bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-07-09: Prevalence and effects of off-label use of chemotherapeutic agents in elderly breast cancer patients: estimates from Surveillance, Epidemiology and End Results-Medicare data
Authors: Eaton AA , Sima CS , Panageas KS 
Published: August 2014

Abstract
Purpose: To gain FDA approval, drug companies submit evidence from clinical trials demonstrating that a drug is safe and efficacious in a certain setting. Current regulations allow oncologists to prescribe approved drugs for uses other than those for which the drug was approved (off-label use). While there seems to be a consensus that off-label use is common in oncology, there is a lack of published data on recent trends and on utilization in different populations.
The strength of evidence demonstrating safety and efficacy varies for drugs used in the off-label setting, and patients may be at risk for unacceptable toxicity. The risk of toxicity may be higher among older patients, whose ability to tolerate chemotherapy is compromised by age-related organ decline and comorbidities. Our objective was to describe the prevalence of off-label use of chemotherapeutic agents in elderly breast cancer patients with Medicare coverage and to compare toxicity between patients using off-label drugs and patients using only approved drugs.
Materials and Methods: We identified women 65 and older with a first primary breast cancer diagnosed in 2000–2007 from Surveillance, Epidemiology and End Results (SEER) cancer registry data linked with Medicare claims. Specific chemotherapeutic agents used following diagnosis were identified in Medicare claims and classified as on- or off-label use based on whether the drug was approved for breast cancer as of May 2012. Thirty-day toxicity (ER visit, hospitalization or death) was compared between patients whose first line regimen contained only approved drugs and patients whose first line regimen contained at least one off-label drug using the Cochran-Mantel-Haenszel test.
Results: The most commonly-used approved drugs were cyclophosphamide (used in 14% of patients), doxorubicin (10%), docetaxel (5%), fluorouracil (5%), and paclitaxel (5%).

In total, forty-five off-label agents were used. Vinorelbine and carboplatin were each used in 1% of patients. No other off-label drug was used in more than 109 (0.11%) of patients.
Toxicity was significantly higher for patients treated with off-label agents compared to patients treated with only approved drugs, after adjusting for stage at diagnosis (p = 0.01).
Conclusions: In this population-based cohort, rates of chemotherapy use were generally low, and rates of off-label use were even lower, with only 3% of patients treated off-label. Off-label use became more common as stage at diagnosis increased, with use increasing from 1% in stage 0/1 patients to 12% in stage 4 patients. The higher toxicity rates observed in patients treated with off-label drugs may indicate that these drugs are less safe than approved agents. This result will be confirmed in a matched analysis accounting for age, stage and comorbidities.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-09.
Abstract P3-07-12: Risk Factors for Breast Cancer in Women Served in Odete Valadares Maternity, Belo Horizonte-MG
Authors: Sediyama CMNO , Peluzio MCG , Abranches MV 
Published: August 2014

Abstract
With changes in lifestyle of the population and changes in women reproductive patterns in the last century, the profile of mortality among women has changed, today the prevailing non-infectious chronic diseases, like cancer, including breast cancer. This paper is a case-control population-based, with the objective of evaluating the risk factors and their association with breast cancer in a population of women seen in Odete Valadares Maternity, in the Hospital Foundation of the State of Minas Gerais, in Belo Horizonte, between January and July 2006. Inclusion criteria were age over 18 years and referral for mammography service. Women with abnormal mammography and confirmation of malignancy of the breast were invited to participate in the study, and those with normal mammography were invited to compose the control group. We evaluated 710 women and 456 selected to participate in the study, 261 with breast cancer and 195 healthy controls.

The participants were interviewed, answered a questionnaire on reproductive aspects and lifestyle habits (smoking, alcohol consumption, physical activity, children, age at menarche and menopause, oral contraceptive use and hormone replacement therapy and breast-feeding) and was measured anthropometric data. The association between several independent variables and the presence of breast cancer was evaluated by Student's t test, Mann-Whitney and chi square test. We estimated odds ratio and their respective confidence intervals.

