Combined Pill may raise breast cancer risk

The combined pill contains oestrogen and, as it is known oestrogen can stimulate breast cancer cells to grow, the potential for extra oestrogen to increase the risk of breast cancer has been recognised for some time. However, any increase in risk needs to be seen in context. The baseline risk of women of a fertile age developing breast canceris small, so a 50% increase in this risk doesn’t amount to a “high” risk. Also, this risk needs to be measured against the potential benefits of the pill protecting against other types of cancer, such as ovarian cancer. Unfortunately, there are often no easy answers when weighing up the benefits and risk.

What we can say is this was a robust study that included more than 1,000 US women aged 20 to 49 who had been diagnosed with breast cancer, and an age-matched control group. The researchers checked if the women used combined oral contraceptive pills in the year before their cancer diagnosis.

Overall use of any combined pill in the past year was associated with a 50% increased risk of developing breast cancer, compared with never using the combined pill or using it more than one year ago. High-strength pills more than doubled risk, but these are no longer prescribed in the UK. You should not suddenly stop your contraceptive use based on this study alone. If you have any questions or concerns, it is best to discuss the possible options with your GP.

What did the story come from? – The study was carried out by researchers from the Group Health Research Institute, the Fred Hutchinson Cancer Research Center, and the University of Washington, all in the US. It was funded by grants from the US National Cancer Institute and the US National Institutes for Health. The study was published in the peer-reviewed medical journal, Cancer Research.

In general the media reports are accurate, but the high-strength pills associated with the more than doubled risk are no longer prescribed in the UK. Similarly, some of the other preparations associated with higher risk may not be relevant to the UK.

The Times deserves praise for making an effort to put the increased risk into a meaningful context, equating it to the same risk associated with “drinking a large glass of wine a day”.

What kind of research was this? – This was a case-control study including more than 1,000 US women aged 20 to 49 who had been diagnosed with breast cancer, and a group of age-matched women without breast cancer as a control. Use of the combined oral contraceptive pill in the year before cancer diagnosis was compared between the groups using pharmacy records.

The researchers say the relationship between oral contraceptive use and breast cancer risk has been extensively studied.

Combined oral contraceptive pills, commonly called the pill, contain the hormone oestrogen. It is known oestrogen can stimulate some breast cancer cells to grow and it is possible taking synthetic oestrogen could increase risk.

New formulations of the combined pill are continually being developed. This study aimed to focus on newer combined oral contraceptive formulations used between 1989 and 2009 by women enrolled on a large US health plan.

What did the research involve? – The study included women aged 20 to 49 enrolled on a healthcare delivery system (Group Health Cooperative, GHC) serving the Seattle Puget Sound area in the US state of Washington between 1989 and 2009. New cases of breast cancer were identified using the local cancer registry, the Cancer Surveillance System (CSS). For each case of breast cancer, the researchers randomly sampled up to 20 controls matched for age and time of enrolment into the healthcare system. Information on combined pill use came from the GHC electronic pharmacy database. The researchers focused on prescriptions filled by cases and controls in the 12 months before the breast cancer diagnosis. They classified the prescriptions by formulation, the strength of synthetic oestrogen and the type of progestogen it contained. They classified the number of pills used in the previous year as less than 190 or 190 and above to estimate exposure for more or less than half of the previous year, and to assess a potential dose-response effect. After excluding women taking progestogen-only pills, they had a sample of 1,102 cases and 21,952 controls.

What were the basic results? – The researchers found that compared with never using the pill or use more than one year ago, combined pill use in the previous year was associated with a 50% increased risk of breast cancer risk (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.3 to 1.9).

As may be expected, there was a slightly stronger association between combined pill use and oestrogen receptor-positive breast cancers (these are known as ER+ cancers, where oestrogen stimulates growth) than for oestrogen receptor-negative cancers.

There was a significant trend for the risk of breast cancer in general, and ER+ breast cancers specifically, to increase with the increasing number of pills dispensed over the past year.

The researchers also found varied risk with the different formulations containing different oestrogen strength and progestogen type.

