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1.  Latinas and Breast Cancer Outcomes: Population-based sampling, Ethnic Identity and Acculturation Assessment 
Purpose
Latinas and African-Americans with breast cancer, especially those of lower socioeconomic status and acculturation, have been underrepresented in studies assessing treatment satisfaction, decision making and quality of life. A study was designed to recruit a large and representative sample of these subgroups.
Methods and Materials
Incident cases were selected by Rapid Case Ascertainment (RCA) by the Los Angeles SEER Registry in 2005-2006, with oversampling of Latinas and African-Americans. Patients were mailed a questionnaire and $10 incentive 5-6 months after diagnosis; non-respondents were contacted by telephone. Multivariate analysis was used to assess possible response bias. The RCA definition of Hispanic origin was validated by self reports. The SASH acculturation index for Latina respondents was used.
Results
1,698 eligible breast cancer cases were selected and 1,223 participated for a response rate of 72.0%, which varied little by race/ethnicity. Age, race/ethnicity, and clinical factors were not associated with response; however respondents were slightly more likely to be married and from higher socioeconomic status census tracts than non-respondents. The RCA definition of Hispanic identity was highly sensitive (94.6%) and specific (90.0%). Lower acculturation was associated with lower education and literacy among Latinas.
Discussion
High response rates among all subgroups were achieved due to use of RCA, an incentive, extensive telephone follow-up, a native Spanish speaking interviewer, and a focused questionnaire. The low acculturation index category identified a highly vulnerable subgroup. This large sample representing subgroups with greater problems will provide a basis for developing better interventions to assist these women.
doi:10.1158/1055-9965.EPI-09-0238
PMCID: PMC4147726  PMID: 19549806
Breast Cancer; Treatment Decision; Latinas; Acculturation; Survey Research; Cancer Registry; Population-Based
2.  Cancer Incidence Trends Among Native Hawaiians and Other Pacific Islanders in the United States, 1990–2008 
Background
Lack of annual population estimates for disaggregated Native Hawaiian and Other Pacific Islander (NHOPI) populations limits the ability to examine cancer incidence rates and trends to understand the cancer burdens among NHOPIs.
Methods
Utilizing 1990 and 2000 population census data, we estimated the annual populations by age and sex for Native Hawaiians, Samoans, and Guamanians/Chamorros for 1990–2008 in regions covered by 13 of the National Cancer Institute’s SEER registries. Cancer diagnoses during 1990–2008 from these registries were used to calculate the age-adjusted (2000 US Standard) incidence rates by sex, calendar year/period, and cancer type for each population. The annual percentage change (APC) in incidence rates was estimated with the 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates.
Results
Statistically significant declining trends were found in Native Hawaiians, in men for lung and stomach cancers (APC = –2.3%; 95% CI = –3.3 to –1.3; and APC = –3.8%; 95% CI = –6.0 to –1.6, respectively), and in women for breast cancer (APC = –4.1%; 95% CI = –5.7 to –2.5) since 1998 and lung cancer (APC = –6.4%; 95% CI = –10.7 to –1.8) since 2001. Rising incidence trends were experienced by Samoans, especially by Samoan women for breast (APC = 2.7%; 95% CI = 0.9 to 4.5) and uterus (APC = 7.3%; 95% CI = 6.2 to 8.4) cancers. With limited data, Guamanians/Chamorros demonstrated lower, but increasing, incidence rates than other NHOPIs.
Conclusions
Population-based cancer incidence rates for disaggregated NHOPI populations help identify disparities in cancer burden and provide valuable information to improve cancer control efforts among NHOPIs.
doi:10.1093/jnci/djt156
PMCID: PMC3735461  PMID: 23878354
3.  Cancer Incidence Trends Among Asian American Populations in the United States, 1990–2008 
Background
National cancer incidence trends are presented for eight Asian American groups: Asian Indians/Pakistanis, Chinese, Filipinos, Japanese, Kampucheans, Koreans, Laotians, and Vietnamese.
Methods
Cancer incidence data from 1990 through 2008 were obtained from 13 Surveillance, Epidemiology, End Results (SEER) registries. Incidence rates from 1990 through 2008 and average percentage change were computed using SEER*Stat and Joinpoint software. The annual percentage change (APC) in incidence rates was estimated with 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates. Rates for non-Hispanic whites are presented for comparison.