This study found a positive association between physical inactivity, menopause, nulliparity, lack of breastfeeding and family history of breast cancer and the diagnosis of breast cancer, and alcohol conferred a protective effect in this population.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-12.
Abstract P3-08-01: The prospective risk of ovarian cancer in 1433 women in a breast cancer family history clinic: no increased risk in families testing negative for BRCA1 and BRCA2.
Authors: Evans DGR , Ingham SL , Sahin S , Buchan I , Warwick J , O'Hara C , Moran A , Howell A 
Published: August 2014

Abstract
Since the identification of the BRCA1 and BRCA2 genes speculation has continued regarding the breast and ovarian cancer risk associated with mutations in these genes. Also, as to whether mutations in these genes account for the majority of the association between breast and ovarian cancer. Identification of RAD51C and RAD51D mutations in breast/ovarian cancer families has reawakened the debate as to whether it is safe to reassure women from BRCA negative families that they are not at increased risk of ovarian cancer. 1433 women from breast cancer families that had tested negative for BRCA1/2 were followed for a total of between 0.04 and 25 years and checked against a cancer registry for ovarian cancer incidence. Data was censored at ovarian cancer diagnosis, oophorectomy or death. During 16358 women years of follow up no invasive epithelial ovarian cancer occurred, although 2 borderline tumors were diagnosed. Expected rates for this cohort from cancer registry data were 2.75 epithelial ovarian tumors with 2.52 for invasive cancer and 0.23 for borderline tumors. The upper confidence limit for invasive RR was 1.3 and for borderline tumors 0.97–31. In conclusion this the largest prospective follow up of a BRCA negative cohort has demonstrated that there is no increase in risk of invasive ovarian cancer in families that have tested negative for BRCA1/2.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-01.
Abstract P3-08-03: Urinary levels of prostaglandin E2 metabolite and postmenopausal breast cancer
Authors: Kim S , Taylor JA , Sandler DP 
Published: August 2014

Abstract
Estrogens are considered a key player in the mammary carcinogenesis. In postmenopausal women, peripheral aromatization of androgens is the predominant source of estrogens. Given that prostaglandin E2 (PGE2) is a potent activator of aromatase expression, we hypothesized that endogenous level of PGE2 would influence estrogen bioavailability and subsequent breast cancer risk in postmenopausal women. In addition, because PGE2 synthesis is suppressed by treatment of non-steroidal anti-inflammatory drugs (NSAIDs) via inhibition of cyclooxygenase enzyme activity, we further hypothesized that regular use of NSAIDs may modify the association between PGE2 and postmenopausal breast cancer risk. We carried out a case-cohort analysis within the NIEHS Sister Study, a prospective cohort study of 50,884 women. Postmenopausal women who were aged 50 or older and did not report current use of hormones were eligible for the present analysis (N = 11,338). Urinary levels of a major PGE2 metabolite (PGE-M), which is generally accepted as the most accurate index of endogenous PGE2 formation, were quantified using liquid chromatography/tandem mass spectrometry in 302 incident breast cancer cases and 305 subcohort members who were randomly selected by frequency matching for age among cases. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Prentice's pseudo-likelihood approach with Barlow's weighting scheme. Several factors were associated with higher levels of urinary PGE-M in the multivariable analysis, including current smoking, obesity, high caloric intake from saturated fat and surgical menopause. No associations were observed for dietary intake of omega 3 fatty acids, use of vitamin supplements and physical activity. Overall, there was no association between urinary PGE-M and postmenopausal breast cancer risk. After including the interaction terms between NSAID use and urinary levels of PGE-M in the model, however, high levels of urinary PGE-M were associated with an increased risk of breast cancer in postmenopausal women who did not regularly use NSAIDs (likelihood ratio test p &lt;0.01).

Taking into account use of NSAIDs 1 day prior to urine collection did not change results. NSAID use may modify the conversion of androgens to estrogen and thereby lower breast cancer risk. Expected data on estrogen and estrogen metabolites will help us better understand these findings.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-03.
Abstract P3-08-06: Triple Negative Breast Cancer and BRCA Status: Implications for Genetic Counseling
Authors: Haque R , Alvarado M , Ahmed SA , Shi JM , Chung JWL , Avila CC , Zheng CX , Tiller GE 
Published: August 2014

