bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-09-10: Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study
Authors: Ye F , Hu X , Shao Z
Published: February 2018

Background: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. Because of its lymphotropic nature at initial presentation, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC). The aim of this study was to identify risk factors accounting for its lymphotropic features and to develop a nomogram to predict the probability of lymph node involvement in IMPC.

Patients and Methods: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. Ethical approval of the study was granted by the Institutional Review Board of Fudan University Shanghai Cancer Center. Multiple logistic regression analysis was conducted. A logistic regression model was used to construct the nomogram in the training set and then validated in the validation set. Nomogram performance was quantified with respect to discrimination and calibration.

Results: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. The demographic characteristics were comparable within sets. Larger lesion, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95 percent confidence interval 0.692 to 0.777), demonstrating a good prediction performance. A calibration curve for the nomogram was plotted to evaluate the agreement between actual (observed) outcomes and expected probabilities. The slope of the calibration curve was close to 1, which indicated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, in which AUC was 0.734 (95 percent confidence interval 0.701 to 0.767).

Conclusions: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinical parameters was established, which could accurately predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients, especially in neoadjuvant settings.

Citation Format: Ye F, Hu X, Shao Z. Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-10.
Abstract P4-10-19: Disparities in use of adjuvant radiotherapy following lumpectomy among California regions
Authors: Huang RJ , Mukhtar RA , Alvarado M
Published: February 2018

Background

Women undergoing lumpectomy for invasive breast cancer typically receive radiotherapy (RT) to reduce risk of recurrence. Previous studies have reported disparities in the utilization of RT by race, socioeconomic status (SES), and age. In this study, we evaluate whether various sociodemographic factors are associated with use of RT in the different regions of California.

Methods

Utilizing data from the California Cancer Registry, the authors identified cases of women whose first primary invasive breast cancer was diagnosed between January 1, 2007 and December 31, 2012, whose primary surgery was breast conserving surgery, and for whom information was complete (n = 71,767). Multivariate logistic regression was used to determine whether demographic factors (SES, race, payer status, age) were significantly associated with use of RT following lumpectomy (p < .05), adjusting for tumor characteristics (size, stage, grade, hormone receptor status, and nodal status).

Results

In three out of eight regions in California, black race was associated with decreased odds of RT use (San Francisco, OR = 0.79, 95% CI = 0.68-0.92; Desert Sierra, OR = 0.72, 95% CI = 0.58-0.90; Los Angeles, OR = 0.78, 95% CI = 0.70-0.87). In Sacramento and Los Angeles regions, lower socioeconomic status was associated with declined odds of RT use. Age (70 years or older) was also associated with lower likelihood of RT use across all regions.

Conclusions

Even after accounting for payer status, racial and socioeconomic disparities persist in the use of RT. These disparities, previously documented in the time period of 2000-2007, have not disappeared. Hispanic race was not shown to be associated with decreased odds of RT use in Los Angeles, contrary to the results of a previous study. Women aged 70 years or older are less likely to receive RT.

Citation Format: Huang RJ, Mukhtar RA, Alvarado M. Disparities in use of adjuvant radiotherapy following lumpectomy among California regions [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-19.
Abstract P4-10-23: Not presented
Authors: Gao J , Song W , Zhang X , Guo F
Published: February 2018

This abstract was not presented at the symposium.
Abstract P4-12-02: Cost-effectiveness of genetic testing with a hereditary cancer panel in women at risk of hereditary breast cancer
Authors: Li Y , Arellano AR , Bare LA , Devlin JJ
Published: February 2018

Background: The role of the BRCA1/2 genes in breast cancer risk has been well characterized. However, pathogenic variants in additional genes also confer hereditary breast cancer risk and if detected can lead to interventions that can facilitate increased life expectancy. For example, the National Comprehensive Cancer Network (NCCN) guidelines (Version 2.2017) recommend MRI screening for women who carry a pathogenic variant in CHEK2 and MRI screening or risk-reducing mastectomy for women who carry a pathogenic variant in PALB2. Testing women at risk of hereditary breast cancer with a 7-gene panel was recently reported to be more cost-effective than testing only BRCA1/2 genes (Li et al. Value Health, 2017).

Objectives: To evaluate the cost-effectiveness of a multigene panel testing strategy including 11 genes with risk reduction recommendations by the NCCN guidelines compared with testing only BRCA1/2 genes.

Methods: Using a Markov model modified from the recent Li et al. publication, the 11-gene model was used to estimate life expectancies and total healthcare costs from a payers' perspective. The model included costs for genetic testing, genetic consultation, and cancer treatment as well as risk reduction strategies recommended by the guidelines: prophylactic surgery, MRI surveillance, and mammography. Probabilistic sensitivity analyses were carried out to determine the robustness of the modeling.

