Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Population
2.2. Data Collection
2.3. Diagnosis of Breast Cancer
2.4. MHT Use
2.5. BMI Data
2.6. Statistical Analysis
Demographic Characteristics and Breast Cancer Risk Factors amongst MHT Users and Non-Users
2.7. MHT Use and BC Risk
2.8. MHT Use, Breast Cancer Risk and Effect Modification by Current BMI and Early BMI and Age of First Pregnancy
3. Results
3.1. Flow Diagram
3.2. Demographic Characteristics and Breast Cancer Risk Factors According to MHT Use
3.3. MHT Use Status and Breast Cancer Risk
3.4. Current BMI and MHT and Breast Cancer Risk
3.5. Early Adulthood BMI and MHT and Breast Cancer Risk
3.6. Combined Stratified Model with Current BMI, Early BMI and MHT and Breast Cancer Risk
3.7. Effects of Oestrogen Only and Combined MHT and Current and Early BMI and Breast Cancer Risk
3.8. MHT Use and Age at First Pregnancy
3.9. Effects of Oestrogen Only and Combined MHT and Age of First Pregnancy
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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A | ||||
MHT use | BMI < 26.4 kg/m2 | BMI ≥ 26.4 kg/m2 | ||
N (%) BC/ no BC | HR (95% CI) | N (%) BC/no BC | HR (95% CI) | |
Never | 474 (2.5)/18,381 (97.5) | 1.00 (Ref) | 524 (3.2)/16016 (96.8) | 1.44 (1.26–1.64) |
Former | 256 (3.2)/7858 (96.8) | 1.12 (0.95–1.32) | 251 (3.2)/7508 (96.8) | 1.29 (1.09–1.53) |
Current | 101 (3.9)/2457 (96.1) | 1.60 (1.28–1.98) | 57 (3.2)/1725 (96.8) | 1.45 (1.09–1.92) |
B | ||||
BMI age 20 < 21.6 kg/m2 | BMI age 20 ≥ 21.6 kg/m2 | |||
N (%) BC/noBC | HR (95% CI) | N (%)BC/no BC | HR (95% CI) | |
Never | 439 (3.0)/14,292 (97.0) | 1.00 (Ref) | 559 (2.7)/20,105 (97.3) | 0.85 (0.75–0.97) |
Former | 235 (3.3)/6878 (96.7) | 0.98 (0.83–1.16) | 272 (3.1)/8488 | 0.89 (0.75–1.05) |
Current | 80 (4.0)/1943 (96.0) | 1.37 (1.08–1.75) | 78 (3.4)/2239 (96.6) | 1.11 (0.86–1.41) |
C | ||||
BMI age 20 < 21.6 kg/m2 | BMI age 20 ≥ 21.6 kg/m2 | |||
N (%) BC/no BC | HR (95% CI) | N (%) BC/no BC | HR (95% CI) | |
Never BMI < 26.4 kg/m2 | 259 (2.6)/9737 (97.4) | 1.00 (Ref) | 139 (2.2)/6171 (97.8) | 0.86 (0.70–1.06) |
Never BMI ≥ 26.4 kg/m2 | 180 (3.8)/4555 (96.2) | 1.53 (1.26–1.85) | 420 (2.9)/13,934 (97.1) | 1.20 (1.02–1.40) |
Former BMI < 26.4 kg/m2 | 142 (3.2)/4249 (96.8) | 1.12 (0.90–1.38) | 83 (3.0)/2726 (97.0) | 1.03 (0.80–1.33) |
Former BMI ≥ 26.4 kg/m2 | 93 (3.4)/2629 (96.6) | 1.23 (0.97–1.57) | 189 (3.2)/5762 (96.8) | 1.17 (0.96–1.43) |
