bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-10-07: Family history and risk of pregnancy-associated breast cancer (PABC)
Authors: Lambe M , Johansson ALV , Andersson TM , Hsieh C-C , Cnattingius S , Dickman PW 
Published: May 2016

Abstract
Background: The risk of breast cancer is at least doubled in young women with a family history of breast cancer. Pregnancy has a dual effect on breast cancer risk; a short-term increase followed by a long-term protection. It has been hypothesized that women with a genetic predisposition for breast cancer are particularly susceptible to physiological changes during childbearing that may influence short term risk.
Materials & methods: We followed a cohort of women aged 15 to 44 years between 1963 and 2009 identified in Swedish registers. Family history was defined as having a mother or sister with breast cancer. In a case-cohort analysis, we estimated incidence rate ratios of breast cancer during pregnancy and time intervals up to 10 years post-delivery.
Results: In 3,452,506 women, there were 15,548 cases of breast cancer (1,208 were pregnancy-associated (PABC), defined as breast cancer during or within 2 years of pregnancy). Compared to nulliparous women, the risk of breast cancer was decreased during pregnancy, similar during 1st year and increased during 2nd year post-delivery. The pattern was similar in women with or without family history of breast cancer. A peak in risk was observed 5-6 years following the first birth regardless of family history. After a second birth, this peak was only present in women with a family history.
Conclusions: Our results indicate that women with a family history of breast cancer do not have a different breast cancer risk during and within 10 years following pregnancy compared to women without a family history.
Citation Format: Lambe M, Johansson ALV, Andersson TM, Hsieh C-C, Cnattingius S, Dickman PW. Family history and risk of pregnancy-associated breast cancer (PABC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-07.
Abstract P6-10-17: Rates of prophylactic surgeries among BRCA 1 or 2 mutation carriers: A single institution experience
Authors: Raphael J , Hewitt P , Graham T , Ott K , Mancuso T , Lorentz J , Emmerson M , Eisen A 
Published: May 2016

Abstract
Background
Women with identified BRCA1/2 mutation have a substantially increased risk of developing several types of cancer, mainly breast and ovarian, during their lifetime. Management options included close surveillance, chemoprevention and prophylactic surgeries. The aim of this study is to assess the rate of prophylactic surgeries among BRCA1/2 carriers counseled and screened at a single institution in the last 2 decades.
Methods
We retrospectively captured all women with a BRCA1/2 mutation that were identified in our genetic clinic between 2000 and 2015. The incidence of breast and ovarian cancer among all BRCA carriers was reported. The rates of prophylactic surgeries were calculated and analyzed in all identified carriers.
Results
Six hundred and eighty four women were identified to carry a deleterious BRCA mutation, among them 364 BRCA1 (53%) and 320 BRCA2 (47%). Three hundred and twenty seven (48%) were diagnosed with breast cancer and 80 (12%) had either ovarian or fallopian tumor. Forty percent (N=271) of the women assessed were healthy carriers. Prophylactic bilateral salpingo-oophorectomies (BSO) were performed in 342 women (50%) and prophylactic mastectomies (PM) (bilateral or unilateral) in 190 (28%). Furthermore, 154 women (23%) had both BSO and PM. Of note, 79 women (12%) were less than 35 years old and 122 were less than 40 years old (18%), the majority of those were waiting to have BSO later on. If we remove the young women from the analysis, 57 and 61% of the women would have had BSO (less than 35 and 40 years excluded respectively). If we only analyze the women who had a recent follow up in our clinic (2014-2015), 422 women would be eligible. Among those, 58 and 84 were less than 35 and 40 years old (y) respectively. For this cohort, the rates of BSO would be 61% (257/422)(whole cohort), 71% (excluding women less than 35y) and 76% (excluding women less than 40y).
Conclusion
A promising rate of BSO was reported in our cohort of BRCA carriers as compared to the literature. This rate was even higher (from 50 to over 70%) when we only analyzed patients with recent follow up in clinic and when we excluded young women waiting to have BSO. More efforts are needed to determine why the rates of PM are lower, for example limited breast reconstruction resources, in order to reduce the incidence of subsequent invasive breast cancer in this high-risk population.
Citation Format: Raphael J, Hewitt P, Graham T, Ott K, Mancuso T, Lorentz J, Emmerson M, Eisen A. Rates of prophylactic surgeries among BRCA 1 or 2 mutation carriers: A single institution experience. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-17.
Abstract P6-10-19: Clinicopathologic features of breast cancers that develop in women with previous benign breast disease
Authors: Visscher DW , Frost MH , Hartmanan LC , Frank RD , Vierkant RA , McCullough AE , Winham SJ , Vachon C , Ghosh K , Brandt KR , Farrell AM , Tarabishy Y , Hieken TJ , Haddad TC , Kraft RA , Radisky DC , Degnim AC 
Published: May 2016