Results
Prostate cancer was the most common malignancy among most groups, followed by lung, colorectal, liver, and stomach cancers. Breast cancer was generally the most common cancer in women, followed by colorectal and lung cancers; liver, cervix, thyroid, and stomach cancers also ranked highly. Among men, increasing trends were observed for prostate (Asian Indians and Pakistanis: APC 1990–2003 = 2.2, 95% CI = 0.3 to 4.1; Filipinos: APC 1990–1994 = 19.0, 95% CI = 4.5 to 35.4; Koreans: APC 1990–2008 = 2.9, 95% CI = 1.8 to 4.0), colorectal (Koreans: APC 1990–2008 = 2.2, 95% CI = 0.9 to 3.5), and liver cancers (Filipinos: APC 1990–2008 = 1.6, 95% CI = 0.4 to 2.7; Koreans: APC 1990–2006 = 2.1, 95% CI = 0.4 to 3.7; Vietnamese: APC 1990–2008 = 1.6, 95% CI = 0.3 to 2.8), whereas lung and stomach cancers generally remained stable or decreased. Among women, increases were observed for uterine cancer (Asian Indians: APC 1990–2008 = 3.0, 95% CI = 0.3 to 5.8; Chinese: APC 2004–2008 = 7.0, 95% CI = 1.4 to 12.9; Filipina: APC 1990–2008 = 3.0, 95% CI = 2.4 to 3.7; Japanese: APC 1990–2008 = 1.1, 95% CI = 0.1 to 2.0), colorectal cancer (Koreans: APC 1990–2008 = 2.8, 95% CI = 1.7 to 3.9; Laotians: APC: 1990–2008 = 5.9, 95% CI = 4.0 to 7.7), lung cancer (Filipinas: APC 1990–2008 = 2.1, 95% CI = 1.4 to 2.8; Koreans: APC 1990–2008 = 2.1, 95% CI = 0.6 to 3.6), thyroid cancer (Filipinas: APC 1990–2008 = 2.5, 95% CI = 1.7 to 3.3), and breast cancer in most groups (APC 1990–2008 from 1.2 among Vietnamese and Chinese to 4.7 among Koreans). Decreases were observed for stomach (Chinese and Japanese), colorectal (Chinese), and cervical cancers (Laotians and Vietnamese).
Conclusions
These data fill a critical knowledge gap concerning the cancer experience of Asian American groups and highlight where increased preventive, screening, and surveillance efforts are needed—in particular, lung cancer among Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and Filipino, Kampuchean, and Vietnamese men.
doi:10.1093/jnci/djt157
PMCID: PMC3735462  PMID: 23878350
4.  Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium 
Milne, Roger L. | Burwinkel, Barbara | Michailidou, Kyriaki | Arias-Perez, Jose-Ignacio | Zamora, M. Pilar | Menéndez-Rodríguez, Primitiva | Hardisson, David | Mendiola, Marta | González-Neira, Anna | Pita, Guillermo | Alonso, M. Rosario | Dennis, Joe | Wang, Qin | Bolla, Manjeet K. | Swerdlow, Anthony | Ashworth, Alan | Orr, Nick | Schoemaker, Minouk | Ko, Yon-Dschun | Brauch, Hiltrud | Hamann, Ute | Andrulis, Irene L. | Knight, Julia A. | Glendon, Gord | Tchatchou, Sandrine | Matsuo, Keitaro | Ito, Hidemi | Iwata, Hiroji | Tajima, Kazuo | Li, Jingmei | Brand, Judith S. | Brenner, Hermann | Dieffenbach, Aida Karina | Arndt, Volker | Stegmaier, Christa | Lambrechts, Diether | Peuteman, Gilian | Christiaens, Marie-Rose | Smeets, Ann | Jakubowska, Anna | Lubinski, Jan | Jaworska-Bieniek, Katarzyna | Durda, Katazyna | Hartman, Mikael | Hui, Miao | Yen Lim, Wei | Wan Chan, Ching | Marme, Federick | Yang, Rongxi | Bugert, Peter | Lindblom, Annika | Margolin, Sara | García-Closas, Montserrat | Chanock, Stephen J. | Lissowska, Jolanta | Figueroa, Jonine D. | Bojesen, Stig E. | Nordestgaard, Børge G. | Flyger, Henrik | Hooning, Maartje J. | Kriege, Mieke | van den Ouweland, Ans M.W. | Koppert, Linetta B. | Fletcher, Olivia | Johnson, Nichola | dos-Santos-Silva, Isabel | Peto, Julian | Zheng, Wei | Deming-Halverson, Sandra | Shrubsole, Martha J. | Long, Jirong | Chang-Claude, Jenny | Rudolph, Anja | Seibold, Petra | Flesch-Janys, Dieter | Winqvist, Robert | Pylkäs, Katri | Jukkola-Vuorinen, Arja | Grip, Mervi | Cox, Angela | Cross, Simon S. | Reed, Malcolm W.R. | Schmidt, Marjanka K. | Broeks, Annegien | Cornelissen, Sten | Braaf, Linde | Kang, Daehee | Choi, Ji-Yeob | Park, Sue K. | Noh, Dong-Young | Simard, Jacques | Dumont, Martine | Goldberg, Mark S. | Labrèche, France | Fasching, Peter A. | Hein, Alexander | Ekici, Arif B. | Beckmann, Matthias W. | Radice, Paolo | Peterlongo, Paolo | Azzollini, Jacopo | Barile, Monica | Sawyer, Elinor | Tomlinson, Ian | Kerin, Michael | Miller, Nicola | Hopper, John L. | Schmidt, Daniel F. | Makalic, Enes | Southey, Melissa C. | Hwang Teo, Soo | Har Yip, Cheng | Sivanandan, Kavitta | Tay, Wan-Ting | Shen, Chen-Yang | Hsiung, Chia-Ni | Yu, Jyh-Cherng | Hou, Ming-Feng | Guénel, Pascal | Truong, Therese | Sanchez, Marie | Mulot, Claire | Blot, William | Cai, Qiuyin | Nevanlinna, Heli | Muranen, Taru A. | Aittomäki, Kristiina | Blomqvist, Carl | Wu, Anna H. | Tseng, Chiu-Chen | Van Den Berg, David | Stram, Daniel O. | Bogdanova, Natalia | Dörk, Thilo | Muir, Kenneth | Lophatananon, Artitaya | Stewart-Brown, Sarah | Siriwanarangsan, Pornthep | Mannermaa, Arto | Kataja, Vesa | Kosma, Veli-Matti | Hartikainen, Jaana M. | Shu, Xiao-Ou | Lu, Wei | Gao, Yu-Tang | Zhang, Ben | Couch, Fergus J. | Toland, Amanda E. | Yannoukakos, Drakoulis | Sangrajrang, Suleeporn | McKay, James | Wang, Xianshu | Olson, Janet E. | Vachon, Celine | Purrington, Kristen | Severi, Gianluca | Baglietto, Laura | Haiman, Christopher A. | Henderson, Brian E. | Schumacher, Fredrick | Le Marchand, Loic | Devilee, Peter | Tollenaar, Robert A.E.M. | Seynaeve, Caroline | Czene, Kamila | Eriksson, Mikael | Humphreys, Keith | Darabi, Hatef | Ahmed, Shahana | Shah, Mitul | Pharoah, Paul D.P. | Hall, Per | Giles, Graham G. | Benítez, Javier | Dunning, Alison M. | Chenevix-Trench, Georgia | Easton, Douglas F. | Berchuck, Andrew | Eeles, Rosalind A. | Olama, Ali Amin Al | Kote-Jarai, Zsofia | Benlloch, Sara | Antoniou, Antonis | McGuffog, Lesley | Offit, Ken | Lee, Andrew | Dicks, Ed | Luccarini, Craig | Tessier, Daniel C. | Bacot, Francois | Vincent, Daniel | LaBoissière, Sylvie | Robidoux, Frederic | Nielsen, Sune F. | Cunningham, Julie M. | Windebank, Sharon A. | Hilker, Christopher A. | Meyer, Jeffrey | Angelakos, Maggie | Maskiell, Judi | van der Schoot, Ellen | Rutgers, Emiel | Verhoef, Senno | Hogervorst, Frans | Boonyawongviroj, Prat | Siriwanarungsan, Pornthep | Schrauder, Michael | Rübner, Matthias | Oeser, Sonja | Landrith, Silke | Williams, Eileen | Ryder-Mills, Elaine | Sargus, Kara | McInerney, Niall | Colleran, Gabrielle | Rowan, Andrew | Jones, Angela | Sohn, Christof | Schneeweiß, Andeas | Bugert, Peter | Álvarez, Núria | Lacey, James | Wang, Sophia | Ma, Huiyan | Lu, Yani | Deapen, Dennis | Pinder, Rich | Lee, Eunjung | Schumacher, Fred | Horn-Ross, Pam | Reynolds, Peggy | Nelson, David | Ziegler, Hartwig | Wolf, Sonja | Hermann, Volker | Lo, Wing-Yee | Justenhoven, Christina | Baisch, Christian | Fischer, Hans-Peter | Brüning, Thomas | Pesch, Beate | Rabstein, Sylvia | Lotz, Anne | Harth, Volker | Heikkinen, Tuomas | Erkkilä, Irja | Aaltonen, Kirsimari | von Smitten, Karl | Antonenkova, Natalia | Hillemanns, Peter | Christiansen, Hans | Myöhänen, Eija | Kemiläinen, Helena | Thorne, Heather | Niedermayr, Eveline | Bowtell, D | Chenevix-Trench, G | deFazio, A | Gertig, D | Green, A | Webb, P | Green, A. | Parsons, P. | Hayward, N. | Webb, P. | Whiteman, D. | Fung, Annie | Yashiki, June | Peuteman, Gilian | Smeets, Dominiek | Brussel, Thomas Van | Corthouts, Kathleen | Obi, Nadia | Heinz, Judith | Behrens, Sabine | Eilber, Ursula | Celik, Muhabbet | Olchers, Til | Manoukian, Siranoush | Peissel, Bernard | Scuvera, Giulietta | Zaffaroni, Daniela | Bonanni, Bernardo | Feroce, Irene | Maniscalco, Angela | Rossi, Alessandra | Bernard, Loris | Tranchant, Martine | Valois, Marie-France | Turgeon, Annie | Heguy, Lea | Sze Yee, Phuah | Kang, Peter | Nee, Kang In | Mariapun, Shivaani | Sook-Yee, Yoon | Lee, Daphne | Ching, Teh Yew | Taib, Nur Aishah Mohd | Otsukka, Meeri | Mononen, Kari | Selander, Teresa | Weerasooriya, Nayana | staff, OFBCR | Krol-Warmerdam, E. | Molenaar, J. | Blom, J. | Brinton, Louise | Szeszenia-Dabrowska, Neonila | Peplonska, Beata | Zatonski, Witold | Chao, Pei | Stagner, Michael | Bos, Petra | Blom, Jannet | Crepin, Ellen | Nieuwlaat, Anja | Heemskerk, Annette | Higham, Sue | Cross, Simon | Cramp, Helen | Connley, Dan | Balasubramanian, Sabapathy | Brock, Ian | Luccarini, Craig | Conroy, Don | Baynes, Caroline | Chua, Kimberley
Human Molecular Genetics  2014;23(22):6096-6111.
Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04–1.10, P = 2.9 × 10−6], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03–1.07, P = 1.7 × 10−6) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07–1.12, P = 5.1 × 10−17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05–1.10, P = 1.0 × 10−8); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04–1.07, P = 2.0 × 10−10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
doi:10.1093/hmg/ddu311
PMCID: PMC4204770  PMID: 24943594
5.  Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women 
Introduction
The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality.
Methods
We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score.
Results
After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (Ptrend = 0.0003) and the ER H-score (Ptrend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (Ptrend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both Ptrend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (Ptrend = 0.01) and black women (Ptrend = 0.03) with ER + tumors.
Conclusions
Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity.
doi:10.1186/bcr3486
PMCID: PMC3978823  PMID: 24070170
6.  Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status 
BMC Cancer  2013;13:225.
Background
Black women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status.
Methods
Four biomarkers were assessed by immunohistochemistry in paraffin-embedded breast tumor tissue from 1,204 (523 black, 681 white) women with invasive breast cancer, aged 35–64 years at diagnosis, who accrued a median of 10 years’ follow-up. Multivariable Cox proportional hazards regression models were fit to assess subtype-specific black-white differences in mortality risk.
Results
No black-white differences in mortality risk were observed for women with triple negative (ER-negative [ER-], PR-, and HER2-) subtype. However, older (50–64 years) black women had greater overall mortality risk than older white women if they had been diagnosed with luminal A (ER-positive [ER+] or PR+ plus HER2-) breast cancer (all-cause hazard ratio, HR, 1.88; 95% confidence interval, CI, 1.18 to 2.99; breast cancer-specific HR, 1.51; 95% CI, 0.83 to 2.74). This black-white difference among older women was further confined to those with luminal A/p53- tumors (all-cause HR, 2.22; 95% CI, 1.30 to 3.79; breast cancer-specific HR, 1.89; 95% CI, 0.93 to 3.86). Tests for homogeneity of race-specific HRs comparing luminal A to triple negative subtype and luminal A/p53- to luminal A/p53+ subtype did not achieve statistical significance, although statistical power was limited.
Conclusions
Our findings suggest that the subtype-specific black-white difference in mortality risk occurs mainly among older women diagnosed with luminal A/p53- breast cancer, which is most likely treatable. These results further suggest that factors other than subtype may be relatively more important in explaining the increased mortality risk seen in older black women.
doi:10.1186/1471-2407-13-225
PMCID: PMC3648503  PMID: 23642215
Breast cancer; Mortality; Racial disparity; Triple negative; Luminal A; ER; PR; HER2; p53
7.  Invasive Breast Cancer Incidence Trends by Detailed Race/Ethnicity and Age 
Racial/ethnic disparities in breast cancer incidence may contain important evidence for understanding and control of the disease. Monitoring the incidence trends of breast cancer by race/ethnicity allows identification of high risk groups and development of targeted prevention programs.
Using population-based cancer registry data from the Los Angeles Cancer Surveillance Program, we examined the invasive female breast cancer incidence trends among the diverse racial/ethnic populations in Los Angeles County, California, from 1972 to 2007. Age-adjusted incidence rates (AAIR) and age-specific incidence rates (ASIR) were calculated and examined respectively for non-Hispanic (NH) white, black, Hispanic, Chinese, Filipina, Japanese, and Korean women by calendar year and time period.
Rising trends of AAIR were found in all racial/ethnic groups during the 1980s and 1990s. The breast cancer risk increased more substantially in Japanese and Filipinas than in Chinese and Koreans. During 2000–2007, the trends of AAIR declined significantly among NH white women and slightly in blacks, remained unchanged for Hispanics, and continued to rise significantly among all Asian subgroups. The patterns of ASIR by race/ethnicity changed dramatically over time. By 2000–2007, younger Hispanic women had the lowest breast cancer risk, replacing the Chinese and Koreans who formerly had the lowest risk.
Rapidly increasing breast cancer incidence trends among Asian-Americans underline the importance of behavioral and lifestyle changes as a result of acculturation on the development of the disease. The unique trends of breast cancer incidence by race/ethnicity suggest the need for targeted breast cancer control programs for different racial/ethnic populations.
doi:10.1002/ijc.26004
PMCID: PMC3196818  PMID: 21351091
Breast cancer; Incidence; Race/Ethnicity; Trends
8.  Obesity and Survival Among Black Women and White Women 35 to 64 Years of Age at Diagnosis With Invasive Breast Cancer 
Journal of Clinical Oncology  2011;29(25):3358-3365.
Purpose
To evaluate the effect of obesity on survival among black women and white women with invasive breast cancer and to determine whether obesity explains the poorer survival of black women relative to white women.