Results: In the base case, the incremental cost-effectiveness ratio (ICER) for the 11-gene multigene testing strategy compared with BRCA1/2 testing was $22,377 per life-year gained ($47,240 per quality-adjusted life-year gained) for a 40-year-old cohort and $36,690 per life-year gained ($63,384 per quality-adjusted life-year gained) for a 50-year-old cohort. The sensitivity analysis indicated that the multigene testing strategy had a 97% chance of costing less than $100,000 per quality-adjusted life-year gained for the 40-year-old cohort.

Conclusion: In patients at risk of hereditary breast cancer, testing using a multigene panel followed by risk reducing interventions is cost-effective compared with testing only BRCA1/2 genes.

Citation Format: Li Y, Arellano AR, Bare LA, Devlin JJ. Cost-effectiveness of genetic testing with a hereditary cancer panel in women at risk of hereditary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-02.
Abstract P4-12-08: Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis
Authors: Raphael J , Helou J , Naimark DM
Published: February 2018

Introduction

The addition of palbociclib to letrozole improves progression free survival (PFS) and response rates compared to letrozole alone in the 1st line treatment of hormone receptor positive advanced breast cancer. However palbociclib increases toxicity (i.e. neutropenia) and costs more than $6,250 per month in Canada. This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective.

Methods

To evaluate the cost-utility of palbociclib, a probabilistic discrete event simulation model was developed. The model was parameterized with data from the phase 2 and 3 PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted 5% annually. The time to progression and death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty.

Results

Compared to letrozole alone, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999 per QALM gained. Assuming a willingness to pay (WTP) of $4,167 per QALM, the addition of palbociclib was not cost-effective and the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,667 per QALM gained, the probability of palbociclib to be cost-effective was 50%.

Conclusion

Compared with letrozole alone, the addition of palbociclib is unlikely to be cost-effective for the treatment of advanced breast cancer from a Canadian healthcare perspective with its current price. While advanced breast cancer patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable.

Citation Format: Raphael J, Helou J, Naimark DM. Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-08.
Abstract P4-12-09: Molecular test for BRCA 1 and 2: Hereditary breast and ovarian cancer syndrome. Analysis of cost effectiveness of its implementation
Authors: Paez MC , Riggi MC , Gogorza SJ , Petracchi F
Published: February 2018

Introduction

Breast cancer is the leading cause of women cancer. Hereditary cause represents 5% -10% of cases. Molecular testing for BRCA1 and BRCA2 allows physicians to identify breast and ovarian cancer high risk women. Screening, diagnosis and treatment for high risk women differ from general population ones. As new drugs have been increasing health costs, the need of cost-effective strategies has raised. In Argentina, molecular tests are still very expensive and most health insurances do not cover it.

Objectives

To evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 molecular testing in women with no personal history of cancer and >=10% mutation risk based on family history criteria, compared to no testing women.

Methods

We performed a decision-analytic model (decision tree) to compare the risks of breast and ovarian cancer, mortality rates, and costs and effects (life-years and QALYs) in women with and without molecular testing for BRCA1 and BRCA2. Carrier's probability undergoing risk-reducing surgeries was considered.

This data has been analized in two private hospitals of Buenos Aires, Argentina.

Results

BRCA testing in all women with >=10% mutation risk based on family history criteria resulted cost-effective and even cost-saving in our country, with an incremental cost-effectiveness ratio of -$315.353/QALY and -$1.357.143/life-year. Our results demonstrate to be robust after sensitivity analyses varying the input parameters.

Conclusion

BRCA testing is cost-saving in our country probably because of prophylactic risk-reducing surgeries in BRCA carriers. This leads to a reduction of breast and ovarian cancer cases.

Citation Format: Paez MC, Riggi MC, Gogorza SJ, Petracchi F. Molecular test for BRCA 1 and 2: Hereditary breast and ovarian cancer syndrome. Analysis of cost effectiveness of its implementation [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-09.
Abstract P4-13-15: A retrospective head-to-head comparison between TiLoop Bra/TiMesh and seragyn in 320 cases of reconstructive breast surgery
Authors: Eichler C , Schulz C , Brunnert K , Mathias W
Published: February 2018

Background: As an alternative option to ADMs (acellular dermal matrices) synthetic meshes are a cheaper and equally effective option in implanted breast reconstruction. However, clinical data concerning these synthetic meshes is limited. Also, direct comparisons between titanium-coated polypropylene mesh (TiLoop Bra/TiMesh) and partially absorbable polypropylene mesh (Seragyn) have not yet been reported. Therefore, this work will report clinical complication rate data on 320 cases of synthetic meshes TiLoop Bra/TiMesh and Seragyn.

Methods: This analysis represents a retrospective single surgeon multi-center study of 320 cases over 14 years (2003 until 2016) using either TiLoop Bra/TiMesh (n=192) or Seragyn (n=128) in breast reconstruction. Patient recruitment was consecutive. 124 cases of the TiLoop Bra /TiMesh cohort and 74 cases in the Seragyn cohort were oncological interventions. Results were correlated with ADM based reconstructions (Epiflex and SurgiMend) performed by the same surgeon.

