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1. Performance of the Breast Cancer Risk Assessment Tool Among Women Aged 75 Years and Older

Author

Schonberg, Mara A, Li, Vicky W, Eliassen, A Heather, Davis, Roger B, LaCroix, Andrea Z, McCarthy, Ellen P, Rosner, Bernard A, Chlebowski, Rowan T, Rohan, Thomas E, Hankinson, Susan E, Marcantonio, Edward R, and Ngo, Long H

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Aging, Breast Cancer, Clinical Research, Human Genome, Genetics, Cancer, Good Health and Well Being, Age Factors, Aged, Aged, 80 and over, Breast Neoplasms, Cause of Death, Early Detection of Cancer, Female, Follow-Up Studies, Humans, Incidence, Mammography, Mass Screening, Middle Aged, Models, Statistical, Odds Ratio, Risk Assessment, Risk Factors, United States, Whites, Women's Health, White People, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundThe Breast Cancer Risk Assessment Tool (BCRAT, "Gail model") is commonly used for breast cancer prediction; however, it has not been validated for women age 75 years and older.MethodsWe used Nurses' Health Study (NHS) data beginning in 2004 and Women's Health Initiative (WHI) data beginning in 2005 to compare BCRAT's performance among women age 75 years and older with that in women age 55 to 74 years in predicting five-year breast cancer incidence. BCRAT risk factors include: age, race/ethnicity, age at menarche, age at first birth, family history, history of benign breast biopsy, and atypia. We examined BCRAT's calibration by age by comparing expected/observed (E/O) ratios of breast cancer incidence. We examined discrimination by computing c-statistics for the model by age. All statistical tests were two-sided.ResultsSeventy-three thousand seventy-two NHS and 97 081 WHI women participated. NHS participants were more likely to be non-Hispanic white (96.2% vs 84.7% in WHI, P < .001) and were less likely to develop breast cancer (1.8% vs 2.0%, P = .02). E/O ratios by age in NHS were 1.16 (95% confidence interval [CI] = 1.09 to 1.23, age 57-74 years) and 1.31 (95% CI = 1.18 to 1.45, age ≥ 75 years, P = .02), and in WHI 1.03 (95% CI = 0.97 to 1.09, age 55-74 years) and 1.10 (95% CI = 1.00 to 1.21, age ≥ 75 years, P = .21). E/O ratio 95% confidence intervals crossed one among women age 75 years and older when samples were limited to women who underwent mammography and were without significant illness. C-statistics ranged between 0.56 and 0.58 in both cohorts regardless of age.ConclusionsBCRAT accurately predicted breast cancer for women age 75 years and older who underwent mammography and were without significant illness but had modest discrimination. Models that consider individual competing risks of non-breast cancer death may improve breast cancer risk prediction for older women.

