Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Aug 11;8(46):81109-81124.
doi: 10.18632/oncotarget.20154. eCollection 2017 Oct 6.

Change in risk of breast cancer after receiving hormone replacement therapy by considering effect-modifiers: a systematic review and dose-response meta-analysis of prospective studies

Kang Wang  1 , Feng Li  2 , Li Chen  1 , Yan-Mei Lai  1 , Xiang Zhang  1 , Hong-Yuan Li  1
Affiliations

Change in risk of breast cancer after receiving hormone replacement therapy by considering effect-modifiers: a systematic review and dose-response meta-analysis of prospective studies

Kang Wang et al. Oncotarget. .

Abstract

We synthesize the current literatures and use the power of meta-analysis to examine trends on association between hormone replacement therapy (HRT) and the risk of breast cancer (BC). We performed a comprehensive literature search using PubMed, EMBASE, and Web of Science from their inception until Jan 2017. Prospective studies that provided adjusted risk estimates of HRT and BC risk were eligible. Categorical and dose-response meta-analyses followed the PRISMA were conducted using random effects model and restricted cubic spline model, respectively. Forty-seven publications from thirty-five unique studies were included, involving 3,898,376 of participants and 87,845 of BC cases. Compared with non-users, RR for current estrogen-only therapy (ET) users was 1.14 (95% confidence interval (CI) = 1.05-1.22), and for per year increases was 1.02 (95% CI = 1.02-1.02). Moreover, RR for current estrogen plus progestin therapy (EPT) users was 1.76, (95% CI = 1.56-1.96), and for per year increases was 1.08 (95% CI = 1.08-1.08). Dose-response analyses revealed 8-10 years' onset peaks, and indicated residual increased BC risk remained after stopping use of ET regimen rather than for EPT. Effect-modifiers like BMI, duration of use, race/ethnicity, routes of administration were recognized. In Conclusions, current use of EP or EPT and ever use of tibolone are associated with an elevated risk of BC. Compared with slim HRT users and non-users, lower BC risks were found among overweight/obese HRT users and former EPT users, respectively. Both ET and EPT users are associated with higher risk of lobular BC than ductal BC, and more ER-positive than negative BC cases were detected among EPT users.

Keywords: body mass index; breast cancer; estrogen plus progestin therapy; estrogen-alone therapy; hormone replacement therapy.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1. The flowchart of selecting eligible studies
Figure 2
Figure 2
Dose-response meta-analyses on (A) duration of ET use (year) and the risk of BC compared with non-users, (B) time (year) since last ET use and the risk of BC compared with current ET users, (C) BMI (kg/m2) and the risk of BC among current ET users.
Figure 3
Figure 3
Dose-response meta-analyses on (A) duration of EPT use (year) and the risk of BC compared with non-users, (B) time (year) since last ET use and the risk of BC compared with current ET users, (C) BMI (kg/m2) and the risk of BC among current ET users.
Figure 4
Figure 4. ET and the risk of BC
Figure 5
Figure 5. EPT and the risk of BC
See this image and copyright information in PMC

References

    1. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321–33. - PubMed
    1. Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Galichet L, Cogliano V. A review of human carcinogens--Part A: pharmaceuticals. Lancet Oncol. 2009;10:13–4. - PubMed
    1. Pharmaceuticals Volume 100 A. A review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum. 2012;100:1–401. - PMC - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30. https://doi.org/10.3322/caac.21332 - DOI - PubMed
    1. Roman M, Sakshaug S, Graff-Iversen S, Vangen S, Weiderpass E, Ursin G, Hofvind S. Postmenopausal hormone therapy and the risk of breast cancer in Norway. Int J Cancer. 2016;138:584–93. https://doi.org/10.1002/ijc.29810 - DOI - PubMed