Results: Major complication rates (i.e. revision surgery) occurred in 3.9 % (Seragyn) and 8.3 % (TiLoop Bra/TiMesh) of all cases. (not statistically significant). Minor complications (i.e. seroma requiring aspiration, infection requiring antibiotics, red breast syndrome/rash (RBS) and wound dehiscence occurred in 18 % (Seragyn) and 8.9 % (TiLoop Bra/TiMesh). Overall minor complication rates did also not differ statistically significant. However, subgroup analysis showed RBS to occur more often in the Seragyn group (3.9 % Seragyn vs. 0.5 % TiLoop Bra/TiMesh, p<0.05). A significant difference between SurgiMend and Epiflex compared to the synthetic meshes could also not been shown.

Conclusion: This retrospective analysis shows that titanium-coated polypropylene meshes like TiLoop Bra/TiMesh and partially absorbable meshes like Seragyn do not differ significantly in complication rates. Compared to the exponentially more expensive ADM alternatives complication rates did also not differ significantly. Synthetic meshes seem to be a cheaper and equally effective option.

Citation Format: Eichler C, Schulz C, Brunnert K, Mathias W. A retrospective head-to-head comparison between TiLoop Bra/TiMesh and seragyn in 320 cases of reconstructive breast surgery [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-15.
Abstract P4-15-12: Evaluating the significance of the Van Nuys prognostic index for the management of ductal carcinoma in situ – one center's experience
Authors: Niwinska A , Galecki J , Nagadowska M , Piechocki J , Kunkiel M , Jagiello-Gruszfeld AI , Nowecki Z
Published: February 2018

Aim: This was to assess the treatment outcomes of ductal carcinoma of the breast (DCIS) based on the Van Nuys Prognostic Index.

Material and Methods: 634 consecutive patients with DCIS were treated at the Warsaw Cancer Center, Poland between 1996 and 2008 based on the VNPI score. Tumorectomy without radiotherapy (T) was performed in 123 (20%) patients, breast conserving treatment (BCT) in 206 (32%) and mastectomy (M) in 305 (48%). Disease-free survival (DFS) and overall survival (OS) were analysed within 3 groups and a multivariate analysis was performed to determine the most important factor affecting local relapse.

Results: 5-year, 10-year and 15-year DFS in the M group were respectively 98%, 97% and 97% whilst 5-year, 10-year and 15-year DFS in the BCT group were respectively 91%, 87% and 80%. 5-year, 10-year and 15-year DFS in the T group were respectively 92%, 73% and 67%. Local recurrence was observed in 54 patients. In 40% cases this was noninvasive and in 60 % invasive. Only 4 of 54 patients with recurrence died due to breast cancer. 5-year, 10-year and 15-year OS in the M group were respectively 96%, 92% and 89%. 5-year, 10-year and 15-year OS in the BCT group were respectively 99%, 94% and 85%. 5-year, 10-year and 15-year OS in the T group were respectively 95%, 90% and 73% (p=0.422). Tumor size assessed by mammography was the only variable affecting DFS.

Conclusions: Treatment outcomes of DCIS based on the Van Nuys Prognostic Index are comparable with those cited the literature, however, the recurrence rate in the T group seems to be very high. This group requires that new risk factors be sought for prior to taking a treatment decision.

Citation Format: Niwinska A, Galecki J, Nagadowska M, Piechocki J, Kunkiel M, Jagiello-Gruszfeld AI, Nowecki Z. Evaluating the significance of the Van Nuys prognostic index for the management of ductal carcinoma in situ – one center's experience [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-12.
Abstract P5-03-01: Not presented
Authors: Schneider RJ , Dhage S , Ernlund A , Ruggles K , Axelrod D , Berman R , Roses D
Published: February 2018

This abstract was not presented at the symposium.
Abstract P5-03-04: Not presented
Authors: Giamas G , Vella V , Ditsiou A , Teresa T
Published: February 2018

This abstract was not presented at the symposium.
Abstract P5-07-13: MicroRNA-mediated restoration of tamoxifen sensitivity in triple negative breast cancer through modulation of estrogen receptor alpha/beta ratio using Myrothamnus flabellifolius
Authors: Fultang N , Klase Z , Mercier I , Peethambaran B
Published: February 2018