Current BMI < 26.4 kg/m2 | 54 (3.8)/1385 (96.2) | 1.48 (1.10–2.00) | 34 (4.0)/808 (96.0) | 1.60 (1.12–2.30) |
Current BMI ≥ 26.4 kg/m2 | 558 (95.5)/26 (4.5) | 1.84 (1.22–2.76) | 1431 (97.0)/44 (3.0) | 1.24 (0.90–1.71) |
Age at Pregnancy < 30 | Age at Pregnancy ≥ 30 | |||
N (%) BC/ no BC | HR (95% CI) | N (%) BC/ no BC | HR (95% CI) | |
Never | 670 (2.7)/24,126 (97.3) | 1.00 (Ref) | 328 (3.1)/10,271 (96.9) | 1.20 (1.05–1.38) |
Former | 391 (3.1)/12,401 (96.9) | 0.99 (0.86–1.13) | 116 (3.8)/2965 (96.2) | 1.25 (1.02–1.53) |
Current | 110 (3.5)/3076 (96.5) | 1.31 (1.06–1.60) | 48 (4.2)/1106 (95.8) | 1.64 (1.22–2.20) |
Oestrogen only | ||||
Age at Pregnancy < 30 | Age at Pregnancy ≥ 30 | |||
N (%) BC/ no BC | HR (95% CI) | N (%) BC/ no BC | HR (95% CI) | |
Never | 670 (2.7)/24,126 (97.3) | 1.00 (Ref) | 182 (3.2)/5465 (96.8) | 1.28 (1.09–1.51) |
Former | 151 (2.7)/5399 (97.3) | 0.89 (0.73–1.09) | 14 (3.5)/390 (96.5) | 1.22 (0.71–2.09) |
Current | 46 (2.6)/1715 (97.4) | 0.96 (0.71–1.31) | 9 (4.6)/187 (95.4) | 1.81 (0.93–3.53) |
Combined | ||||
Age at Pregnancy < 30 | Age at Pregnancy ≥ 30 | |||
N (%) no BC/BC | HR (95% CI) | N (%) no BC/BC | HR (95% CI) | |
Never | 670 (2.7)24,126 (97.3) | 1.00 (Ref) | 182 (3.2)/5465 (96.8) | 1.29 (1.09–1.52) |
Former | 240 (3.3)/7002 (96.7) | 1.07 (0.92–1.26) | 41 (4.0)/984 (96.0) | 1.36 (0.99–1.87) |
Current | 64 (4.5)/1361 (95.5) | 1.74 (1.34–2.25) | 16 (4.6)/331 (95.4) | 1.90 (1.16–3.13) |
A | ||||
BMI < 26.4 kg/m2 | BMI ≥ 26.4 kg/m2 | |||
N (%) BC/ no BC | HR (95% CI) | N (%) BC/ no BC | HR (95% CI) | |
Never | 439 (3.0)/14,292 (97.0) | 1.00 (Ref) | 559 (2.7)/20,105 (97.3) | 1.48 (1.29–1.69) |
Former oestrogen only | 79 (2.9)/2664 (97.1) | 1.06 (0.81–1.38) | 26 (2.1)/1199 (97.9) | 1.23 (0.98–1.54) |
Former combined | 156 (3.6)/4214 (96.4) | 1.17 (0.96–1.42) | 52 (4.8)/1040 (95.2) | 1.40 (1.15–1.69) |
Current oestrogen only | 37 (4.8)/984 (95.2 | 1.29 (0.90–1.85) | 112 (3.0)/3670 (97.0) | 1.16 (0.79–1.70) |
Current combined | 43 (4.3)/959 (95.7) | 1.86 (1.40–2.47) | 160 (3.2)/4818 (96.8) | 2.11 (1.53–2.92) |
B | ||||
BMI age 20 < 21.6 kg/m2 | BMI age 20 ≥ 21.6 kg/m2 | |||
N (%) BC / no BC | HR (95% CI) | N (%) BC/ no BC | HR (95% CI) | |
Never | 439 (3.0)/14,292 (97.0) | 1.00 (Ref) | 559(2.7)/20,105 (97.3) | 0.84 (0.74–0.96) |
Former oestrogen only | 79 (2.9)/2664 (97.1) | 0.85 (0.66–1.10) | 112 (3.0)/3670 (97.0) | 0.83 (0.66–1.04) |
Former combined | 156 (3.6)/4214 (96.4) | 1.04 (0.86–1.25) | 160 (3.2)/4818 (96.8) | 0.88 (0.73–1.06) |