Patients and Methods
We observed 4,538 (1,604 black, 2,934 white) women who were 35 to 64 years of age when diagnosed with incident invasive breast cancer between 1994 and 1998. Multivariate Cox regression models were used to examine the effect of body mass index (BMI, in kilograms per square meter) 5 years before diagnosis on risk of death from any cause and from breast cancer.
Results
During a median of 8.6 years of follow-up, 1,053 women died (519 black, 534 white), 828 as a result of breast cancer (412 black, 416 white). Black women were more likely to die than white women (multivariate-adjusted relative risk [RR], 1.33; 95% CI, 1.16 to 1.53). Compared with women with BMI of 20 to 24.9 kg/m2, those who were obese (BMI ≥ 30 kg/m2) had a greater risk of all-cause mortality (RR, 1.23; 95% CI, 1.04 to 1.47) and breast cancer–specific mortality (RR, 1.20; 95% CI, 0.99 to 1.46). These associations were observed among white women (all-cause RR, 1.54; 95% CI, 1.21 to 1.96; breast cancer RR, 1.46; 95% CI, 1.11 to 1.92), but not among black women (all-cause RR, 1.03; 95% CI, 0.81 to 1.29; breast cancer RR, 1.02; 95% CI, 0.79 to 1.33).
Conclusion
Obesity may play an important role in mortality among white but not black patients with breast cancer. It is unlikely that differences in obesity distributions between black women and white women account for the poorer survival of black women.
doi:10.1200/JCO.2010.34.2048
PMCID: PMC3164241  PMID: 21788570
9.  Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study 
We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and stratified Cox proportional hazards models were fit to estimate relative risks (RR) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95%CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95%CI=0.83-1.33) overall, or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95%CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.
doi:10.1002/ijc.25730
PMCID: PMC3258672  PMID: 20957632
non-Hodgkin lymphoma; oral contraceptives; menopausal hormonal therapy; hysterectomy; bilateral oophorectomy
10.  Oral contraceptive use and survival in women with invasive breast cancer 
Background
Oral contraceptives (OCs) are widely used in the U.S. Although the relation between OC use and breast cancer incidence has been widely studied, the few studies examining associations between OC use prior to breast cancer diagnosis and survival are inconsistent.
Methods
Women with invasive breast cancer participating in the Women's Contraceptive and Reproductive Experiences (CARE) Study, a population-based case-control study (4565 women ages 35–64 years), and the California Teachers Study (CTS) cohort (3929 women ages 28–91 years) were followed for vital status. 1064 women died in the CARE Study (median follow-up, 8.6 years) and 523 died in the CTS (median follow-up, 6.1 years). Cox proportional hazards regression provided hazard rate ratio estimates (RRs) with 95% confidence intervals (CIs) for risk of death from any cause and from breast cancer.
Results
No association was observed for any OC use prior to diagnosis and all-cause mortality (CARE Study: RR=1.01 (95% CI=0.86–1.19); CTS: RR=0.84 (95% CI=0.67–1.05)). A decreased risk of all-cause mortality was observed in the CTS among women with more than 10 years of OC use (RR=0.67, 95% CI=0.47–0.96); however, no trend of decreasing risk with increasing OC duration was observed (P-trend=0.22), and no association was observed in the CARE study. No associations were observed for breast cancer-specific mortality.
Conclusions
OC use is not associated with all-cause or breast cancer-specific mortality among women with invasive breast cancer.
Impact
These two independent studies demonstrated no overall association between OC use and survival among women with breast cancer.
doi:10.1158/1055-9965.EPI-11-0022
PMCID: PMC3132273  PMID: 21551244
Oral contraceptives; breast cancer; survival; risk assessment
11.  Does Hormone Therapy Counter the Beneficial Effects of Physical Activity on Breast Cancer Risk in Postmenopausal Women? 
Cancer causes & control : CCC  2011;22(3):515-522.
Objective
Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002.
Methods
The Women’s Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35–64 years, and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT).
Results
Among postmenopausal women (1908 cases, 2013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and current ET users; Ptrend values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use.
Conclusion
Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.
doi:10.1007/s10552-010-9719-y
PMCID: PMC3229264  PMID: 21213036
Hormone therapy; physical activity; breast cancer
12.  Breast Cancer Risk and Ovariectomy, Hysterectomy, and Tubal Sterilization in the Women's Contraceptive and Reproductive Experiences Study 
American Journal of Epidemiology  2010;173(1):38-47.
Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35–64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor–positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.
doi:10.1093/aje/kwq339
PMCID: PMC3025644  PMID: 21109566
breast neoplasms; case-control studies; hysterectomy; ovariectomy; sterilization, tubal
13.  Body size and the risk of ovarian cancer by hormone therapy use in the California Teachers Study cohort 
Cancer causes & control : CCC  2010;21(12):2241-2248.
Objective
To investigate whether obesity and hormone therapy (HT) are associated with ovarian cancer risk among women in the California Teachers Study cohort.
Methods
Of 56,091 women age ≥45 years, 277 developed epithelial ovarian cancer between 1995 and 2007. Multivariate Cox regression was performed.
