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Table 3 Associations between estrogen receptor, progesterone receptor, family history of breast cancer, age at first breast cancer diagnosis, chemotherapy, radiotherapy, hormone replacement therapy, age at menopause, and parity and risk of CBC, stratified by high/low weighted PRS (239 SNPs) in Non-Hispanic White women

From: A genome-wide association study of contralateral breast cancer in the Women’s Environmental Cancer and Radiation Epidemiology Study

 

Below median PRS

Above median PRS

 

CBCs No. (%)

UBCs No. (%)

RR (95%CI)

P

CBCs No. (%)

UBCs No. (%)

RR (95%CI)

P

PHeterogeneity

ER status at first breast cancer

         

Positive

204 (54.9)

430 (65.5)

Ref

 

359 (70.1)

458 (73.6)

Ref

  

Negative

168 (45.1)

227 (34.5)

1.33 (0.95–1.86)

0.09

153 (29.9)

164 (26.4)

1.11 (0.79–1.55)

0.55

0.41

PR status at first breast cancer

         

Positive

194 (54.2)

408 (63.3)

Ref

 

339 (68.6)

440 (71.2)

Ref

  

Negative

164 (45.8)

237 (36.7)

1.24 (0.88–1.74)

0.22

153 (31.4)

178 (28.8)

1.21 (0.87–1.68)

0.26

0.92

Family history of breast cancer

       

No

284 (67.3)

592 (79.8)

Ref

 

384 (64.5)

544 (75.1)

Ref

  

Yes

138 (32.7)

150 (20.2)

1.67 (1.23–2.25)

0.0009

211 (35.5)

180 (24.9)

1.66 (1.27–2.16)

0.0002

1

Age at first breast cancer diagnosis

       

 < 45

177 (41.9)

295 (39.8)

Ref

 

219 (36.8)

284 (39.2)

Ref

  

 ≥ 45

245 (58.1)

447 (60.2)

0.66 (0.28–1.55)

0.34

376 (63.2)

440 (60.8)

0.66 (0.28–1.53)

0.33

0.96

Chemotherapy

         

No

167 (39.6)

300 (40.4)

Ref

 

284 (47.7)

292 (40.3)

Ref

  

Yes

255 (60.4)

442 (59.6)

0.90 (0.67–1.22)

0.51

311 (52.3)

432 (59.7)

0.61 (0.46–0.81)

0.0005

0.04

Radiotherapya

         

No

172 (40.8)

182 (37.2)

Ref

 

239 (40.2)

153 (37.3)

Ref

  

Yes

250 (59.2)

559 (62.8)

1.05 (0.80–1.38)

0.71

356 (59.8)

571 (62.7)

0.95 (0.74–1.22)

0.67

0.59

HRT at first breast cancer diagnosis

       

No

320 (76.4)

571 (77.5)

Ref

 

461 (78.3)

579 (80.3)

Ref

  

Yes

99 (23.6)

166 (22.5)

1.08

0.67

128 (21.7)

142 (19.7)

1.22

0.25

0.59

   

(0.76–1.53)

   

(0.87–1.70)

  

Age at menopauseb

         

Postmenopausal 45+

106 (25.3)

153 (20.8)

Ref

 

145 (24.5)

168 (23.4)

Ref

 

0.46

Postmenopausal < 45

82 (19.6)

144 (19.5)

0.86

0.49

103 (17.4)

121 (16.8)

1.10

0.63

 
   

(0.57–1.32)

   

(0.74–1.65)

  

Premenopausal

231 (55.1)

440 (59.7)

0.78

0.20

343 (58.1)

430 (59.8)

1.03

0.86

 
   

(0.54–1.13)

   

(0.73–1.46)

  

Parity at first breast cancer diagnosis

       

Parous

329 (78.3)

597 (80.6)

Ref

 

449 (75.8)

555 (77.0)

Ref

  

Nulliparous

91 (21.7)

144 (19.4)

1.10

0.60

143 (24.2)

166 (23.0)

0.99

0.95

0.65

   

(0.78–1.54)

   

(0.74–1.33)

  
  1. Non-Hispanic White women only, WECARE I and WECARE II Studies combined
  2. CBC, contralateral breast cancer; CI, confidence interval; ER, estrogen receptor; No., number; PR, progesterone receptor; PRS, polygenic risk score; RR, rate ratio; UBC, unilateral breast cancer; HRT, hormone replacement therapy
  3. Adjusted for the top five principal components, log-weight offset term, age at first breast cancer diagnosis, age at menarche, age at menopause, number of full-term pregnancies, stage of first breast cancer, histology of first breast cancer, family history of breast cancer, chemotherapy, and hormone therapy
  4. aControl proportions account for counter-matched sampling of the WECARE I Study and do not represent true distributions in this population
  5. b1 year prior to breast cancer diagnosis to preclude treatment-induced menopause
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Breast Cancer Research

ISSN: 1465-542X

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