Current oestrogen only | 37 (4.8)/984 (95.2) | 1.23 (0.87–1.73) | 26 (2.1)/1199 (97.9) | 0.67 (0.45–1.00) |
Current combined | 43 (4.3)/959 (95.7) | 1.47 (1.07–2.01) | 52 (4.8)/1040 (95.2) | 1.54 (1.15–2.06) |
C | ||||
Oestrogen only MHT | BMI age 20 < 21.6 kg/m2 | BMI age 20 ≥ 21.6 kg/m2 | ||
N (%) BC/ no BC | HR (95% CI) | N (%) BC/ no BC | HR (95% CI) | |
Never BMI < 26.4 kg/m2 | 259 (2.6)9737 (97.4) | 1.00 (Ref) | 6171 (97.8)/139 (2.2) | 0.86 (0.70–1.05) |
Never BMI ≥ 26.4 kg/m2 | 180 (3.8)/4555 (96.2) | 1.54 (1.27–1.86) | 420 (2.9)/13,934 (97.1) | 1.20 (1.02–1.41) |
Former BMI < 26.4 kg/m2 | 45 (2.9)/1484 (97.1) | 1.05 (0.76–1.47) | 30 (2.8)/1031 (97.2) | 1.00 (0.67–1.48) |
Former BMI ≥ 26.4 kg/m2 | 34 (2.8)/1180 (97.2) | 1.04 (0.72–1.50) | 82 (3.0)/2639 (97.0) | 1.15 (0.87–1.50) |
Current BMI < 26.4 kg/m2 | 23 (3.4)/663 (96.6) | 1.33 (0.86–2.05) | 11 (2.7)/395 (97.3) | 1.06 (0.58–1.95) |
Current BMI ≥ 26.4 kg/m2 | 14 (4.2)/321 (95.8) | 1.68 (0.97–2.90) | 15 (1.8)/804 (98.2) | 0.75 (0.44–1.28) |
Combined MHT | BMI age 20 < 21.6 kg/m2 | BMI age 20 ≥ 21.6 kg/m2 | ||
N (%) BC/ no BC | HR (95% CI) | N (%) BC/ no BC | HR (95% CI) | |
Never BMI < 26.4 kg/m2 | 259 (2.6)9737 (97.4) | 1.00 (Ref) | 6171 (97.8)/139 (2.2) | 0.86 (0.70–1.05) |
Never BMI ≥ 26.4 kg/m2 | 180 (3.8)/4555 (96.2) | 1.52 (1.25–1.84) | 420 (2.9)13,934 (97.1) | 1.19 (1.01–1.39) |
Former BMI < 26.4 kg/m2 | 97 (3.4)/2765 (96.6) | 1.14 (0.90–1.45) | 53 (3.0)/1695 (97.0) | 1.04 (0.77–1.40) |
Former BMI ≥ 26.4 kg/m2 | 59 (3.9)/1449 (96.1) | 1.36 (1.02–1.82) | 107 (3.3)/3123 (96.7) | 1.16 (0.92–1.47) |
Current BMI < 26.4 kg/m2 | 31 (4.1)/722 (95.9) | 1.60 (1.10–2.32) | 23 (5.3)/413 (94.7) | 2.08 (1.35–3.18) |
Current BMI ≥ 26.4 kg/m2 | 12 (4.8)/237 (95.2) | 1.96 (1.10–3.51) | 29 (4.4)/627 (95.6) | 1.80 (1.22–2.65) |
Status of MHT Use | ||||
---|---|---|---|---|
Total | Never | Former | Current | |
Number of women (%) | 56,489 (100) | 35,933 (63.6) | 16,149 (28.6) | 4407 (7.8) |
Ethnicity | ||||
White | 53,571 (94.8) | 33,695 (93.8) | 15,634 (96.8) | 4242 (96.3) |
Other | 2918 (5.2) | 2238 (6.2) | 515 (3.2) | 165 (3.7) |
Unknown | 1799 | 1027 | 648 | 124 |
Age at study entry | ||||
Median (IQR) | 56.9 (51.6–63.6) | 53.9 (50.7–60.8) | 62.9 (58.3–66.6) | 55.2 (51.5–60.6) |
Mean (SD) | 57.8 (7.0) | 56.0 (6.7) | 62.3 (5.8) | 56.4 (6.0) |
Menopausal status | ||||
premenopausal and perimenopausal | 18,764 (33.2) | 16,742 (46.6) | 821 (5.1) | 1201 (27.3) |
postmenopausal | 37,725 (66.8) | 19,191 (53.4) | 15,328 (94.9) | 3206 (72.7) |