Results
Among women who never used HT, greater adult weight gain, waist circumference and waist-to-height ratio, but not adult BMI, increased risk of ovarian cancer. Compared to women who never used HT and had a stable adult weight, risk of ovarian cancer was increased in women who gained ≥40 lb (relative risk (RR) 1.8, 95% confidence interval (CI): 1.0–3.0) or used HT for >5 years (RR 2.3 95% CI: 1.3–4.1). Having both exposures (RR 1.9, 95% CI: 0.99–3.5), however, did not increase risk more than having either alone. Results were similar for waist circumference and weight-to-height ratio; however, differences across HT groups were not statistically significant.
Conclusions
This study suggests that abdominal adiposity and weight gain, but not overall obesity, increase ovarian cancer risk and that there may be a threshold level beyond which additional hormones, whether exogenous or endogenous, do not result in additional elevation in risk. However, large pooled analyses are needed to confirm these findings.
doi:10.1007/s10552-010-9647-x
PMCID: PMC3120052  PMID: 20924664
Ovarian cancer; Obesity; Abdominal adiposity; Hormone therapy
14.  Body size and the risk of endometrial cancer by hormone therapy use in postmenopausal women in the California Teachers Study cohort 
Cancer causes & control : CCC  2010;21(9):1407-1416.
Objective
To investigate whether hormone therapy (HT) and obesity are associated with endometrial cancer risk among postmenopausal women in the California Teachers Study cohort.
Methods
Of 28,418 postmenopausal women, 395 developed type 1 endometrial cancer between 1995 and 2006. Multivariate Cox regression was performed to estimate relative risks (RR), stratified by HT use (never used, ever estrogen-alone (ET), or exclusively estrogen-plus-progestin (EPT)).
Results
Among women who never used HT, overall and abdominal adiposity were associated with increased risk; when evaluated simultaneously, abdominal adiposity was more strongly associated (RR 2.2, 95% confidence interval (CI): 1.1–4.5 for waist ≥35 vs. <35 inches). Among women who ever used ET, risk was increased in women with BMI ≥25 kg/m2 (RR 1.6, 95% CI: 1.1–2.3 vs. <25 kg/m2). Neither overall nor abdominal obesity was associated with risk in women who exclusively used EPT (P-interaction<0.001 for BMI by HT use).
Conclusions
Among women who never used HT, risk was strongly positively related to obesity and may have been influenced more by abdominal than overall adiposity; however, due to small numbers, this latter finding requires replication. Among women who ever used ET, being overweight at baseline predicted higher risk, whereas use of EPT mitigated any effect of obesity.
doi:10.1007/s10552-010-9568-8
PMCID: PMC2925506  PMID: 20431936
endometrial cancer; obesity; abdominal adiposity; hormone therapy
15.  Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study 
Background
Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the impact of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype.
Methods
We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years 2,857 invasive breast cancers were diagnosed.
Results
Compared to women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had 19% greater risk of breast cancer (95% Confidence Interval (CI), 1.03-1.37), while women using EPT for 15 or more years had 83% greater risk (95% CI, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with body mass index (BMI)<29.9 kg/m2 but not for women with BMI≥30 kg/m2. Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2- tumors.
Conclusions
Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Further, risks varied by BMI and tumor subtype.
Impact
These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use.
doi:10.1158/1055-9965.EPI-10-0162
PMCID: PMC2936672  PMID: 20699377
16.  Meat consumption, non-steroidal anti-inflammatory drugs, and mortality among colorectal cancer patients in the California Teachers Study 
A low meat diet and regular non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased mortality among colorectal cancer (CRC) patients. Here we investigated the association between pre-diagnosis usual meat consumption and CRC-specific mortality, and whether meat consumption modifies the previously noted association between NSAID use and CRC-specific mortality among women in the California Teachers Study (CTS) cohort. Women joining CTS in 1995–1996 without prior CRC diagnosis, diagnosed with incident CRC during follow-up through December 2007, were eligible for inclusion. Meat intake (frequency and serving size) and NSAID use (aspirin or ibuprofen use) were ascertained via self-administered questionnaires before diagnosis. Vital status and cause of death were determined by linkage with mortality files. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HR) for death and 95% confidence intervals (CI). Pre-diagnosis meat consumption was not associated with CRC-specific mortality among 704 CRC patients (and 201 CRC-specific deaths), comparing patients in the lowest consumption tertile (0–5.4 medium-size servings/week) to those with higher consumption. Regular NSAID use (1–3 times/week, 4–6 times/week, daily) vs. none was associated with decreased CRC-specific mortality among patients in the lowest meat consumption tertile (HR=0.22, 95% CI 0.06–0.82), but not among patients in the higher meat intake tertiles. The previously observed mortality risk reduction among female CRC patients associated with regular NSAID use was restricted to patients who reported low meat intake before diagnosis. These findings have implications for CRC survivorship and tertiary CRC prevention.
doi:10.1158/1940-6207.CAPR-09-0262
PMCID: PMC2931369  PMID: 20551290
17.  A Case-Control Study of Body Mass Index and Breast Cancer Risk in White and African American Women 
Objective
Large body size has been associated with decreased risk of breast cancer in premenopausal, but with increased risk in postmenopausal women. Limited information is available about African American women and differences by estrogen- and progesterone-receptor (ERPR) status.
