Every 5-year increase in duration of oral contraceptive use was associated with about a 13% decrease in the risk of invasive ovarian cancers, and this protective effect persisted for all histologic subtypes except mucinous tumors, according to results of a meta-analysis.

“Oral contraceptives continue to be an important preventive factor for most types of ovarian cancer. Few other risk factors for ovarian cancer are modifiable, and those that are, such as smoking and obesity, did not show clear associations with serous carcinomas, the most common and fatal subtype,” Dr. Nicolas Wentzensen of the National Cancer Institute and his associates wrote June 20 in the Journal of Clinical Oncology.

Ovarian cancer is heterogeneous and its etiology poorly understood. Power limitations have prevented individual studies from parsing risk factors for distinct ovarian cancer histotypes, the researchers added. To solve this issue, they examined links between 14 different hormonal, reproductive, and lifestyle characteristics and histologic subtypes of tumors in the Ovarian Cancer Cohort Consortium .

Their analysis included 5,584 invasive ovarian cancers from more than 1.3 million women enrolled in 21 prospective studies (J Clin Oncol. 2016 Jun. doi: 10.1200/JCO.2016.66.8178).

Patients who reported having ever used oral contraceptives were about 16% less likely to develop any type of invasive epithelial ovarian cancer, compared with those who had never used oral contraceptives (relative risk, 0.84; 95% confidence interval, 0.79-0.89). Associations were similar for high-grade serous, endometrioid, and clear cell histotypes, although OC use did not appear to protect against mucinous tumors, the researchers wrote.

Some of the strongest associations were for endometrioid and clear cell carcinomas, they noted. For example, the risk of endometrioid carcinoma fell by about 22% for every birth (RR per birth, 0.78; 95% CI, 0.74-0.83), and the risk of clear cell carcinoma fell by about 32% per birth (RR, 0.68; 95% CI, 0.61-0.76).

“Likewise, age at menopause, endometriosis, and tubal ligation were associated only with clear cell and endometrioid tumors,” the researchers wrote.

Smoking was tied to a higher risk of mucinous tumors (RR per 20 pack-years, 1.20; 95% CI, 1.04-1.39) but was associated with a lower risk of clear cell tumors (RR, 0.68; 95% CI, 0.53-0.89).

“The substantial heterogeneity of individual risk factor associations across ovarian cancer subtypes [suggests] that subtypes are indeed different diseases, and underscores the importance of evaluating risk factors and biomarkers by ovarian cancer subtypes,” the researchers concluded. “Due to weaker associations observed for high-grade serous carcinomas, prediction of the clinically most important subtype may perform worse than for other types, which underscores the importance of finding better risk factors for serous carcinomas.”

The consortium plans to search for more tumor predictors by analyzing circulating biomarkers and genetic data.

Dr. Wentzensen reported having no financial disclosures. Other researchers reported financial relationships with GlaxoSmithKline and Cepheid.


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