Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

Journal: Journal Of The National Cancer Institute

Published: December 31, 2010

Abstract

Background: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.

Methods: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.

Results: In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.

Conclusions: This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Authors

Xiaohong Yang, Jenny Chang Claude, Ellen Goode, Fergus Couch, Heli Nevanlinna, Roger Milne, Mia Gaudet, Marjanka Schmidt, Annegien Broeks, Angela Cox, Peter Fasching, Rebecca Hein, Amanda Spurdle, Fiona Blows, Kristy Driver, Dieter Flesch Janys, Judith Heinz, Peter Sinn, Alina Vrieling, Tuomas Heikkinen, Kristiina Aittomäki, Päivi Heikkilä, Carl Blomqvist, Jolanta Lissowska, Beata Peplonska, Stephen Chanock, Jonine Figueroa, Louise Brinton, Per Hall, Kamila Czene, Keith Humphreys, Hatef Darabi, Jianjun Liu, Laura Van 't Veer, Flora Van Leeuwen, Irene Andrulis, Gord Glendon, Julia Knight, Anna Mulligan, Frances O'malley, Nayana Weerasooriya, Esther John, Matthias Beckmann, Arndt Hartmann, Sebastian Weihbrecht, David Wachter, Sebastian Jud, Christian Loehberg, Laura Baglietto, Dallas English, Graham Giles, Catriona Mclean, Gianluca Severi, Diether Lambrechts, Thijs Vandorpe, Caroline Weltens, Robert Paridaens, Ann Smeets, Patrick Neven, Hans Wildiers, Xianshu Wang, Janet Olson, Victoria Cafourek, Zachary Fredericksen, Matthew Kosel, Celine Vachon, Helen Cramp, Daniel Connley, Simon Cross, Sabapathy Balasubramanian, Malcolm W Reed, Thilo Dörk, Michael Bremer, Andreas Meyer, Johann Karstens, Aysun Ay, Tjoung-won Park Simon, Peter Hillemanns, Jose Arias Pérez, Primitiva Menéndez Rodríguez, Pilar Zamora, Javier Benítez, Yon-dschun Ko, Hans-peter Fischer, Ute Hamann, Beate Pesch, Thomas Brüning, Christina Justenhoven, Hiltrud Brauch, Diana Eccles, William Tapper, Sue Gerty, Elinor Sawyer, Ian Tomlinson, Angela Jones, Michael Kerin, Nicola Miller, Niall Mcinerney, Hoda Anton Culver, Argyrios Ziogas, Chen-yang Shen, Chia-ni Hsiung, Pei-ei Wu, Show-lin Yang, Jyh-cherng Yu, Shou-tung Chen, Giu-cheng Hsu, Christopher Haiman, Brian Henderson, Loic Le Marchand, Laurence Kolonel, Annika Lindblom, Sara Margolin, Anna Jakubowska, Jan Lubiński, Tomasz Huzarski, Tomasz Byrski, Bohdan Górski, Jacek Gronwald, Maartje Hooning, Antoinette Hollestelle, Ans M Van Den Ouweland, Agnes Jager, Mieke Kriege, Madeleine M Tilanus Linthorst, Margriet Collée, Shan Wang Gohrke, Katri Pylkäs, Arja Jukkola Vuorinen, Kari Mononen, Mervi Grip, Pasi Hirvikoski, Robert Winqvist, Arto Mannermaa, Veli-matti Kosma, Jaana Kauppinen, Vesa Kataja, Päivi Auvinen, Ylermi Soini, Reijo Sironen, Stig Bojesen, David Ørsted, Diljit Kaur Knudsen, Henrik Flyger, Børge Nordestgaard, Helene Holland, Georgia Chenevix Trench, Siranoush Manoukian, Monica Barile, Paolo Radice, Susan Hankinson, David Hunter, Rulla Tamimi, Suleeporn Sangrajrang, Paul Brennan, James Mckay, Fabrice Odefrey, Valerie Gaborieau, Peter Devilee, P E Huijts, R A E Tollenaar, C Seynaeve, Gillian Dite, Carmel Apicella, John Hopper, Fleur Hammet, Helen Tsimiklis, Letitia Smith, Melissa Southey, Manjeet Humphreys, Douglas Easton, Paul Pharoah, Mark Sherman, Montserrat Garcia Closas

Relevant Conditions

Breast Cancer, Obesity

Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

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