Methods
We analyzed data from the Women's Contraceptive and Reproductive Experiences (CARE) Study among 3,997 white and African American breast cancer case patients diagnosed in 1994-98 and 4,041 control participants aged 35 to 64. We calculated multivariate odds ratios (ORs) as measures of relative risk of breast cancer associated with self-reported body mass index (BMI) at age 18 and 5 years before diagnosis (recent BMI).
Results
Risk tended to decrease with increasing BMI at age 18 in all women (ORBMI≥25 kg/m2 vs <20kg/m2=0.76, 95% CI:0.63–0.90, Ptrend=0.005) and with recent BMI in premenopausal women (ORBMI ≥35 kg/m2 vs <25kg/m2=0.81, 95% CI:0.61–1.06, Ptrend=0.05), unmodified by race. Among postmenopausal white but not African American women, there was an inverse relation between recent BMI and risk. High recent BMI was associated with increased risk of ERPR positive tumors among postmenopausal African American women (ORBMI ≥35 kg/m2 vs <25kg/m2=1.83, 95% CI:1.08–3.09, Ptrend=0.03).
Conclusion
Among women at age 35-64, BMI at age 18 is inversely associated with risk of breast cancer, but association with recent BMI varies by menopause status, race and hormone receptor status.
Impact
Our findings indicate that studies of BMI and breast cancer should consider breast cancer subtypes.
doi:10.1158/1055-9965.EPI-10-0025
PMCID: PMC2891096  PMID: 20501755
African American; Body Mass Index; Breast cancer; Premenopausal; Postmenopausal
18.  Hormone Therapy and Fatal Breast Cancer 
Purpose
Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen-plus-progestin therapy (CHT) increases risk of developing fatal breast cancer, i.e developing and dying of breast cancer. Using a population-based case-control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non-users by type, duration, and recency of HT use.
Methods
HT use prior to breast cancer diagnosis in 278 women who died of breast cancer within 6 years of diagnosis (cases) was compared with use in 2,224 controls never diagnosed with breast cancer using conditional logistic regression. Measures taken to address potential bias and confounding inherent in case-control studies included collecting and adjusting for detailed data on demographic and other factors potentially associated both with hormone therapy use and breast cancer.
Results
Fifty-six percent of cases and 68% of controls reported HT use. Among current 3+ year HT users, odds ratios and 95% confidence intervals for death were 0.83 (0.50, 1.38) and 0.69 (0.44, 1.09), respectively, for exclusive use of CHT or of ET, and were 0.94 (0.59, 1.48) and 0.70 (0.45, 1.07) for any use of CHT or of ET regardless of other hormone use.
Conclusion
Point estimates suggest no increased risk of fatal breast cancer with HT use, although 50% increases in risk in longer-term current CHT users cannot be ruled out.
doi:10.1002/pds.1941
PMCID: PMC3098621  PMID: 20336635
Hormone replacement therapy; estrogen replacement therapy; estrogen progestin combination therapy; breast neoplasms; death; menopause; case-control
19.  Recruitment and follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study 
Journal of Cancer Survivorship  2011;5(3):305-314.
Introduction
Cancer is rare in adolescents and young adults (AYA), but these patients have seen little improvement in survival in contrast to most other age groups. Furthermore, participation in research by AYAs is typically low. We conducted a study to examine the feasibility of recruiting a population-based sample of AYA survivors to examine issues of treatment and health outcomes.
Methods
Individuals diagnosed in 2007–08 and age 15–39 at the time of diagnosis with acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell cancer or sarcoma were identified by 7 Surveillance, Epidemiology, and End-Results (SEER) cancer registries, mailed surveys within 14 months after diagnosis and again a year later, and had medical records reviewed.
Results
525 (43%) of the eligible patients responded, 39% refused and 17% were lost to follow-up. Extensive efforts were required for most potential respondents (87%). 76% of respondents completed the paper rather than online survey version. In a multivariate model, age, cancer site, education and months from diagnosis to the first mailing of the survey were not associated with participation, although males (p < 0.01), Hispanics and non-Hispanic blacks (p < 0.001) were less likely to participate. 91% of survivors completing the initial survey completed the subsequent survey.
Discussion
Despite the response rate, those who participated adequately reflected the population of AYA cancer survivors. The study demonstrates that cancer registries are valuable foundations for conducting observational, longitudinal population-based research on AYA cancer survivors.
Implications for Cancer Survivors
Achieving a reasonable response rate in this population is possible, but requires extensive resources.
doi:10.1007/s11764-011-0173-y
PMCID: PMC3159756  PMID: 21274648
Adolescent cancer; Young adult cancer; Survey; Response rates; Medical records; Consent forms
20.  Feasibility Study for Collection of HER2 Data by NCI Surveillance, Epidemiology and End Results (SEER) Program Central Cancer Registries 
The clinical importance of human epidermal growth factor receptor-2 (HER2) in breast cancer is now clearly established given that expression of this tumor marker is used to guide therapy and as a prognostic indicator. Despite its now routine evaluation in breast cancer patients, population-based data are lacking because information on HER2 status is not routinely collected in the majority of population-based cancer registries. We assessed feasibility of collecting HER2 data and its completeness in three registries in the Surveillance, Epidemiology and End Result (SEER) Program. Among a sample of invasive first primary breast cancer patients diagnosed between June and December 2007, HER2 tests had been performed on 96.5% (N=522), and test results were available for 95.2% (N=515) of patients. The majority of HER2 tests were performed by immunohistochemistry (IHC) alone (50.9%), 35.3% by both IHC and fluorescence in situ hybridization (FISH) and 11.8% of tests by FISH alone. As a result of these findings SEER registries will collect HER2 data on all invasive breast cancer patients as an optional data element for those diagnosed in 2009 and HER2 will likely be a required data element for these patients in 2010.