Published
2016

2. Identification of Novel Genetic Markers of Breast Cancer Survival

Author

Guo, Qi, Schmidt, Marjanka K., Kraft, Peter, Canisius, Sander, Chen, Constance, Khan, Sofia, Tyrer, Jonathan, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Michailidou, Kyriaki, Lush, Michael, Kar, Siddhartha, Beesley, Jonathan, Dunning, Alison M., Shah, Mitul, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Lambrechts, Diether, Weltens, Caroline, Leunen, Karin, Bojesen, Stig E., Nordestgaard, Børge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Blomqvist, Carl, Aittomäki, Kristiina, Fagerholm, Rainer, Muranen, Taru A., Couch, Fergus J., Olson, Janet E., Vachon, Celine, Andrulis, Irene L., Knight, Julia A., Glendon, Gord, Mulligan, Anna Marie, Broeks, Annegien, Hogervorst, Frans B., Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Hopper, John L., Tsimiklis, Helen, Apicella, Carmel, Southey, Melissa C., Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Giles, Graham G., Milne, Roger L., McLean, Catriona, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Hooning, Maartje J., Hollestelle, Antoinette, Martens, John W. M., van den Ouweland, Ans M. W., Marme, Federik, Schneeweiss, Andreas, Yang, Rongxi, Burwinkel, Barbara, Figueroa, Jonine, Chanock, Stephen J., Lissowska, Jolanta, Sawyer, Elinor J., Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Holleczek, Bernd, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Li, Jingmei, Brand, Judith S., Humphreys, Keith, Devilee, Peter, Tollenaar, Rob A. E. M., Seynaeve, Caroline, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Mariani, Paolo, Fasching, Peter A., Beckmann, Matthias W., Hein, Alexander, Ekici, Arif B., Chenevix-Trench, Georgia, Balleine, Rosemary, Phillips, Kelly-Anne, Benitez, Javier, Zamora, M. Pilar, Arias Perez, Jose Ignacio, Menéndez, Primitiva, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Hamann, Ute, Kabisch, Maria, Ulmer, Hans Ulrich, Rüdiger, Thomas, Margolin, Sara, Kristensen, Vessela, Nord, Silje, Evans, D. Gareth, Abraham, Jean E., Earl, Helena M., Hiller, Louise, Dunn, Janet A., Bowden, Sarah, Berg, Christine, Campa, Daniele, Diver, W. Ryan, Gapstur, Susan M., Gaudet, Mia M., Hankinson, Susan E., Hoover, Robert N., Hüsing, Anika, Kaaks, Rudolf, Machiela, Mitchell J., Willett, Walter, Barrdahl, Myrto, Canzian, Federico, Chin, Suet-Feung, Caldas, Carlos, Hunter, David J., Lindstrom, Sara, García-Closas, Montserrat, Hall, Per, Easton, Douglas F., Eccles, Diana M., Rahman, Nazneen, Nevanlinna, Heli, and Pharoah, Paul D. P.

Published
2015
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3. Leveraging Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

Author

Schully, Sheri D., Carrick, Danielle M., Mechanic, Leah E., Srivastava, Sudhir, Anderson, Garnet L., Baron, John A., Berg, Christine D., Cullen, Jennifer, Diamandis, Eleftherios P., Doria-Rose, V. Paul, Goddard, Katrina A. B., Hankinson, Susan E., Kushi, Lawrence H., Larson, Eric B., McShane, Lisa M., Schilsky, Richard L., Shak, Steven, Skates, Steven J., Urban, Nicole, Kramer, Barnett S., Khoury, Muin J., and Ransohoff, David F.

Published
2015
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5. Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status

Author

Jung, Seungyoun, Spiegelman, Donna, Baglietto, Laura, Bernstein, Leslie, Boggs, Deborah A., van den Brandt, Piet A., Buring, Julie E., Cerhan, James R., Gaudet, Mia M., Giles, Graham G., Goodman, Gary, Hakansson, Niclas, Hankinson, Susan E., Helzlsouer, Kathy, Horn-Ross, Pamela L., Inoue, Manami, Krogh, Vittorio, Lof, Marie, McCullough, Marjorie L., Miller, Anthony B., Neuhouser, Marian L., Palmer, Julie R., Park, Yikyung, Robien, Kim, Rohan, Thomas E., Scarmo, Stephanie, Schairer, Catherine, Schouten, Leo J., Shikany, James M., Sieri, Sabina, Tsugane, Schoichiro, Visvanathan, Kala, Weiderpass, Elisabete, Willett, Walter C., Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zhang, Shumin M., Zhang, Xuehong, Ziegler, Regina G., and Smith-Warner, Stephanie A.

Published
2013
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6. Circulating Carotenoids and Risk of Breast Cancer: Pooled Analysis of Eight Prospective Studies

Author

Eliassen, A. Heather, Hendrickson, Sara J., Brinton, Louise A., Buring, Julie E., Campos, Hannia, Dai, Qi, Dorgan, Joanne F., Franke, Adrian A., Gao, Yu-tang, Goodman, Marc T., Hallmans, Göran, Helzlsouer, Kathy J., Hoffman-Bolton, Judy, Hultén, Kerstin, Sesso, Howard D., Sowell, Anne L., Tamimi, Rulla M., Toniolo, Paolo, Wilkens, Lynne R., Winkvist, Anna, Zeleniuch-Jacquotte, Anne, Zheng, Wei, and Hankinson, Susan E.

