BACKGROUND: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. METHODS: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. RESULTS: Breast cancer risk was not significantly related to age at menopause [hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; >or=55 years, 1.12 [0.12-5.02], as compared with premenopausal women]. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. CONCLUSIONS: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
BACKGROUND: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. METHODS: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. RESULTS:Breast cancer risk was not significantly related to age at menopause [hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; >or=55 years, 1.12 [0.12-5.02], as compared with premenopausal women]. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. CONCLUSIONS: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
Authors: M M Blokhuis; G E Pietersen; P A Goldberg; U Algar; L Van der Merwe; N Mbatani; A A Vorster; R S Ramesar Journal: Fam Cancer Date: 2010-09 Impact factor: 2.375
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Authors: Susan M Domchek; Tara M Friebel; Christian F Singer; D Gareth Evans; Henry T Lynch; Claudine Isaacs; Judy E Garber; Susan L Neuhausen; Ellen Matloff; Rosalind Eeles; Gabriella Pichert; Laura Van t'veer; Nadine Tung; Jeffrey N Weitzel; Fergus J Couch; Wendy S Rubinstein; Patricia A Ganz; Mary B Daly; Olufunmilayo I Olopade; Gail Tomlinson; Joellen Schildkraut; Joanne L Blum; Timothy R Rebbeck Journal: JAMA Date: 2010-09-01 Impact factor: 56.272
Authors: Patricia G Moorman; Edwin S Iversen; P Kelly Marcom; Jeffrey R Marks; Frances Wang; Eunjung Lee; Giske Ursin; Timothy R Rebbeck; Susan M Domchek; Banu Arun; Lisa Susswein; Claudine Isaacs; Judy E Garber; Kala Visvanathan; Constance A Griffin; Rebecca Sutphen; Jennifer Brzosowicz; Stephen Gruber; Dianne M Finkelstein; Joellen M Schildkraut Journal: Breast Cancer Res Treat Date: 2010-03-23 Impact factor: 4.872
Authors: Joanne Kotsopoulos; Jan Lubinski; Henry T Lynch; Charmaine Kim-Sing; Susan Neuhausen; Rochelle Demsky; William D Foulkes; Parviz Ghadirian; Nadine Tung; Peter Ainsworth; Leigha Senter; Beth Karlan; Andrea Eisen; Charis Eng; Jeffrey Weitzel; Dawna M Gilchrist; Joanne L Blum; Dana Zakalik; Christian Singer; Taya Fallen; Ophira Ginsburg; Tomasz Huzarski; Ping Sun; Steven A Narod Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-05-07 Impact factor: 4.254