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Use of oral contraceptives may increase risk of breast cancer, although the overall absolute increase was relatively small, according to a study from Denmark.

Current and recent hormonal contraceptive users reported an increased risk for breast cancer versus those who never used hormonal contraceptives (relative risk 1.20, 95% CI 1.14-1.26), reported Lina S. Mørch, PhD, of the University of Copenhagen, and colleagues.

Duration of use also contributed to associated breast cancer risk. Women who used any form hormonal contraception for more than 10 years (1.38, 95% CI 1.26-1.51) had a higher risk compared to those who reported less than 1 year of use (1.09, 95% CI 0.96-1.23)(P=0.002), they wrote online in the New England Journal of Medicine.

However, the overall absolute increase for breast cancer cases was relatively small, marked by an increased of around one new breast cancer case per 7,690 current and recent users of hormonal contraception (13 per 100,000 person-years, 95% CI 10-16).

Mørch explained to 番茄社区 that "there was a lack of evidence on contemporary hormonal contraception and risk of breast cancer. In particular the knowledge of risk with newer progestins was sparse."

The prospective study included a cohort of 1,797,932 women from Denmark ages 15-49, participating in The Danish Sex Hormone Register Study. Exclusion criteria included women with venous thromboembolism, history of cancer excluding nonmelanoma skin cancer, and a history of infertility treatment.

Breast cancer data was collected from the Danish Cancer Registry. Data on hormonal contraceptive use was collected from prescription information in the National Register of Medicinal Product Statistics. "Recent use" was defined as a discontinuation of hormonal contraceptives within 6 months prior, while "previous use" was classified as discontinuation of use beyond 6 months prior, each based upon date of prescription purchase.

For current or recent use of oral contraceptives, relative risk for breast cancer varied among specific types of combined ethinyl estradiol (20-40 µg) prescriptions, after adjustment for age, year, education level, polycystic ovary syndrome history, endometriosis, parity, and familial female-related cancer history:

• Norethisterone: adjusted RR 1.09 (95% CI 0.80-1.50)
• Levonorgestrel: 1.33 (1.20-1.48)
• Norgestimate: 1.22 (1.20-1.48)
• Desogestrel: 1.12 (1.01-1.25)
• Gestodene: 1.20 (1.11-1.30)
• Drospirenone: 1.05 (0.86-1.28)
• Cyproterone: 1.44 (1.15-1.81)
• Estradiol valerate and dienogest: 1.62 (0.77-3.41)

Non-oral combined hormonal contraception options, including the patch and vaginal ring, reported a slightly lowered adjusted relative risk for breast cancer for recent and current users (0.85, 95% CI 0.21-3.41 and 0.97, 95% CI 0.62-1.50; respectively).

Oral progestin-only products showed a similar associated risk compared to their combined ethinyl estradiol counterparts:

• Norethisterone: aRR 1.00 (95% CI 0.80-1.25)
• Levonorgestrel: 1.93 (1.18-3.16)
• Desogestrel: 1.18 (0.87-1.60)

The non-oral progestin-only levonorgestrel-releasing intrauterine system also showed an adjusted relative risk increase for breast cancer (1.21, 95% CI 1.11-1.33).

Mørch told 番茄社区 that she was not surprised by these findings. "Prior studies have shown similar findings. However, the risk also with newer progestins was more consistent and convincing than expected, in particular the increased risk with hormone IUD (includes only progestin)."

"The increased risk also with newer progestins in hormonal contraceptives has not been shown consistently before, though progestins in postmenopausal therapy has also been found to increase the risk of breast cancer," she added.

In an , David J. Hunter, MB, BS, ScD, of the University of Oxford in England, applauded the researchers for confirming the findings of previous literature in this area with a "much larger sample size." However, he noted that the clinical implications of this study "must be placed in the context of the low incidence rates of breast cancer among younger women," pointing out that most of the new breast cancer cases occurring in the study were among women using oral contraceptives over the age of 40.

He also added the risks associated with hormonal contraception must be weighed against the benefits. "Beyond the fact that they provide an effective means of contraception and may benefit women with dysmenorrhea or menorrhagia, the use of oral contraceptives is associated with substantial reductions in the risks of ovarian, endometrial, and colorectal cancers later in life," he wrote, highlighting this further emphasizes the need for a new form of hormonal contraceptive that does not carry an associated breast cancer risk.

Mørch said that "knowledge is needed on the potential beneficial influence of newer contraceptives on the risk of ovarian and colorectal cancer, since evidence currently relates to older types of hormonal contraceptives."