Unknown | 2831 | 2673 | 76 | 82 |
Age at menopause | ||||
Median (IQR) | 50.0 (46.0–53.0) | 50.0 (48.0–53.0) | 50.0 (45.0–53.0) | 48.0 (44.0–51.0) |
Mean (SD) | 49.0 (5.6) | 49.9 (4.7) | 48.1 (6.4) | 47.1 (6.6) |
Unknown | 46 (0.1) | 29 (0.1) | 15 (0.1) | 2 (<0.1) |
Age at menarche | ||||
Median (IQR) | 13.0 (12.0–14.0) | 13.0 (12.0–14.0) | 13.0 (12.0–14.0) | 13.0 (12.0–14.0) |
Mean (SD) | 12.9 (1.6) | 12.9 (1.6) | 12.8 (1.6) | 12.9 (1.6) |
Unknown | 1186 (2.1) | 762 (2.1) | 319 (2.0) | 105 (2.4) |
Parity and age at first pregnancy | ||||
Nulliparous | 7330 (13.0) | 5028 (14.0) | 1681 (10.4) | 621 (14.1) |
<30 | 41,408 (73.3) | 25,259 (70.2) | 13,013 (18.5) | 3236 (73.4) |
≥30 | 7751 (13.7) | 5706 (15.8) | 1455 (2.2) | 550 (12.5) |
Median age at first pregnancy (IQR) | 24.0 (21.0–28.0) | 24.0 (21.0–28.0) | 23.0 (20.0–26.0) | 23.0 (20.0–27.0) |
Mean age at first pregnancy (SD) | 24.4 (5.3) | 25 (5.3) | 23.5 (4.6) | 24.1 (5.2) |
Unknown | 4 (<0.1) | 3 (<0.1) | 1 (<0.1) | 0 (<0.1) |
BMI | ||||
Underweight or normal weight (<25 kg/m2) | 20,216 (35.9) | 12,931 (36.1) | 5486 (34.1) | 1799 (41.0) |
Overweight (25–29.9 kg/m2) | 22,249 (39.5) | 13,813 (38.5) | 6660 (41.4) | 1776 (40.4) |
Obese (≥30 kg/m2) | 13,868 (24.6) | 9091 (25.4) | 3959 (24.6) | 818 (18.6) |
Median (IQR) | 26.4 (23.8–29.9) | 26.4 (23.7–30.0) | 26.4 (24.0–29.9) | 26.0 (23.4–28.7) |
Mean (SD) | 27.4 (5.4) | 27.5 (5.5) | 27.4 (5.1) | 26.5 (4.7) |
Unknown | 3801 | 2587 | 933 | 281 |
BMI at age 20 | ||||
Underweight or normal weight (<25 kg/m2) | 50,119 (88.8) | 31,673 (88.2) | 14,456 (89.6) | 3990 (90.6) |
Overweight (25–29.9 kg/m2) | 5105 (9.0) | 3369 (9.4) | 1388 (8.6) | 348 (7.9) |
Obese (≥30 kg/m2) | 1243 (2.2) | 877 (2.4) | 298 (1.8) | 68 (1.5) |
Median (IQR) | 21.6 (20.3–23.0) | 21.6 (20.3–23.2) | 21.6 (20.2–23.0) | 21.6 (20.0–22.8) |
Mean (SD) | 22.0 (3.1) | 22.1 (3.1) | 21.9 (2.9) | 21.8 (2.9) |
Unknown | 6777 | 4694 | 1600 | 483 |
Mean Height (SD) | 1.62 (0.07) | 1.62 (0.07) | 1.61 (0.06) | 1.62 (0.06) |
Median Height (IQR) | 1.63 (1.57–1.65) | 1.63 (1.57–1.65) | 1.60 (1.57–1.65) | 1.63 (1.57–1.68) |
Unknown | 1111 | 766 | 269 | 76 |
Oophorectomy | ||||
Yes | 6696 (12.0) | 1999 (5.6) | 3584 (22.2) | 1213 (27.5) |
No | 49,693 (88.0) | 33,934 (94.4) | 12,565 (77.8) | 3194 (72.5) |
Unknown | 8709 | 5183 | 2716 | 810 |
MHT type | ||||
Oestrogen only | 8895 (43.2) | 6617 (41.0) | 2278 (51.7) | |
Combined | 11,661 (56.7) | 9532 (59.0) | 2129 (48.3) | |
Unknown | 13,456 | 12,441 | 1015 | |