Abstract
Background
Women with benign breast disease (BBD) have an increased risk for breast cancer (BC). Almost 30% of all BCs develop in women with prior BBD. Information about the features of the expected BCs after BBD would enable individualized surveillance and prevention strategies for these women. We sought to characterize BCs developing in a large cohort of women with BBD.
Methods
Our cohort includes 13,485 women who underwent breast biopsy for mammographic or palpable concern between 1967-2001. Biopsy slides were reviewed and classified as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed.
Results
With a median follow-up of 15.8 years, 1273 women developed BC. Most BCs were invasive (81%), among which 61% were ductal, 13% mixed ductal/lobular, and 14% lobular. Two thirds were intermediate or high-grade, and 29% were node positive. Cancer characteristics were similar across the three histologic categories of BBD, with similar frequency of DCIS and invasive disease, tumor size, time to invasive BC, histologic type of BC, nodal positivity and HER2 positivity. Women with AH had a higher frequency of ER+ BC (91%) vs women with PD (80%) or NP (85%), p=0.02.
Conclusion
A substantial proportion of all BCs develop in women with prior BBD. We show that the majority of BCs after BBD are invasive tumors of ductal type, with a substantial proportion node positive. 84% of cancers were ER-positive. Chemoprevention should be strongly encouraged in higher-risk women with BBD.
Citation Format: Visscher DW, Frost MH, Hartmanan LC, Frank RD, Vierkant RA, McCullough AE, Winham SJ, Vachon C, Ghosh K, Brandt KR, Farrell AM, Tarabishy Y, Hieken TJ, Haddad TC, Kraft RA, Radisky DC, Degnim AC. Clinicopathologic features of breast cancers that develop in women with previous benign breast disease. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-19.
Abstract P6-11-01: Cost-effectiveness of pertuzumab in HER2+ metastatic breast cancer
Authors: Qian Y , Durkee BY , Pollom EL , King M , Dudley SA , Shaffer JB , Chang DT , Gibbs IC , Goldhaber-Fiebert JD , Horst KC 
Published: May 2016

Abstract
Purpose
The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab (P) to docetaxel and trastuzumab (TH) as first-line treatment for patients with HER2 overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of the addition of pertuzumab to docetaxel and trastuzumab.
Patient and Methods
We developed a decision-analytic Markov model to evaluate the cost-effectiveness of TH with or without P in U.S. patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included: stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. One-way and multi-way deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions.
Results
Modeled median survival was 39.4 months (TH) and 56.9 months (THP). The addition of pertuzumab resulted in an additional 1.81 life years gained (0.62 QALYs) at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost-effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost-effectiveness at a willingness-to-pay of $100,000 per QALY gained.
Conclusion
The addition of pertuzumab to docetaxel and trastuzumab in patients with metastatic HER2+ breast cancer is unlikely to be cost-effective in the United States.
Citation Format: Qian Y, Durkee BY, Pollom EL, King M, Dudley SA, Shaffer JB, Chang DT, Gibbs IC, Goldhaber-Fiebert JD, Horst KC. Cost-effectiveness of pertuzumab in HER2+ metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-11-01.
Abstract P6-13-12: Comparative similarity of ABP 980 and trastuzumab: Results of functional similarity and human pharmacokinetic assessment
Authors: Hanes V , Born T , Chow V , Zhang N , Howard M , Schulz A , Markus R 
Published: May 2016