Published
2012
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8. Interactions Between Genetic Variants and Breast Cancer Risk Factors in the Breast and Prostate Cancer Cohort Consortium

Author

Campa, Daniele, Kaaks, Rudolf, Le Marchand, Loïc, Haiman, Christopher A., Travis, Ruth C., Berg, Christine D., Buring, Julie E., Chanock, Stephen J., Diver, W. Ryan, Dostal, Lucie, Fournier, Agnes, Hankinson, Susan E., Henderson, Brian E., Hoover, Robert N., Isaacs, Claudine, Johansson, Mattias, Kolonel, Laurence N., Kraft, Peter, Lee, I-Min, McCarty, Catherine A., Overvad, Kim, Panico, Salvatore, Peeters, Petra H.M., Riboli, Elio, Sanchez, Maria José, Schumacher, Fredrick R., Skeie, Guri, Stram, Daniel O., Thun, Michael J., Trichopoulos, Dimitrios, Zhang, Shumin, Ziegler, Regina G., Hunter, David J., Lindström, Sara, and Canzian, Federico

Published
2011
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9. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

Author

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

Published
2011
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28. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women

Author

Hankinson, Susan E., Willett, Walter C., Manson, Joann E., Colditz, Graham A., Hunter, David J., Spiegelman, Donna, Barbieri, Robert L., and Speizer, Frank E.

Subjects
Breast cancer -- Risk factors, Postmenopausal women -- Health aspects, Estrogen -- Measurement, Health
Abstract

Background: A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study. Methods: Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection. Results: From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23-4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy. Conclusion: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer. [J Natl Cancer Inst 1998;90: 1292-9]

Published
1998

29. Physical activity and breast cancer risk in a cohort of young women

Author

Rockhill, Beverly, Willett, Walter C., Hunter, David J., Manson, Joann E., Hankinson, Susan E., Spiegelman, Donna, and Colditz, Graham A.

Subjects
Breast cancer -- Risk factors, Women's fitness -- Health aspects, Health
Abstract

Background: Increased physical activity has been hypothesized to be a means of breast cancer prevention. We examined the associations between physical activity at two different times in life and breast cancer risk. Methods: We analyzed data from the Nurses' Health Study II, a prospective study of women aged 25-42 years in 1989. On the baseline survey, women were asked, 'While in high school and between the ages 18 and 22 years, how often did you participate in strenuous physical activity at least twice a week?' We averaged answers to these two questions to develop a measure of late adolescent activity. Women were also asked at baseline to report the number of hours per week they currently spent in different nonoccupational activities. During 6 years of follow-up, we identified 372 cases of invasive breast cancer. Data were analyzed by use of multivariate pooled logistic regression to produce relative risk (RR) and confidence intervals (CIs) of being diagnosed with the disease. Results: Women who were more active in late adolescence were not at reduced risk of breast cancer compared with less active women. For those women who reported engaging in strenuous activity at least twice per week for 10-12 months per year in late adolescence, the RR of cancer, compared with those who never engaged in such activity, was 1.1 (95% CI = 0.8-1.6). Similarly, higher levels of recent nonoccupational physical activity were not associated with reduced risk of breast cancer (RR for [is greater than or equal to] 7 hours of activity/week relative to [is less than] 1 hour/week = 1.1; 95% CI = 0.8-1.5). Conclusion: Our findings do not support a link between physical activity, in late adolescence or in the recent past, and breast cancer risk among young adult women. [J Natl Cancer Inst 1998;90:1155-60]

Published
1998

30. Geographic variation in breast cancer incidence rates in a cohort of U.S. women

Author

Laden, Francine, Spiegelman, Donna, Neas, Lucas M., Colditz, Graham A., Hankinson, Susan E., Manson, Joann E., Byrne, Celia, Rosner, Bernard A., Speizer, Frank E., and Hunter, David J.