Triple negative breast cancer (TNBC) represents approximately 20% of all breast cancer cases worldwide. Prognosis for this subtype of cancer is especially dire due to the absence of Estrogen (ER), Progesterone and Human Epidermal Growth Factor receptors, usually targeted by neoadjuvant therapies like Tamoxifen. Myrothamnus flabellifolius (MF), a well-studied South African medicinal herb, has shown significant potency against TNBC with minimal effect on normal cells. In this study, we use miRNA profiling, Ingenuity Pathway Analysis (Qiagen), MTT, immunoblots and immunofluorescence to characterize the targeted cytotoxic mechanism of MF in TNBC. We found deregulation in the expression of several oncogenic and anti-cancer miRNAs in TNBC post MF treatment. Using Ingenuity Pathway Analysis to analyze the miRNA expression profiles of the treated cells, we determined Estrogen Signaling as a pathway significantly affected by MF in TNBC. Immunoblots confirmed increase of the ERa/ERß ratio in TNBC, a well-studied marker for Tamoxifen-therapy sensitivity in TNBC. MTT cell viability assay and Annexin V staining confirmed increased sensitivity to Tamoxifen post treatment with low doses of MF, with up to 70% cell death at half the IC50 of Tamoxifen in TNBC. This study establishes a potential non-toxic therapeutic to supplement Estrogen-receptor targeting therapies in TNBC by increasing the ERa/ERß ratio. The data also evaluates the ERa/ERß ratio as a potential target for combination therapies in TNBC.

Citation Format: Fultang N, Klase Z, Mercier I, Peethambaran B. MicroRNA-mediated restoration of tamoxifen sensitivity in triple negative breast cancer through modulation of estrogen receptor alpha/beta ratio using Myrothamnus flabellifolius [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-13.
Abstract P5-09-04: Not presented
Authors: Wang X , Zhang X , Li F
Published: February 2018

This abstract was not presented at the symposium.
Abstract P5-12-02: B-vitamin intake from diet and supplements and breast cancer risk in middle-aged women: Results from the prospective NutriNet-Santé cohort
Authors: Egnell M , Fassier P , Lécuyer L , Zelek L , Vasson M-P , Hercberg S , Latino-Martel P , Galan P , Deschasaux M , Touvier M
Published: February 2018

Experimental studies suggest a protective effect of B-vitamins on breast cancer risk, potentially modulated by alcohol intake. However, epidemiological studies are limited, especially regarding non-folate B-vitamins. Furthermore, few of them included quantitative assessment of supplemental intake. This prospective study aimed at investigating the associations between intakes of B-vitamins (dietary, supplemental, total) and breast cancer risk. 27,853 women aged ≥45y from the NutriNet-Santé cohort (2009-2016) were included, with a median follow-up time of 4.2 years. Dietary data were collected using repeated 24h records. A specific questionnaire assessed dietary supplement use over a 12-month period. A composition database of 8000 supplements was developed. Associations were characterized by multivariable Cox models. 462 incident breast cancers were diagnosed. Dietary (HRQ4vs.Q1=0.74(0.55,0.99), P-trend=0.05), supplemental (HRQ4vs.Q1=0.61(0.38,0.98), P-trend=0.05) and total (HRQ4vs.Q1=0.67(0.50,0.91), P-trend=0.01) pyridoxine intakes were inversely associated with breast cancer risk. Total thiamin intake was borderline inversely associated with breast cancer risk (HRper 1-unit increment=0.78(0.61,1.00), P=0.05). Statistically significant interactions between alcohol consumption and B-vitamin (thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folate, and cobalamin) supplemental intake were observed, the latter being inversely associated with breast cancer risk in non-to-low alcohol drinkers but not in higher drinkers. This large prospective study, including quantitative assessment of supplemental intake, suggests a potential protective effect of pyridoxine and thiamin on breast cancer risk in middle-aged women.

Citation Format: Egnell M, Fassier P, Lécuyer L, Zelek L, Vasson M-P, Hercberg S, Latino-Martel P, Galan P, Deschasaux M, Touvier M. B-vitamin intake from diet and supplements and breast cancer risk in middle-aged women: Results from the prospective NutriNet-Santé cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-12-02.
Abstract P5-14-02: Effects of bazedoxifene and/or letrozole in the prevention of chemically-induced mammary cancers
Authors: Dunn BK , Grubbs CJ
Published: February 2018

