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Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.
J Natl Cancer Inst. 2011 Feb 02; 103(3):250-63.JNCI

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+Show Affiliations

Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Sciences, Rockville, MD 20852, USA. royang@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info 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Pub Type(s)

Journal Article
Meta-Analysis
Research Support, American Recovery and Reinvestment Act
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21191117

Citation

Yang, Xiaohong R., et al. "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, vol. 103, no. 3, 2011, pp. 250-63.
Yang XR, Chang-Claude J, Goode EL, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011;103(3):250-63.
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), 250-63. https://doi.org/10.1093/jnci/djq526
Yang XR, et al. Associations of Breast Cancer Risk Factors With Tumor Subtypes: a Pooled Analysis From the Breast Cancer Association Consortium Studies. J Natl Cancer Inst. 2011 Feb 2;103(3):250-63. PubMed PMID: 21191117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. AU - Yang,Xiaohong R, AU - Chang-Claude,Jenny, AU - Goode,Ellen L, AU - Couch,Fergus J, AU - Nevanlinna,Heli, AU - Milne,Roger L, AU - Gaudet,Mia, AU - Schmidt,Marjanka K, AU - Broeks,Annegien, AU - Cox,Angela, AU - Fasching,Peter A, AU - Hein,Rebecca, AU - Spurdle,Amanda B, AU - Blows,Fiona, AU - Driver,Kristy, AU - Flesch-Janys,Dieter, AU - Heinz,Judith, AU - Sinn,Peter, AU - Vrieling,Alina, AU - Heikkinen,Tuomas, AU - Aittomäki,Kristiina, AU - Heikkilä,Päivi, AU - Blomqvist,Carl, AU - Lissowska,Jolanta, AU - Peplonska,Beata, AU - Chanock,Stephen, AU - Figueroa,Jonine, AU - Brinton,Louise, AU - Hall,Per, AU - Czene,Kamila, AU - Humphreys,Keith, AU - Darabi,Hatef, AU - Liu,Jianjun, AU - Van 't Veer,Laura J, AU - van Leeuwen,Flora E, AU - Andrulis,Irene L, AU - Glendon,Gord, AU - Knight,Julia A, AU - Mulligan,Anna Marie, AU - O'Malley,Frances P, AU - Weerasooriya,Nayana, AU - John,Esther M, AU - Beckmann,Matthias W, AU - Hartmann,Arndt, AU - Weihbrecht,Sebastian B, AU - Wachter,David L, AU - Jud,Sebastian M, AU - Loehberg,Christian R, AU - Baglietto,Laura, AU - English,Dallas R, AU - Giles,Graham G, AU - McLean,Catriona A, AU - Severi,Gianluca, AU - Lambrechts,Diether, AU - Vandorpe,Thijs, AU - Weltens,Caroline, AU - Paridaens,Robert, AU - Smeets,Ann, AU - Neven,Patrick, AU - Wildiers,Hans, AU - Wang,Xianshu, AU - Olson,Janet E, AU - Cafourek,Victoria, AU - Fredericksen,Zachary, AU - Kosel,Matthew, AU - Vachon,Celine, AU - Cramp,Helen E, AU - Connley,Daniel, AU - Cross,Simon S, AU - Balasubramanian,Sabapathy P, AU - Reed,Malcolm W R, AU - Dörk,Thilo, AU - Bremer,Michael, AU - Meyer,Andreas, AU - Karstens,Johann H, AU - Ay,Aysun, AU - Park-Simon,Tjoung-Won, AU - Hillemanns,Peter, AU - Arias Pérez,Jose Ignacio, AU - Menéndez Rodríguez,Primitiva, AU - Zamora,Pilar, AU - Benítez,Javier, AU - Ko,Yon-Dschun, AU - Fischer,Hans-Peter, AU - Hamann,Ute, AU - Pesch,Beate, AU - Brüning,Thomas, AU - Justenhoven,Christina, AU - Brauch,Hiltrud, AU - Eccles,Diana M, AU - Tapper,William J, AU - Gerty,Sue M, AU - Sawyer,Elinor J, AU - Tomlinson,Ian P, AU - Jones,Angela, AU - Kerin,Michael, AU - Miller,Nicola, AU - McInerney,Niall, AU - Anton-Culver,Hoda, AU - Ziogas,Argyrios, AU - Shen,Chen-Yang, AU - Hsiung,Chia-Ni, AU - Wu,Pei-Ei, AU - Yang,Show-Lin, AU - Yu,Jyh-Cherng, AU - Chen,Shou-Tung, AU - Hsu,Giu-Cheng, AU - Haiman,Christopher A, AU - Henderson,Brian E, AU - Le Marchand,Loic, AU - Kolonel,Laurence N, AU - Lindblom,Annika, AU - Margolin,Sara, AU - Jakubowska,Anna, AU - Lubiński,Jan, AU - Huzarski,Tomasz, AU - Byrski,Tomasz, AU - Górski,Bohdan, AU - Gronwald,Jacek, AU - Hooning,Maartje J, AU - Hollestelle,Antoinette, AU - van den Ouweland,Ans M W, AU - Jager,Agnes, AU - Kriege,Mieke, AU - Tilanus-Linthorst,Madeleine M A, AU - Collée,Margriet, AU - Wang-Gohrke,Shan, AU - Pylkäs,Katri, AU - Jukkola-Vuorinen,Arja, AU - Mononen,Kari, AU - Grip,Mervi, AU - Hirvikoski,Pasi, AU - Winqvist,Robert, AU - Mannermaa,Arto, AU - Kosma,Veli-Matti, AU - Kauppinen,Jaana, AU - Kataja,Vesa, AU - Auvinen,Päivi, AU - Soini,Ylermi, AU - Sironen,Reijo, AU - Bojesen,Stig E, AU - Ørsted,David Dynnes, AU - Kaur-Knudsen,Diljit, AU - Flyger,Henrik, AU - Nordestgaard,Børge G, AU - Holland,Helene, AU - Chenevix-Trench,Georgia, AU - Manoukian,Siranoush, AU - Barile,Monica, AU - Radice,Paolo, AU - Hankinson,Susan E, AU - Hunter,David J, AU - Tamimi,Rulla, AU - Sangrajrang,Suleeporn, AU - Brennan,Paul, AU - McKay,James, AU - Odefrey,Fabrice, AU - Gaborieau,Valerie, AU - Devilee,Peter, AU - Huijts,P E A, AU - Tollenaar,R A E M, AU - Seynaeve,C, AU - Dite,Gillian S, AU - Apicella,Carmel, AU - Hopper,John L, AU - Hammet,Fleur, AU - Tsimiklis,Helen, AU - Smith,Letitia D, AU - Southey,Melissa C, AU - Humphreys,Manjeet K, AU - Easton,Douglas, AU - Pharoah,Paul, AU - Sherman,Mark E, AU - Garcia-Closas,Montserrat, Y1 - 2010/12/29/ PY - 2010/12/31/entrez PY - 2010/12/31/pubmed PY - 2011/3/11/medline SP - 250 EP - 63 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 103 IS - 3 N2 - 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. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/21191117/Associations_of_breast_cancer_risk_factors_with_tumor_subtypes:_a_pooled_analysis_from_the_Breast_Cancer_Association_Consortium_studies_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djq526 DB - PRIME DP - Unbound Medicine ER -