Abstract
BACKGROUND: Controversy exists whether women newly diagnosed with triple negative breast cancer (TNBC) should be referred to genetic counseling as they may be more likely to be BRCA carriers. However, prior studies included small numbers of carriers and their results have had limited influence on practice guidelines. The objective of this study was to determine the association of breast cancer molecular subtype and BRCA status in a large group of medically insured women.
METHODS: We examined a cohort of 2,105 women with breast cancer history tested for BRCA mutations in a large California health plan from 1997–2011. BRCA test results were recorded in the health plan's clinical genetics registry. Of the 2,105 breast cancer patients, 249 were BRCA mutation carriers (143 BRCA1 carriers, and 106 BRCA2 carriers). We conducted data linkages of all patients with the health plan's NCI-SEER affiliated tumor registry and identified ER, PR, and HER2. HER2 status was also captured from pathology reports using natural language processing. ER, PR, and HER2 status were assessed by immunohistochemical or FISH techniques. Patients were classified into four main biologic subtypes: triple negative (ER−/PR−/HER2−); luminal A (ER+ and/or PR+/HER2−); luminal B (ER+ and/or PR+/HER2+); and HER2-enriched (HER2+/ER−). We examined the association between molecular subtypes (collapsed into TNBC vs. non TNBC categories) and BRCA1/2 mutation status using contingency table analyses. P-values (two-sided) were estimated using chi-square analysis. Multivariable logistic regression was used to estimated adjusted odds ratios (OR) and 95% confidence intervals.
RESULTS: TNBC subtype was strongly associated with BRCA status (P &lt; 0.0001). Women with TNBC tumors were five-fold more likely to be BRCA carriers than women who had non-TNBC breast tumors (OR = 5.6, 95% CI: 4.1–7.5). Specifically, the association of TNBC with BRCA1 was more robust (OR = 12.2, 95% CI: 8.3–17.9). Adjusting for age and stage of breast cancer diagnosis and race/ethnicity did not materially modify the association between TNBC and BRCA1 status. TNBC was not associated with BRCA2 status (OR = 1.6, 95% CI: 0.9–2.7).

CONCLUSION: TNBC was strongly associated with BRCA1 status, but not with BRCA2 status. Statistically significant numbers of patients with BRCA mutations have a TNBC profile. These patients should therefore be referred to clinical genetics for further evaluation and possible testing.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-06.
Abstract P3-08-07: HER2 positive breast carcinomas: trend in evolution between 1998 and 2008 and relationship with clinico-pathological characteristics in a population based study.
Authors: Beltjens F , Bertaut A , Pigeonnat S , Pouget N , Guiu S , Poillot M-L , Charon-Barra C , Coudert B , Dabakuyo S , Fumoleau P , Arveux P , Arnould L 
Published: August 2014

Abstract
Background: Determination of HER2 status in invasive breast carcinomas is now mandatory for the optimal treatment of the patient. A vast majority of initial published studies described positivity in about 20 to 25 % of breast carcinomas, but the proportion of HER2 positive gene expression in women with breast cancer varies in the literature from 9 to 74%. The population of the tumor analyzed (for example histologic types, stage, age), the type of the assays used and the lack of uniformity or quality controls in detection assays may partly explain these differences. Our study describes the evolution of HER2 positive invasive breast cancer proportions during a period of 10 years and identifies clinical and pathological characteristics of these positive tumors.
Methods: Based on the regional, population-based breast cancer registry, we identify 2396 patients diagnosed with invasive breast cancer in the Côte-d'Or department and treated in a single institution between 1998 and 2008. The HER2 status was determined by immunohistochemistry and by fluorescence in situ hybridization by a single team that performed regular internal quality controls and participated to multiannual external international quality control programs.
Results: During the 1998–2008 period, 12.8% of invasive breast cancers were identified as HER2 positive, with no trend to annual variations (p = 0.27). During the same period, despite an increase of 45% of the annual diagnosed cancers in the institution, the clinical and pathological characteristics such as age, tumor size, grade, hormonal receptors expression remain stable. We only noticed a slight but significant increase of lobular carcinomas (p = 0.036). In multivariate analysis, HER2 positivity was as expected associated with: hormonal receptor negative status (OR = 1.7 [IC95%: 1.2–2.4], p = 0.0035), metastatic presentation at diagnosis (OR = 2 [IC95%: 1.2–3.4], p = 0.0092), ductal subtype (OR = 1.9 [IC95%: 1.1–3.1], p = 0.0178) and high SRB grade (OR = 2.8 [IC95%: 1.7–4.5] for SBR II, OR = 5.4 [IC95%: 3.2–9.1] for SBR III, p = 0.0035). Conversely, patients older than 75 years presented mostly HER2 negative tumors (OR = 0.5 [IC95%: 0.3–0.8], p &lt; 0.0001).
Conclusions: This population based study on HER2 breast cancer status emphasizes that in a population with stable clinical and tumoral characteristics, when standardized and controlled assays are used, the proportion of HER positive tumors remains stable over a large period and is lower than usually reported (12.8%).
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-07.
Abstract P3-08-09: Clinical and Pathological Characteristics of Breast Cancer in Women with Neurofibromatosis Type 1
Authors: Yap Y-S , Wong J , Chan M , Yong W-S , Ong K-W , Lo S-K , Ngeow J , Tan B , Madhukumar P , Tan M-H , Ang P , Teh B-T , Tan P-H , Lee AS-G 
Published: August 2014

