New evidence is suggesting that women who recently used oral contraceptives (OC) containing high-dose estrogen and a few other formulations may have an increased risk for breast cancer.

However, it is too early to make any changes in the recommendations about OC use until further studies are completed.

Researchers at Fred Hutchinson Cancer Research Center in Seattle, Washington, conducted a nested case-control study with 1,102 women aged 20 to 49 years. All of the women were diagnosed with invasive breast cancer between 1990 and 2009.

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They looked at use of contemporary OCs and found that certain formulations were associated with an increased breast cancer risk.1 Overall, the study found that recent use of OCs involving high-dose estrogen, ethynodiol diacetate, or triphasic dosing with an average of 0.75 mg of norethindrone was associated with a particularly elevated breast cancer risk.

Despite these new findings, it may be premature to say women who are cancer survivors or have a family history of breast cancer need to stop using these types of OCs. Research suggests that women who use OCs may have a reduced risk of ovarian and endometrial cancer. It is uncertain just how much the total overall increase in cancer risk may result from individual OC formulations.

“We have debated this issue for a long time. We think the risk is real, but it is very small,” said Kurt Barnhart, MD, of the University of Pennsylvania in Philadelphia, Pennsylvania.

Dr. Barnhart said the current study by Elisabeth Beaber, PHD, MPH, a research scientist at Fred Hutchinson Cancer Research Center, and colleagues1 adds to the growing body of evidence that there is an association between OC use and breast cancer risk.

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However, he also said more research is needed before clinicians can make changes in their prescribing practices. “Their finding of a very small risk with oral contraceptives and breast cancer is important, but likely will not change care. Of note, the risk is very small, if it exists,” Dr. Barnhart told Cancer Therapy Advisor.

“This should certainly not scare women who want to use oral contraceptives for very valid and good reasons. The last thing you want is women to not take their contraceptives and have an unintended pregnancy because they are worried about a potential slight increase in risk.”

The relationship between OC use and breast cancer risk has been extensively studied. However, more recent formulations (synthetic progestins and the extended cycle OCs) are now widely used and have not been closely examined. Dr. Beaber said she and her colleagues utilized electronic pharmacy data, which may have reduced misclassification and allowed for categorizing by formulation. The investigators were able to analyze which OC was prescribed, the dosage, and duration of use.

“The vast majority of other studies used self-reported formulation on information. So, they are asking a woman to recall,” explained Dr. Beaber. “By having pharmacy information, we are able to use a standard use of information and accurately see what prescriptions were filled. So you don’t have a problem with incorrect recall by women.”

Dr. Beaber and her colleagues found that recent OC use increased breast cancer risk by 50% compared with never or former use. They found that OCs containing high-dose estrogen increased breast cancer risk 2.7-fold and OCs containing moderate-dose estrogen increased the risk 1.6-fold. OCs containing ethynodiol diacetate increased the risk 2.6-fold and triphasic combination OCs containing an average of 0.75 mg of norethindrone increased the risk 3.1-fold. However, OCs containing low-dose estrogen did not increase breast cancer risk.1

“The progestins desogestrel and norgestimate in oral contraceptives began to be used in the United States in the late 1980s and drospirenone was introduced in the early 2000s. Given that our study results have not yet been replicated and the importance of assessing both the benefits and risks of OC use, we cannot make any clinical recommendations based on results from this single study,” Dr. Beaber said in an interview with Cancer Therapy Advisor.