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Home > Understanding Breast Cancer > Breast Cancer Research > Table 8: Menopausal hormone therapy (postmenopausal hormone use) and breast cancer risk

  


Table 8: Menopausal hormone therapy (postmenopausal hormone use) and breast cancer risk

 

This summary table contains detailed information about research studies. Summary tables offer an informative look at the science behind many breast cancer guidelines and recommendations. However, they should be viewed with some caution. In order to read and interpret research tables successfully, it is important to understand some key concepts. Learn how to read a research table.

Introduction: There are two main types of menopausal hormone therapy (MHT) used today:

  • Estrogen plus progestin
  • Estrogen alone

Estrogen alone raises the risk of uterine cancer, so it is only used by women who no longer have a uterus (those who have had a hysterectomy). Women who still have a uterus most often use estrogen plus progestin.

Estrogen plus progestin

Results from the Women’s Health Initiative (WHI)--a large randomized clinical trial--confirmed what other studies had long suggested: long-term use of MHT containing estrogen plus progestin increases the risk of breast cancer [1,2].

Estrogen alone

The results are not yet conclusive for MHT containing estrogen alone. The WHI found a slight decrease in risk of breast cancer after short-term use [3]. However, other cohort studies and pooled analyses (listed below) have found the use of MHT containing estrogen alone increases breast cancer risk. The Nurses’ Health Study found an increase in risk only after 20 or more years of use [4]. 

Learn more about menopausal hormone therapy and breast cancer risk.

Learn about the strengths and weaknesses of different types of studies.

See how this risk factor compares with other risk factors for breast cancer.

Study selection criteria: Randomized clinical trials, prospective cohort studies and pooled analyses with at least 300 breast cancer cases with data on estrogen alone or estrogen plus progestin therapy.

Table note: Relative risk above 1 indicates increased risk. Relative risk below 1 indicates decreased risk.

Study 

Study Population
(number of participants)
 

Menopausal Hormone Therapy
(MHT)
 

Relative Risk of Breast Cancer in Women Using
Estrogen Alone Compared to Women who Never Used MHT,
RR (95% CI)
 

Relative Risk of Breast Cancer in Women Using
Estrogen plus Progestin Compared to Women who Never Used MHT,
RR (95% CI)
 

Current, Recent, Past or Ever Use 

Duration
of Use
 

Randomized clinical trials 

Women's Health Initiative [1,2]

12,788
(678 cases)

Current or past use

11 years


 

1.25
(1.07-1.46)

Women's Health Initiative [3]

10,739
(350 cases)

Current or past use

5.9 years

0.77
(0.62-0.95)


 

Cohort studies 

Million Women Study [5]

828,923
(9,364 cases)

Current use

Any

1.3
(1.21-1.40)

2.0
(1.88-2.12)

EPIC [6]

133,744
(4,312 cases)

Current use

Any

1.42
(1.23-1.64)

1.77
(1.40-2.24)

     

1 year or less

1.01
(0.70-1.46)

1.44
(1.09-1.89)

     

1-3 years

1.39
(1.07-1.81)

1.73
(1.44-2.08)

     

3-5 years

1.40
(1.01-1.93)

1.81
(1.44-2.29)

     

5-10 years

1.63
(1.26-2.09)

1.93
(1.58-2.35)

     

More than 10 years

1.72
(1.15-2.57)

1.98
(1.12-3.50)

Breast Cancer Detection Demonstration Project [7]

46,355
(2,082 cases)

Current or recent use (within the past 4 years)

10 years for estrogen alone

4 years for estrogen plus progestin

1.2
(1.0-1.4)

1.4
(1.1-1.8)

Nurses' Health Study [4,8]

58,520
(1,761 cases)

Current use

10 years


 

1.7
(1.2-2.4)


 

28,835*
(934 cases)

Current use

Less than 5 years

0.96
(0.75-1.22)


 

 

 

 

5-9.9 years

0.90
(0.73-1.12)


 

 

 

 

10-14.9 years

1.06
(0.86-1.30)


 

 

 

 