Bazedoxifene is described as a third-generation selective estrogen receptor modulator (SERM) that has been approved in Europe for the prevention and treatment of postmenopausal osteoporosis. The agent has also been shown to have therapeutic activity against estrogen receptor positive (ER+) breast cancer. Our laboratory has evaluated bazedoxifene for chemopreventive efficacy against mammary cancers when given alone or in combination with the aromatase inhibitor letrozole. Initially, the agents were evaluated alone to determine effective chemopreventive doses in the methylnitrosourea (MNU) ER+ mammary cancer model using female Sprague-Dawley rats. Bazedoxifene was mixed directly into a standard (Teklad, 4% fat) diet, while letrozole was gavaged 7x/week (vehicle was ethanol: PEG 400, 10:90, v/v). When evaluated alone in rats receiving MNU at 50 days of age, bazedoxifene (started one week after MNU) at doses of 100 and 30 mg/kg diet decreased mammary cancer multiplicity by 93 and 88%, respectively. In a similar protocol, letrozole at a dose of 0.1 mg/kg BW/day reduced cancer multiplicity by 89%, while a dose of 0.05 mg/kg BW/day reduced the number by 47%. In a separate study evaluating lower doses of bazedoxifene (5 mg/kg diet) and letrozole (0.04 mg/kg BW/day), mammary cancer multiplicity was decreased by 73% by both agents. When the agents were given in combination at these lower dose levels, cancer number was reduced by 91%. It is obvious that bazedoxifene is as effective as letrozole in the prevention of ER+ mammary cancers. Furthermore, administration of the agents in combination suggests an additive effect. The large increase in body weight gain generally noted in letrozole treated rats was not observed in rats receiving bazedoxifene; of interest, rats receiving the combination also had no increase in body weights. Several published invitro studies suggested that bazedoxifene might also be effective in preventing ER- mammary cancers; e.g., the agent is a novel inhibitor of IL-6/GP130 protein-protein interactions using multiple ligand simultaneous docking and drug repositioning approaches that result in apoptosis. In an initial study using MMTV/Neu mice (N=21/group) that received dimethylbenzanthracene (DMBA), we showed that administering bazedoxifene (15 mg/kg diet) would reduce the mammary tumor multiplicity from 5.4/mouse in controls to 1.1/mouse (an 80% decrease). These studies suggested that bazedozxifene is superior to other similar agents in that both ER+ and ER- mammary cancers are prevented at non-toxic doses. Supported by NCI contract HHSN261201200021I, Task Order HHSN26100007.

Citation Format: Dunn BK, Grubbs CJ. Effects of bazedoxifene and/or letrozole in the prevention of chemically-induced mammary cancers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-14-02.
Abstract P5-14-03: Withdrawn
Authors: Britt KL , Dall GV , Vieusseux J , Seyed-Razavi Y , Godde N , Ludford-Menting M , Russell SM , Ashworth A , Anderson RL , Risbridger GP , Shackleton M
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P5-18-04: Bridging gaps in breast cancer care: A pilot forum for mental health professionals
Authors: Yang R , Rabinowitz B , Frank M , Schapira L , Wapnir I
Published: February 2018

Introduction:

Supporting the emotional needs of women diagnosed with breast cancer is a recognized priority for cancer clinicians and a core component of high quality care and survivorship programs. We hypothesized that mental health professionals would benefit from an educational program directed to enhance their practical knowledge of breast cancer.

Methods:

We designed an innovative educational forum for mental health professionals to broaden their practical knowledge regarding the physical and psychosocial effects of breast cancer. Diverse mental health professionals working in the Bay Area were invited. The day-long forum consisted of presentations and interactive discussion led by breast cancer physicians, mental health providers and patient advocates. An evaluation survey was administered at the end of the program. Descriptive statistics were performed of categorical results and open response items were aggregated.

Results:

Of 40 local pre-registrants, 18 mental health professionals (8 social workers, 6 psychologists, 3 other mental health professionals) attended. 88.2% of participants worked in a medical-based practice; 64.7% worked in an oncology-based practice. The majority of participants agreed the forum was relevant to their practice (82.3%), was well-organized (88.2%), would improve their care of patients (76.5%), and that they would recommend it to others (76.5%). The overall rating of the forum was positive (94.0%).

Conclusion:

The format and content of this forum represents a multidisciplinary educational model to enhance mental health professionals' understanding of breast cancer in order to better serve this unique patient population. Breast cancer clinicians, advocates and psychotherapists generated much enthusiasm and broad insights about meeting the psycho-emotional needs of breast cancer patients. This model can be replicated and extended to a national audience and to other cancer subpopulations.

Citation Format: Yang R, Rabinowitz B, Frank M, Schapira L, Wapnir I. Bridging gaps in breast cancer care: A pilot forum for mental health professionals [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-04.
Abstract P5-19-02: Withdrawn
Authors: Young-Afat D , Klassen A , Gibbons C , Vickers A , Cano S , Pusic A
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P5-19-07: Defining priorities for research: Interim results of the Canadian metastatic breast cancer priority setting partnership
Authors: Nixon N , Simmons C , Lemieux J , Verma S
Published: February 2018

Background: Research priorities are generally determined by funders and researchers without direct involvement and input from patients and caregivers. Certain disease areas have incorporated the patient voice to determine patient driven priorities. In this study, this approach was employed to better understand the needs and priorities of metastatic breast cancer patients and their caregivers.

Methods: This study was conducted using methodology outlined by the James Lind Alliance. A steering committee of patients, physicians, patient advocates, and allied health care professionals was assembled to oversee the research study. The initial survey collected unanswered research questions from patients, caregivers, and clinicians. Responses were collected and categorized by consensus of the steering committee. Here we present the results from the national survey.

