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Age at Menarche and Menopause and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study

¹ Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany; ² Institut National de la Sante et de la Recherche Medicale (INSERM), U794, Service de Biostatistiques, Institut Curie, Paris, France; ³ The Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, Netherlands; ⁴ Cancer Research UK, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; ⁵ Ferguson-Smith Centre for Clinical Genetics, Glasgow, United Kingdom; ⁶ Department of Clinical Genetics, Guy's Hospital, London, United Kingdom; ⁷ Clinical Genetics Unit, Birmingham Woman's Hospital, Birmingham, United Kingdom; ⁸ Centre René Huguenin, Saint Cloud, France; ⁹ Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France; ¹⁰ Institut Paoli-Calmettes, Marseille, France; ¹¹ Department of Human Genetics and Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands; ¹² Department of Human Genetics, Spanish National Cancer Center, Madrid, Spain; ¹³ Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik, Iceland; ¹⁴ Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan and FIRC Institute of Molecular Oncology Foundation, Milan, Italy; and ¹⁵ IARC, Lyon, France

Requests for reprints: Jenny Chang-Claude, Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280 69120 Heidelberg, Germany. Phone: 49-6221-422373; Fax: 49-6221-422203. E-mail: j.chang-claude{at}dkfz-heidelberg.de or Nadine Andrieu, INSERM U794/Service de Biostatistiques, Institut Curie, 26 one Miller, 75248 Paris Cedex 05, France. Phone: 33-15543163; Fax: 33-155431469. E-mail: nadine.andrieu{at}curie.net

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]; 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. (Cancer Epidemiol Biomarkers Prev 2007;16(4):740–6)