What is the relationship between oral contraceptives (OCs) and breast cancer risk?

Oral Contraceptives and Breast Cancer Risk

Current or recent oral contraceptive use is associated with a small but measurable increase in breast cancer risk (relative risk 1.2-1.6), but this risk disappears completely within 10 years of discontinuation, and the absolute risk remains very low in young women despite elevated relative risks. 1, 2

Magnitude and Timing of Risk

For current users, the evidence consistently demonstrates:

• Relative risk of approximately 1.24-1.31 for current users compared to never-users 1, 2
• More recent data shows relative risk of 1.08 for current users 1
• Risk increases with duration: women using oral contraceptives for >5 years show relative risks of 1.33-1.56 3, 4
• The risk elevation is confined to active use and resolves within 10 years after stopping 1, 2

Critical temporal pattern: The FDA label confirms that among current or recent users (<6 months since last use), relative risks range from 1.19 to 1.33, with longer duration of current use showing relative risks up to 1.4 with more than 8-10 years of use 2. However, five studies comparing ever-users (current or past) versus never-users found no association, with effect estimates ranging from 0.90 to 1.12 2.

Age-Specific Considerations

Young women face the highest relative risk but lowest absolute risk:

• Women under 34 years have the highest relative risk increase, though baseline breast cancer incidence remains extremely low 1
• A relative risk of 1.5 in a 25-year-old translates to minimal absolute risk increase given breast cancer rarity at that age 1
• Women aged 40-49 who used oral contraceptives for ≥5 years may have persistent risk for up to 9 years after discontinuation, though this was based on older high-dose formulations (≥50 mcg estrogen) 2

Special Populations: Family History and BRCA Carriers

Women with family history or BRCA mutations can use oral contraceptives:

• Current evidence shows women with family history do not have significantly amplified breast cancer risk with oral contraceptive use 1, 5, 6
• The NCCN states that oral contraceptive use is acceptable for contraception in BRCA carriers, with the risk/benefit ratio uncertain due to contradictory evidence 3
• Meta-analyses show no significant association between oral contraceptive use and breast cancer risk in BRCA1/2 carriers 3
• One case-control study found modest increased risk in BRCA1 carriers (OR 1.20) with ≥5 years use (OR 1.33), particularly before age 40 (OR 1.38) 3
• Another study found increased risk in BRCA2 carriers with ≥5 years use (OR 2.06) 3
• Conversely, one study found low-dose oral contraceptives decreased breast cancer risk in BRCA1 carriers (OR 0.22) 3

The substantial ovarian cancer benefit must be weighed: Oral contraceptives reduce ovarian cancer risk by 45-60% in BRCA1/2 carriers, with risk decreasing further with longer duration of use 3, 5

Absolute Contraindications

Do not prescribe oral contraceptives in these situations:

• Current breast cancer (Category 4 - unacceptable health risk) because breast cancer is hormonally sensitive and prognosis may worsen 1, 2
• Past breast cancer with <5 years disease-free (Category 3 - risks usually outweigh benefits) 1
• Smokers aged ≥35 years (Category 4 due to cardiovascular risks, not breast cancer) 1, 7

Formulation-Specific Risks

Certain progestin formulations show higher associations:

• Levonorgestrel in triphasic regimens: RR 2.83 4
• Levonorgestrel in extended cycle regimens: RR 3.49 4
• Norgestrel in monophasic regimens: RR 1.91 4
• No significant associations observed for norethindrone, norethindrone acetate, ethynodiol diacetate, desogestrel, norgestimate, or drospirenone, though sample sizes were limited 4

Balancing Cancer Risks and Benefits

Oral contraceptives provide significant cancer protection:

• Endometrial cancer risk significantly reduced 1
• Ovarian cancer risk reduced by approximately 50% in general population 1
• Colorectal cancer risk may be reduced by about 20% 1

Clinical Decision Algorithm

1. Exclude absolute contraindications: Current breast cancer or breast cancer within past 5 years 1, 2

2. Assess cardiovascular risk factors: Age ≥35 with smoking, hypertension, diabetes, or cardiovascular disease significantly increases VTE, MI, and stroke risk beyond breast cancer concerns 1, 7

3. For women with family history or BRCA mutations:

   • Provide genetic counseling and testing if not already done 3, 5
   • Oral contraceptives are acceptable given no consistent evidence of amplified breast cancer risk and substantial ovarian cancer protection 1, 5
   • Consider low-dose formulations which may have more favorable risk profiles 3

4. For women over 40 without risk factors:

   • Combined oral contraceptives are Category 2 (benefits generally outweigh risks) 1, 7
   • Consider progestin-only methods or copper IUD as Category 1 alternatives 7

5. Counsel on temporal risk pattern: Emphasize that any increased breast cancer risk resolves within 10 years of stopping 1, 2

Common Pitfalls to Avoid

• Do not overestimate absolute risk in young women: Despite relative risks of 1.5-2.0, the absolute risk increase is minimal given low baseline breast cancer incidence at younger ages 1
• Do not assume permanent risk: Risk elevation is confined to current/recent use and disappears within 10 years of cessation 1, 2
• Do not unnecessarily restrict in women with family history: Evidence does not support significantly amplified risk in this population 1, 5, 6
• Do not overlook ovarian cancer benefit: When focusing solely on breast cancer risk, the substantial 50% ovarian cancer risk reduction may be overlooked, particularly critical in BRCA carriers 5
• Do not use older data to counsel patients: Studies from the 1970s used high-dose formulations (≥50 mcg estrogen); current low-dose formulations have different risk profiles 2