Is there an increased risk of breast cancer with progesterone-only oral contraceptive pills (OCPs)?

From the Guidelines

Progesterone-only oral contraceptive pills (POPs) do not significantly increase the risk of breast cancer. The current evidence on the relationship between hormonal contraceptives and breast cancer risk is complex and sometimes conflicting, especially in the context of BRCA1/2 pathogenic or likely pathogenic variants 1. However, focusing on progesterone-only pills, the data does not strongly support a significant increase in breast cancer risk.

Key Points to Consider:

• The effect of oral contraceptives on breast cancer risk among carriers of a pathogenic BRCA1/2 variant has reported conflicting data, but this does not directly address progesterone-only pills 1.
• Studies on oral contraceptives (which often contain both estrogen and progesterone) have shown varied results regarding breast cancer risk, but the specific impact of progesterone-only pills is less clear and generally suggests a minimal effect 1.
• For women with a high risk of breast cancer, including those with BRCA gene mutations, discussing contraceptive options with a healthcare provider is crucial, as individual risk factors may influence recommendations 1.
• Non-hormonal contraceptive methods might be preferable for higher-risk individuals, but the absolute risk increase associated with hormonal contraception, including progesterone-only pills, remains small for most women 1.
• Regular breast cancer screening according to age-appropriate guidelines is important regardless of contraceptive choice 1. Given the complexity of the relationship between hormonal contraception and breast cancer, and considering the need to prioritize morbidity, mortality, and quality of life, the use of progesterone-only oral contraceptive pills does not appear to significantly increase the risk of breast cancer. Therefore, for women considering contraceptive options, including those at higher risk for breast cancer, discussing the benefits and risks of progesterone-only pills with a healthcare provider is recommended to make an informed decision based on individual circumstances 1.

From the FDA Drug Label

The relationship between progestin-only oral contraceptives and these risks have not been established and there are no studies definitely linking progestin-only pill (POP) use to an increased risk of heart attack or stroke. Some epidemiologic studies of oral contraceptive users have reported an increased relative risk of developing breast cancer, particularly at a younger age and apparently related to duration of use These studies have predominantly involved combined oral contraceptives and there is insufficient data to determine whether the use of POPs similarly increase the risk.

The use of progesterone-only oral contraceptives may not have a directly established link to an increased risk of breast cancer. However, due to insufficient data, no conclusion can be drawn about the risk of breast cancer with progesterone-only OCP use 2.

From the Research

Breast Cancer Risk and Progesterone-Only OCP

• The association between progesterone-only oral contraceptive pills (OCPs) and breast cancer risk has been investigated in several studies 3, 4, 5, 6.
• A UK nested case-control study and meta-analysis found that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, similar in magnitude to that associated with combined hormonal contraceptives 3.
• A systematic review of epidemiologic studies found that five of the six studies reported no association between progestin-only formulations and breast cancer risk, although the literature is limited by small sample sizes 4.
• A prospective cohort study found that current oral contraceptive use was associated with a higher risk for invasive breast cancer, regardless of disease subtype, and that associations were observed for select formulations containing levonorgestrel and norgestrel 5.
• A nested case-control study found that levonorgestrel intrauterine system and etonogestrel implant use was associated with breast cancer risk, but depot-medroxyprogesterone acetate was not, except when used for 5 or more years 6.

Key Findings

• Current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk 3.
• The risk of breast cancer associated with progesterone-only OCPs does not appear to vary by mode of delivery 3.
• The absolute excess risk associated with use of oral contraceptives is estimated to be smaller in women who use it at younger rather than at older ages 3.
• Long-acting, reversible contraceptives have similar cancer associations to the oral contraceptive pill, including reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk 6.

Study Limitations

• The studies had limitations, including small sample sizes 4 and inability to adjust for all potential confounders 6.
• Further research is needed to corroborate the findings and to understand the associations between different oral contraceptive formulations and breast cancer risk 4, 5.