Duration of MHT use (years) | ||||
Μedian (IQR) | 5 (2.0–10.0) | 5 (2.0–10.0) | 7 (2.5–13.0) | |
Mean (SD) | 7.3 (4.6) | 6.2 (5.4) | 8.6 (7.2) | |
Unknown | 2433 | 1178 | 1255 | |
VAS Density | ||||
Median (IQR) | 24.8 (14.9–35.8) | 24.8 (15.6–35.8) | 22.4 (12.9–34.4) | 29.5 (18.9–41.0) |
Mean (SD) | 27.1 (16.2) | 27.5 (16.1) | 25.3 (15.8) | 31.3 (16.8) |
Family History of Breast and/ or Ovarian Cancer * | ||||
Yes | 15,738 (27.9) | 10,185 (28.3) | 4379 (27.1) | 1174 (26.6) |
No | 40,748 (72.1) | 25,748 (71.7) | 11,768 (72.9) | 3232 (73.4) |
Median exercise hours per week (IQR) | 3.5 (1.5–7.0) | 3.5 (1.0–6.0) | 3.5 (2.0–8.0) | 3.5 (2.0–7.0) |
Unknown | 17,085 | 11,171 | 4630 | 1284 |
Median alcohol units per week (IQR) | 4.0 (0.0–10.0) | 4.0 (0.0–10.0) | 4.0 (0.0–10.0) | 4.0 (1.0–10.0) |
Unknown | 2512 | 1593 | 723 | 196 |
Median ΕΙΜD score 2010 (IQR) ** | 18.9 (10.4–35.1) | 19.4 (10.5–35.4) | 18.7 (10.6–34.9) | 17.6 (9.7–32.5) |
Unknown | 312 | 176 | 111 | 25 |
MHT Use Status | N% BC/ N% no BC | HR (95% CI) | p-Value | HR (95% CI) | p-Value |
---|---|---|---|---|---|
Never | 998 (2.8)/ 34,397 (97.2) | 1.00 | 1.00 | ||
Former | 507 (3.2)/ 15,366 (96.8) | 0.98 (0.88–1.10) | 0.765 | 1.03 (0.91–1.17) | 0.614 |
Current | 158 (3.6)/ 4182 (96.4) | 1.27 (1.07–1.50) | 0.006 | 1.35 (1.13–1.60) | 0.001 |
MHT type | |||||
Never | 998 (2.8)/ 34,397 (97.2) | 1.00 | 1.00 | ||
Former oestrogen only | 191 (2.9)/ 6334 (97.1) | 0.90 (0.76–1.05) | 0.189 | 0.95 (0.79–1.14) | 0.558 |
Former combined | 316 (3.4)/ 9032 (96.6) | 1.04 (0.91–1.19) | 0.586 | 1.06 (0.93–1.22) | 0.398 |
Current oestrogen only | 63 (2.8)/ 2183 (97.2) | 0.96 (0.74–1.24) | 0.754 | 1.03 (0.79–1.34) | 0.835 |
Current combined | 95 (4.5)/ 1999 (95.5) | 1.60 (1.30–1.98) | <0.001 | 1.64 (1.32–2.03) | <0.001 |
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Leventea, E.; Harkness, E.F.; Brentnall, A.R.; Howell, A.; Evans, D.G.; Harvie, M. Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy? Cancers 2021, 13, 2710. https://doi.org/10.3390/cancers13112710
Leventea E, Harkness EF, Brentnall AR, Howell A, Evans DG, Harvie M. Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy? Cancers. 2021; 13(11):2710. https://doi.org/10.3390/cancers13112710
Chicago/Turabian StyleLeventea, Eleni, Elaine F. Harkness, Adam R. Brentnall, Anthony Howell, D. Gareth Evans, and Michelle Harvie. 2021. "Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy?" Cancers 13, no. 11: 2710. https://doi.org/10.3390/cancers13112710