Is There A Correlation Between Endometriosis And Ovarian Cancer?

From the ERC (www.endocenter.org), posted to their listserv at http://groups.yahoo.com/group/erc:
Endometriosis-ovarian cancer link ‘underestimated’
Source: Human Reproduction 2006; 21: 1237-42
Researchers assess the relative risks of individual cancers over a long period of follow-up among women with endometriosis.
Women with endometriosis appear to be up to twice as likely as the general population to develop ovarian cancer, say researchers.
Co-existence of endometriosis and cancer has been reported several times. One study showed an overall relative risk of 1.2 in women with endometriosis compared with those without it, and risks for ovarian cancer and non-Hodgkin’s lymphoma of 1.9 and 1.8, respectively.
Anna Melin (Karolinska University Hospital, Stockholm, Sweden) and colleagues evaluated whether these risk ratios stood in an extended study. They identified women (n = 64,492) who were discharged from a Swedish hospital with a diagnosis of endometriosis between 1969 and 2000, and assessed their incidence of cancer, using the National Swedish Cancer Register.
Excluding the first year of follow-up, there were 3349 cases of cancer. The overall risk of cancer was no higher than that expected on the basis of the female Swedish population, but ovarian cancer (standardized incidence ratio [SIR] = 1.43), endocrine tumors (SIR = 1.36), non-Hodgkin’s lymphoma (SIR = 1.24), and brain tumors (SIR = 1.22) were all more prevalent.
An even higher risk of ovarian cancer was seen in women with early diagnosed (SIR = 2.01) and long-standing (SIR = 2.23) endometriosis, respectively.
“This study has shown an increased risk of some types of malignancy, above all ovarian cancer, in women with endometriosis,” the researchers conclude.
“The material indicates that the risk might have been underestimated.”
19 April 2006
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Endometriosis & Malignancies
We know that Endometriosis can impact every aspect of our lives, from our interpersonal relationships to our careers; from our ability to have children to our ability to get out of bed in the morning. It can change our views on life and how we think about ourselves - and how we think about others. The consequences of Endometriosis touch every part of us, inside and out, prompting some women to refer to their disease as a “benign cancer.” Can Endometriosis go one step further and actually turn malignant? Can it even place us at risk for certain cancers and other illnesses? Unfortunately, research shows that for some women, it may.
Malignant transformation of Endometriosis can and does occur. Some researchers even estimate that approximately 0.7-1.0% of patients with Endometriosis have lesions that will ultimately undergo malignant transformation, and urge consideration of performing bilateral oophorectomy at the time of abdominal surgery in patients with significant disease.(1)
We have also begun learning of the elevated risks women with the disease have for certain cancers, including non-Hodgkin’s lymphoma. The reasons why remain unclear; however, women with Endometriosis are more likely take certain drugs, such as Progestagens, and are more likely to have had their ovaries or uterus removed, another factor that influences hormone levels and possibly increases cancer risk. One patient undergoing Tamoxifen therapy was discovered to have malignant endometrioid neoplasia arising within her Endometriosis, suggesting to her physicians that the Tamoxifen, as a result of its estrogenic effects, caused proliferative and malignant changes in her disease.(2)
In a similar study targeting women who had undergone hysterectomy with oophorectomy because of Endometriosis, authors noted that “Endometriosis can undergo estrogen-dependent changes similar to the endometrium and may carry a risk of developing hyperplasia and carcinoma during unopposed estrogen stimulation.” The researchers concluded that unopposed estrogen therapy may lead to premalignant or malignant transformation in the residual foci of Endometriosis and encouraged the addition of progestins to estrogen replacement therapy.(3)
It is also possible that women with Endometriosis may be screened more often certain cancers (i.e., breast) and therefore are more likely to be diagnosed. Endometriosis has also been linked to a lack of physical activity and exposure to the environmental contaminant, dioxin. These two factors may be to blame for the cancer risk, rather than Endometriosis itself.
Another link being investigated is the role genetic alterations might play in the development and potentially malignant progression of the Endometriotic lesions.(4)
Age may also be a factor. One study specifically investigating the connection between endometrioid carcinoma of the ovary and Endometriosis in postmenopausal women suggested that ovarian Endometriosis in the postmenopausal patient has the potential to undergo malignant transformation and, when detected, “should be removed surgically.”(5)
Still further overwhelming evidence exists of these malignant transformations and elevated risks. Findings of a survey conducted of over 4,000 Endometriosis patients in the United States and Canada have indicated possible links to other serious medical conditions, including a 9.8% incidence of melanoma, compared with 0.01% in the general population, a 26.9% incidence of breast cancer, compared with 0.1% in the general population and an 8.5% incidence of ovarian cancer, as compared with 0.04% in the general population. Women with Endometriosis who participated in the survey also had a greater incidence of autoimmune conditions and Meniere’s disease.(6)
In a study of 20,686 Swedish women hospitalized for Endometriosis, results showed that the women had a 20% greater risk of developing cancer overall, particularly of the breast, ovaries, blood and lymph cells during an 11-year period. The women actually had a lower risk of cancer of the cervix.(7)
In another study of 79 patients with Stage I epithelial ovarian cancer at Massachusetts General Hospital, evidence of Endometriosis was found in 22 of the 79 cases (28%), leading researchers to conclude that “Endometriosis may play a role in the pathogenesis of some early stage malignant ovarian epithelial neoplasms.”(8) In a similar study,(9) researchers reviewed 147 cases of ovarian Endometriosis to clarify the incidence of malignant transformation. Authors noted that “malignant change in ovarian Endometriosis occurred in 0.7% of this disease.”
