Associations of breast cancer risk factors with tumor subtypes: A pooled analysis from the breast cancer association consortium studies

Xiaohong R. Yang, Jenny Chang-Claude, Ellen L. Goode, Fergus J. Couch, Heli Nevanlinna, Roger L. Milne, Mia Gaudet, Marjanka K. Schmidt, Annegien Broeks, Angela Cox, Peter A. Fasching, Rebecca Hein, Amanda B. Spurdle, Fiona Blows, Kristy Driver, Dieter Flesch-Janys, Judith Heinz, Peter Sinn, Alina Vrieling, Tuomas HeikkinenKristiina 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 J. Van 'T Veer, Flora E. Van Leeuwen, Irene L. Andrulis, Gord Glendon, Julia A. Knight, Anna Marie Mulligan, Frances P. O'Malley, Nayana Weerasooriya, Esther M. John, Matthias W. Beckmann, Arndt Hartmann, Sebastian B. Weihbrecht, David L. Wachter, Sebastian M. Jud, Christian R. Loehberg, Laura Baglietto, Dallas R. English, Graham G. Giles, Catriona A. McLean, Gianluca Severi, Diether Lambrechts, Thijs Vandorpe, Caroline Weltens, Robert Paridaens, Ann Smeets, Patrick Neven, Hans Wildiers, Xianshu Wang, Janet E. Olson, Victoria Cafourek, Zachary Fredericksen, Matthew Kosel, Celine Vachon, Helen E. Cramp, Daniel Connley, Simon S. Cross, Sabapathy P. Balasubramanian, Malcolm W R Reed, Thilo Dörk, Michael Bremer, Andreas Meyer, Johann H. Karstens, Aysun Ay, Tjoung Won Park-Simon, Peter Hillemanns, Jose Ignacio 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 M. Eccles, William J. Tapper, Sue M. Gerty, Elinor J. Sawyer, Ian P. 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 A. Haiman, Brian E. Henderson, Loic Le Marchand, Laurence N. Kolonel, Annika Lindblom, Sara Margolin, Anna Jakubowska, Jan Lubiński, Tomasz Huzarski, Tomasz Byrski, Bohdan Górski, Jacek Gronwald, Maartje J. Hooning, Antoinette Hollestelle, Ans M W Van Den Ouweland, Agnes Jager, Mieke Kriege, Madeleine M A 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 E. Bojesen, David Dynnes Ørsted, Diljit Kaur-Knudsen, Henrik Flyger, Børge G. Nordestgaard, Helene Holland, Georgia Chenevix-Trench, Siranoush Manoukian, Monica Barile, Paolo Radice, Susan E. Hankinson, David J. Hunter, Rulla Tamimi, Suleeporn Sangrajrang, Paul Brennan, James McKay, Fabrice Odefrey, Valerie Gaborieau, Peter Devilee, P. E A Huijts, Raem Tollenaar, C. Seynaeve, Gillian S. Dite, Carmel Apicella, John L. Hopper, Fleur Hammet, Helen Tsimiklis, Letitia D. Smith, Melissa C. Southey, Manjeet K. Humphreys, Douglas Easton, Paul Pharoah, Mark E. Sherman, Montserrat Garcia-Closas

Research output: Contribution to journalArticle

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 35568 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/m2) 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. Conclusion sThis 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.

Original languageEnglish
Pages (from-to)250-263
Number of pages14
JournalJournal of the National Cancer Institute
Volume103
Issue number3
DOIs
Publication statusPublished - Feb 2 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Yang, X. R., Chang-Claude, J., Goode, E. L., Couch, F. J., Nevanlinna, H., Milne, R. L., Gaudet, M., Schmidt, M. K., Broeks, A., Cox, A., Fasching, P. A., Hein, R., Spurdle, A. B., Blows, F., Driver, K., Flesch-Janys, D., Heinz, J., Sinn, P., Vrieling, A., ... Garcia-Closas, M. (2011). Associations of breast cancer risk factors with tumor subtypes: A pooled analysis from the breast cancer association consortium studies. Journal of the National Cancer Institute, 103(3), 250-263. https://doi.org/10.1093/jnci/djq526