Reproductive and hormonal risk factors for luminal, HER2-overexpressing, and triple-negative breast cancer in Japanese women.
BACKGROUND
Although the clinical relevance of the molecular subtypes of breast cancer is evident, etiological differences among subtypes have not been well established, especially among Asian. Here, we evaluated the hypothesis that the etiologic impact of reproductive and hormonal features differs among molecular subtypes.


METHODS
We conducted a case-control study in pre- and postmenopausal Japanese. We examined 706 breast cancer patients and 1412 age- and menopausal status-matched noncancer controls. Immunohistochemical stains for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were used to classify the cases into 554 luminal (hormone receptor positive), 84 HER2-overexpressing (hormone receptor negative, HER2 positive), and 68 triple-negative cases (hormone receptor negative, HER2 negative). Associations were evaluated using multivariate polytomous logistic regression models.


RESULTS
A significant association was observed between early age at menarche and risk of luminal disease (odds ratios = 1.67, 95% confidence interval: 1.22-2.29; P trend = 0.001). No significant differences in association with parity, age at first live birth, breastfeeding history, age at menopause, or synthetic hormonal use were seen across molecular subtypes of breast cancer.


CONCLUSIONS
These findings indicate that reproductive events in adolescence have differential impact on the risk of breast cancer molecular subtypes in Japanese.
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya.
T
T
Islam
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya. Electronic address: kmatsuo@aichi-cc.jp.
K
K
Matsuo
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
H
H
Ito
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
S
S
Hosono
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
M
M
Watanabe
Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
H
H
Iwata
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya.
K
K
Tajima
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya; Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya.
H
H
Tanaka
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007564:Japan; D008572:Menarche; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010298:Parity; D017698:Postmenopause; D017697:Premenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012306:Risk; D011795:Surveys and Questionnaires
D003278:Contraceptives, Oral, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human