While ovarian neoplasms are among the most common malignancies,(10) other sites have been found to undergo malignant changes as well, including clear cell carcinoma arising in an Endometriosis implant in a low abdominal transverse scar,(11) a clear cell carcinoma arising in a cesarean section scar,(12) and even the liver.(13)
These are just a few examples of such accounts. The increase in such findings should encourage surgeons to excise and biopsy Endometriosis - particularly recurrent disease - as malignant transformation can and does occur.(14)
These important research findings are not meant to frighten women with Endometriosis, but rather, to make them aware of the true significance and potential impact of the disease. By knowing the risks, patients can take measures to protect themselves; measures such as a change in their diet/nutrition, stopping (or starting) specific medications, getting regularly screened for concerns other than just Endometriosis, and adopting an overall improvement in their lifestyle habits if necessary. Not every woman with Endometriosis is at an elevated risk for other conditions, nor will she develop such malignancies, but every woman with the disease can take steps to help prevent such transformations and opportunistic illnesses from affecting her.
References:
1) “Endometrial stromal sarcoma of the vulva arising in extraovarian endometriosis: a case report and literature review,” Gynecol Oncol 1998 Nov;71(2):313-6. Irvin W; Pelkey T; Rice L; Andersen W.
2) “Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis in association with tamoxifen therapy,” Int J Gynecol Pathol 2000 Jul;19(3):276-9. McCluggage WG; Bryson C; Lamki H; Boyle DD.
3) “Malignancy arising in extraovarian endometriosis during estrogen stimulation,” Eur J Gynaecol Oncol 1998;19(1):39-41. Gucer F; Pieber D; Arikan MG.
4) “Increased heterogeneity of chromosome 17 aneuploidy in endometriosis,” Am J Obstet Gynecol 1999;180:792-7. Yoshinori Kosugi, MD, Sherman Elias, MD, L. Russell Malinak, MD, Junko Nagata, MD, Keiichi Isaka, MD, Masaomi Takayama, MD, Joe Leigh Simpson, MD, Farideh Z. Bischoff, PhD.”
5) “Endometrioid carcinoma of the ovary and endometriosis: the association in postmenopausal women,” Gynecol Oncol 1992 Oct;47(1):71-5. De Priest PD; Banks ER; Powell DE; van Nagell JR Jr; Gallion HH; Puls LE; Hunter JE; Kryscio RJ; Royalty MB.
6) Endometriosis & Cancer: What is the Connection?” 1999; Duczman, Linda & Ballweg, Mary Lou, 8585 N. 76th Pl., Milwaukee, WI 53223.
7) “Cancer risk after a hospital discharge diagnosis of endometriosis,” Am J Obstet Gynecol 1997;176:572-9. Brinton, Louise A., PhD; Gridley, Gloria, MS; Persson, Ingemar, MD; Baron, John, MD; Bergqvist, Agneta MD, PhD.
“Histologic transformation of benign endometriosis to early epithelial ovarian cancer,” Gynecol Oncol 1996 Feb;60(2):238-44. Sainz de la Cuesta R; Eichhorn JH; Rice LW; Fuller AF Jr; Nikrui N; Goff BA.
9) “Malignant Transformation of Ovarian Endometriosis,” Gynecol Obstet Invest 2000 Oct;50 Suppl S1:18-25. Nishida M; Watanabe K; Sato N; Ichikawa Y.
10) “Ovarian atypical endometriosis: its close association with malignant epithelial tumours,” Histopathology 1997 Mar;30(3):249-55. Fukunaga M; Nomura K; Ishikawa E; Ushigome S.
11) “Clear cell carcinoma arising in extragonadal endometriosis in a caesarean section scar during pregnancy,” Gynecol Oncol 1998 Jul;70(1):127-30. Miller DM; Schouls JJ; Ehlen TG.
12) “Clear cell carcinoma arising in a Cesarean section scar endometriosis: a case report,” J Korean Med Sci (Korea 1999 Apr;14(2):217-9. Park SW; Hong SM; Wu HG; Ha SW.
13) “CT diagnosis of perihepatic endometriosis complicated by malignant transformation,” Abdom Imaging 1998 Mar-Apr;23(2):183-4. Weinfeld RM; Johnson SC; Lucas CE; Saksouk FA.
14) “Vaginal adenosarcoma arising from endometriosis,” Gynecol Oncol 2000 Jan;76(1):123-5. Judson PL; Temple AM; Fowler WC Jr; Novotny DB; Funkhouser WK Jr.