Results: Between November 2016 and April 2017, 733 responses from 311 individuals were collected (62% patients, 11% physicians, 9% caregivers or relatives, 5% nurses/allied health professionals, 2% patient organization representatives, and 10% other). The main themes for key patient priorities are: 136 (19%) related to treatment and monitoring, 78 (11%) linked lifestyle and alternative therapy, 58 (8%) regarded tumour biology, 53 (7%) regarded psychosocial aspects, 46 (6%) to diagnosis, 35 (5%) to toxicity, 24 (3%) to prevention, and 17 (2%) to young or pre-menopausal population. Two hundred and eighty-six (39%) were considered out of scope. The most frequently identified priorities included the role of alternative therapies for improving survival, the role of immune therapy for treating metastatic breast cancer, and the potential for improving outcomes with early detection/surveillance with modern treatment and diagnostic modalities.

Conclusion: Patient derived research priorities in advanced breast cancer point to an improved understanding of alternative therapies, integration of immune therapy and a focus on early detection of relapse. These priorities should be addressed by the research community to meet the needs of our patients with advanced breast cancer.

Citation Format: Nixon N, Simmons C, Lemieux J, Verma S. Defining priorities for research: Interim results of the Canadian metastatic breast cancer priority setting partnership [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-19-07.
Abstract P5-21-05: Withdrawn
Authors: Smyth LM , Oliveira M , Ciruelos E , Tamura K , El-Khoueiry A , Mita A , You B , Renouf DJ , Sablin M-P , Lluch A , Mayer IA , Bando H , Yamashita H , Ambrose H , de Bruin E , Carr TH , Corcoran C , Foxley A , Lindemann JPO , Maudsley R , Pass M , Rutkowski A , Schiavon G , Banerji U , Scaltriti M , Taylor BS , Chandarlapaty S , Baselga J , Hyman DM
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P5-21-31: Treatment patterns and outcomes of pertuzumab in combination with trastuzumab and docetaxel as first-line treatment of metastatic HER-2 positive breast cancer : Comparison of Czech clinical registry and CLEOPATRA trial data
Authors: Studentova H , Petrakova K , Tesarova P , Buchler T , Chloupkova R , Hejduk K , Melichar B
Published: February 2018

Key words: pertuzumab, HER-2 positive, breast cancer

Background: The present retrospective analysis was conducted to evaluate efficacy of pertuzumab, a monoclonal antibody, used in combination with trastuzumab and docetaxel as first-line therapy for metastatic HER-2 positive breast cancer in real-world clinical practice. The database of the Czech Clinical Registry of cancer patients treated with pertuzumab was used.

Materials and methods: Data of patients included in the national registry were analyzed and the outcomes were compared with the results of the Phase III CLEOPATRA trial (Baselga et al 2012). The registry is estimated to cover at least 95% of patients treated with the regimen outside of clinical trials.

Results: : A total of 182 patients (mean age 56.5 years) were included in the present analysis. Patients had performance status of 0 (61.0%) or 1 (39%), 64.6% were postmenopausal, 62,6% had visceral disease and 36.8% received neo/adjuvant trastuzumab. The median progression-free survival of 21.2 months (95% CI 12.2–NR [not reached]) for patients included in the registry was longer, compared to 18.5 months reported in the CLEOPATRA trial, although the difference did not reach statistical significance (p=0.13). Best response was evaluable in 79.7% of patients. The overall response and disease control rates were 57.2% and 98.6%, respectively. Median overall survival has not been reached; the survival at 18 months was 86.6% (95% CI 75.7%-92.9%). Pertuzumab with trastuzumab and docetaxel was well tolerated with adverse events (AEs) attributed to pertuzumab reported in 8 patients. No AEs were life- threatening.

Conclusion: Pertuzumab in combination with trastuzumab and docetaxel is an effective and well-tolerated first-line therapy for patients with metastatic HER-2 positive breast cancer in real-world clinical practice setting. The PFS observed was consistent with data of CLEOPATRA trial.

Citation Format: Studentova H, Petrakova K, Tesarova P, Buchler T, Chloupkova R, Hejduk K, Melichar B. Treatment patterns and outcomes of pertuzumab in combination with trastuzumab and docetaxel as first-line treatment of metastatic HER-2 positive breast cancer : Comparison of Czech clinical registry and CLEOPATRA trial data [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-31.
Abstract P5-22-17: Withdrawn
Authors: Hayes MK , Bloomquist EV , Wright HR
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P5-22-19: Nipple sparing mastectomy in unselect patients: Experience of an academic center in the south of Brazil
Authors: Frasson A , Zerwes F , Souza A , Rossato N , Miranda I , Trindade V , Vollbrecht B , Santos M , Viegas J
Published: February 2018

INTRODUCTION: Nipple sparing mastectomy (NSM) consists in the complete excision of the breast gland, mantaining the subcutaneous tissue, skin and nipple-areola complex (NAC). Recently, the NSM was developed as a therapeutic option not just for the patients that need risk-reducing surgery, but also for patients that have tumors not involving the NAC.