Subjects
Breast cancer -- Demographic aspects, Medical geography -- Research, Health
Abstract

Background: Breast cancer mortality and incidence rates vary by geographic region in the United States. Previous analytic studies have measured mortality, not incidence, and have used regional prevalences to control for geographic variation in risk factors rather than adjusting for risk factors measured at the level of the individual. We prospectively evaluated regional variation in breast cancer incidence rates in the Nurses' Health Study and assessed the influence of breast cancer risk factors measured at the individual level. Methods: The Nurses' Health Study cohort was established in 1976 when 121700 female nurses aged 30-55 years living in 11 U.S. states were enrolled. These states represent all four regions of the continental United States. We identified 3603 incident cases of invasive breast cancer through 1992 (1794565 person-years of follow-up). We calculated relative risks (RRs) adjusted for age and for age and established risk factors (i.e., multivariate-adjusted analysis), comparing California, the Northeast, and the Midwest with the South. Results: For premenopausal women, there was little evidence of regional variation in breast cancer incidence rates, either in age-adjusted or in multivariate-adjusted analyses. For postmenopausal women in California, age-adjusted risk was modestly elevated (RR = 1.24; 95% confidence interval [CI] = 1.05-1.47); after adjusting for age and for established risk factors, the excess rate in California was attenuated by 25% (RR = 1.18; 95% CI = 1.00-1.40). No excess of breast cancer incidence was observed for postmenopausal women in either the Northeast or the Midwest. Conclusions: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California. Adjustment for differences in the distribution of established risk factors explained some of the excess risk in California. [J Natl Cancer Inst 1997; 89:1373-8]

Published
1997

31. Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women

Author

Hankinson, Susan E., Willett, Walter C., Manson, Joann E., Hunter, David J., Colditz, Graham A., Stampfer, Meir J., Longcope, Christopher, and Speizer, Frank E.

Subjects
Postmenopausal women -- Health aspects, Drinking of alcoholic beverages -- Health aspects, Stature -- Health aspects, Adipose tissues -- Health aspects, Estrogen -- Measurement, Prolactin -- Measurement, Breast cancer -- Risk factors, Health
Abstract

Background: Alcohol use, height, and postmenopausal adiposity have each been positively associated with postmenopausal breast cancer risk in most epidemiologic studies. The mechanism underlying these associations is unclear, although an effect of these factors on hormone levels has been hypothesized. Few previous studies have evaluated the relationship of either alcohol consumption or height with plasma hormone levels. A positive association between adiposity and plasma estrogen levels in postmenopausal women has been reported consistently. Purpose: Using archived frozen plasma samples and corresponding data from participants in the Nurses' Health Study, we determined plasma hormone levels and assessed these levels in relation to alcohol consumption, height, and adiposity among postmenopausal women. Methods: Blood samples were collected from a subset of participants in the Nurses' Health Study in 1989 and 1990, then stored in liquid nitrogen. Hormone concentrations in 217 archived plasma samples (from healthy postmenopausal women) were analyzed in 1993. Spearman correlation coefficients were calculated to assess the linear association between alcohol consumption during the previous year (mean daily intake in grams per day ascertained from semiquantitative food-frequency questionnaires completed in 1990 or 1991), height, and adiposity (as measured by body mass index [BMI] in kg/[m.sup.2] with weight reported at time of blood collection), and plasma hormone levels. Two-sided P values were also calculated. Results: After controlling for age, height, smoking status, and BMI, alcohol consumption was positively associated with estrone sulfate concentrations (r = .17; P = .02); no statistically significant association was noted for the other plasma hormones measured. Mean plasma estrone sulfate levels were 159 pg/mL in women who reported no alcohol use versus 211 pg/mL in women consuming 30 g or more of alcohol per day. After adjusting for the other covariates, we observed a strong positive correlation between BMI and plasma estrogens (r ranging from .37 for estrone and estrone sulfate to .63 for bioavailable estradiol, with all P values

Published
1995

32. 1,1-Dichloro-2,2,bis(p-chlorophenyl) ethylene and Polychlorinated Biphenyls and Breast Cancer: Combined Analysis of Five U.S. Studies

Author

Laden, Francine, Collman, Gwen, Iwamoto, Kumiko, Alberg, Anthony J., Berkowitz, Gertrud S., Freudenheim, Jo L., Hankinson, Susan E., Helzlsouer, Kathy J., Holford, Theodore R., Huang, Han-Yao, Moysich, Kristen B., Tessari, John D., Wolff, Mary S., Zheng, Tongzhang, and Hunter, David J.

