Endometriosis Linked to Certain Subtypes of Ovarian Cancer

Roxanne Nelson

February 21, 2012

February 21, 2012 — A new study has defined the histologic subtypes of endometriosis that are associated with an increased risk for invasive epithelial ovarian cancer. Specifically, a history of endometriosis is only associated with an increased risk for invasive low-grade serous, clear-cell, and endometrioid ovarian cancer.

A pooled analysis published online today in the Lancet Oncology has shown that endometriosis is linked to a more than 3-fold chance of developing clear-cell ovarian cancers, and more than double the risk of developing endometrioid tumors.

No association was observed between endometriosis and the risk for high-grade serous or invasive ovarian cancer, or borderline tumors of either type.

Identifying an association between particular histologic subtypes and not others adds weight to the increasing evidence that these histologic subtypes are distinct disease entities, writes Charlie Gourley, MB ChB, PhD, in an accompanying comment.

"There is still much to learn about the cellular origins and molecular basis of these distinctions, but identification of the subtypes affected by processes like endometriosis should help in the task of detailing the process and developing strategies to allow successful prevention or treatment," writes Dr. Gourley, who is a reader and honorary consultant in medical oncology at the University of Edinburgh Cancer Research Centre, United Kingdom.

How these results are applicable to screening programs is still unclear.

Lead investigator of the pooled analysis, Celeste Leigh Pearce, MD, assistant professor in the Department of Preventive Medicine at the Keck School of Medicine, University of Southern California, Los Angeles, said in a statement: "This breakthrough could lead to better identification of women at increased risk of ovarian cancer and could provide a basis for increased cancer surveillance of the relevant population, allowing better individualization of prevention and early detection approaches such as risk-reduction surgery and screening."

However, in his comment, Dr. Gourley notes that the increased risk for epithelial ovarian cancer seen in the study is "perhaps not in itself sufficient to justify targeted ovarian cancer screening of patients with a history of endometriosis," But, he adds, the fact that some of the associated histologic subtypes predominantly present at an early stage make screening a consideration.

These data reaffirm the necessity to be vigilant.

"Additionally, the extent of this increased risk and the predominantly associated lesions have implications for the multidisciplinary team when they come to assess lesions of uncertain cause in a patient with a history of endometriosis," he writes. "These data reaffirm the necessity to be vigilant for the possibility that invasive disease might be present."

Linked to 2 Subtypes Only

The analysis by Dr. Pearce and colleagues was an international collaborative effort; it pooled data from 13 ovarian cancer case–control studies that were part of the Ovarian Cancer Association Consortium. Cases were analyzed for histologic subtype, grade, and stage, and patient age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models.

The cohort consisted of 13,226 control subjects and 7911 women with invasive ovarian cancer. Of this group, 818 (6.2%) of the control women and 738 (9.3%) of ovarian cancer patients reported having a history of endometriosis. In addition, 1907 women had borderline ovarian cancer, with 168 (8.8%) of them reporting a history of endometriosis.

Overall, a history of endometriosis was reported by 136 of 674 (20.2%) women with clear-cell, 169 of 1220 (13.9%) women with endometrioid, 31 of 516 (6.0%) women with mucinous, 261 of 3659 (7.1%) women with high-grade serous, and 31 of 336 (9.2%) women with low-grade serous subtypes of invasive ovarian cancer.

In addition, 103 of 1140 (9.0%) women with borderline serous and 65 of 767 (8.5%) women with borderline mucinous tumors reported having a history of endometriosis.

Confounders, including breast feeding, weight, height, body mass index, tubal ligation, and a family history of ovarian cancer, did not influence the association between cancer risk and endometriosis.

The analysis showed that a history of endometriosis was more commonly reported by patients with invasive clear-cell, serous low-grade, and endometrioid ovarian cancers than in those with invasive serous high-grade or invasive mucinous ovarian cancers (P < .02 for all comparisons). Endometriosis was also more strongly linked to invasive clear-cell ovarian cancer than to the invasive endometrioid subtype (odds ratio [OR], 1.64; P = .001), and was more strongly associated with invasive low-grade than with high-grade serous ovarian cancer (OR, 1.94; P = .01).

The study was funded by multiple international sources, as noted in the paper. The authors and the editorialist have disclosed no relevant financial relationships.

Lancet Oncol. Published online February 21, 2012. Abstract, Comment

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