The protective benefits of oral contraceptive pills have long been recognized, Dr. Galina Lurie and her associates note in their report, published in the March issue of Obstetrics & Gynecology. However, over the last 30 years the doses of hormone have decreased to reduce the frequency of side effects. Research conducted to determine how the potency changes have affected ovarian cancer risk has yielded inconsistent results.

To clarify these issues, Dr. Lurie’s group conducted a population-based case-control study in Hawaii and Los Angeles. Included were 745 women diagnosed with epithelial ovarian carcinoma between 1993 and 2005. The 943 randomly selected control subjects were matched to cases by age and ethnicity.

Data were collected by standard questionnaires, and interviewers used photo albums to help subjects identify the specific oral contraceptive pills they had used.

The researchers defined the estrogen potency by the dose of ethinyl estradiol equivalents. Progestational activity was expressed in milligrams of norgestrel equivalent. The cutoff point between high and low estrogen potency was 0.035 mg of ethinyl E2 equivalents; for progestin, it was 0.3 mg of norgestrel equivalents.

Overall, use of oral contraceptive pills was associated with a 50% reduction in risk of epithelial ovarian cancer, the investigators report.

However, compared with never-users, the odds ratio for ovarian carcinoma was 0.62 for subjects using high estrogen and high progestin formulations compared with 0.19 for those taking pills with low potency for both hormones.

“Up to 42% of ovarian cancers might have been avoided if all women used some form of combined oral contraceptive pills,” Dr. Lurie and her associates indicate. “An estimated 73% of ovarian cancers might have been avoided if all women used oral contraceptive pill formulation of low estrogen and low progestin.”

The researchers also evaluated the relationship between use of a single progestin, norethindrone, and ovarian cancer risk among 76 cases and 129 controls. The odds ratios ranged from 0.13 for women who used 0.4 or 0.5 mg norethindrone, to 0.89 for those who used 2 mg daily. However, among women who used 10 mg daily, the risk of ovarian cancer was actually increased (odds ratio, 1.23).

“We identified a tumor vascular cell profile of ovarian cancer that was distinct from the vascular profile of normal ovary and other tumors,” report Dr. George Coukos from University of Pennsylvania, Philadelphia and colleagues in the March 1st issue of the Journal of Clinical Oncology.

Using immunohistochemistry-guided laser-capture microdissection and gene expression profiling, they identified 70 genes as potential tumor vascular markers that were differentially expressed in vascular cells from 21 human epithelial ovarian cancer and 4 healthy ovaries.

“From the cancer vascular profile, we validated 12 novel tumor vascular markers and demonstrated that three tumor vascular markers have prognostic value,” the team reports.

“Several of these could function as tumor biomarkers or therapeutic targets; they were expressed at high levels in ovarian cancer and were either absent or expressed at significantly lower levels in normal tissues,” Dr. Coukos and colleagues point out.

Importantly, they discovered that overexpression of any one of three ovarian tumor vascular markers by vascular cells correlated significantly with reduced disease-free survival (all p < 0.005).

Some of the ovarian tumor vascular markers identified were expressed by a variety of other tumor types, which suggests that they may have prognostic potential outside of ovarian cancer. Additional studies are needed to determine the clinical relevance of the biomarkers identified, the investigators conclude.

Although oncologists have traditionally recommended total abdominal hysterectomy for women with ovarian cancer, the authors explain, many oncologists now recommend supracervical hysterectomy for those who will receive intraperitoneal chemotherapy because it may limit vaginal leakage of the chemotherapeutic agents.

Dr. Pedro T. Ramirez from University of Texas M. D. Anderson Cancer Center, Houston, and associates compared clinical outcomes in 47 women who underwent supracervical hysterectomy and 190 women who underwent total abdominal hysterectomy for advanced ovarian cancer.

Although intraoperative complications did not differ between the two groups, the authors report, a greater proportion of women who underwent total abdominal hysterectomy had optimal tumor cytoreduction (64.7% versus 30% for supracervical hysterectomy).

The two groups did not differ significantly in progression or rates of recurrence, vaginal bleeding, vaginal discharge or and dysuria during follow-up.

Overall survival and progression-free survival also did not differ in the two groups, the researchers note.

There were no difficulties in physical examinations due to the presence of the cervical stump in the supracervical hysterectomy group and fewer cases of tumor erosion into the vagina compared with the total abdominal hysterectomy group.