Subjects
Breast cancer -- Risk factors, Organochlorine compounds -- Health aspects, Health
Abstract

Background: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. Methods: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. Results: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/[m.sup.2]); however, the risk was statistically nonsignificantly decreased among heavier women. Conclusions: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States. [J Natl Cancer Inst 2001;93:768-76]

Published
2001

33. Performance of the Breast Cancer Risk Assessment Tool Among Women Age 75 Years and Older

Author

Schonberg, Mara A., primary, Li, Vicky W., additional, Eliassen, A. Heather, additional, Davis, Roger B., additional, LaCroix, Andrea Z., additional, McCarthy, Ellen P., additional, Rosner, Bernard A., additional, Chlebowski, Rowan T., additional, Rohan, Thomas E., additional, Hankinson, Susan E., additional, Marcantonio, Edward R., additional, and Ngo, Long H., additional

Published
2015
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34. Ovarian cancer among black women

Author

Colditz, Graham A., Hankinson, Susan E., and Avery, Byllye Y.

Subjects
Ovarian cancer -- Risk factors, African American women -- Diseases, Disease susceptibility -- Research, Health
Published
1993

35. Central Adiposity and Subsequent Risk of Breast Cancer by Menopause Status.

Author

Houghton SC, Eliassen H, Tamimi RM, Willett WC, Rosner BA, and Hankinson SE

Subjects
Adiposity, Body Mass Index, Female, Humans, Premenopause, Prospective Studies, Risk Factors, Waist Circumference, Breast Neoplasms epidemiology, Breast Neoplasms etiology
Abstract

Background: Increased body mass index (BMI) is associated with higher postmenopausal breast cancer risk and lower premenopausal breast cancer risk. Less is known about the central adiposity-breast cancer risk association, particularly for tumor subtypes., Methods: We used prospective waist (WC) and hip circumference (HC) measures in the Nurses' Health Studies. We examined associations of WC, HC, and waist-to-hip ratio (WHR) with breast cancer independent of BMI, by menopausal status. Cox proportional hazards models estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for breast cancer risk factors, with and without BMI., Results: Adjusting for BMI, WC and HC were not associated, and WHR was positively associated with premenopausal breast cancer risk (WHR, quintile 5 vs 1: HRQ5vQ1, BMI-adjusted = 1.27, 95% CI = 1.04 to 1.54; Ptrend = .01), particularly for estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) and basal-like breast cancers. Premenopausal WC, HC, and WHR were not associated with postmenopausal breast cancer risk, with or without BMI adjustment. Postmenopausal WC, HC, and WHR were each positively associated with postmenopausal breast cancer (eg, WC HRQ5vsQ1 = 1.59, 95% CI = 1.36 to 1.86); after adjustment for BMI, only WC remained statistically significant (HRQ5vsQ1, BMI-adjusted = 1.38, 95% CI = 1.15 to 1.64; Ptrend = .002). In postmenopausal women, associations were stronger among never-users of hormone therapy and for ER+/PR+ breast cancers., Conclusions: Central adiposity was positively associated with pre- and postmenopausal breast cancers independent of BMI. This suggests that mechanisms other than estrogen may also play a role in the relationship between central adiposity and breast cancer. Maintaining a healthy waist circumference may decrease pre- and postmenopausal breast cancer risk., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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36. Early-Life Body Adiposity and the Breast Tumor Transcriptome.

Author

Wang J, Peng C, Guranich C, Heng YJ, Baker GM, Rubadue CA, Glass K, Eliassen AH, Tamimi RM, Polyak K, and Hankinson S

Subjects
Adiposity genetics, Adolescent, Adult, Child, Female, Humans, Obesity genetics, Phosphatidylinositol 3-Kinases genetics, Young Adult, Breast Neoplasms pathology, Transcriptome
Abstract