15-19.9 years

1.18
(0.95-1.48)


 

 

 

 

20 or more years

1.42
(1.13-1.77)


 

Danish Cancer Registry [9]

48,812
(869 cases)

Current, recent, or past use

Any

1.35
(1.01-1.80)

1.52
(1.21-1.93)

Olsson et al. [10]

29,508
(556 cases)

Ever use

At least 4 years

0.58
(0.22-1.55)

3.13
(1.70-5.75)

Cancer Prevention Study II-Nutrition Cohort [11]

67,754
 (471 cases)

Current use

10-19 years for estrogen alone 

At least 10 years for estrogen plus progestin

Ductal breast cancer:
0.95
(0.77-1.17)

Lobular breast cancer:
1.59
(1.07-2.35)

Ductal breast cancer:
2.07
(1.70-2.52)

Lobular breast cancer:
2.19
(1.50-3.22)

   

Past use

At least 5 years

Ductal breast cancer:
0.94
(0.75-1.18)

Lobular breast cancer:
0.86
(0.54-1.37)

Ductal breast cancer:
1.53
(1.14-2.06)

Lobular breast cancer:
1.06
(0.52-2.17)

Women's Health Study-US [12,13]

17,835
(411 cases)

Current use

5 or more years


 

1.76
(1.29-2.39)


 

12,718
(305 cases)

Current use

8 or more years

1.35
(0.90-2.02)


 

Pooled analyses 

CGHFBC [14]


 

Current or recent use (within the past 4 years)

5 or more years

1.34

1.53

Collins et al. [15]


 

Current or recent use (past 1-4 years)

5 or more years

1.24
(1.07-1.44)

1.89
(1.54-2.31)

 

References  

  1. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 288(3):321-33, 2002.
  2. Chlebowski RT, Anderson GL, Gass M, et al. for the WHI Investigators. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 304(15):1684-92, 2010.
  3. Lacroix AZ, Chlebowski RT, Manson JE, et al. for the WHI Investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 305(13):1305-1314, 2011.
  4. Chen WY, Manson JE, Hankinson SE, et al. Unopposed estrogen therapy and risk of invasive breast cancer. Arch Intern Med. 166(9):1027-1032, 2006.
  5. Beral V for the Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 362:419-27, 2003.
  6. Bakken K, Fournier A, Lund E, et al. Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 128(1):144-56, 2011.
  7. Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA. 283(4):485-491, 2000.
  8. Colditz GA and Rosner B. Cumulative risk of breast cancer to age 70 according to risk factor status: data from the Nurses’ Health Study. Am J Epidemiol. 152(10):950-64, 2000.
  9. Ewertz M, Mellemkjaer L, Poulsen AH, et al. Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study. Br J Cancer. 92(7):1293-7, 2005.
  10. Olsson HL, Ingvar C, Bladstrom A. Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden. Cancer. 97(6):1387-92, 2003.
  11. Calle EE, Feigelson HS, Hildebrand JS, Teras LR, Thun MJ, Rodriguez C. Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype. Cancer. 115(5):936-45, 2009.
  12. Porch JV, Lee IM, Cook NR, Rexrode KM, Burin JE. Estrogen-progestin replacement therapy and breast cancer risk: the Women’s Health Study (United States). Cancer Causes Control. 13(9):847-54, 2002.
  13. Zhang SM, Manson JE, Rexrode KM, Cook NR, Buring JE, Lee IM. Use of oral conjugated estrogen alone and risk of breast cancer. Am J Epidemiol. 165(5):524-9, 2007.
  14. Collaborative Group on Hormonal Factors in Breast Cancer. Breast Cancer and Hormone Replacement Therapy: Collaborative Reanalysis of Data from 51 Epidemiological Studies of 52,705 women with Breast Cancer and 108,411 women without Breast Cancer. Lancet. 350:1047-1059, 1997.
  15. Collins JA, Blake JM, Crosignani PG. Breast cancer risk with postmenopausal hormonal treatment. Hum Reprod Update. 11(6):545-60, 2005.

Updated 08/28/13