Abstract
Background: ABP 980 is being developed as a biosimilar to trastuzumab, a monoclonal antibody (mAb) that binds human epidermal growth factor receptor 2 (HER2), resulting in proliferation inhibition (PI) and induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Biosimilar mAbs are likely to have minor differences with the reference product due to variances in expression systems, bioprocess, and purification; demonstration of analytical, pharmacologic, and pharmacokinetic (PK) similarity is the foundation for biosimilarity. Functional (PI, ADCC, and tumor xenograft models) and PK similarity between ABP 980 and EU-authorized trastuzumab reference product has been previously evaluated.
Objective: To demonstrate functional and PK similarity between ABP 980 and FDA-licensed trastuzumab reference product.
Methods: Potency of ABP 980 and FDA-licensed trastuzumab was compared by measuring PI and recombinant HER2 (rHER2) binding affinity. PI activity was evaluated using BT-474 cells. Surface plasmon resonance analysis was used to determine the equilibrium binding affinity (Kd) to rHER2. PK similarity was evaluated in a randomized, single-blind, single-dose, parallel-group study in healthy adult men. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUCinf) and maximum observed serum concentration (Cmax). Secondary endpoints were safety, tolerability, and immunogenicity.
Results:
ABP 980 displayed PI and rHER2 binding activities comparable to trastuzumab. The range of relative potency by PI was 82%–114% for ABP 980 and 91%–116% for trastuzumab. The Kd ranged from 75–79 pM for ABP 980 and 67–80 pM for trastuzumab. PK similarity was demonstrated for the comparison of ABP 980 with trastuzumab. The geometric mean (GM) ratios for Cmax and AUCinf were 1.04 (90% CI, 0.995–1.079) and 1.06 (90% CI, 0.997–1.117). Both CIs fell within the standard prespecified bioequivalence criteria of 0.80–1.25. After 6 mg/kg intravenous infusion, the GM of Cmax and AUCinf were 135.90 µg/mL and 34061.43µg·h/mL for ABP 980 and 131.19µg/mL and 32271.67µg·h/mL for trastuzumab. The incidence of treatment-emergent adverse events (TEAEs) was comparable between treatment groups. TEAEs occurred in 84% subjects receiving ABP 980 and 75% of subjects receiving trastuzumab; no anti-drug antibodies were detected.
Conclusions: ABP 980 has been shown to be similar to FDA-licensed trastuzumab in functional tests and binding affinity to antigen, as well as in a phase 1 human PK study.
Citation Format: Hanes V, Born T, Chow V, Zhang N, Howard M, Schulz A, Markus R. Comparative similarity of ABP 980 and trastuzumab: Results of functional similarity and human pharmacokinetic assessment. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-12.
Abstract P6-19-03: Overexpression of FOXM1 is a potential prognostic marker in male breast cancer
Authors: Rahal K , Abdeljaoued S , Bettaieb I , Bouzaiene H , Adouni O , Miladi S , Goucha A , Bouaziz H , Makhlouf R , Hechiche M , Benna F , Boussen H , El May A , Gamoudi A 
Published: May 2016

Abstract
Background
The Forkhead box M1 (FOXM1) transcription factor is known to play an important role in the development and progression of many cancer types including breast cancer. The important role of FOXM1 in cancer affirms its significance for clinical use and therapeutic intervention. Elevated expression of FOXM1 in female breast cancer correlates with undifferentiated tumor phenotype and negative clinical outcome. However, whether FOXM1 has any indication for prognosis in male breast cancer (MBC) patients is still unknown. The purpose of this study was to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival.
Methodsl
Immunohistochemical analysis for FOXM1 was performed in a total of 80 male breast cancer specimens, all with linked clinical outcome data. Kaplan-Meier method and Cox proportional hazards analysis were used to relate FOXM1 expression to clinicopathological variables and overall survival (OS).
Results
We observed high expression of the FOXM1 protein in 39 % of MBC samples (31/80). FOXM1 overexpression was significantly associated with higher histological grade (p=0.05), lymph node metastasis (p=0.04), tumor size (p=0.05), and estrogen receptor expression (p=0.04). Patients with FOXM1 expression had a significantly poorer overall survival than those without FOXM1 expression (p=0.02). Multivariate analyses indicated that FOXM1 positivity was an independent prognostic factor for OS (p=0.03).
Conclusion
These results show that FOXM1 may represent a novel MBC marker with prognostic significance that could be included into the limited marker panels for MBC.
Citation Format: Rahal K, Abdeljaoued S, Bettaieb I, Bouzaiene H, Adouni O, Miladi S, Goucha A, Bouaziz H, Makhlouf R, Hechiche M, Benna F, Boussen H, El May A, Gamoudi A. Overexpression of FOXM1 is a potential prognostic marker in male breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-19-03.
Abstract PD3-04: PAK-1 amplified breast cancer cell lines are preferentially sensitive to PAK inhibition with G-5555
Authors: Ong CC , Blackwood E , Jakubiak D , Daemen A , Ramaswamy S , Heise C , Schmidt M , Sanders L , Wilson TR , Huw L , Ndubaku C , Rudolph J , Hoeflich KP , Friedman L , O'Brien T 
Published: May 2016