“At present, supracervical hysterectomy is not routinely performed or recommended at M. D. Anderson Hospital,” the investigators note. “However, supracervical hysterectomy may merit further consideration given the findings of our present study and the recent findings of improved survival in patients treated with intraperitoneal chemotherapy for ovarian cancer.”

“The option of supracervical hysterectomy should be reviewed with patients preoperatively during a discussion of potential indications for and benefits of different surgical techniques,” the researchers conclude.

The findings suggest that a single definition of years of ovulation may not be suitable for gauging the impact of ovulation on ovarian cancer risk, the authors note.

Dr. Claudio Pelucchi, from Istituto di Richerche Farmacologiche “Mario Negri” in Milan, Italy, and colleagues analyzed data from two case-control studies to determine the impact of various anovulatory factors on ovarian cancer risk. Data from 1822 confirmed cases and 4631 controls were included in the analysis.

Consistent with previous research, as lifetime ovulatory cycles increased, so did the risk of ovarian cancer, the report indicates. For example, compared with women in the lowest quartile of lifetime ovulatory cycles, those in the second, third, and highest quartiles were 60%, 65%, and 81% more likely, respectively, to have ovarian cancer.

One year of anovulation cut the risk of ovarian cancer by 2.5% in general, but the reason for lack of ovulation affected the risk reduction. If the anovulatory year was related to parity, abortion, or oral contraceptive use, the risk fell by 9%, 10%, and 8%, respectively; if the reason was age at menarche or age at menopause, the risk reduction was 1%, and 3%, respectively.

“Parity and oral contraceptive use provided a stronger protective effect than expected for anovulatory action alone,” Dr. Pelucchi and colleagues conclude. “The influence of full-term pregnancy, which implies approximately 1 year of anovulation, was much stronger than that of a year delay of age at menarche or a year anticipation of age at menopause, which indicates that similar anovulation-related factors have different impacts on ovarian cancer risk.”

High numbers of ovulatory cycles combined with a family history of ovarian/breast cancer, raised the risk of ovarian cancer by 3.27-fold, the researchers note.

“When patients with cancer are nearing the end of life, they need to made as comfortable and free of pain as possible,” Dr. Sharon J. Rolnick, of HealthPartners Research Foundation, Minneapolis, Minnesota, and colleagues write. “Yet, research indicates that medical care is not always optimal; many such patients are undertreated and thus suffer significant and unnecessary pain … despite the availability of analgesic drug therapies and treatment protocols.”

In their study, the researchers examined medication use for pain management during the last 6 months of life in 421 women who died of ovarian cancer, using data from three large health maintenance organizations.

Medications used during the last 6 months of life were obtained from pharmacy databases. Each medication was categorized based on the World Health Organization classification for pain management (step 1, mild; step 2, moderate; and step 3, intense).

As the women approached death, the intensity of medication increased (p < 0.001), the investigators found.

Fifty-five percent of women were either on no pain medication or were taking a step 1 medication at 5-6 months before death. Only 9% were using step 3 medications at this point. At 3-4 months before death, 22% of women were using the highest intensity regimen, and this increased only to 54% of women at 1-2 months before death.

The researchers report that older women were less likely to be prescribed the highest intensity medication. Overall, 44% of women aged 70 and older were on step 3 medications at the end of life, compared with 70% of women under age 50 years (p < 0.001).

The use of high intensity medications did not differ by race, marital status, stage at diagnosis, or comorbidity.

The team says the findings indicate “room for improvement” in end-of-life care in this patient population.

“Because it is often possible to alleviate pain as one approaches death, it is essential that adequate assessment takes place so that suffering can be reduced,” Dr. Rolnick and colleagues point out. “Taking time to communicate with the patient is important to provide the opportunity for this evaluation, as is giving the patient permission to relay this information,” they add.

Even so, “Achieving appropriate pain management … remains a challenge.”

Even though standard therapy for all cases of ovarian cancer is supposed to include lymphadenectomy, many of the 25% of cases diagnosed with early stage disease fail to undergo a complete staging procedure, Dr. John K. Chan and associates note in their report, published in the January issue of Obstetrics and Gynecology.

To assess the potential therapeutic benefits of lymph node dissection in these patients, Dr. Chan, from Stanford University School of Medicine, and associates in California examined the records of 6,686 women with stage I invasive ovarian cancer diagnosed between 1988 and 2001.