doi:10.1158/1055-9965.EPI-09-0807
PMCID: PMC2805457  PMID: 20056633
21.  Non-steroidal anti-inflammatory drugs: effects on mortality after colorectal cancer diagnosis 
Cancer  2009;115(24):5662-5671.
Background
Non-steroidal anti-inflammatory drug (NSAID) use has been associated with decreased colorectal cancer (CRC) risk. However, NSAID effects on clinical outcomes after CRC diagnosis are not well-defined. We investigated the association of pre-diagnosis NSAID use and mortality after CRC diagnosis among women in the California Teachers Study (CTS) cohort.
Methods
Women under 85 years participating in the CTS, without prior CRC diagnosis at baseline (1995-1996), and diagnosed with CRC during follow-up through December 2005, were eligible for analysis of the association of pre-diagnosis NSAID use and mortality. NSAID use (including aspirin, and ibuprofen) was collected through a self-administered questionnaire. Cancer occurrence was identified through California Cancer Registry linkage. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HR) for death and 95% confidence intervals (CI).
Results
Among 621 CRC cases identified, 64% reported no pre-diagnosis regular NSAID use, 17% reported use 1-6 days/week, and 20% reported daily use; duration of NSAID use < 5 years was reported by 17% and ≥5 years reported by 18%. Regular pre-diagnosis NSAID use (1-3 days/week, 4-6 days/week, daily) vs. none was associated with improved overall survival (OS) (HR=0.71, 95% CI 0.53-0.95) and CRC-specific survival (CRC-SS) (HR=0.58, 95% CI 0.40-0.84) after adjustment for clinically relevant factors. Pre-diagnosis NSAID use ≥5 years (versus none) was associated with improved OS (HR=0.55, 95% CI 0.37-0.84) and CRC-SS (HR=0.40, 95% CI 0.23-0.71) in adjusted analyses.
Conclusions
When used regularly or over a prolonged duration prior to CRC diagnosis, NSAIDs are associated with decreased mortality among female CRC cases.
doi:10.1002/cncr.24705
PMCID: PMC3008399  PMID: 19827153
Colon cancer; colorectal cancer; non-steroidal anti-inflammatory drugs; NSAIDs; rectal cancer; survival
22.  Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study 
Introduction
Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival.
Methods
California Teachers Study cohort members provided information in 1995–1996 on long-term (high school through age 54 years) and recent (past 3 years) participation in moderate and strenuous recreational physical activities. The 3,539 women diagnosed with invasive breast cancer after cohort entry and through December 31, 2004, were followed through December 31, 2005. Of these, 460 women died, 221 from breast cancer. Moderate and strenuous physical activities were combined into low (≤0.50 hr/wk/yr of any activity), intermediate (0.51–3.0 hr/wk/yr of moderate or strenuous activity but no activity >3.0 hr/wk/yr) or high activity (>3.0 hr/wk/yr of either activity type). Multivariable relative risks (RR) and 95% confidence intervals (CI) for mortality were estimated using Cox proportional hazards methods, adjusting for race/ethnicity, estrogen receptor status, disease stage, and baseline information on comorbidities, body mass index, and caloric intake.
Results
Women with high or intermediate levels of long-term physical activity had lower risk of breast cancer death (RR=0.53, 95% CI=0.35–0.80; and RR=0.65, 95% CI=0.45–0.93, respectively) than women with low activity levels. These associations were consistent across estrogen receptor status and disease stage, but confined to overweight women. Deaths due to causes other than breast cancer were related only to recent activity.
Conclusions
Consistent long-term participation in physical activity before breast cancer diagnosis may lower risk of breast cancer death, providing further justification for public health strategies to increase physical activity throughout the lifespan.
doi:10.1158/1055-9965.EPI-09-0538
PMCID: PMC2783945  PMID: 19843680
23.  Relationship between Migraine History and Breast Cancer Risk among Premenopausal and Postmenopausal Women 
Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the impact of migraine triggers, that are also well established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multi-center population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio (OR): 0.74, 95% confidence interval (CI): 0.66–0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers.
doi:10.1158/1055-9965.EPI-09-0291
PMCID: PMC2756173  PMID: 19589913
Breast cancer; migraine; histology; estrogen receptor; progesterone receptor
24.  Pregnancy-related factors and the risk of breast carcinoma in situ and invasive breast cancer among postmenopausal women in the California Teachers Study cohort 
Introduction
Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear.
Methods
Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia.
Results
Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend < 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors.
Conclusions
These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration.
doi:10.1186/bcr2589
PMCID: PMC2917030  PMID: 20565829

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