Abstract
The small GTP-binding proteins Rac1 and Cdc42 stimulate activity of the serine/threonine kinase p21-activated kinase-1 (PAK-1) to drive growth factor signaling networks and Ras-driven tumorigenesis. Genomic amplification and over-expression of PAK1 are prevalent in luminal breast cancer and correlate with poor clinical outcome. Here we use a novel and selective small molecule inhibitor, G-5555, of the group I PAKs (PAK1, 2, and 3) to evaluate the importance of PAK1 in promoting growth of PAK1 amplified breast cancer cells. Cell lines with amplification of PAK1 were found to be more sensitive to PAK1 inhibition than non-amplified cell lines. Additionally, reverse phase protein array (RPPA) was used to assess the effects of PAK1 inhibition on a wide range of signaling pathways in both amplified and non-amplified cell lines. Reduced levels of phosphorylation of MEK S298 was observed in all cell lines exposed to G-5555 irrespective of amplification status, consistent with PAK1 inhibition in these cell lines. However, modulation of this downstream PAK1 substrate did not correlate with inhibition of cell proliferation or induction of cell death. Cell lines that showed inhibition of proliferation in response to G-5555 also showed enhanced levels of cell death along with apoptosis. Moreover, G-5555 reduced tumor growth in the PAK1 amplified MDA-MB-175 xenograft tumor model. Finally, we compared the in vitro activity of G-5555 with palbociclib, a recently approved inhibitor of the cyclin-dependent kinases CDK4 and CDK6, in PAK1 amplified luminal breast cancer cell lines. Our data supports PAK1 as an attractive target in PAK1 amplified cells and tumors and suggests that inhibiting PAK1 rather than CDK4/6 in this context may be a more attractive therapeutic strategy.
Citation Format: Ong CC, Blackwood E, Jakubiak D, Daemen A, Ramaswamy S, Heise C, Schmidt M, Sanders L, Wilson TR, Huw L, Ndubaku C, Rudolph J, Hoeflich KP, Friedman L, O'Brien T. PAK-1 amplified breast cancer cell lines are preferentially sensitive to PAK inhibition with G-5555. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD3-04.
Abstract PD4-04: Psychosocial factors related to interruptions in adjuvant hormonal therapy among women with breast cancer: The breast cancer quality of care study (BQUAL)
Authors: Hershman DL , Kushi LH , Hillyer GC , Coromilis E , Buono D , Lamerato LE , Bovbjerg DH , Mandelblatt8 JS , Tsai W-Y , Jacobson JS , Wright JD , Neugut AI 
Published: May 2016

Abstract
Background. Adjuvant hormonal therapy (HT) for hormone-sensitive breast cancer decreases risk of breast cancer recurrence and improves survival. However, some women are non-adherent to this life-saving treatment.
Methods. In a cohort of women recruited at diagnosis of breast cancer in an integrated healthcare system, we investigated factors related to HT interruption (≥90 day gap). Serial interviews were conducted at baseline and during treatment to examine psychological factors as well as sociodemographic factors, tumor characteristics, and treatment factors. A series of multivariate models assessed potential predictors of HT interruptions.
Results. Of the 569 women in our cohort who initiated HT, 137 (24%) interrupted it, including 18 (3%) who did so prior to the first follow-up interview. In a multivariate analysis of clinical and demographic factors, only household income remained associated with HT interruption (OR 0.42, 95%CI 0.24-0.76). At first follow-up, after controlling for income, race and age, lower scores on all quality of life subscales, lower scores on global treatment satisfaction, and poorer scores on the intrusive and avoidant thought subscales of the Impact of Events scale were associated with higher odds of HT interruptions (P&lt;0.001 for all predictors). Scores on social support and on interpersonal processes of care measures were not associated with HT interruptions. However, a higher score on the single question "How often did your doctor speak too fast?" was associated with higher risk of HT interruptions (OR 1.32, p=0.02).
Conclusions: Patients under greater duress and those with lower physical, functional, emotional or social quality of life appeared to be at the highest risk of HT interruption and thus received poorer quality care. A better understanding of psychological factors that can result in poor quality care may pave the way to targeted interventions to improve adherence.
Citation Format: Hershman DL, Kushi LH, Hillyer GC, Coromilis E, Buono D, Lamerato LE, Bovbjerg DH, Mandelblatt8 JS, Tsai W-Y, Jacobson JS, Wright JD, Neugut AI. Psychosocial factors related to interruptions in adjuvant hormonal therapy among women with breast cancer: The breast cancer quality of care study (BQUAL). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-04.