PURPOSE:

• Previous studies looking at hormonal contraception and breast cancer risk often used formulations with higher estrogen doses with conflicting results   
• Current contraceptive methods use lower estrogen doses, new progestins and new routes of delivery  
• Previous studies focused on risks in postmenopausal women 
• Mørch and colleagues (NEJM, 2017) sought to address the above deficiencies and report their findings using a nationwide epidemiologic analysis of prospectively collected data

METHODS:

• Prospective Cohort Study  
• Danish Nationwide Registries  
• Eligibility: Women in living in Denmark prior to 1995: 15 to 49 years of age on January 1, 1995, and were 15 years of age before December 31, 2012 (a total of 1,837,297 women)  
• Exclusion: Women with cancer (except nonmelanoma skin cancer); VTE; infertility treatment  
• Confounders ascertained from national registries 

RESULTS:

Overall Risk of Breast Cancer 

Current or recent users compared to women who never used hormonal contraception .

• Increased Risk of breast cancer: Relative Risk (RR): 1.20 (95% CI, 1.14 to 1.26) 
• Risk increased with duration of use: RR 1.09 (95% CI, 0.96 to 1.23) at < 1 year vs 1.38 (95% CI, 1.26 to 1.51) after > 10 years (P=0.002)  
• Risk remains elevated after ≥5 years but not < 5 years  

Combined oral contraceptives (OCP)  

Little evidence of major differences between various combined oral contraceptives after statistical adjustments for multiple testing 

• Triphasic RR (1.21; 95% CI, 1.04 to 1.41) vs monophasic RR (1.45; 95% CI, 1.26 to 1.67)  levonorgestrel containing OCPs were similar  
• In norethisterone or levonorgestrel containing pills, no differences were seen between doses of 50 μg vs 20 – 40 μg of estrogen  
• When analyses adjusted for the estrogen dose in each product, the RR only remained elevated with gestodene products  
• For OCPs with 20 – 40 μg of estrogen, the risk of breast cancer depended on duration of use, although the effect was only significance for gestodene containing formulations  

LARC  

Levonorgestrel-releasing intrauterine system (LNG-IUD)  

• No significant differences compared to OCPs 
• RR of breast cancer was 1.21 (95% CI, 1.11 to 1.33) 

Contraceptive implants  

• Few breast-cancer events among users of the progestin-only implant and depot medroxyprogesterone acetate 

Subgroup Analyses 

• No strong evidence of different patterns in  
  • Women <35 years of age 
  • Nulliparous women  
  • BMI (data only available for parous women)  
  • Smoking  
  • Age at first birth  
• ‘Suggestion’ that starting hormonal contraceptives < 20 years of age and long duration of use may be associated with increased risk but authors caution that risk estimates were imprecise 

CONCLUSION:

• Authors state:

The difference in the risk of breast cancer between women who had never used hormonal contraception and current and recent users of any type of hormonal contraception was 13 (95% CI, 10 to 16) per 100,000 person-years; approximately one extra breast cancer was diagnosed for every 7690 women using hormonal contraception for 1 year

This risk should be weighed against important benefits of hormonal contraceptives such as good contraceptive efficacy and reduced risks of ovarian, endometrial, and perhaps colorectal cancer

Learn More – Primary Sources:

Contemporary Hormonal Contraception and the Risk of Breast Cancer

Related ObG Topics:

Hormonal Contraception Benefits – Beyond Pregnancy Prevention

CDC Resources: Contraception in Women with Medical Conditions (US MEC)

Is there a Link Between Oral Contraception Use and Cancer Risk?

ACOG & SMFM Guidance on the Use of IUDs and Contraceptive Implants