Abstract
Background: Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disorder affecting 1 in 3,000 individuals worldwide. Risk of cancer, including breast cancer, is increased, as NF1 is a tumour suppressor gene. There is limited data on the characteristics of breast cancer in individuals with NF1.
Objectives: To study the clinical and pathological characteristics of breast cancer in women with NF1.
Methodology: Patients with both NF1 and breast cancer were identified retrospectively from hospital records as well as prospectively when seen at National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH). All women had histologically proven breast cancer and fulfilled at least 2 of the 7 criteria developed by the NIH Consensus Conference for clinical diagnosis of NF1. Germline NF1 mutation sequencing is being performed on patients with blood specimens available. Details on patient demographics, tumour grade, stage, receptor status and clinical outcome were evaluated. The pathological characteristics of NF1-associated breast cancer were then compared to sporadic breast cancers in our 2001–2004 cohort, with a focus on grade and HER2 positivity rate.
Results: We identified 13 women with NF1 and breast cancer seen at our institutions from 2001 to present date. Average age of breast cancer diagnosis for women testing positive was 48 years (range 30–64). All 13 patients had invasive ductal carcinoma; of which 5 were stage 3 or 4 at diagnosis. To date, 4 out of 12 patients with stage 1–3 breast cancer have relapsed. Grade, estrogen, progesterone and HER2 receptor status were fully available for 12 patients. Ten out of 12 tumours (83%) were grade 3, compared to 45% (705/1578) among our sporadic breast cancers (p = 0.007). Eight out of 12(67%) NF1-associated breast cancers were HER2 positive (IHC 3+ or FISH positive), compared to 27% (367/1367) in sporadic cancers (p = 0.002). Two other NF1-associated tumours were triple negative, and two were hormone receptor positive and HER2 negative. Six out of 12 (50%) NF1-associated cancers were estrogen receptor (ER) positive, compared to 67% (1124/1689) in sporadic cancers (p = 0.2).
Conclusion: Our findings suggest that NF1-associated breast cancer tends to be more aggressive, with a higher frequency of grade 3 and HER2 positive tumours compared to sporadic breast cancer. Further genomic profiling of these tumours (in progress) may elucidate the role of NF1 in breast cancer. This may also have implications for sporadic tumours with somatic NF1 mutations in individuals without NF1.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-09.
Abstract P3-09-01: Odds of the triple negative subtype and survival of stages 1–3 breast cancer: Variation by race/ethnicity
Authors: Parise C , Caggiano V 
Published: August 2014

Abstract
Background: Triple negative (TN) breast cancer is known to be more common in black and Hispanic women and associated with poor survival. This study assesses the differences in the odds and survival of the TN versus the ER+/PR+/HER2− (the most common subtype) by race/ethnicity separately for AJCC stages 1, 2, and 3.
Methods: Using the California Cancer Registry for years 2000–2010, we examined 91,393 cases of stages 1–3 TN and ER+/PR+/HER2− first primary female invasive breast cancer. Race/ethnicity was defined as white, black, Hispanic, and Asian/Pacific Islander (API). Logistic regression was used to assess the association of race with odds of the TN subtype. Kaplan-Meier was used to compute 6-year survival. Cox proportional hazards was used to assess the risk of mortality of the TN subtype by race adjusting for age, grade, year of diagnosis, and socioeconomic status. All analyses were run separately for stages 1, 2, and 3.
Results: The table shows the distribution of the TN and ER+/PR+/HER2-subtypes by stage and race/ethnicity.