OBJECTIVES: Evaluate the overall survival, disease-free survival and local recurrence of the patients that underwent NSM. The only exclusion criteria for NSM was lesion at the NAC.

MATERIAL AND METHODS: Retrospective study that evaluate the number of cases of NSM performed between 2003 and 2015 in a private sector in the south of Brazil.

RESULTS: A total of 224 patients underwent NSM during the period of 2003-2015. The mean age was 47 years. From the total, 43 patients underwent risk-reducing NSM and 181 therapeutic NSM (64 unilateral and 117 bilateral). In those cases of bilateral procedures all of them underwent risk-reducing surgery on the contralateral breast (there were no bilateral cancers). Of this 181 cases, 108 (59%) have familiar history of breast cancer, considering first, second and third-degree relatives. Twenty six patients (14%) have history of previous breast cancer diagnosed. In this group of 181 patients with therapeutic NSM, 29 (16%) developed any unfavorable outcomes, 13 (7%) local recurrence, 4 (2%) ipsilateral node recurrence, 3 (1,6%) contralateral recurrence and 9 (5%) distant metastasis. None of the local recurrences occurred at the NAC, neither the cited unfavorable outcomes occurred in the risk-reducing setting. In a median follow-up of 47,7 months, the overall survival was 95% (8 deaths related to breast cancer) and the disease-free survival was 83,7%.

CONCLUSIONS: The overall survival rates of 95% at 47 months of follow-up is similar to the literature rates, that range from 93 to 97% in 5 years, depending on study's inclusion criterias. In our study, 14% of patients had previous breast cancer and 59% of patients treated for breast cancer by NSM had positive familiar history of breast cancer. This results in an unselected group of patients confirms the safety of this therapeutic method as an option for breast cancer patients.

Citation Format: Frasson A, Zerwes F, Souza A, Rossato N, Miranda I, Trindade V, Vollbrecht B, Santos M, Viegas J. Nipple sparing mastectomy in unselect patients: Experience of an academic center in the south of Brazil [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-19.
Abstract P6-05-04: mRNA expression of PTK6V1 and PTKV2 in human breast cancer
Authors: El Hage Chehade H , Harvey A , Wazir U , Jiang WG , Mokbel K
Published: February 2018

BACKGROUND:

Protein tyrosine kinase 6 (PTK6) is an intracellular protein that is upregulated in several human cancers and its localization to the plasma-membrane facilitates its various oncogenic roles in breast cancer cell proliferation, survival, and migration. The full length protein (PTK6V1) and alternative splice variant (PTK6V2) seem to play different roles with the latter being negative regulator of the former.

In this study, the level of mRNA expression of PTK6V1 and PTK6V2 were assessed in normal and malignant breast tissue using real time Q-PCR in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters and clinical outcome.

MATERIALS AND METHODS:

Breast cancer tissues (n = 127) and normal background tissues (n = 33) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against beta-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analysed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period.

RESULTS:

The median copy number of transcripts of PTK6V1 were higher in malignant compared with normal breast tissue (23 vs.7) and overall increased with advancing tumour stage (374 vs. 13 for TNM3 vs. TNM1 respectively p=0.019 and 374 vs.23 for TNM3 vs. TNM2 p=0.0244). however these associations did reach statistical significance. PTK6V1 levels were associated with oestrogen receptor (ER) positivity (p = 0.061). The transcript levels were significantly higher in patients who developed recurrence (p=0.03) or died of breast cancer (p=0.003). PTK6V2 transcript levels were generally higher in normal breast tissue than in malignant tissues and decreased with increasing tumour stage and grade however these associations did not reach stastical significance. After a median follow up of 10 years, there was a trend for higher PTK6V2 expression to be associated with longer overall survival (OS) and disease free survival (DFS). PTK6V2/PTK6V1 ratio was a significant predictor of OS.

Conclusions

Our observations suggest that the two variants of PTK6 play opposing roles in mammary oncogenesis. These findings could have prognostic and therapeutic implications.

Citation Format: El Hage Chehade H, Harvey A, Wazir U, Jiang WG, Mokbel K. mRNA expression of PTK6V1 and PTKV2 in human breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-04.
Abstract P6-06-01: Comprehensive analysis of the DNA damage repair and maintenance pathways that regulate TNBC sensitivity to replication stress
Authors: Redwood AB , Seth S , Cai S , Piwnica-Worms H
Published: February 2018

Agents that induce replication stress, such as inhibitors of Chk1 or ATR, are advancing in clinical development and are being tested for treatment of various solid tumors, including triple-negative breast cancer (TNBC). While the preclinical data are encouraging, additional studies are needed to predict with precision (i) which patients will most likely benefit from these inhibitors, (ii) the genetic and proteomic contexts in which these inhibitors will provide maximum therapeutic benefit as a single agent, or require additional sensitization via combination with a targeted- or chemotherapeutic agent, and (iii) exactly which targeted/chemotherapeutic agent will provide maximum therapeutic benefit for combination with replication stress inducers. To address these challenges in TNBC, we have attempted to gain a comprehensive understanding of how the DNA damage response pathways regulate TNBC cell survival in response to Chk1 inhibitors, by performing high throughput loss-of-function screens.

