado State University, University of Colorado at Boulder and University of Colorado Denver) and five institutions (The Children’s Hospital, Denver Health, Denver VA Medical Center, National Jewish Health and University of Colorado Hospital). Together, our 440+ members are working to ease the cancer burden through cancer care, research, education and prevention and control. Learn more at www.uccc.info.

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Girls with Stage I Ovarian Germ-Cell Tumors Can Safely Skip Chemotherapy Until Recurrence

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Researchers from Dana-Farber/Children’s Hospital Cancer Center found that as many as 50 percent of young girls treated for germ-cell ovarian tumors may be safely spared chemotherapy using a “watch and wait” strategy to determine whether follow-up treatment is needed.

Researchers from Dana-Farber/Children’s Hospital Cancer Center (DF/CHCC) found that as many as 50 percent of young girls treated for germ-cell ovarian tumors may be safely spared chemotherapy using a “watch and wait” strategy to determine whether follow-up treatment is needed.

In contrast to the current practice of administering chemotherapy to all patients following removal of these rare tumors, researchers said the study demonstrated that treatment could safely be delayed and given only when the cancer recurred.

Data from the trial involving 25 young women ages 9 to 16 was presented at the 42nd Congress of the International Society of Paediatric Oncology (SIOP) in Boston on Friday, October. 22.

Lindsay Frazier, M.D., Pediatric Oncologist, Dana-Farber / Children's Hospital Cancer Center; Chair, Germ Cell Tumor Committee, Children's Oncology Group

The study was led by Lindsay Frazier, MD, a pediatric oncologist at DF/CHCC and chair of the Germ Cell Tumor Committee of the Children’s Oncology Group.

“I personally think that not giving chemotherapy to half the patients [women with germ cell ovarian tumors] is a good thing,” said Frazier. “The chemotherapy is just as effective given when the disease recurs. I would recommend that parents consider a watching and waiting strategy.”

Germ cell tumors are malignancies that develop in precursors of sperm cells in boys and egg cells in girls. Some forms of the tumors are most often detected immediately following birth; other types are most common between the ages of 10 and 30.

Previous trials had shown that delaying chemotherapy was safe and effective in Stage 1 germ cell testicular tumors in boys. Over time, 30 percent of the patients developed a recurrence, but they were all cured by chemotherapy.

“So instead of giving 100 percent of them chemotherapy, only 30 percent needed it,” explained Frazier, who said it’s been found that the usual three cycles of chemotherapy administered for the tumors doubles the long-term risk of cardiovascular disease or second cancers.

The current study was undertaken to test a similar watch-and-wait approach in female patients. Frazier said 25 girls with Stage 1 germ cell ovarian tumors were recruited from about 100 medical centers — an indication of the cancer’s rarity. In all cases, the tumors had been completely removed by surgery.

Instead of undergoing chemotherapy immediately, the girls were monitored closely for signs of recurrence. Every three weeks their blood was tested for biochemical markers signifying a regrowth of the cancer, and every three months they were scanned with CT or MRI imaging.

“The median time to relapse was two months, and the latest relapse was at 9 months, so the families were not living with uncertainty for a long time,” Frazier said.

The recurrence rate was 50 percent — higher than in the boys with germ cell tumors — but the delayed treatment was similarly effective though one girl died, yielding a survival rate of 96 percent.

Preventing unnecessary chemotherapy treatment for half of girls with such tumors is still desirable, said Frazier, “because there is evidence that girls are even more susceptible to long-term harm from chemo than boys are.”

The study was supported by the National Cancer Institute.

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