Blacks had increased odds of the TN compared with whites for stages 1 (OR = 2.24; 95%CI=1.96–2.56); 2 (OR = 2.01; 95%CI=1.81–2.25) and 3 (OR = 2.00; 95%CI=1.66–2.40).
Hispanics had increased odds for the TN in stages 1 (OR = 1.23; 95%CI=1.11–1.35) and 2(OR = 1.20; 95%CI=1.11–1.31). APIs had decreased odds of the TN in stages 2 (OR = 0.85; 95%CI=0.77–0.93) and 3 (OR = 0.77; 95%CI=0.64–0.92).
KM survival showed that APIs had the best 72 month survival for the TN in stages 1 (86%), 2 (78%), and 3(59%).
Hazard ratios (HRs) indicated that all races with TN had the same risk of mortality in stage 1. Only in stage 2 did blacks have an increased risk of mortality (HR = 1.17; 95%CI=1.02–1.36) while APIs had a decreased risk (HR = 0.78; 95%CI=0.65–0.94). In stage 3, Hispanics (HR = 0.85; 95%CI=0.72–0.99) and APIs (HR = 0.70; 95%CI=0.55–0.89) had decreased risk of mortality compared with whites.
Conclusions: Race/ethnicity is an important factor for survival of the TN subtype: 1. Although blacks and Hispanics are more likely to have the TN subtype, blacks have an increased risk of mortality compared with whites only in stage 2.2. For stage 1, all races have the same risk of mortality.3. Hispanics have decreased risk of mortality in stage 3.4. APIs have decreased risk of mortality in both stages 2 and 3.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-09-01.
Abstract P3-09-02: The HER2 –positive subtypes by stage and race/ethnicity
Authors: Caggiano V , Parise C 
Published: August 2014

Abstract
HER2-positivity is often associated with poor survival. The purpose of this study is to determine if there are differences in mortality among the HER-positive subtypes when stratified by stage and race/ethnicity.
Methods: Using the California Cancer Registry for years 2000–2010, we examined 99,897 cases of stages 1–3 ER+/PR+/HER2− and all HER2-positive first primary female invasive breast cancers. Race/ethnicity was defined as white, black, Hispanic, and Asian/Pacific Islander (API). Kaplan-Meier (KM) and the Log-Rank test were used to compute 6-year survival. Cox proportional hazards was used to assess the risk of mortality of each of the HER2-positive subtypes when compared with the ER+/PR+/HER2− subtype (the most common subtype). All analyses were adjusted for age, grade, year of diagnosis (&lt;2007, 2007+), and socioeconomic status and run separately by race for stages 1, 2, and 3.

Results: For all stages combined, of the subtypes comprising the luminal B-HER2 positive category, the ER+/PR+/HER2+ had the best survival (85%), only 2% less than the ER+/PR+/HER2−.
When compared with the ER+/PR+/HER2− subtype, no difference in KM survival was noted for stage 1 luminal B (ER+/PR+/HER2+;ER+/PR−/HER2+; ER−/PR+/HER2+). Both had 90% 72-month survival. The ER−/PR−/HER2+ had 88% survival (p &lt; 0.02).
For stage 2, luminal B had 83% survival and ER−/PR−/HER2+ had 76% survival. Both were significantly different (p &lt; 0.001) from the ER+/PR+/HER2− subtype (86%).
The luminal B had 68% survival and the ER−/PR−/HER2+ had 55% survival for stage 3. Both were statistically significantly worse (p &lt;.006) than the ER+/PR+/HER2− (72%).
Adjusted mortality for the ER+/PR+/HER2+ was only increased for blacks in stage 1 (HR = 1.59; 95%CI=1.09–2.33). Mortality for the ER−/PR−/HER2+ was increased for whites in all stages; for blacks in stages 1 (HR = 1.82; 95%CI=1.11–3.00) and 3 (HR = 1.90; 95%CI=1.36–2.66); for Hispanics in stages 2 (HR = 1.58; 95%CI=1.28–1.95) and 3 (HR = 2.19; 95%CI=1.73–2.78); and APIs only in stage 2 (HR = 1.70; 95%CI=1.31–2.19)
Year of diagnosis made no difference in risk of mortality in stage 1 for any race. For stage 2, blacks had slightly reduced mortality if diagnosed in 2007 or later, and for stage 3, all races except blacks had reduced risk of mortality when diagnosed in 2007 or later.
Conclusions:  1. There is variation in survival among the luminal B-HER2 positive subtypes.2. The driving force behind the increased mortality of the HER2 positive subtype is the ER−/PR−/HER2+ subtype, the molecularly defined HER2 overexpressing subtype.3. Year of diagnosis does not influence survival in stage 1 for any race.4. There are differences in mortality among the HER2 positive subtypes when stratifying by stage and race and adjusting for age, grade, year of diagnosis, and SES.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-09-02.