Table 7.
Risk of breast cancer: results of studies comparing oral and transdermal administration of hormone replacement therapy
| Author, year | Study type | Compared groups | Results |
|---|---|---|---|
| Beral V et al. 2003 | Cohort study |
Group 1 Oral Transdermal Group 2 Controls |
HRT increased the risk of breast cancer compared to controls (RR 1.66 [95% CI 1.58–1.75], p < 0.0001) HRT increased mortality compared to controls (RR 1.22 [1.00–1.48], p = 0.05) Risk for breast cancer slightly higher on oral HRT group compared to as transdermal HRT, but difference was statistically insignificant [RR 1.32 (1.21–1.45)] vs [RR 1.24 (1.11–1.39)] Oral combined therapy had a higher risk compared with estrogen-only preparation (RR 2.00 vs 1.30, p < 0.0001) |
| Fournier A et al. 2005 | Cohort study |
Group 1 Oral Group 2 Transdermal Group 3: controls |
HRT increased risk of breast cancer compared to controls (RR 1.22; 1–1-1.4) Oral HRT with RR 1.5 (1.1–1.9), transdermal HRT route RR 1.4 (1.2–1.7, p < 0.001), with statistically insignificant difference between the two routes of administration Estrogen-only therapy RR 1.1 (0,8–1,6); Estrogen combined with oral progestogens RR 1.3 (1.1–1.5) The risk is higher with HRT containing synthetic preogestins than micronized progesterone |
| Lyytinen H et al. 2006 | Cohort study |
Group 1 Oral E2 Group 2 Transdermal E2 Group 3 Vaginal estrogens |
HRT < 5 yr is not associated with an increased risk for breast cancer (OR 0.93; 0.80–1.04) HRT > 5 yr associated with an increased risk (OR 1.44; 1.29–1.59) Oral and transdermal preparations similar risk for breast cancer Vaginal estrogen not associated with an increased risk Low doses of E2: oral [OR 1.15 (0.71–1.75)]; transdermal [1.60 (0.77–2.95)] Medium doses of E2: oral [ OR 1.38 (0.84–2.12)]; transdermal [1.32 (1.12–1.64)] High doses of E2: oral [1.49 (1.25–1.75)]; transdermal [1.44 (0.88- 2.22)] |
| Fournier A et al. 2008 – E3N | Cohort study |
Group 1 Oral Group 2 Transdermal |
Oral combined HRT [RR of 1.31 (0.76–2.29)]; transdermal combined HRT [1.28 (0.98–1.69)] Oral [OR 0.77 (0.36–1.62)] and transdermal [1.18 (0.95–1.48)] E2 combined with dydrogesterone had no increased risk Oral [OR 2.74 (1.42–5.29)] and transdermal [2.03 (1.39–2.97) E2 combined with MPA had increased risk Oral [RR 2.02 (1.00–4.06)] and transdermal E2 [RR 1.48 (1.05–2.09)]combined with CMA had increased risk Oral [RR 1.62 (0.94–2.82)] and transdermal E2 [RR 1.52 (1.19–1.96)] combined with promegestone had increased risk Oral [RR 1.10 (0.55–2.21)] and transdermal E2[1.60 (1.28–2.01)] combined with NMA had increased risk |
| Opatrny S et al. 2008 | Case–control study |
Group 1 Oral opposed estrogens Group 2 Transdermal opposed estrogens Group 3 Non-opposed HRT Group 4: controls |
Oral opposed estrogens HRT had an increased risk [OR 1.38(1.27–1.48)] Transdermal opposed estrogens HRT had not an increased risk [OR 1.08 (0.81–1.43)] No difference between sequential or continuous regimen of combined HRT Non-opposed HRT had no increased risk for breast cancer [RR 0.97 (0.86–1.09)] |
| Corrao G et al. 2008 | Cohort study |
Group 1: HRT > 2 years Oral Transdermal Group 2: HRT < 6 months Oral Transdermal |
HRT > 2 years higher risk than HRT therapy < 6 months [RR 1.34(1.13–1.58)] Oral HRT: RR 2.14(1.43–3.21) Transdermal HRT: RR 1.27(1.07–1.51) |
| Lyytinen H et al. 2009 | Cohort study |
Group 1 Oral Group 2 Transdermal |
Up to 3 yr oral and transdermal HRT did not increase risk for breast cancer (RR 1.05; 0.99–1.12, 931 cases vs RR 0.99: 0.79–1.23, 82 cases) Between 3rd and 5th: oral [RR 1.27 (1.15–1-39)] transdermal [RR 1.38 (1.01–1.85)] After 5 years: oral [RR 1.81 (1.73–1.89)] transdermal [RR 1.60 (1.11–2.23)] Preparations with NETA had a higher risk for breast cancer compared to preparations with dydrogesterone and MPA |
HRT hormone replacement therapy, RR relative risk, OR odds ratio, NETA norethisterone acetate, CMA chlormadinone acetate, MPA medroxyrogeterone acetate, NMA nomegestrol acetate