The investigators observed that only 42.8% of patients had a lymphadenectomy. When the procedure was performed, the median number of nodes resected was 9 (range 1-84).

Characteristics associated with significantly higher likelihood of undergoing a lymphadenectomy included age < 50 years, non-African race, residence in the western region of the US, having a clear-cell cancer, and diagnosis in the most recent time period (between 1998 and 2001) (p < 0.001 for each).

Overall, 5-year disease specific survival was 92.6% for those who underwent removal of lymph nodes versus 87.0% for the remainder (p < 0.001). Significant improvements in survival were noted for women age 50 or older, Caucasian women, and those with non-clear cell epithelial ovarian cancer. The authors note that women of other races experienced similar benefit, but the differences did not attain statistical significance.

The outcomes for other types of ovarian cancer – clear cell, sarcoma, germ cell and sex cord stromal tumors – were not affected significantly by lymphadenectomy.

Dr. Chan’s group suggests several ways that lymphadenectomy may help. It may be that patients receive more accurate staging and hence more appropriate adjuvant treatment.

Another possibility is that, even though metastatic lymph nodes were not observed, micrometastatic disease may have been removed. Or it may be that “the removal of resistant clones of cells and regions of poor blood supply” provides the survival benefit, “rather than a dramatic reduction in tumor volume.”

“Without the explicit ability to prove that an ovarian tumor is benign preoperatively or during surgery, consultation with a physician with advanced training in gynecologic cancer surgery should be considered,” Dr. Chan and his colleagues conclude, “because our data suggest that women with stage I non-clear cell epithelial ovarian cancers who underwent lymphadenectomy had a significant improvement in survival.”

The researchers, from the Queensland Institute of Medical Research in Brisbane, Australia, examined factors potentially linked to ovarian inflammation, including talcum powder use, endometriosis, and pelvic inflammatory disease (PID), in 1576 women with invasive and low malignant potential (LMP) ovarian tumors and 1509 population-based controls.

The use of talcum powder in the pelvic region was associated with a significant increase in the risk of all types of ovarian cancer combined (adjusted odds ratio (OR) = 1.17). The increased risk was strongest for serous and endometrioid tumors although it was only statistically significant for serous tumors (OR = 1.21 and 1.18, respectively).

No associations were observed between PID, HPV infection, or mumps and the risk of ovarian cancer overall.

“A reported history of genital herpes was not associated with the risk of all subtypes of ovarian cancer combined (OR = 1.17),” Dr. Webb’s team reports. “However, a significant positive association was seen with risk of serous tumors, with similar nonsignificant increases observed for both invasive and LMP serous tumors.”

As in other studies, a history of endometriosis was associated with an increased risk of endometrioid and clear cell subtypes (OR = 1.85 and 2.66, respectively).

“Overall we conclude that chronic inflammation does not play a major role in the development of ovarian cancer,” the investigators state.

“These findings are encouraging news for BRCA mutation carriers,” senior author Dr. Siegal Sadetzki, from Chaim Sheba Medical Center in Tel Hashomer, Israel, said in a statement. “It’s possible that patients with these mutations respond better to chemotherapy. Hopefully, once we learn more about the mechanisms of this response, tailoring treatment will further improve survival.”

The findings stem from a study of 605 Ashkenazi ovarian cancer patients, including 213 (35.2%) with a mutation in the BRCA1/2 genes. The clinical features for each patient were assessed through medical record review.

With a median follow-up period of 6.2 years, the median survival period for mutation carriers was 53.7 months, significantly longer than the 37.9 months noted for noncarriers (p = 0.002).

The overall 5-year survival rate for the entire study group was 39%, the researchers found; it was 46.0% for mutation carriers versus 34.4% for noncarriers.

The mutation-based differences in 5-year survival were most dramatic for women diagnosed with advanced disease (38.1% for carriers vs. 24.5% for noncarriers) and for those with poor grade disease (45.4% for carriers vs. 31.5% for noncarriers), the authors note (p < 0.001 for both). Both differences remained statistically significant after accounting for age at diagnosis, tumor grade, and morphology.

Further analysis indicated that carriage of either BRCA1 or BRCA2 mutations conferred a survival benefit relative to noncarriage, Dr. Sadetzki’s team reports.

“The current study confirms that among Ashkenazi ovarian cancer patients, BRCA1/2 mutations are associated with improve long-term survival. This may be a result of distinct clinical behavior and/or a better response to chemotherapy,” the investigators conclude.