Background: Cumulative epidemiologic evidence has shown that early-life adiposity is strongly inversely associated with breast cancer risk throughout life, independent of adult obesity. However, the molecular mechanisms remain poorly understood., Methods: We assessed the association of early-life adiposity, defined as self-reported body size during ages 10-20 years from a validated 9-level pictogram, with the transcriptome of breast tumor (N = 835) and tumor-adjacent histologically normal tissue (N = 663) in the Nurses' Health Study. We conducted multivariable linear regression analysis to identify differentially expressed genes in tumor and tumor-adjacent tissue, respectively. Molecular pathway analysis using Hallmark gene sets (N = 50) was further performed to gain biological insights. Analysis was stratified by tumor estrogen receptor (ER) protein expression status (n = 673 for ER+ and 162 for ER- tumors)., Results: No gene was statistically significantly differentially expressed by early-life body size after multiple comparison adjustment. However, pathway analysis revealed several statistically significantly (false discovery rate < 0.05) upregulated or downregulated gene sets. In stratified analyses by tumor ER status, larger body size during ages 10-20 years was associated with decreased cellular proliferation pathways, including MYC target genes, in both ER+ and ER- tumors. In ER+ tumors, larger body size was also associated with upregulation in genes involved in TNFα/NFkB signaling. In ER- tumors, larger body size was additionally associated with downregulation in genes involved in interferon α and interferon γ immune response and Phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling; the INFγ response pathway was also downregulated in ER- tumor-adjacent tissue, though at borderline statistical significance (false discovery rate = 0.1)., Conclusions: These findings provide new insights into the biological and pathological underpinnings of the early-life adiposity and breast cancer association., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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37. Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk.

Author

Reeves KW, Díaz Santana M, Manson JE, Hankinson SE, Zoeller RT, Bigelow C, Sturgeon SR, Spiegelman D, Tinker L, Luo J, Chen B, Meliker J, Bonner MR, Cote ML, Cheng TD, and Calafat AM

Subjects
Aged, Biomarkers, Tumor, Breast Neoplasms metabolism, Case-Control Studies, Creatinine urine, Female, Humans, Middle Aged, Odds Ratio, Risk Assessment, Risk Factors, Biomarkers, Breast Neoplasms etiology, Breast Neoplasms urine, Disease Susceptibility, Phthalic Acids urine
Abstract

Background: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking., Methods: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up., Results: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years., Conclusions: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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38. Androgen Receptor Expression and Breast Cancer Survival: Results From the Nurses' Health Studies.

Author

Kensler KH, Poole EM, Heng YJ, Collins LC, Glass B, Beck AH, Hazra A, Rosner BA, Eliassen AH, Hankinson SE, Winer EP, Brown M, and Tamimi RM

Subjects
Adult, Breast metabolism, Breast pathology, Breast Neoplasms epidemiology, Breast Neoplasms pathology, Cancer Survivors, Female, Gene Expression Regulation, Neoplastic genetics, Humans, Kaplan-Meier Estimate, Middle Aged, Prognosis, Proportional Hazards Models, Receptors, Progesterone genetics, Biomarkers, Tumor genetics, Breast Neoplasms genetics, Receptors, Androgen genetics, Receptors, Estrogen genetics
Abstract

Background: Hormone receptor signaling is critical in the progression of breast cancers, although the role of the androgen receptor (AR) remains unclear, particularly for estrogen receptor (ER)-negative tumors. This study assessed AR protein expression as a prognostic marker for breast cancer mortality., Methods: This study included 4147 pre- and postmenopausal women with invasive breast cancer from the Nurses' Health Study (diagnosed 1976-2008) and Nurses' Health Study II (1989-2008) cohorts. AR protein expression was evaluated by immunohistochemistry and scored through pathologist review and as a digitally quantified continuous measure. Hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer mortality were estimated from Cox proportional hazards models, adjusting for patient, tumor, and treatment covariates., Results: Over a median 16.5 years of follow-up, there were 806 deaths due to breast cancer. In the 7 years following diagnosis, AR expression was associated with a 27% reduction in breast cancer mortality overall (multivariable HR = 0.73, 95% CI = 0.58 to 0.91) a 47% reduction for ER+ cancers (HR = 0.53, 95% CI = 0.41 to 0.69), and a 62% increase for ER- cancers (HR = 1.62, 95% CI = 1.18 to 2.22) (P heterogeneity < .001). A log-linear association was observed between AR expression and breast cancer mortality among ER- cancers (HR = 1.14, 95% CI = 1.02 to 1.26 per each 10% increase in AR), although no log-linear association was observed among ER+ cancers., Conclusions: AR expression was associated with improved prognosis in ER+ tumors and worse prognosis in ER- tumors in the first 5-10 years postdiagnosis. These findings support the continued evaluation of AR-targeted therapies for AR+/ER- breast cancers., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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