Preparations containing low-dose oestrogen were not associated with increased risk, while preparations containing moderate doses were associated with 60% increased risk (OR 1.6, 95% CI 1.3 to 2.0) and high-dose oestrogen more than doubled risk (OR 2.7, 95% CI 1.1 to 6.2).

Triphasic preparations (where three different types of tablets are used during different phases of the menstrual cycle) containing a particular type and strength of progestogen (0.75 mg of norethindrone), or preparations containing another progestogen (ethynodiol diacetate), were associated with more than doubled risk.

As may be expected, the researchers found women with and without breast cancer differed on a number of other potential risks factors identified in their medical records. These included:

  • family history of breast cancer
  • how many children they had had
  • body mass index (BMI)
  • attendance for mammography screening

However, none of these factors were found to be confoundingthe relationship between combined pill use and breast cancer. Combined pill use had an independent effect on breast cancer risk.

How did the researchers interpret the results? – The researchers say their results “suggest that recent use of contemporary oral contraceptives is associated with an increased breast cancer risk, which may vary by formulation.

“If confirmed, consideration of the breast cancer risk associated with different oral contraceptive types could impact discussions weighing recognised health benefits and potential risks.”

Conclusion – The combined oral contraceptive pill contains oestrogen and it is known oestrogen can stimulate breast cancer cells to grow. The potential for synthetic oestrogen to increase risk has been recognised for some time.

In this case-control study, researchers found overall combined oral contraceptive use in the previous year was associated with a 50% increased relative risk of developing breast cancer compared with never-use or use more than one year ago.

As may be expected, there was also a slightly stronger association between combined pill use and oestrogen receptor-positive breast cancers (cancers where oestrogen stimulates growth).

Based on several large studies, Cancer Research UK currently advises there seems to be a small increase in risk of breast cancer while women are taking the combined pill. However, the risk goes back to normal 10 years after women have stopped taking the pill. This case-control study seemed to support the idea combined pill use only increases risk while you are taking the extra oestrogen, as all risk increases with recent use were compared with women who had never used the pill or had used it more than one year ago. As Cancer Research UK points out, fewer breast cancers develop among younger women compared with older women. So a small increase in risk related to taking the pill during this time would lead to quite a small number of extra cases of breast cancer. The charity also highlights that balanced against this, the pill reduces the risk of some other cancers, including ovarian and womb cancers.

There is no single potential risk factor for breast cancer. You caninfluence some of these risk factors, such as being overweight or obese, drinking alcohol and smoking, by taking action to lose weight, stopping smoking and watching how much you drink.

The results of this particular case-control study are likely to be reliable and may be applicable to wider populations of combined pill users. But the findings need to be confirmed in other studies, particularly those more relevant to the UK population. A more important point of note relates to the higher risk this study found with certain combined pill formulations, as these may differ from those used in other countries. Currently, in the UK combined pills are only prescribed containing standard moderate-strength (30 to 35 micrograms) or low-strength (20 micrograms) oestrogen. High-strength pills are no longer prescribed.

Similarly, the specific progestogen types associated with a particularly high risk of breast cancer are not contained in current UK preparations. This study adds to the large existing body of research on the association between taking the pill and breast cancer.

If you are worried about using the combined oral contraceptive pill, there are other reliable methods of contraception you may want to consider, such as progesterone-only methods (including pills, injections and implants), the coilmale condoms ordiaphragms.

For more information, visit the NHS Choices Contraception guide, speak to your GP, or talk to a reproductive health charity such as FPA or Brook.

Analysis by 
Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links to the headlines

Some contraceptive pills double risk of breast cancer. The Daily Telegraph, August 1 2014

High-oestrogen contraceptive pills could raise breast cancer risk by 50%, study suggests. The Independent, August 1 2014

Taking the Pill ‘raises the risk of breast cancer by 50 per cent’. Daily Mail, August 1 2014

Links to the science

Beaber EF, Buist DSM, Barlow WE, et al. Recent Oral Contraceptive Use by Formulation and Breast Cancer Risk among Women 20 to 49 Years of Age. The Journal of Cancer Research. Published online August 1 2014


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