We have identified genes whose loss induces death of TNBC cells in the presence of (1) CHK1i alone, (2) chemotherapy alone or (3) CHK1i plus chemotherapy. In addition, given the role of TP53 as the most frequently mutated gene in TNBC, we also determined whether distinct vulnerabilities could be identified in TNBC cells that are p53-proficient versus p53-deficient. Thus, we have also identified the top synthetic lethal interactions that are either common to both p53-proficient and p53-deficient TNBC, or unique to p53-deficient TNBC; we are currently performing in vitro studies to validate the identified mechanisms. We anticipate these studies to be applicable to other agents that induce replication stress and cell cycle checkpoint bypass. Ongoing in vivo preclinical studies, which utilize patient-derived xenografts (PDXs) of TNBC to validate these findings are expected to impact patient selection for clinical trials, and also allow us to predict which chemotherapeutic agents will be most effective for combination with different cell-cycle checkpoint inhibitors.

Citation Format: Redwood AB, Seth S, Cai S, Piwnica-Worms H. Comprehensive analysis of the DNA damage repair and maintenance pathways that regulate TNBC sensitivity to replication stress [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-06-01.
Abstract P6-06-03: Withdrawn
Authors: Cruz C , Bonache S , Montalban G , Castroviejo-Bermejo M , Llop-Guevara A , Vivancos A , Saura C , Arribas J , Díez O , Serra V , Gutiérrez-Enríquez S , Balmaña J
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P6-07-01: Withdrawn
Authors: Jiagge EM , Wong S , Gilani R , Luthur T , Bensenhaver J , Oppong JK , Kyei I , Adjei E , Awuah B , Li J , Carpten J , Wicha M , Newman L , Merajver S
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P6-08-01: Race and recurrence by PAM50 intrinsic subtype and ROR-PT score: The Carolina breast cancer study
Authors: Sun X , Reeder-Hayes KE , Kirk EL , Olsson L , Tse C-K , Bell MB , Earp HS , Carey LA , Perou CM , Olshan AF , Troester MA
Published: February 2018

Compared with white women, black women have higher breast cancer mortality. Racial differences have been reported in frequency of PAM50 intrinsic subtypes, and PAM50 intrinsic subtype is associated with prognosis. However, there is a paucity of data from large population-based studies with adequate representation of black women to evaluate its role in racial differences in breast cancer outcomes. We studied breast cancer recurrence in relation to PAM50 intrinsic subtype using data from the Carolina Breast Cancer Study Phase III (CBCS3), a large population-based prospective cohort study oversampled black women.

The current analysis included 472 black and 463 white women with stage I-III tumor and available Nanostring gene expression data for PAM50 subtype and risk of recurrence score (ROR-PT, a score calculated based on subtype, proliferation level, and tumor size; categorized as low, medium, and high). Cox proportional hazard regression was used to estimate the association of recurrence with PAM50 intrinsic subtype and ROR-PT, overall and stratified by race, adjusted for tumor size, grade, and lymph node status.

During a median follow-up of 5.78 years (range=0.39-8.22), 110 recurrent cases were identified (68 blacks and 42 whites). Consistently with previous data, basal-like tumors had the highest risk for recurrence (reference=luminal A, adjusted hazard ratio [HR]=2.85, 95% confidence interval [CI]=1.44-5.66), followed by luminal B (adjusted HR=2.35, 95%CI=1.18-4.69) and Her2-enriched (adjusted HR=2.19, 95%CI=1.01-4.74). High-ROR-PT score was also associated with increased risk in both black (adjusted HR=1.55, 95%CI=0.93-2.60) and white (adjusted HR=2.07, 95%CI=1.04-4.11). Recurrence rate for black women with medium/low ROR-PT scores was suggested higher than that for white women with similar scores (adjusted HR=1.54, 95%CI=0.69-3.42).

Our results demonstrate that PAM50 subtype and ROR-PT score are associated with breast cancer recurrence in both black and white women. Given the higher relative frequency of poor prognosis subtypes in black women, these findings help explain prognosis disparities by race.

Citation Format: Sun X, Reeder-Hayes KE, Kirk EL, Olsson L, Tse C-K, Bell MB, Earp HS, Carey LA, Perou CM, Olshan AF, Troester MA. Race and recurrence by PAM50 intrinsic subtype and ROR-PT score: The Carolina breast cancer study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-01.