medwireNews: The current or recent use of progestagen-only contraceptives is associated with an increased risk for developing breast cancer, irrespective of the mode of delivery, suggests research published in PLOS Medicine.
The study authors note, however, that the increase in risk is “slight” and “similar in magnitude to that associated with combined hormonal contraceptives.”
They also stress that “[t]hese excess risks must be viewed in the context of the well-established benefits of contraceptive use in women’s reproductive years.”
Outlining the rationale for the study, Kirstin Pirie, from the University of Oxford in the UK, and colleagues explain that “[u]se of progestagen-only hormonal contraceptives has increased substantially over the last decade,” but there is limited information on the associated breast cancer risk.
The team drew on a UK primary care database – the Clinical Practice Research Datalink – to identify 9498 women aged 20–49 years with incident invasive breast cancer diagnosed between January 1996 and September 2017. They were matched by index date, year of birth (within 2 years), general practice, and duration of observation period (time before diagnosis with reliable prescription data) to 18,171 controls without breast cancer.
In all, 44% of women with breast cancer and 39% of controls had one or more prescriptions for a hormonal contraceptive during the observation period.
The likelihood of incident breast cancer was significantly higher among women with at least one hormonal contraceptive prescription than for those with none, with an adjusted odds ratio (OR) of 1.25.
The findings were similar by type of hormonal contraceptive last prescribed, with significant ORs for breast cancer risk of 1.23, 1.26, 1.25, and 1.32 for oral combined, oral progestagen-only, injectable progestagen, and progestagen-releasing intrauterine devices (IUDs). The only exception was progestagen implants, which were associated with a numerical increase in risk (OR=1.22) but this did not reach statistical significance, likely due to the small numbers, say the researchers.
An analysis by time since last use, which focused on women whose last prescription was for oral preparations, showed that the risk was highest for current users (last prescription <12 months before diagnosis), at a significant OR of 1.33, and decreased with time, at significant ORs of 1.17 and 1.15 for those with last use 1–4 years and 5 or more years ago, respectively.
Pirie and colleagues also conducted a meta-analysis combining the current results with those of 12 previously published studies evaluating the breast cancer risk in premenopausal women using progestagen-only preparations.
This gave similar results to the main analysis, although in this case the relative risks (RRs) were significant for all preparation types, at 1.29 for oral progestagen, 1.18 for injectable progestagen, 1.28 for implants, and 1.21 for progestagen-releasing IUDs.
Once again, the risk decreased with time since last use, at a significant RR of 1.27 for current users, 1.16 for those whose last prescription was 1–4 years ago, and 1.08 for those with a last prescription 5–9 years ago. There was “no excess risk 10 or more years after stopping use,” note Pirie et al.
They also used the RRs to estimate the absolute risks by age over a 15-year period from starting oral contraceptives – covering both the excess risk during 5 years of use and in the 10 years after discontinuation – and found that the results reflected the fact that “[b]reast cancer incidence in nonusers is extremely rare before about age 30 and increases sharply with age thereafter.”
Specifically, the 15-year excess absolute risk for breast cancer for users of oral preparations at 16–20 years of age was around 8 per 100,000 users, while it was approximately 61 per 100,000 users at 25–29 years and around 265 per 100,000 users at 35–39 years.
The 15-year incidence for users versus nonusers in these age brackets was 0.09% versus 0.08%, 0.57% versus 0.50%, and 2.2% versus 2.0%, respectively.
Discussing the results, the authors say that “[w]hile a lack of complete prescription data makes it difficult to assess the long-term effects of contraceptive use, it does not unduly affect estimates of the short-term effects of such use, which is the main focus of these investigations.”
And they conclude: “Further research is therefore needed to elucidate the mechanisms behind the similar associations of recent use of combined and progestagen-only contraceptives with breast cancer risk observed here.”
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